Formation of chloromethoxybenzaldehyde during composting of organic household waste.
Standardized household waste was mixed with different litter amendments, straw, leaves, hardwood shavings, softwood shavings, paper, and sphagnum peat, resulting in six compost mixtures. In addition non-amended household waste was composted. Composting was done in small rotatable bins and compost samples were taken on a regular basis until day 590. Extraction and analysis of wet compost samples showed no evidence for the presence of chloroorganic compounds. Drying and re-wetting of compost samples, however, revealed that chloromethoxybenzaldehyde (CMBA) was formed in all composts at concentrations varying between 5.6 and 73.4 microg kg(-1) dry matter. CMBA was not present in the original materials. During composting, there was a clear positive relation between formation of CMBA and microbial activity, as indicated by C losses and temperature. Formation took place during the most intensive phase of composting when C losses were highest. Under anaerobic conditions, however, which prevailed initially in the non-amended compost, no CMBA was formed. Calculation of total amounts of CMBA in composts revealed that there was a small decrease during storage in the hardwood, peat, and softwood composts. However, all composts contained CMBA after 590 days. The mean concentration was 33.4 microg kg(-1) dry matter (s.d. = 21.9). Possible biocidal effects of composts when used in cultivation may be explainable by the presence of natural toxic compounds formed during composting.


Gold nanoparticle-fluorophore complex for conditionally fluorescing signal mediator.
Fluorescent contrast agents with high specificity and sensitivity are valuable for accurate disease detection and diagnosis. Spherical gold nanoparticles (GNPs) can be smartly utilized for developing highly effective agents. The strong electromagnetic (plasmon) field on their surface can be very effective in influencing the electrons of fluorophores and, thus, manipulating the fluorescence output (i.e., either quenching or enhancement). Fluorescence quenching can be used for negative sensing, or for conditional de-quenching to increase the specificity. Fluorescence enhancement allows sensing to be more sensitive. The level of fluorescence alteration depends on the GNP size, the excitation and emission wavelengths and quantum yield of the fluorophore, and the distance between the GNP and the fluorophore. To understand the mechanisms of the fluorescence change by GNP, we have theoretically analyzed the parameters involved in the fluorescence alteration for commonly used fluorophores, with an emphasis on quenching. The results showed that the fluorescence of fluorophores with the excitation (Ex) and emission (Ex) wavelengths close to the GNP resonance peak tended to be significantly quenched by GNPs. For those fluorophores emitting fluorescence in red or near infrared, to achieve quenching, the distance between GNP and the fluorophore was required to be very short. In general, a shorter distance resulted in more quenching. Bigger GNPs require a shorter distance to achieve the same level of quenching. The fluorescence of a fluorophore with a lower quantum yield (especially the one with emission in far-red or near-infrared) is more difficult to be quenched by GNPs (requires very short distance). Instead, it can be enhanced. Based on the theoretical study, we have developed a near-infrared contrast agent, i.e., Cypate conjugated GNP via a short peptide spacer. Normally the fluorescence of Cypate was quenched. The spacer has a motif of a substrate for urokinase type plasminogen activator (uPA; cancer-secreting enzyme). This contrast agent emits fluorescence only in the presence of uPA, where the uPA cleaves the spacer. This design can be used in characterization of the cancer type and also in diagnosing other diseases with signature enzymes.


[Dieldrin, aldrin, endrin, isodrin, endosulfan 1 and 2 on fish in the Gulf of Gdańsk].
The residues of dieldrin, aldrin, endrin, isodrin, endosulfan 1 and 2 has been determined in a several species of fish caught in the Gulf of Gdańsk in 1992. The method of measurement was capillary gas chromatograph and low resolution mass spectrometry (HRGC/LRMS) after a nondestructive extraction and clean-up step with a further fractionation of the extract on Florisil column. Apart from dieldrin no other cyclodiene pesticides studied were found in fishes in detectable amounts, and for dieldrin concentrations ranged from 0.84 to 6.6 ng/g wet weight.


Synthesis and antibacterial activity of asparagine derivatives of aminobenzylpenicillin.
In order to improve the antibacterial activity of aminobenzylpenicillin, penicillin derivatives having an asparagine moiety in the 6-acyl side chain (11a approximately g, 12a, b, f, g) were synthesized. The structure-activity relationship of new penicillins, N4-alkyl-asparaginylaminobenzylpenicillins, was investigated. N4-Methyl-D-asparaginylamoxicillin (11a), TA-058, was found to possess a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria. In acute toxicity, TA-058 showed good tolerance in mice (LD50 greater than 10 g/kg, i.v.).


Evaluation of enantiomeric purity of magnesium-L-aspartate dihydrate.
Magnesium supplementation in form of organic magnesium salts is a very popular practice. We examined the enantiomeric purity of "Magnesium aspartate dihydrate" monographed in the European Pharmacopeia. A chiral capillary zone electrophoresis using (2-hydroxypropyl)-β-cyclodextrin coupled to laser induced fluorescence detection and a HPLC-fluorescence method with chiral derivatization using o-phthaldialdehyde and N-acetyl-L-cysteine as an orthogonal method were developed and validated. Two batch samples of this substance and three drug products containing the salt were analyzed by means of both methods. The concentration of the D-enantiomer of aspartic acid ranged from 0.03 to 0.12%. Simulations of the synthesis revealed that the d-aspartic acid content is elevated if the dissolution of L-aspartic acid was performed at acidic pH values.


Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: a randomized, placebo-controlled crossover trial.
The reported effects of flavanol-rich foods such as cocoa, dark chocolate, and apples on blood pressure and endothelial function may be due to the monomeric flavanols [mainly (-)-epicatechin (EC)], the oligomeric flavanols [procyanidins (PCs)], or other components. Reports of well-controlled intervention studies that test the effects of isolated oligomeric flavanols on biomarkers of cardiovascular health are lacking. We studied the acute and chronic effects of an EC-rich apple flavanol extract and isolated apple PCs on systolic blood pressure (BP) and other cardiometabolic biomarkers. Forty-two healthy men and women with moderately elevated BP completed this randomized, double-blind, placebo-controlled, 4-arm crossover trial. Participants ingested a single dose of an apple flavanol extract (70 mg monomeric flavanols, 65 mg PCs), a double dose of this extract (140 mg monomeric flavanols, 130 mg PCs), an apple PC extract (130 mg PCs, 6.5 mg monomeric flavanols), or placebo capsules once daily for 4 wk, in random order. Biomarkers of cardiovascular disease risk and vascular function were measured before and 2 h after ingestion of the first dose and after the 4-wk intervention. Compared with placebo, none of the isolated flavanol treatments significantly (P < 0.05) changed systolic or diastolic BP (peripheral and aortic), plasma nitric oxide (NO) reaction products, or measures of arterial stiffness (carotid femoral pulse-wave velocity, brachial-ankle pulse-wave velocity, or Augmentation Index) after 2 h or 4 wk of the intervention. There were no changes in plasma endogenous metabolite profiles or circulating NO; endothelin 1; total, HDL, or LDL cholesterol; triglycerides; fasting glucose; fructosamine; or insulin after 4 wk of the intervention. Our data suggest that, in isolation, neither monomeric flavanols nor PCs affect BP, blood lipid profiles, endothelial function, or glucose control in individuals with moderately elevated BP. The reported benefits of consuming flavanol-rich cocoa, chocolate, and apple products appear to be dependent on other components, which may work in combination with monomeric flavanols and PCs. This trial was registered at www.clinicaltrials.gov as NCT02013856.


Role of Remote Interfacial Phonon (RIP) Scattering in Heat Transport Across Graphene/SiO2 Interfaces.
Heat transfer across interfaces of graphene and polar dielectrics (e.g., SiO2) could be mediated by direct phonon coupling, as well as electronic coupling with remote interfacial phonons (RIPs). To understand the relative contribution of each component, we develop a new pump-probe technique called voltage-modulated thermoreflectance (VMTR) to accurately measure the change of interfacial thermal conductance under an electrostatic field. We employed VMTR on top gates of graphene field-effect transistors and find that the thermal conductance of SiO2/graphene/SiO2 interfaces increases by up to ΔG ≈ 0.8 MW m-2 K-1 under electrostatic fields of <0.2 V nm-1. We propose two possible explanations for the small observed ΔG. First, because the applied electrostatic field induces charge carriers in graphene, our VMTR measurements could originate from heat transfer between the charge carriers in graphene and RIPs in SiO2. Second, the increase in heat conduction could be caused by better conformity of graphene interfaces under electrostatic pressure exerted by the induced charge carriers. Regardless of the origins of the observed ΔG, our VMTR measurements establish an upper limit for heat transfer from unbiased graphene to SiO2 substrates via RIP scattering; for example, only <2% of the interfacial heat transport is facilitated by RIP scattering even at a carrier concentration of ∼4 × 1012 cm-2.


Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1beta converting enzyme deficient mice.
Interleukin-1beta (IL-1beta) is expressed after cerebral ischemia and blocking its action reduces subsequent ischemic brain injury. However, the mechanisms by which IL-1beta affects ischemic brain are not understood. To investigate the role of IL- 1beta in regulation of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) during focal cerebral ischemia, the authors studied mutant mice deficient in the IL-1 converting enzyme (ICE) gene (ICE knockout [KO] mice). Ninety-four adult male ICE KO and wild-type mice underwent 3, 6, 12, and 24 hours of permanent middle cerebral artery occlusion using the suture method. Expression of TNF-alpha and ICAM-1 protein in ischemic brain was examined using immunohistochemistry and Western blot analysis. Neither ICE KO nor wild-type mice had significant differences in CBF and body temperature measurements during the ischemic procedure. TNF-alpha expression increased in the ipsilateral hemisphere after 3 hours of occlusion, peaked at 12 hours and decreased at 24 hours of ischemia in both ICE KO and wild-type mice. ICAM-1 immunohistochemistry showed that the number of ICAM-1-positive vessels in the ischemic hemisphere was reduced in ICE KO mice (P < .05). Western blot analysis showed that ICAM-1 protein expression was significantly attenuated in the ipsilateral hemisphere in the ICE KO mice, which paralleled the immunohistochemistry results. The authors' results indicate that TNF-alpha expression is increased in both ICE KO and wild-type mice suggesting that TNF-alpha expression is not related to or upregulated by IL-1beta . ICAM-1 expression is significantly reduced in the ICE KO mice suggesting that IL-1beta plays an important role in the upregulation of adhesion molecules during focal cerebral ischemia.


