Micronutrient deficiencies in maternity and child health: a review of environmental and social context and implications for Malawi.
It is well documented that micronutrient malnutrition is of increasing concern in the developing world, resulting in poor health and high rates of mortality and morbidity. During pregnancy, deficiency of iron and zinc can produce cognitive and growth impairment of the foetus, which may continue into infancy. Iron and zinc are essential micronutrients for both plant growth and human nutrition. Despite significant work in the areas of soil fertility, crop biofortification and dietary interventions, the problems of micronutrient deficiencies persist in Africa. There is a need to examine why communities have not embraced intervention strategies which may offer health benefits. Bottom-up, interdisciplinary approaches are required to effectively study the relationships between local communities and their environment, and to assess the impact their behaviour has on the cycling of micronutrients within the soil-plant-human system. From a detailed consideration of diverse influencing factors, a methodological model is suggested for studying the barriers to improving micronutrient uptake within rural communities. It combines environmental understanding with health and social factors, emphasising the need for and potential benefits of understanding and coherence in true interdisciplinary working.


Clinical prediction model to identify vulnerable patients in ambulatory surgery: towards optimal medical decision-making.
Ambulatory surgery patients are at risk of adverse psychological outcomes such as anxiety, aggression, fatigue, and depression. We developed and validated a clinical prediction model to identify patients who were vulnerable to these psychological outcome parameters. We prospectively assessed 383 mixed ambulatory surgery patients for psychological vulnerability, defined as the presence of anxiety (state/trait), aggression (state/trait), fatigue, and depression seven days after surgery. Three psychological vulnerability categories were considered-i.e., none, one, or multiple poor scores, defined as a score exceeding one standard deviation above the mean for each single outcome according to normative data. The following determinants were assessed preoperatively: sociodemographic (age, sex, level of education, employment status, marital status, having children, religion, nationality), medical (heart rate and body mass index), and psychological variables (self-esteem and self-efficacy), in addition to anxiety, aggression, fatigue, and depression. A prediction model was constructed using ordinal polytomous logistic regression analysis, and bootstrapping was applied for internal validation. The ordinal c-index (ORC) quantified the discriminative ability of the model, in addition to measures for overall model performance (Nagelkerke's R (2) ). In this population, 137 (36%) patients were identified as being psychologically vulnerable after surgery for at least one of the psychological outcomes. The most parsimonious and optimal prediction model combined sociodemographic variables (level of education, having children, and nationality) with psychological variables (trait anxiety, state/trait aggression, fatigue, and depression). Model performance was promising: R (2) = 30% and ORC = 0.76 after correction for optimism. This study identified a substantial group of vulnerable patients in ambulatory surgery. The proposed clinical prediction model could allow healthcare professionals the opportunity to identify vulnerable patients in ambulatory surgery, although additional modification and validation are needed. (ClinicalTrials.gov number, NCT01441843).


Sex as a biological variable: Mechanistic insights and clinical relevance in solid organ transplantation.
Biological sex affects immunity broadly, with recognized effects on the incidence and severity of autoimmune diseases, infections, and malignancies. Consequences of sex on alloimmunity and outcomes in solid organ transplantation are less well defined. Clinical studies have shown that donor and recipient sex independently impact transplant outcomes, which are further modified by aging. Potential mechanisms have thus far not been detailed and may include hormonal, genetic, and epigenetic components. Here, we summarize relevant findings in immunity in addition to studies in clinical and experimental organ transplantation detailing the effects of biological sex on alloimmunity. Understanding both clinical impact and mechanisms is expected to provide critical insights on the complexity of alloimmune responses, with the potential to fine-tune treatment and allocation while providing a rationale to include both sexes in transplant research.


Inhalation of foreign bodies in children. Report of 500 cases.
Inhalation of foreign bodies is a major cause of accidental death during childhood. Aspiration of foreign bodies is common in children aged 1 to 3 years, especially in boys. A past history of foreign body aspiration is itself an indication for bronchoscopic examination of the airways, because some children with aspirated foreign bodies are without symptoms and chest x-ray films may not show abnormalities. Bronchoscopic removal of the foreign bodies requires close communication between the anesthesiologist and the endoscopist. Forgotten foreign bodies in the airways cause chronic pulmonary infections, allergic asthma, bronchiectatic changes, and lung abscess. Foreign bodies that cannot be grasped by bronchoscopic forceps should be removed by thoracotomy and bronchotomy. This report describes our experience in 500 children with suspected foreign body inhalation. We routinely use prednisolone, 1 to 2 mg. per kilogram, and nebulization just after bronchoscopic examination of the airways. This medication greatly diminishes the rate of postbronchoscopic complications such as laryngeal edema, which require tracheostomy. In our series of 500 case, the incidence of postbronchoscopic tracheostomy is 1.4 per cent and the total mortality rate is 1.8 per cent.