Morphometric and cytogenetic characteristics of testicular germ cells and Sertoli cell secretory function in men with non-mosaic Klinefelter's syndrome.
Klinefelter's syndrome is the most frequent chromosomal abnormality in infertile men. In this study, the chromosomes of round spermatids and spermatogonia/primary spermatocytes from men with non-mosaic Klinefelter's syndrome were examined, together with the Sertoli cell secretory function and sperm morphometry. Twenty-four men with non-mosaic Klinefelter's syndrome and nine men with obstructive azoospermia underwent therapeutic testicular biopsy. When spermatozoa in the final filtrate were present, they were processed for sperm morphometry or ICSI. Sperm morphometry was evaluated by the maximal length and width of the sperm head, the length of the midpiece and the ratio of the acrosomal region to the total surface area of the head. When round spermatids were present, they were processed for fluorescent in-situ hybridization (FISH). FISH was also applied to fragments of seminiferous tubules. Sertoli cell secretory function was measured by the amount of androgen binding protein (ABP) secreted in vitro. More than 93% of the evaluated round spermatids were normal. The proportions of 24,XY and of 24,XX round spermatids to the total number were significantly larger in men with Klinefelter's syndrome than in obstructed azoospermic men. Men with Klinefelter's syndrome who had spermatozoa in their testicular tissue (n = 12) were positive for both 46,XY and 47,XXY spermatogonia in their seminiferous tubules. In contrast, men with Klinefelter's syndrome without spermatozoa in their testicular tissue (n = 12) were positive for 47,XXY spermatogonia but negative for 46,XY spermatogonia in their seminiferous tubules. ABP profiles were significantly smaller in men with Klinefelter's syndrome who were negative for spermatozoa compared with men who were positive. Four pregnancies were achieved and five healthy babies were born. This study suggests that few 46,XXY spermatogonia undergo meiosis with an XX pairing and a Y univalent type of pairing. Hyperhaploid round spermatids (24,XY and 24,XX) may be produced by meiosis of 47,XXY spermatogonia. Men with Klinefelter's syndrome who are negative for testicular spermatozoa have a greater degree of Sertoli cell secretory dysfunction compared with men with Klinefelter's syndrome who are positive for spermatozoa. There are several defects in sperm morphometry with functional significance in men with Klinefelter's syndrome.


Hemostatic markers before operation in patients with acutely symptomatic nonruptured and ruptured infrarenal abdominal aortic aneurysm.
In patients with acutely symptomatic but nonruptured abdominal aortic aneurysm (AAA), emergent repair is associated with an increased mortality rate as compared with semi-elective repair. Previous results have shown that ruptured but not asymptomatic AAA repair is associated with intense thrombin generation and inhibition of systemic fibrinolysis. The purpose of this study was to determine whether circulating markers of coagulation and fibrinolysis may be used to distinguish acutely symptomatic nonruptured and ruptured AAA. A prospective study was performed of 44 patients who underwent emergency AAA repair for suspected rupture. Platelet count, fibrinogen level, prothrombin time, activated partial thromboplastin time, tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI) activity, prothrombin fragment (PF) 1+2 level, and D dimer level were measured before surgery. When compared with ruptured AAAs (n = 37), acutely symptomatic nonruptured AAAs (n = 7) were associated with increased fibrinogen level (P =.033), reduced activated partial thromboplastin time (P =.043), increased t-PA activity (P =.023), reduced PAI activity (P =.005), reduced PF 1+2 level (P =.001), and reduced D dimer level (P =.005; all P values determined with Mann-Whitney test). The differences in t-PA activity (P =.01), PAI activity (P =.004), and PF 1+2 level (P =.01) persisted in patients whose conditions were normotensive. In all patients, a PF 1+2 level of greater than or equal to 2.5 nmol/L was associated with a sensitivity, specificity, and positive and negative predictive value for rupture of 89%, 86%, 97%, and 60%, respectively. In patients whose conditions were normotensive, PAI activity of greater than or equal to 16 AU/mL was associated with a sensitivity, specificity, and positive and negative predictive value of 83%, 100%, 100%, and 88%, respectively. These data show that acutely symptomatic nonruptured AAA is associated with increased systemic fibrinolysis (caused by reduced fibrinolytic inhibition) and reduced thrombin generation as compared with rupture. Preoperative hemostatic markers, particularly PF 1+2 level and PAI activity, may distinguish acutely symptomatic nonruptured from ruptured AAA.


Dexamethasone decreases substance P expression in human tendon cells: an in vitro study.
Glucocorticoid injections are used by rheumatologists to treat chronic tendinopathy. Surprisingly, the mechanisms by which corticosteroids induce pain relief in this condition have not been investigated. Previous studies have shown local substance P (SP) levels to be correlated with tendon pain and tissue pathology. The objective of this study was to determine whether SP production in human tenocytes is modulated by exposure to dexamethasone. Human tendon fibroblasts were cultured in the presence or absence of dexamethasone (1-400 nM), an inhibitor of the glucocorticoid receptor, RU486, recombinant TGF-β (2.5 or 5.0 ng/ml) or an inhibitor of the TGF-β receptor (A83.01), recombinant human IL-1β and IL-6. Expression levels of the genes encoding for SP (TAC1) and its preferred receptor (NK1R), IL-1α, IL-1β and IL-6 were determined with quantitative PCR and protein levels of SP were examined by EIA and western blot. Exposure of human tendon cells to dexamethasone resulted in a time-dependent reduction of mRNA for SP in both hamstrings and Achilles tenocytes, whereas NK1R was unaffected. The reduction of SP mRNA was dependent on signalling through the glucocorticoid receptor. SP protein was substantially decreased by dexamethasone. Dexamethasone also prevented induction of SP by IL-1β and by cyclic mechanical loading. This study demonstrates that dexamethasone treatment of human tendon fibroblasts reduces the expression of SP through a glucocorticoid receptor-dependent pathway. Drugs interfering with SP signalling could be a future target in the treatment of tendinopathy.


A tipping point in parapatric speciation.
More than two loci are involved in reproductive isolation in most cases of putative recent speciation. We study the speciation between two geographically isolated populations connected by infrequent migration, in which incompatibility is controlled by quantitative loci. Incompatibility genetic distance is defined as the fraction of compatibility controlling loci that are different between individuals. Speciation is established when genetic distance reaches a threshold level in spite of occasional migration and subsequent hybridization that reduce genetic distance. With stochastic analysis, we investigate how the time to speciation depends on the manner in which the magnitude of incompatibility increases with genetic distance. Results are: (1) The time to speciation is short if the migration rate is smaller than the mutation rate, or if intermediate levels of genetic distance cause mild incompatibility, making migrants less effective in reducing genetic distance. (2) Genetic distance may fluctuate around a positive quasi-equilibrium level for a long time, and suddenly show a quick passage to speciation when it goes beyond a "tipping point." Notably a gradual increase in incompatibility can result in a sudden and rapid formation of a new species. (3) Speciation becomes very slow if incompatibility is effective for individuals differing at only one locus. These findings provide testable predictions on reproductive traits controlled by specific incompatibility accumulation forms that facilitate the speciation process.


Shock treatment: using immersive digital realism to restage and re-examine milgram's 'obedience to authority' research.
Attempts to revisit Milgram's 'Obedience to Authority' (OtA) paradigm present serious ethical challenges. In recent years new paradigms have been developed to circumvent these challenges but none involve using Milgram's own procedures and asking naïve participants to deliver the maximum level of shock. This was achieved in the present research by using Immersive Digital Realism (IDR) to revisit the OtA paradigm. IDR is a dramatic method that involves a director collaborating with professional actors to develop characters, the strategic withholding of contextual information, and immersion in a real-world environment. 14 actors took part in an IDR study in which they were assigned to conditions that restaged Milgrams's New Baseline ('Coronary') condition and four other variants. Post-experimental interviews also assessed participants' identification with Experimenter and Learner. Participants' behaviour closely resembled that observed in Milgram's original research. In particular, this was evidenced by (a) all being willing to administer shocks greater than 150 volts, (b) near-universal refusal to continue after being told by the Experimenter that "you have no other choice, you must continue" (Milgram's fourth prod and the one most resembling an order), and (c) a strong correlation between the maximum level of shock that participants administered and the mean maximum shock delivered in the corresponding variant in Milgram's own research. Consistent with an engaged follower account, relative identification with the Experimenter (vs. the Learner) was also a good predictor of the maximum shock that participants administered.


Molecular basis and bleeding manifestations of factor XI deficiency in 11 Turkish families.
Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by variable bleeding tendency. In the present study, the gene encoding FXI (F11) was analyzed by direct sequencing in 33 individuals belonging to 11 unrelated Turkish families, and the bleeding tendency was quantitatively assessed by means of a bleeding questionnaire in 27 individuals with low FXI clotting activity and/or mutated F11 gene. We identified 10 distinct mutations (five missense, three nonsense and two splice site), four of which were novel. No mutation was found in one family. Of the four novel mutations, homozygosity for a c.89T>C (p.Phe30Ser) mutation and compound heterozygosity for a c.646G>A (p.Asp216Asn) mutation with the known c.403G>T (p.Glu135) type II Jewish mutation were associated with severe deficiency, whilst heterozygosity for the novel c.1655A>C (p.His552Arg) and c.1627G>A (p.Glu543Lys) mutations was associated with partial deficiency. p.Glu135 was found in 19% (5/27) of the mutated alleles. Bleeding score was positive in 57% (4/7) of individuals with severe and 39% (7/18) of those with partial deficiency. It was significantly correlated with clinical severity of bleeding (r = 0.43, P = 0.02), but not with FXI clotting activity (P > 0.05). There was no optimal cut-off level of the bleeding score that could predict FXI deficiency. We conclude that the spectrum of mutations found in this study reflects the genetic heterogeneity of FXI deficiency in the Turkish population. Quantitative assessment of the bleeding symptoms by a bleeding questionnaire seems to be useful for evaluating the severity of bleeding episodes, but it can not be recommended as a screening tool for FXI deficiency.


Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality.
To examine the cardiovascular risk factors in patients with psoriasis and the association between psoriasis and coronary artery, cerebrovascular, and peripheral vascular diseases. Observational study. Large Department of Veterans Affairs hospital. The study included 3236 patients with psoriasis and 2500 patients without psoriasis (controls). Using International Classification of Diseases, Ninth Revision, Clinical Modification, codes, we compared the prevalence of traditional cardiovascular risk factors and other vascular diseases as well as mortality between patients with psoriasis and controls. Similar to previous studies, we found a higher prevalence of diabetes mellitus, hypertension, dyslipidemia, and smoking in patients with psoriasis. After controlling for these variables, we found a higher prevalence not only of ischemic heart disease (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.51-2.11) but also of cerebrovascular (OR, 1.70; 95% CI, 1.33-2.17) and peripheral vascular (OR, 1.98; 95% CI, 1.32-2.82) diseases in patients with psoriasis compared with controls. Psoriasis was also found to be an independent risk factor for mortality (OR, 1.86; 95% CI, 1.56-2.21). Psoriasis is associated with atherosclerosis. This association applies to coronary artery, cerebrovascular, and peripheral vascular diseases and results in increased mortality.


Eight-year follow-up of Axenfeld-Rieger syndrome with Turner syndrome.
To report a case of Turner syndrome associated with iridogoniodysgenesis accompanied by somatic malformations. A 29-year-old woman underwent complete ophthalmologic and general examination. Incomplete development of the angle with iris stromal hypoplasia and prominent posterior embryotoxon with iris adhesions were noted. Disc drusen was confirmed by ultrasonography. Visual fields were normal other than bilateral enlargement of blind spot. Intraocular pressure was under 21 mm Hg during 8 years of follow-up without medication. The patient had atrial septal defect, sensorineural hearing loss, polycystic ovaries, hirsutism, glomerulosclerosis, dental anomalies, and low intelligence. A chromosome analysis revealed that she had mosaic Turner syndrome with a 45,X/46,XX karyotype. Few reported cases in the literature describe the coexistence of Axenfeld-Rieger syndrome and Turner syndrome mosaicism. Somatic and anterior chamber malformations in this patient represent a developmental disorder of the neural crest. General examination and chromosomal analysis are indicated in patients presenting with anterior chamber dysgenesis.


Impact of Clinical Pharmacy Specialists on the Design and Implementation of a Quality Improvement Initiative to Decrease Inappropriate Medications in a Veterans Affairs Emergency Department.
As the proportion of older adult patients who interface with the health care system grows, clinical pharmacy specialists (CPS) have a pivotal role in reducing potentially inappropriate medication (PIM) use in this population. To (a) describe CPS involvement in the design and implementation of a quality improvement (QI) initiative to decrease PIM prescribing in a Veterans Affairs (VA) emergency department (ED) and (b) report on changes in PIM prescribing before and after the initiative. Enhancing Quality of Prescribing Practices for Veterans Discharged from the Emergency Department (EQUiPPED) is an ongoing multisite QI project that aims to decrease ED PIM prescribing. We used a mixed-method approach that applied qualitative and quantitative measures in describing the CPS role and evaluating PIM rates. PIMs were defined using the 2012 Beers Criteria. We reported monthly PIM rates in patients aged 65 years and older who were discharged from the ED from January 2012 to November 2014. A piecewise, nonlinear regression model evaluated the pattern in PIM prescriptions over time. At the Durham, North Carolina, VA Medical Center, a total of 4 CPS were involved with tailoring the design and implementation of the EQUiPPED intervention for local use. CPS input led to 3 key innovations: academic detailing performed by a physician-CPS pair, medication alert messages identifying medications as PIMs in the computerized patient record system, and automated reports describing the frequency and type of PIMs prescribed by each ED provider. Between February 2013 and November 2014, 73 ED providers received the academic detailing. The ED facility experienced a relative reduction of 47.5% in the rate of PIM prescribing over the observation period. This QI project resulted in a meaningful decrease in PIM prescribing in older ED adults. CPS contributions to QI can extend beyond pharmacotherapy and provider education to also include information technology tools using formulary management expertise.


Torsades de pointes with high-dose loperamide.
A 41year-old male presented with torsades de pointes. The patient was taking over 100mg of loperamide per day to self-medicate for chronic pain. Coronary angiography, cardiac magnetic resonance imaging, and genetic testing were negative for pre-disposing ischemia, cardiomyopathy, or genetic variant respectively. Patients without predisposing genetic or cardiac abnormalities are at risk of life-threatening QTc prolongation and torsades with use of high-dose loperamide. The authors suggest consideration of regulating the quantity of loperamide that can be purchased at a single time similar to the regulations in place for other over-the-counter medications with high potential for misuse.


Extracranial Carotid Plaque Calcification and Cerebrovascular Ischemia: A Systematic Review and Meta-Analysis.
Although coronary calcification quantification is an established approach for cardiovascular risk assessment, the value of quantifying carotid calcification is less clear. As a result, we performed a systematic review and meta-analysis to evaluate the association between extracranial carotid artery plaque calcification burden and ipsilateral cerebrovascular ischemic events. A comprehensive literature search was performed in the following databases: Ovid MEDLINE(R) 1946 to July 6, 2022; OVID Embase 1974 to July 6, 2022; and The Cochrane Library (Wiley). We performed meta-analyses including studies in which investigators performed a computed tomography assessment of calcification volume, percentage, or other total calcium burden summarizable in a single continuous imaging biomarker and determined the association of these features with the occurrence of ipsilateral stroke or transient ischemic attack. Our overall meta-analysis consisted of 2239 carotid arteries and 9 studies. The presence of calcification in carotid arteries ipsilateral to ischemic stroke or in stroke patients compared with asymptomatic patients did not demonstrate a significant association with ischemic cerebrovascular events (relative risk of 0.75 [95% CI, 0.44-1.28]; P=0.29). When restricted to studies of significant carotid artery stenosis (>50%), the presence of calcification was associated with a reduced risk of ischemic stroke (relative risk of 0.56 [95% CI, 0.38-0.85]; P=0.006). When the analysis was limited to studies of patients with mainly nonstenotic plaques, there was an increased relative risk of ipsilateral ischemic stroke of 1.72 ([95% CI, 1.01-2.91]; P=0.04). Subgroup meta-analyses of total calcium burden and morphological features of calcium showed wide variability in their strength of association with ischemic stroke and demonstrated significant heterogeneity. The presence of calcification in carotid plaque confers a reduced association with ipsilateral ischemic events, although these results seem to be limited among carotid arteries with higher degrees of stenosis. Adoption of carotid calcification measures in clinical decision-making will require additional studies providing more reproducible and standardized methods of calcium characterization and testing these imaging strategies in prospective studies.


Prostate cancer and acromegaly.
Acromegalic patients have an increased prevalence of prostatic disorders compared to age-matched healthy subjects. Increased size of the whole prostate or the transitional zone, together with an elevated incidence of other structural changes, such as nodules, cysts, and calcifications, have been reported. Prostate enlargement in young acromegalic patients with low testosterone levels due to central hypogonadism supports the hypothesis that chronic GH and IGF-I excess cause prostate hyperplasia. The relationship between prostatic carcinoma and acromegaly is, until now, only circumstantial. Long-term follow-up of these patients is necessary since epidemiologic studies showed association between serum IGF-I levels in the upper normal limit and prostate cancer in the general population. This review approaches prostate diseases in patients with acromegaly.


An impact-driven dynamo for the early Moon.
The origin of lunar magnetic anomalies remains unresolved after their discovery more than four decades ago. A commonly invoked hypothesis is that the Moon might once have possessed a thermally driven core dynamo, but this theory is problematical given the small size of the core and the required surface magnetic field strengths. An alternative hypothesis is that impact events might have amplified ambient fields near the antipodes of the largest basins, but many magnetic anomalies exist that are not associated with basin antipodes. Here we propose a new model for magnetic field generation, in which dynamo action comes from impact-induced changes in the Moon's rotation rate. Basin-forming impact events are energetic enough to have unlocked the Moon from synchronous rotation, and we demonstrate that the subsequent large-scale fluid flows in the core, excited by the tidal distortion of the core-mantle boundary, could have powered a lunar dynamo. Predicted surface magnetic field strengths are on the order of several microteslas, consistent with palaeomagnetic measurements, and the duration of these fields is sufficient to explain the central magnetic anomalies associated with several large impact basins.


Fly Pollination of Kettle Trap Flowers of Riocreuxiatorulosa (Ceropegieae-Anisotominae): A Generalized System of Floral Deception.
Elaborated kettle trap flowers to temporarily detain pollinators evolved independently in several angiosperm lineages. Intensive research on species of Aristolochia and Ceropegia recently illuminated how these specialized trap flowers attract particular pollinators through chemical deception. Morphologically similar trap flowers evolved in Riocreuxia; however, no data about floral rewards, pollinators, and chemical ecology were available for this plant group. Here we provide data on pollination ecology and floral chemistry of R. torulosa. Specifically, we determined flower visitors and pollinators, assessed pollen transfer efficiency, and analysed floral scent chemistry. R. torulosa flowers are myiophilous and predominantly pollinated by Nematocera. Pollinating Diptera included, in order of decreasing abundance, male and female Sciaridae, Ceratopogonidae, Scatopsidae, Chloropidae, and Phoridae. Approximately 16% of pollen removed from flowers was successfully exported to conspecific stigmas. The flowers emitted mainly ubiquitous terpenoids, most abundantly linalool, furanoid (Z)-linalool oxide, and (E)-β-ocimene-compounds typical of rewarding flowers and fruits. R. torulosa can be considered to use generalized food (and possibly also brood-site) deception to lure small nematocerous Diptera into their flowers. These results suggest that R. torulosa has a less specific pollination system than previously reported for other kettle trap flowers but is nevertheless specialized at the level of Diptera suborder Nematocera.