Outcome of asthma induced by isocyanates.
Isocyanates are widely used in industry for the manufacture of polyurethanes. Although they are recognized as an important cause of occupational asthma, it is unclear whether asthma persists after avoidance of exposure. We have followed up 50 cases, all of whom had avoided exposure for at least 4 years. At follow-up, 82% continued to have respiratory symptoms and approximately half of these required treatment at least once per week. These results indicate that a significant proportion of those with isocyanate-induced asthma are likely to have persisting symptoms for at least several years after exposure is avoided.


The use of 3D video in medical education: A scoping review.
The use of 3D video in medical education has not been fully explored. This article aims to review the evidence on 3D video currently presented in the medical education literature, including its impact on curriculum activities, to reference future research in this field. According to the guidelines of Arksey and O'Malley, the authors used a systematic search strategy (the last search was in December 2022) to search nine literature databases published in English, and only primary studies were included. Two authors independently screened all articles based on the eligibility criteria and performed a thematic analysis of the included literature. Of 1,302 articles identified, 23 were included for insights into how opportunities for 3D video in medical education are created, how they are experienced, and how they influence and manifest behavior demonstrated partial congruency. Three themes were identified: (a) advantages of using 3D video in medical education; (b) the effect of using 3D video in medical education on students' academic achievement and ability; and (c) students' experience of 3D video in medical education. The application of 3D video in medical education has won the support of most students and educators. However, the effect of using 3D video in medical education is still controversial. Medical educators should combine the curriculum's characteristics, the students' learning situation, and the existing educational resources and choose to use them after careful consideration.


Predictive factors of cervical nodal metastases in N0 squamous cell carcinomas of the mobile tongue - A cohort study.
Squamous cell carcinoma (SCC) of the tongue is one of the most common cancers in the oral region, most frequently associated with lymph nodes metastases which influence the most the prognosis. The identification of predictive factors of occult cervical nodal metastases for N0 tumors will allow to adapt the treatment to the patient, avoiding over or under management. From 2014 to 2019, a cohort of 26 patients with SCC of the mobile tongue was reviewed by analysing the medical history, the epidemiological and clinical parameters, the tumor sites, aspects, diameters, depths of invasion, pathological degree, degree of differentiation, T classification and results of neck dissections. The incidence of occult cervical nodal metastases was up to 26,92% and a significant correlation was only found with the tumor depth invasion and the muscular invasion (p < 0,05). Presently, a low differentiated, highly graded tumor with a high depth and muscular invasion should warn from the high incidence of occult cervical nodal metastases and should recommend an elective neck dissection in all cases of N0 tongue SCC.


Available and future treatments for erectile dysfunction.
There is now a range of treatments for patients with erectile dysfunction (ED) beyond the psychosexual counselling and surgical implants that were the only available management options for many years. Oral treatments, which are minimally invasive, are the favoured first-line option for treatments and include the phosphodiesterase-5 (PDE5) inhibitors, and dopamine agonists such as apomorphine. Psychosexual counselling may still be an appropriate treatment, on its own or in combination, in a minority of patients who do not respond to oral treatment, or where an origin for the ED is likely from the history. The PDE5 inhibitors, sildenafil, tadalafil, and vardenafil, have proven to be effective and well tolerated and facilitate erectile function. Apomorphine is also effective, but causes nausea in a minority of men. The alpha-receptor antagonist yohimbine has been found to be effective in some placebo-controlled trials, but its effectiveness is probably inadequate for treatment of most ED. Intracavernosal injection of drugs such as prostaglandin E1, papaverine, and phentolamine (sometimes in combination) is an effective but invasive treatment. Other treatments include testosterone, vacuum-pump treatment, surgery, and surgical implants, and tend to be used where patients do not respond to oral treatment and counselling.


A simplified approach to the ambulatory care diagnostic summary list.
The Veterans Administration Medical Center at Sepulveda, California, developed a one-page checklist as a "problem summary list." Use of the list has improved legibility of entries, compliance, efficiency, and communication among providers.


Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease.
Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD. Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms of marrow-isolated adult multilineage inducible cells and human neural stem cells both adhered to neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo organotypic model of PD made from brain sagittal slices.


Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat.
Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat.


An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men.
The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure.