The medical and surgical treatment in secondary and tertiary hyperparathyroidism. Review.
Hyperparathyroidism is an alteration of the pathophysiological parathyroid hormone (PTH) secretion due or an independent and abnormal release (primary or tertiary hyperparathyroidism) by the parathyroid or an alteration of calcium homeostasis that stimulates the excessive production of parathyroid hormone (secondary hyperparathyroidism). There is not a standard, clinical or surgical, treatment for hyperparathyroidism. We review current diagnostic and therapeutic methods. In secondary hyperparathyroidism (2HPT) there is a progressive hyperplasia of the parathyroid glands and an increased production of parathyroid hormone. Several causes are proposed: chronic renal insufficiency, vitamin D deficiency, malabsorption syndrome. The tertiary hyperparathyroidism (3HPT) is considered a state of excessive autonomous secretion of PTH due to long-standing 2HPT and it's usually the result of a lack of suppression in the production of PTH. The pathophysiological implications are both skeletal and extraskeletal: it damages the cardiovascular system, nervous system, immune, hematopoietic and endocrine system. The introduction of new drugs has improved the survival of these patients, allowing the inhibition of the synthesis of PTH. Indication for surgical treatment is unresponsive medical therapy. There are no large prospective studies that comparing the medical and surgical treatment. The choice is not unique and we have to consider the singolar case and the clinical condition of the patient.


Ethical issues in family violence research in healthcare settings.
Research ethics is always important. However, it is especially crucial with sensitive research topics such as family violence. The aim of this article is to describe and discuss some crucial issues regarding intimate partner violence and child maltreatment, based on the authors' own research experiences. We focus on and discuss examples concerning the definition of family violence, research design, ethical approval, participant recruitment and safety and data collection and processing. During the research process, the significance of teamwork is emphasized. Support provided by the participants to each other and support given by experienced researchers within the team is very important for high ethical standards.


Patient-controlled postoperative analgesia with alfentanil. Adaptive, on-demand intravenous alfentanil or pethidine compared double-blind for postoperative pain.
A double-blind study comparing alfentanil and pethidine given intravenously by an adaptive, patient-controlled on-demand analgesic system is described. It was demonstrated that, despite its well-known rapid onset of effect, alfentanil took several hours to achieve good quality analgesia. Nevertheless, it had a much more predictable consumption pattern than pethidine. Alfentanil was associated with significantly less sedation during the postoperative period than pethidine, and was also associated with a significantly greater urine output during the 24-hour period of study. There was no evidence of tolerance or accumulation with either of the two drugs.


The cysteine desulfurase, IscS, has a major role in in vivo Fe-S cluster formation in Escherichia coli.
The cysteine desulfurase, IscS, provides sulfur for Fe-S cluster synthesis in vitro, but a role for IscS in in vivo Fe-S cluster formation has yet to be established. To study the in vivo function of IscS in Escherichia coli, a strain lacking IscS was constructed and characterized. Using this iscS deletion strain, we have observed decreased specific activities for proteins containing [4Fe-4S] clusters from soluble (aconitase B, 6-phosphogluconate dehydratase, glutamate synthase, fumarase A, and FNR) and membrane-bound proteins (NADH dehydrogenase I and succinate dehydrogenase). A specific role for IscS in in vivo Fe-S cluster assembly was demonstrated by showing that an Fe-S cluster independent mutant of FNR is unaffected by the lack of IscS. These data support the conclusion that, via its cysteine desulfurase activity, IscS provides the sulfur that subsequently becomes incorporated during in vivo Fe-S cluster synthesis. We also have characterized a growth phenotype associated with the loss of IscS. Under aerobic conditions the deletion of IscS caused an auxotrophy for thiamine and nicotinic acid, whereas under anaerobic conditions, only nicotinic acid was required. The lack of IscS also had a general effect on the growth of E. coli because the iscS deletion strain grew at half the rate of wild type in many types of media even when the auxotrophies were satisfied.


Peptides as Pharmacological Carriers to the Brain: Promises, Shortcomings and Challenges.
Central nervous system (CNS) diseases are among the most difficult to treat, mainly because the vast majority of the drugs fail to cross the blood-brain barrier (BBB) or to reach the brain at concentrations adequate to exert a pharmacological activity. The obstacle posed by the BBB has led to the in-depth study of strategies allowing the brain delivery of CNS-active drugs. Among the most promising strategies is the use of peptides addressed to the BBB. Peptides are versatile molecules that can be used to decorate nanoparticles or can be conjugated to drugs, with either a stable link or as pro-drugs. They have been used to deliver to the brain both small molecules and proteins, with applications in diverse therapeutic areas such as brain cancers, neurodegenerative diseases and imaging. Peptides can be generally classified as receptor-targeted, recognizing membrane proteins expressed by the BBB microvessels (e.g., Angiopep2, CDX, and iRGD), "cell-penetrating peptides" (CPPs; e.g. TAT47-57, SynB1/3, and Penetratin), undergoing transcytosis through unspecific mechanisms, or those exploiting a mixed approach. The advantages of peptides have been extensively pointed out, but so far few studies have focused on the potential negative aspects. Indeed, despite having a generally good safety profile, some peptide conjugates may display toxicological characteristics distinct from those of the peptide itself, causing for instance antigenicity, cardiovascular alterations or hemolysis. Other shortcomings are the often brief lifetime in vivo, caused by the presence of peptidases, the vulnerability to endosomal/lysosomal degradation, and the frequently still insufficient attainable increase of brain drug levels, which remain below the therapeutically useful concentrations. The aim of this review is to analyze not only the successful and promising aspects of the use of peptides in brain targeting but also the problems posed by this strategy for drug delivery.


The effect of GH and IGF1 on linear growth and skeletal development and their modulation by SOCS proteins.
Circulating signalling proteins have often been divided into hormones and cytokines, but it is increasingly being recognised that these substances have a number of common characteristics and mechanisms of action. This is clearly illustrated by the suppressor of cytokine signalling (SOCS) proteins which are increasingly seen as a central component of the regulation of the action of hormones and cytokines that signal through the cytokine receptor complex. The SOCS protein family is probably more extensive than currently recognised; its members may have differential tissue expression and their potency for suppressing cytokine signalling may vary. Recent knockout and transgenic studies in mice have highlighted the role that these proteins play in growth and skeletal development as well as in inflammation. Chronic inflammation is associated with altered growth and skeletal development, and it is possible that SOCS proteins may have an important role to play in mediating these effects.


The Science of In-Training Evaluation: Facilitating learning with qualitative research.
In-training evaluation requires a rigorous approach and high academic standards. Qualitative research principles can be applied to meet student, preceptor, and program needs; methods that enhance trust are helpful. Ideally the student and preceptors should collaborate to explore the student's strengths and weaknesses. While student and preceptor may not agree, the qualitative process clarifies reasons for differences of opinion. A properly performed in-training evaluation not only documents skills attained and learning needs, but also will facilitate learning during the rotation.


Hip and pelvic fracture patients with fear of falling: development and description of the "Step by Step" treatment protocol.
Based on a theoretical framework and sound evidence, this article describes a rehabilitation programme for patients with fear of falling after hip and pelvic fracture. Based on exercise science principles, current knowledge from fall prevention, emotion regulation, and the Health Action Process Approach we developed a theoretical framework, from which the components of the intervention were derived. Description of the intervention: The intervention consists of 6 components: (1) relaxation, (2) meaningful activities and mobility-based goals, (3) falls related cognitions and emotions, coping with high risk tasks and situations, (4) individual exercise programme, (5) planning and implementing exercises and activities, and (6) fall risks and hazards. The intervention comprises of 8 individual sessions during 3 to 5 weeks of inpatient rehabilitation and 4 telephone calls and 1 home visit over a 2-month post-discharge period. Each session or telephone call takes about 30-60 minutes. It is provided to geriatric hip and pelvic fracture patients with concerns about falling and no cognitive impairment. To ensure completeness of reporting, the Template for Intervention Description and Replication (TIDierR) is used. Fifty-seven patients were assigned to the intervention group. All 46 completers met all pre-defined criteria for an intervention per protocol. The programme is feasible to administer. We have completed a randomised controlled trial, which will be submitted in due time (for trial protocol: www.isrctn.org ; ISRCTN79191813).


Involvement of S2 episomal sequences in the generation of NCS4 deletion mutation in maize mitochondria.
Cytoplasmic male sterility (CMS) and the abnormal-growth, nochromosomal stripe (NCS) phenotypes are cytoplasmically determined traits in plants. Mitochondrial DNA rearrangements involving short repeats appear to be responsible for the production of CMS reversions to fertility and NCS mutations. NCS4, a new mutant of maize CMS-S, exhibits both abnormal growth and male fertility. This mutant is unique because both mutations occurred within the same plant. Free S1 and S2 episomes normally found in CMS-S mitochondria have been lost from NCS4 plants. An S2 sequence has recombined aberrantly with a ribosomal protein coding region, rps3/rpl16. One end of the S2 sequence and the 5' end of the rps3/rpl16 transcription unit are absent from the NCS4 recombinant genome. Loss of mitochondrial ribosomal protein function is lethal; therefore, NCS4 plants are heteroplasmic for the rps3 deletion. Loss of S sequences from CMS-S mitochondria is not lethal and plants regain pollen function. Thus, although NCS4 plants have very abnormal plant phenotypes, they are male-fertile.


Greater discounting of delayed rewards in young adults with family histories of alcohol and drug use disorders: studies from the Oklahoma family health patterns project.
Increased discounting of delayed rewards may be a premorbid characteristic and possible risk factor for alcohol and other drug use disorders; however, previous studies have found no or minimal differences in delay discounting in individuals at risk for substance use disorders based on family history. It is possible that increased delay discounting may be more closely associated with antisocial traits, evident in a subset of individuals with positive family histories of alcohol and drug use disorders, and that previous studies were underpowered for detecting subtle to modest overall group differences. In this study, we compared 143 young adults with family histories of alcohol and other drug use disorders (FH+) and 155 young adults with no such histories (FH-) on delay discounting and subsequently examined how delay discounting was related to antisocial traits and other selected psychological and demographic variables. The FH+ group discounted delayed rewards more than the FH- group. Subsequent analyses revealed that increased delay discounting was correlated with having more parents and grandparents with alcohol and drug use disorders, more antisocial traits, more depressive tendencies and lower IQs, and lower income. After controlling for all these relationships, more antisocial traits and lower IQ still predicted greater delay discounting, and subsequent analysis revealed that the greater delay discounting in the FH+ group was mediated by this group's greater number of individuals with antisocial traits. FH+ individuals who discount delayed rewards more may be at increased risk for developing alcohol and other drug use disorders; however, additional descriptive studies and longitudinal studies are needed.


Rhodamines with a Chloronicotinic Acid Fragment for Live Cell Superresolution STED Microscopy*.
Formylation of 2,6-dichloro-5-R-nicotinic acids at C-4 followed by condensation with 3-hydroxy-N,N-dimethylaniline gave analogs of the popular TAMRA fluorescent dye with a 2,6-dichloro-5-R-nicotinic acid residues (R=H, F). The following reaction with thioglycolic acid is selective, involves only one chlorine atom at the carbon between pyridine nitrogen and the carboxylic acid group and affords new rhodamine dyes absorbing at 564/ 573 nm and emitting at 584/ 597 nm (R=H/ F, in aq. PBS). Conjugates of the dyes with "small molecules" provided specific labeling (covalent and non-covalent) of organelles as well as of components of the cytoskeleton in living cells and were combined with fluorescent probes prepared from 610CP and SiR dyes and applied in two-color STED microscopy with a 775 nm STED laser.


Antibacterial and resistance modifying activity of Rosmarinus officinalis.
As part of a project to characterise plant-derived natural products that modulate bacterial multidrug resistance (MDR), bioassay-guided fractionation of a chloroform extract of the aerial parts of Rosmarinus officinalis led to the characterisation of the known abietane diterpenes carnosic acid (1), carnosol (2) and 12-methoxy-trans-carnosic acid. Additionally, a new diterpene, the cis A/B ring junction isomer of 12-methoxy-trans-carnosic acid, 12-methoxy-cis-carnosic acid (5), was isolated. The major components were assessed for their antibacterial activities against strains of Staphylococcus aureus possessing efflux mechanisms of resistance. Minimum inhibitory concentrations ranged from 16 to 64 microg/ml. Incorporation of 1 and 2 into the growth medium at 10 microg/ml caused a 32- and 16-fold potentiation of the activity of erythromycin against an erythromycin effluxing strain, respectively. Compound 1 was evaluated against a strain of S. aureus possessing the NorA multidrug efflux pump and was shown to inhibit ethidium bromide efflux with an IC50 of 50 microM, but this activity is likely to be related to the inhibition of a pump(s) other than NorA. The antibacterial and efflux inhibitory activities of these natural products make them interesting potential targets for synthesis.


Combinatorial delivery of immunosuppressive factors to dendritic cells using dual-sized microspheres.
Microparticulate systems are beginning to show promise for delivery of modulatory agents for immunotherapeutic applications which modulate dendritic cell (DC) functions. Co-administration of multiple factors is an emerging theme in immune modulation which may prove beneficial in this setting. Herein, we demonstrate that localized, controlled delivery of multiple factors can be accomplished through poly (lactic-co-glycolic acid) (PLGA) microparticle systems fabricated in two size classes of phagocytosable and unphagocytosable microparticles (MPs). The immunosuppressive ability of combinatorial multi-factor dual MP systems was evaluated by investigating effects on DC maturation, DC resistance to LPS-mediated maturation and proliferation of allogeneic T cells in a mixed lymphocyte reaction. Phagocytosable MPs (~2 μm) were fabricated encapsulating either rapamycin (RAPA) or all-trans retinoic acid (RA), and unphagocytosable MPs (~30 μm) were fabricated encapsulating either transforming growth factor beta-1 (TGF-β1) or interleukin-10 (IL-10). Combinations of these MP classes reduced expression of stimulatory/costimulatory molecules (MHC-II, CD80 and CD86) in comparison to iDC and soluble controls, but not necessarily to single factor MPs. Dual MP-treated DCs resisted LPS-mediated activation, in a manner driven by the single factor phagocytosable MPs used. Dendritic cells treated with dual MP systems suppressed allogeneic T cell proliferation, generally demonstrating greater suppression by combination MPs than single factor formulations, particularly for the RA/IL-10 MPs. This work demonstrates feasibility of simultaneous targeted delivery of immunomodulatory factors to cell surface receptors and intracellular locations, and indicates that a combinatorial approach can boost immunoregulatory responses for therapeutic application in autoimmunity and transplantation.


Low-grade oils and fats: effect of several impurities on biodiesel production over sulfonic acid heterogeneous catalysts.
Different lipidic wastes and low-grade oils and fats have been characterized and evaluated as feedstocks for the acid-catalyzed production of FAME. The characterization of these materials has revealed significant contents of free fatty acids, Na, K, Ca, Mg, P, unsaponifiable matter and humidity. Arenesulfonic acid-functionalized SBA-15 silica catalyst has provided yields to FAME close to 80% in the simultaneous esterification-transesterification of the different feedstocks, regardless of their nature and properties, using methanol under the following reaction conditions: 160 °C, 2 h, methanol to oil molar ratio of 30, 8 wt.% catalyst loading, and 2000 rpm stirring rate. Nevertheless, reutilization of the catalyst is compromised by high levels of impurities, especially because of deactivation by strong interaction of unsaponifiable matter with the catalytic sites. The conditioning of these materials by aqueous washing in the presence of cationic-exchange resin Amberlyst-15, followed by a drying step, resulted in a lower deactivation of the catalyst.


Biodegradation and proton exchange using natural rubber in microbial fuel cells.
Microbial fuel cells (MFCs) generate electricity from waste but to date the technology's development and scale-up has been held-up by the need to incorporate expensive materials. A costly but vital component is the ion exchange membrane (IEM) which conducts protons between the anode and cathode electrodes. The current study compares natural rubber as an alternative material to two commercially available IEMs. Initially, the material proved impermeable to protons, but gradually a working voltage was generated that improved with time. After 6 months, MFCs with natural rubber membrane outperformed those with anion exchange membrane (AEM) but cation exchange membrane (CEM) produced 109 % higher power and 16 % higher current. After 11 months, polarisation experiments showed a decline in performance for both commercially available membranes while natural rubber continued to improve and generated 12 % higher power and 54 % higher current than CEM MFC. Scanning electron microscope images revealed distinct structural changes and the formation of micropores in natural latex samples that had been employed as IEM for 9 months. It is proposed that the channels and micropores formed as a result of biodegradation were providing pathways for proton transfer, reflected by the steady increase in power generation over time. These improvements may also be aided by the establishment of biofilms that, in contrast, caused declining performance in the CEM. The research demonstrates for the first time that the biodegradation of a ubiquitous waste material operating as IEM can benefit MFC performance while also improving the reactor's lifetime compared to commercially available membranes.


Mitigating the impact of family burden on psychological health in parents of children with special needs: Buffering effects of resilience and social support.
This study examined the link between perceived family burden among parents of children with moderate and severe disabilities and their psychological health, and the potential moderating roles of resilience and social support. 256 parents completed an online questionnaire including Demographic Information Form, Family Burden Assessment Scale, General Health Questionnaire, Brief Resilience Scale, and Revised Parental Social Support Scale. Results revealed negative associations between resilience, social support, and depression-anxiety symptoms. Both resilience and social support played moderating roles in the association between family burden and psychological health. Social support buffered the negative association between family burden and psychological health, alongside psychological resilience. The study highlights the negative effects of family burden on the psychological health of parents of children with disabilities, but also suggests that resilience and social support can mitigate these effects. Therefore, interventions should consider these factors to enhance the psychological well-being of parents.


Learning from the learning curve: factors associated with successful endoscopic correction of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer.
Conflicting reports exist regarding the parameters guiding successful correction of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer. We performed logistic regression analysis to evaluate the effect of injected volume while adjusting for other factors potentially associated with success following dextranomer/hyaluronic acid copolymer injection. Between July 2003 and June 2006, 126 consecutive patients (34 boys and 92 girls) with a mean +/- SD age of 6.5 +/- 3.7 years with primary vesicoureteral reflux (196 refluxing ureters) underwent injection for febrile urinary tract infections. Success was defined as complete reflux resolution. Age, gender, laterality, preoperative vesicoureteral reflux grade, surgeon experience, dextranomer/hyaluronic acid copolymer volume, time to surgery from initial presentation and preoperative treatment for lower urinary tract symptoms were analyzed. Vesicoureteral reflux grade was I to V in 7 (3.5%), 53 (27%), 91 (46.4%), 30 (15.3%) and 15 renal units (7.6%), respectively. The success rate after 1 injection was 50% by patient and 59.2% by ureter. Mean injected volume was 0.9 +/- 0.27 ml in those who had a successful injection vs 0.67 +/- 0.24 ml in those in whom injection failed (p <0.001). The success rate after 1 injection was 78.9% using 0.8 ml or greater dextranomer/hyaluronic acid copolymer compared to 31.7% with less than 0.8 ml. Multivariate analysis confirmed that higher dextranomer/hyaluronic acid copolymer volume (p = 0.001), lower preoperative grade (p = 0.013), surgeon experience (p = 0.025) and treatment for lower urinary tract symptoms (p = 0.009) were associated with successful correction of vesicoureteral reflux. Our analysis strengthens the previously reported association of surgeon experience and vesicoureteral reflux grade with successful endoscopic vesicoureteral reflux correction. The data also revealed an association between injected volume and vesicoureteral reflux correction even while controlling for other variables, highlighting its importance as a true success modifier.


Sperm Storage in a Family-Living Lizard, the Tree Skink (Egernia striolata).
The ability to produce viable offspring without recently mating, either through sperm storage or parthenogenesis, can provide fitness advantages under a suite of challenging ecological scenarios. Using genetic analysis, we demonstrate that 3 wild-caught female Tree Skinks (Egernia striolata) reproduced in captivity with no access to males for over a year, and that this is best explained by sperm storage. To the best of our knowledge, this is the first time female sperm storage has been documented in any monogamous family-living reptile, including social Australian egerniine skinks (from the subfamily Egerniinae). Furthermore, by using paternal reconstruction of genotypes we show that captive-born offspring produced by the same females in the preceding year, presumably without sperm storage, were sired by different males. We qualitatively compared aspects of these females' mates and offspring between years. The parents of each litter were unrelated, but paternal and offspring genotypes from litters resulting from stored sperm were more heterozygous than those inferred to be from recent matings. Family-living egerniine skinks generally have low rates of multiple paternity, yet our study suggests that female sperm storage, potentially from outside social partners, offers the real possibility of benefits. Possible benefits include increasing genetic compatibility of mates and avoiding inbreeding depression via cryptic female choice. Sperm storage in Tree Skinks, a family-living lizard with a monogamous mating system, suggests that females may bet-hedge through extra-pair copulation with more heterozygous males, reinforcing the idea that females could have more control on reproductive outcomes than previously thought.


Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.
We have previously demonstrated that chronic exposure of 3T3-L1 adipocytes to tumour necrosis factor-alpha (TNF) resulted in a marked decrease (approximately 90%) in cellular GLUT4 (insulin-responsive glucose transporter) mRNA content as a result of a decreased transcription rate of the GLUT4 gene (approximately 75%) and a reduced half-life of its mRNA (9 to 4.5 h). Investigation of the signalling mechanism responsible for this regulation demonstrated that in the 3T3-L1 adipocytes, sphingomyelin levels decreased to 50% of control levels within 40 min of exposure to TNF, consistent with activation of a sphingomyelinase. In the same manner as with TNF, treatment of the adipocytes with 1-3 microM C6-ceramide, a membrane-permeable analogue of ceramide, decreased GLUT4 mRNA content by approximately 60%. Subsequent investigations revealed that transcription of the GLUT4 gene was reduced by approximately 65% in response to C6-ceramide, demonstrating that the decrease in mRNA content is mediated by a reduction in the transcription of the genc. No effect on GLUT4 mRNA stability was observed after exposure of the adipocytes to C6-ceramide. These observations are interesting in light of our previous data demonstrating that TNF affects both GLUT4 transcription and mRNA stability in the 3T3-L1 adipocytes. In conclusion, the effect of ceramide on GLUT4 gene expression is at the level of transcription, suggesting that another pathway controls mRNA stability. These data establish that ceramide-initiated signal transduction pathways exist within the adipocyte, and provide a potential mechanism for control of GLUT4 gene expression.


CHLOROPLAST GENETIC TOOL FOR THE GREEN MICROALGAE HAEMATOCOCCUS PLUVIALIS (CHLOROPHYCEAE, VOLVOCALES)(1).
At present, there is strong commercial demand for recombinant proteins, such as antigens, antibodies, biopharmaceuticals, and industrial enzymes, which cannot be fulfilled by existing procedures. Thus, an intensive search for alternative models that may provide efficiency, safety, and quality control is being undertaken by a number of laboratories around the world. The chloroplast of the eukaryotic microalgae Haematococcus pluvialis Flotow has arisen as a candidate for a novel expression platform for recombinant protein production. However, there are important drawbacks that need to be resolved before it can become such a system. The most significant of these are chloroplast genome characterizations, and the development of chloroplast transformation vectors based upon specific endogenous promoters and on homologous targeting regions. In this study, we report the identification and characterization of endogenous chloroplast sequences for use as genetic tools for the construction of H. pluvialis specific expression vectors to efficiently transform the chloroplast of this microalga via microprojectile bombardment. As a consequence, H. pluvialis shows promise as a platform for expressing recombinant proteins for biotechnological applications, for instance, the development of oral vaccines for aquaculture.


Validity of respiratory scores in bronchiolitis.
The primary objective of this study was to establish the validity and reliability of 2 respiratory scores, the Respiratory Distress Assessment Instrument (RDAI) and the Children's Hospital of Wisconsin Respiratory Score (CHWRS), in bronchiolitis. A secondary objective was to identify the respiratory score components that most determine overall respiratory status. This was a prospective cohort study in infants aged < 1 year seen at Children's Hospital of Wisconsin for bronchiolitis. We evaluated: (1) discriminative validity (the score's ability to discriminate between 2 different outcomes) of the respiratory scores to identify emergency department (ED) disposition by using receiver operating characteristic curves; and (2) construct validity (the score's ability to measure what it is thought to measure, overall respiratory status) by using length of stay (LOS) as a proxy for disease severity and comparing correlations between changes in respiratory scores and LOS. Interrater reliability was established by using intraclass correlation. The contribution of individual respiratory score components to determine ED disposition was studied by using multivariate logistic regression. A total of 195 infants were included. The area under the receiver operating characteristic curve was 0.68 for CHWRS versus 0.51 for RDAI in predicting disposition. There was no correlation between initial respiratory scores or change in respiratory scores over the first 24 hours and LOS. Item analysis revealed that oxygen delivery, subcostal retractions, and respiratory rate were independently correlated with ED disposition. The CHWRS was more reliable than the RDAI. The CHWRS had modest discriminative validity in predicting ED disposition. Neither the CHWRS nor the RDAI had good construct validity. Respiratory rate, oxygen need, and presence of retractions were most useful in predicting ED disposition.


Homicide, suicide, and unintentional firearm fatality: comparing the United States with other high-income countries, 2003.
Violent death is a major public health problem in the United States and throughout the world. A cross-sectional analysis of the World Health Organization Mortality Database analyzes homicides and suicides (both disaggregated as firearm related and non-firearm related) and unintentional and undetermined firearm deaths from 23 populous high-income Organization for Economic Co-Operation and Development countries that provided data to the World Health Organization for 2003. The US homicide rates were 6.9 times higher than rates in the other high-income countries, driven by firearm homicide rates that were 19.5 times higher. For 15-year olds to 24-year olds, firearm homicide rates in the United States were 42.7 times higher than in the other countries. For US males, firearm homicide rates were 22.0 times higher, and for US females, firearm homicide rates were 11.4 times higher. The US firearm suicide rates were 5.8 times higher than in the other countries, though overall suicide rates were 30% lower. The US unintentional firearm deaths were 5.2 times higher than in the other countries. Among these 23 countries, 80% of all firearm deaths occurred in the United States, 86% of women killed by firearms were US women, and 87% of all children aged 0 to 14 killed by firearms were US children. The United States has far higher rates of firearm deaths-firearm homicides, firearm suicides, and unintentional firearm deaths compared with other high-income countries. The US overall suicide rate is not out of line with these countries, but the United States is an outlier in terms of our overall homicide rate.


Global Cardioplegia Practices: Results from the Global Cardiopulmonary Bypass Survey.
Despite the ubiquitous use of cardioplegia in cardiac surgery, there is a lack of agreement on various aspects of cardioplegia practice. To discover current cardioplegia practices throughout the world, we undertook a global survey to document contemporary cardiopulmonary bypass practices. A 16-question, Internet-based survey was distributed by regional specialist societies, targeting adult cardiac anesthesiologists. Ten questions concerned caseload and cardioplegia practices, the remaining questions examined anticoagulation and pump-priming practices. The survey was available in English, Spanish, and Portuguese. The survey was launched in June 2015 and remained open until May 2016. A total of 923 responses were analyzed, summarizing practice in Europe (269), North America (334), South America (215), and Australia/New Zealand (105). Inter-regional responses differed for all questions asked (p < .001). In all regions other than South America, blood cardioplegia was the common arrest technique used. The most commonly used cardioplegia solutions were: St. Thomas, Bretschneider, and University of Wisconsin with significant regional variation. The use of additives (most commonly glucose, glutamate, tris-hydroxymethyl aminomethane, and aspartate) varied significantly. This survey has revealed significant variation in international practice with regards to myocardial protection, and is a reminder that there is no clear consensus on the use of cardioplegia. It is unclear why regional practice groups made the choices they have and the clinical impact remains unclear.


GCgx: transcriptome-wide exploration of the response to glucocorticoids.
Glucocorticoids are the cornerstone of immunosuppressive and anti-inflammatory therapy in humans, yet the mechanisms of glucocorticoid immunoregulation and toxicity remain unclear. The response to glucocorticoids is highly cell type-dependent, so translating results from different experimental systems into a better understanding of glucocorticoid effects in humans would benefit from rapid access to high-quality data on the response to glucocorticoids by different cell types. We introduce GCgx, a web application that allows investigators to quickly visualize changes in transcript abundance in response to glucocorticoids in a variety of cells and species. The tool is designed to grow by the addition of datasets based on input from the user community. GCgx is implemented in R and HTML and packaged as a Docker image. The tool and its source code are publicly available.


Transport properties of toad kidney epithelia in culture.
The characteristics of a continuous line of toad kidney epithelial cells (A6) are described. These cells form a monolayer epithelium of high transepithelial electrical resistance (about 5,000 omega . cm2). The cells generate a transepithelial potential difference (apical surface negative) of about 9 mV. The short-circuit current is equivalent to net sodium flux. Net sodium flux is stimulated by aldosterone and by analogues of cAMP. The stimulation is readily reversible. Neither urea permeability nor osmotic water flow is altered by analogues of cAMP. Amiloride eliminates 90% of the short-circuit current. Thus A6 cells form an epithelium with several differentiated properties including hormonal regulation of transport.


Rapid induction of androgen receptor splice variants by androgen deprivation in prostate cancer.
Mechanisms mediating androgen receptor (AR) reactivation in prostate cancer that progresses after castration (castration-resistant prostate cancer; CRPC) and subsequent treatment with abiraterone (CYP17A1 inhibitor that further suppresses androgen synthesis) remain unclear. Prostate cancer xenografts were examined to identify mechanism of progression after castration and abiraterone. AR reactivation in abiraterone-resistant VCaP xenografts was not associated with restoration of intratumoral androgens or alterations in AR coregulators. In contrast, mRNA encoding full-length AR (AR-FL) and a constitutively active splice variant (AR-V7) were increased compared with xenografts before castration, with an increase in AR-V7 relative to AR-FL. This shift toward AR-V7 was due to a feedback mechanism whereby the androgen-liganded AR stimulates expression of proteins that suppress generation of AR-V7 relative to AR-FL transcripts. However, despite the increases in AR-V7 mRNA, it remained a minor transcript (<1%) relative to AR-FL in resistant VCaP xenografts and CRPC clinical samples. AR-V7 protein expression was similarly low relative to AR-FL in castration-resistant VCaP xenografts and androgen-deprived VCaP cells, but the weak basal AR activity in these latter cells was further repressed by AR-V7 siRNA. AR-V7 at these low levels is not adequate to restore AR activity, but its rapid induction after androgen deprivation allows tumors to retain basal AR activity that may be needed for survival until more potent mechanisms emerge to activate AR. Agents targeting AR splice variants may be most effective when used very early in conjunction with therapies targeting the AR ligand-binding domain.


Should emergency contraceptive pills be available without prescription?
Leading health agencies, including the World Health Organization and the US Food and Drug Administration, consider emergency contraceptive pills (ECPs) safe and effective and have called for better access to them. Yet debate about whether ECPs should continue to be available by prescription only has been limited. After measuring the characteristics of ECPs against criteria developed to assess the necessity for prescription status for drugs generally, we argue that ECPs can safely be marketed over the counter. Professional assistance is not necessary since the woman diagnoses her own need for the pills and takes them herself. ECPs do not need to be adjusted for the individual woman and pose no potential threat of overdose or addiction. There are no contraindications except confirmed pregnancy (in which case the therapy will not work), and monitoring is not necessary. We conclude that prescription requirements that keep ECPs from women provide little, if any, benefit.


Generalized anxiety and generalized anxiety disorder: description and reconceptualization.
One hundred eight patients complaining of anxiety were diagnosed using the Anxiety Disorders Interview Schedule and classified into the various anxiety disorder categories as well as major depression. Although patients with a primary diagnosis of generalized anxiety disorder were more chronic than were panic disorder patients, most patients in each category met the DSM-III criteria for generalized anxiety disorder with the exception of simple phobic patients. On the basis of these data, it would seem that generalized anxiety disorder is a residual category within the anxiety disorders, since generalized anxiety disorder symptoms are almost always present. But if one distinguishes anticipatory anxiety, which is often part of panic or phobic disorders, from generalized anxiety, an independent anxiety disorder category emerges. This category is characterized by apprehensive expectation or chronic worry focused on multiple life situations.


CCD Implementation of a Three-Dimensional Video-Tracking Algorithm.
Implementation of a three-dimensional video tracking algorithm using CCD's is presented. The algorithm does not require conventional pattern recognition or continuous segmentation updating. The only requirements, for the class of targets presented, are that the sampling lattice contain only points inside the target and that the background vary slowly. Several well-known segmentation techniques are available for initial segmentation and determination of target points. The use of CCD devices simplifies the architecture of the processor and permits real time processing at a high sampling rate. Some of the vector and matrix operations require either the use of continuously variable tapweight transversal filters or analog multipliers. The use of analog multipliers, which can be on-chip, reduces the number of components and offers higher accuracy than presently available variable tap weight transversal filters.


Outcome and postoperative complications in 73 dogs with thyroid carcinoma with gross vascular invasion managed with thyroidectomy.
Excellent outcomes have been reported following thyroidectomy for thyroid carcinoma in dogs, but outcomes for thyroid carcinomas with gross vascular invasion are poorly described. This study describes the clinical outcomes and complications in dogs with thyroid carcinomas with gross vascular invasion undergoing thyroidectomy. Medical records of dogs that underwent thyroidectomy between January 1st 2010 and December 31st 2019 were reviewed at 10 hospitals. Signalment, diagnostic data, primary and adjuvant treatments performed, and outcome were abstracted. Survival was calculated using Kaplan-Meier analysis. Multiple logistic regression was used to identify variables associated with disease-specific survival. Seventy-three dogs were included, of which 58 underwent unilateral thyroidectomy and 15 underwent bilateral thyroidectomy. Complications were reported in five dogs (three major, two minor; 6.8%) intraoperatively and 12 dogs (two major leading to death, 10 minor; 16.4%) postoperatively. Seven (9.6%) dogs developed locoregional recurrence at a median of 238 days postoperatively (range: 15-730 days). Distant metastasis was suspected or confirmed in nine dogs (12.3%) at a median of 375 days postoperatively (range: 50-890 days). Twenty-seven dogs (37%) received adjuvant therapy (chemotherapy: n = 21; radiotherapy: n = 6). Thirty-nine dogs were euthanized or died, with 20 deaths related to disease (n = 10) or of unknown cause (n = 10), 19 due to unrelated causes, and nine lost to follow-up. Median overall and disease-specific survival were 621 days and not reached respectively. One-year disease-specific survival rate was 82.5%. No variables were associated with disease-specific survival in our dataset. Surgery may be considered for loco-regional therapy in dogs with thyroid carcinoma with gross vascular invasion.


New genus and species of Aporocotylidae (Digenea) from a basal actinopterygian, the American paddlefish, Polyodon spathula, (Acipenseriformes: Polyodontidae) from the Mississippi Delta.
Acipensericola petersoni n. gen., n. sp. (Digenea: Aporocotylidae) infects the heart of the American paddlefish Polyodon spathula (Walbaum, 1792) in the Mississippi Delta. It has robust, spike-like body spines arranged in ventrolateral transverse rows; a bowl-shaped anterior sucker centered on the mouth and having minute spines on the inner anteroventral surface only; a pharynx; an inverse U-shaped ceca extending to near the posterior body end; intercecal testes comprising a pre-ovarian testicular column plus a single testis posteriorly; an extensively lobed ovary located medially and immediately posterior to the testicular column; a spherical ootype that is intercecal and post-ovarian; a Laurer's canal; and a common genital pore. The new species is the first-named aporocotylid collected from a basal actinopterygian. It resembles the chondrichthyan aporocotylids Chimaerohemecus trondheimensis, Orchispirium heterovitellatum, and Hyperandrotrema cetorhini in having an inverse U-shaped ceca, but it is morphologically most similar to the anguilliform aporocotylid Paracardicoloides yamagutii in having that feature plus a comparable anterior sucker, a single testis posteriorly, an intertesticular ovary, and a common genital pore. Sequence data for the complete small subunit ribosomal DNA (18S) do not refute its membership within Aporocotylidae nor its affinity to 1 of those aforementioned aporocotylids: A. petersoni was basal to the few teleost aporocotylids analyzed, and C. trondheimensis was the only taxon basal to A. petersoni. We regard the specimens of Spirorchis sp. previously reported from the shortnose sturgeon Acipenser brevirostrum Lesueur, 1818 as congeneric with the new species.


The comparative effects of signal sensation level and sound-pressure level on interaural time discrimination.
A series of experiments was performed to examine the extent to which precision of interaural time discrimination depends on the sound-pressure level (SPL) and/or sensation level (SL) of the signal. All experiments used a tone burst signal and a continuous white noise masker, which was either diotic or interaurally phase reversed. Results of the first experiment indicate that (1) at equal signal SLs, interaural time and intensity discrimination is more precise when measured with the added diotic noise, and (2) addition of the phase reversed noise, previously shown to cause less precise interaural time discrimination, has a similar effect on interaural intensity discrimination. In the second experiment, interaural time JNDs for a signal of constant SPL were measured as a function of noise level. Results show that a low-level diotic noise can benefit interaural time discrimination, particularly at 500 Hz. The third and fourth experiments were performed to measure interaural time discrimination as a function of increasing signal SPL but constant signal-to-noise ratio. The data show the JND decreasing with increasing signal SPL at nearly the same rate with or without the added noise, indicating that an increase in signal-to-noise ratio is not necessary for improved discrimination.


Does time matter? WhatsApp vs electronic mail for dental education. A pilot study.
WhatsApp is an instant multimedia messaging and social media software which can be used for multiple purposes such as data, text, photographs and document transfer. Due to its versatility and multiple utilities, WhatsApp has been used within the educational setting in medicine and dentistry, proving a positive attitude of students towards its use. To compare the reception time and the response time of WhatsApp with the traditional electronic email within the dental educational environment. A two-group comparative study was designed. Four multiple choice questions were sent via WhatsApp (group WA) and via electronic mail (group eM) to dental students. Data collected focused on the reception time and response time of students. Specifications of WhatsApp were used to collect data whilst an email tracker was used for the eM group. Excel software and Stata/IC version 15.1 software were used for data analysis. Seventy-four dental students from the University x (anonymised for reviewing purposes) dental school agreed to take part in this experience. However, 59 provided their responses (80%). Forty-four were females, and 15 were males. Twenty-seven participants were randomly allocated to the WA group and 32 to the eM group. The statistical analysis revealed a significant difference between groups: Reception time, P: .0286 value and response time, P: .0448 value indicating that the WA group was significantly faster in terms of reception and response time. This pilot study suggests that WhatsApp is more efficient in terms of reception and response time than electronic emails.


A prediction and imputation method for marine animal movement data.
Data prediction and imputation are important parts of marine animal movement trajectory analysis as they can help researchers understand animal movement patterns and address missing data issues. Compared with traditional methods, deep learning methods can usually provide enhanced pattern extraction capabilities, but their applications in marine data analysis are still limited. In this research, we propose a composite deep learning model to improve the accuracy of marine animal trajectory prediction and imputation. The model extracts patterns from the trajectories with an encoder network and reconstructs the trajectories using these patterns with a decoder network. We use attention mechanisms to highlight certain extracted patterns as well for the decoder. We also feed these patterns into a second decoder for prediction and imputation. Therefore, our approach is a coupling of unsupervised learning with the encoder and the first decoder and supervised learning with the encoder and the second decoder. Experimental results demonstrate that our approach can reduce errors by at least 10% on average comparing with other methods.


Impact of common type 2 diabetes risk polymorphisms in the DESIR prospective study.
The emerging picture of type 2 diabetes genetics involves differently assembled gene variants, each modestly increasing risk with environmental exposure. However, the relevance of these genes for disease prediction has not been extensively tested. We analyzed 19 common polymorphisms of 14 known candidate genes for their contribution to prevalence and incidence of glucose intolerance in the DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) prospective study of middle-aged Caucasian subjects, including 3,877 participants (16.8% with hyperglycemia and 7.9% with diabetes after the 9-year study). The GCK (Glucokinase) -30A allele was associated with increased type 2 diabetes risk at the end of the follow-up study (adjusted OR 1.34 [95% CI 1.07-1.69]) under an additive model, as supported in independent French diabetic case subjects (OR 1.22, P = 0.007), with increased fasting glycemia (0.85% per A allele, P = 6 x 10(-5)) and decreased homeostasis model assessment of beta-cell function (4%, P = 0.0009). IL6 (Interleukin- 6) -174 G/C interacts with age in disease risk and modulates fasting glycemia according to age (1.36% decrease over 56 years, P = 5 x 10(-5)). These polymorphisms together with KCNJ11 (Kir6.2)-E23K and TCF7L2-rs7903146 may predict diabetes incidence in the DESIR cohort. Each additional risk allele at GCK, TCF7L2, and IL6 increased risk by 1.34 (P = 2 x 10(-6)), with an OR of 2.48 (95% CI 1.59-3.86), in carriers of at least four at-risk alleles compared with those with none or one risk allele. Our data confirm several at-risk polymorphisms for type 2 diabetes in a general population and demonstrate that prospective studies are valuable designs to complement classical genetic approaches.


SAPHIR: a Shiny application to analyze tissue section images.
Study of cell populations in tissues using immunofluorescence is a powerful method for both basic and medical research. Image acquisitions performed by confocal microscopy notably allow excellent lateral resolution and more than 10 parameter measurements when using spectral or multiplex imaging. Analysis of such complex images can be very challenging and easily lead to bias and misinterpretation. Here, we have developed the Shiny Analytical Plot of Histological Image Results (SAPHIR), an R shiny application for histo-cytometry using scatterplot representation of data extracted by segmentation. It offers many features, such as filtering of spurious data points, selection of cell subsets on scatterplot, visualization of scatterplot selections back into the image, statistics of selected data and data annotation. Our application allows to characterize labeled cells, from their phenotype to their number and location in the tissue, as well as their interaction with other cells. SAPHIR is available from: https://github.com/elodiegermani/SAPHIR.


Anterior, posterior and biomechanical parameters of cornea during pregnancy in healthy eyes: a cohort study.
To investigate the effect of pregnancy on anterior, posterior and biomechanical corneal parameters of healthy eyes. In this prospective cohort study, 70 pregnant participants with clinically healthy eyes underwent corneal topographic imaging evaluation by Pentacam and biomechanical assessment by Ocular Response Analyzer (ORA) before pregnancy, at the third trimester of pregnancy (34th week of pregnancy) and 12 months after delivery. The same number of age-matched non-pregnant females was evaluated at the corresponding appointments as the control group. Assessment of the tomographic, topographic and ORA measurements before pregnancy, at the third trimester of pregnancy and 12 months post partum revealed no statistically significant changes in anterior and posterior corneal flat, steep and mean keratometry, anterior and posterior elevation measurements, central and thinnest corneal thickness, corneal hysteresis, corneal resistance factor and intraocular pressure measurements (p>0.05, repeated measures analysis of variance (ANOVA)). All of the study parameters returned to their baseline levels 1 year after delivery. The ophthalmic parameters of the non-pregnant group remained significantly unchanged during the study period (p>0.05, all comparisons, repeated measures ANOVA). Moreover, no statistically significant differences were found between pregnant and non-pregnant groups in the second (34th week of pregnancy) and third (post partum) appointments (p>0.05, all comparisons, one-way ANOVA). Our findings may suggest a physiological nature for ocular changes during pregnancy that these changes return to baseline values after delivery. The differences between tomographic, topographic and biomechanical corneal parameters before pregnancy, during pregnancy and post partum were not statistically or clinically significant.


Effect of a 9-wk. after-school multiskills club on fundamental movement skill proficiency in 8- to 9-yr.-old children: an exploratory trial.
This exploratory study examined the effects of a 9-wk. after-school multiskills club on fundamental movement skill proficiency in 8- to 9-yr.-old children. Two schools were randomly assigned to either a control (n = 15 children) or multiskill club (n = 19 children) condition. The multiskill club received 18 coaching sessions designed to improve fundamental movement skills. The control group followed normal routines. 7 skills were assessed using process-oriented measures with video analysis. Participation in the multiskill club yielded significant improvements in proficiency at posttest only in static balance, while potentially practically important improvements were observed in performance of the catch, throw, and kick skills. The after-school multiskill club offered a viable opportunity for movement skill acquisition, but any such programme would need to run for a longer duration to assess whether this type of activity could benefit all skills.


Influence of Socio-Economic Inequalities on Access to Renal Transplantation and Survival of Patients with End-Stage Renal Disease.
Public and scientific concerns about the social gradient of end-stage renal disease and access to renal replacement therapies are increasing. This study investigated the influence of social inequalities on the (i) access to renal transplant waiting list, (ii) access to renal transplantation and (iii) patients' survival. All incident adult patients with end-stage renal disease who lived in Bretagne, a French region, and started dialysis during the 2004-2009 period were geocoded in census-blocks. To each census-block was assigned a level of neighborhood deprivation and a degree of urbanization. Cox proportional hazards models were used to identify factors associated with each study outcome. Patients living in neighborhoods with low level of deprivation had more chance to be placed on the waiting list and less risk of death (HR = 1.40 95%CI: [1.1-1.7]; HR = 0.82 95%CI: [0.7-0.98]), but this association did not remain after adjustment for the patients' clinical features. The likelihood of receiving renal transplantation after being waitlisted was not associated with neighborhood deprivation in univariate and multivariate analyses. In a mixed rural and urban French region, patients living in deprived or advantaged neighborhoods had the same chance to be placed on the waiting list and to undergo renal transplantation. They also showed the same mortality risk, when their clinical features were taken into account.


Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews.
Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013. To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS. We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment. MAIN RESULTS: We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181). There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids. Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.


Effects of oral fructose in normal, diabetic, and impaired glucose tolerance subjects.
We studied the acute effects of oral ingestion of 50-g loads of dextrose, sucrose, and fructose on post-prandial serum glucose, insulin, and plasma glucagon responses in 9 normal subjects, 10 subjects with impaired glucose tolerance, and 17 non-insulin-dependent diabetic subjects. The response to each carbohydrate was quantified when the respective carbohydrate was given alone in a drink or when given in combination with protein and fat in a test meal. The data demonstrate that (1) fructose ingestion resulted in significantly lower serum glucose and insulin responses than did sucrose or dextrose ingestion in all study groups, either when given alone or in the test meal; (2) although fructose ingestion always led to the least glycemic response compared with the other hexoses, the serum glucose response to fructose was increased the more glucose intolerant the subject; (3) urinary glucose excretion during the 3 h after carbohydrate ingestion was greatest after dextrose and least after fructose in all groups. In conclusion, fructose ingestion results in markedly lower serum glucose and insulin responses and less glycosuria than either dextrose or sucrose, both when given alone or as a constituent in a test meal. However, as glucose tolerance worsens, an increasingly greater glycemic response to fructose is seen.


Eugenol Administration Improves Liver Damage Induced by a Fructose-Rich Diet.
The prevalence of metabolic syndrome (MetS) is increasing in developing countries that affects the liver in a variety of ways. This study was designed to investigate the protective role of eugenol on liver damage caused by fructose-induced MetS. Thirty male Wistar rats were randomly divided into five groups: 1: tap water (control), 2: fructose, 3: fructose + eugenol solvent, 4: fructose + eugenol 50 mg/kg, and 5: fructose + eugenol 100 mg/kg. At the end of the experiment, blood samples were taken for measurement fast blood glucose (FBG), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), low-density lipoprotein, high-density lipoprotein, cholesterol, and triglyceride. FBG significantly increased in Group 2 compared to Group 1 (P < 0.001); however, it significantly decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). SGOT and SGPT levels significantly increased in Group 2 compared to the control group (P < 0.001). However, SGOT and SGPT levels significantly decreased in Groups 4 and 5. Malondialdehyde (MDA) and liver tissue damage score (LTDS) significantly increased in Group 2 compared with the control group (P < 0.01), whereas MDA and LTDS decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). Eugenol may ameliorate liver damage in a rat model of fructose-induced MetS, and these protective effects may in part be mediated by improving antioxidant status and reducing oxidative stress and lipid peroxidation. It may also reduce hepatic inflammation and fat accumulation as well as fibrosis of liver cells.