Co-consuming green tea with raloxifene decreases raloxifene systemic exposure in healthy adult participants.
Green tea is a popular beverage worldwide. The abundant green tea catechin (-)-epigallocatechin gallate (EGCG) is a potent in vitro inhibitor of intestinal UDP-glucuronosyltransferase (UGT) activity (Ki ~2 μM). Co-consuming green tea with intestinal UGT drug substrates, including raloxifene, could increase systemic drug exposure. The effects of a well-characterized green tea on the pharmacokinetics of raloxifene, raloxifene 4'-glucuronide, and raloxifene 6-glucuronide were evaluated in 16 healthy adults via a three-arm crossover, fixed-sequence study. Raloxifene (60 mg) was administered orally with water (baseline), with green tea for 1 day (acute), and on the fifth day after daily green tea administration for 4 days (chronic). Unexpectedly, green tea decreased the geometric mean green tea/baseline raloxifene AUC0-96h ratio to ~0.60 after both acute and chronic administration, which is below the predefined no-effect range (0.75-1.33). Lack of change in terminal half-life and glucuronide-to-raloxifene ratios indicated the predominant mechanism was not inhibition of intestinal UGT. One potential mechanism includes inhibition of intestinal transport. Using established transfected cell systems, a green tea extract normalized to EGCG inhibited 10 of 16 transporters tested (IC50 , 0.37-12 μM). Another potential mechanism, interruption by green tea of gut microbe-mediated raloxifene reabsorption, prompted a follow-up exploratory clinical study to evaluate the potential for a green tea-gut microbiota-drug interaction. No clear mechanisms were identified. Overall, results highlight that improvements in current models and methods used to predict UGT-mediated drug interactions are needed. Informing patients about the risk of co-consuming green tea with raloxifene may be considered.


Assessment of midperipheral anterior chamber depth in patient with posterior chamber phakic intraocular lens.
We describe a patient who required surgical explantation of a phakic intraocular lens (pIOL) as a result of mechanical angle closure despite the absence of standard preoperative risk factors. An assessment of the patient's records suggested peripheral anterior chamber depth (ACD) values considerably shallower than the central ACD measurement. Subsequently, the midperipheral values of all patients having pIOL implantation at our practice were reviewed to provide potential baseline measurements for comparison against the values of the explanted pIOL eyes. Assessment of midperipheral anterior chamber anatomy may be advantageous in the evaluation of patients for pIOL surgery. No author has a financial or proprietary interest in any material or method mentioned.


Evaluation of direct restorations using the revised FDI criteria: results from a reliability study.
The purpose of this in vitro reliability study was to determine the intra- and inter-examiner agreement of the revised FDI criteria including the categories "fracture of material and retention" (F1) and "caries at restoration margin" (B1). Forty-nine photographs of direct tooth-coloured posterior (n = 25) and anterior (n = 24) restorations with common deficiencies were included. Ten dental experts repeated the assessment in three blinded rounds. Later, the experts re-evaluated together all photographs and agreed on a reference standard. Statistical analysis included the calculation of Cohen's (Cκ), Fleiss' (Fκ), and weighted Kappa (wκ), the development of a logistic regression with a backward elimination model and Bland/Altman plots. Intra- and inter-examiner reliability exhibited mostly moderate to substantial Cκ, Fκ, and wκ values for posterior restorations (e.g. Intra: F1 Cκ = 0.57, wκ = 0.74; B1 Cκ = 0.57, wκ = 0.73/Inter F1 Fκ = 0.32, wκ = 0.53; B1 Fκ = 0.41, wκ = 0.64) and anterior restorations (e.g. Intra F1 Cκ = 0.63, wκ = 0.76; B1 Cκ = 0.48, wκ = 0.68/Inter F1 Fκ = 0.42, wκ = 0.57; B1 Fκ = 0.40, wκ = 0.51). Logistic regression analyses revealed significant differences between the evaluation rounds, examiners, categories, and tooth type. Both the intra- and inter-examiner reliability increased along with the evaluation rounds. The overall agreement was higher for anterior restorations compared to posterior restorations. The overall reliability of the revised FDI criteria set was found to be moderate to substantial. If properly trained, the revised FDI criteria set are a valid tool to evaluate direct and indirect restorations in a standardized way. However, training and calibration are needed to ensure reliable application.


Metabolites of 2,3-diketogulonate delay peroxidase action and induce non-enzymic H2O2 generation: Potential roles in the plant cell wall.
A proportion of the plant's l-ascorbate (vitamin C) occurs in the apoplast, where it and its metabolites may act as pro-oxidants and anti-oxidants. One ascorbate metabolite is 2,3-diketogulonate (DKG), preparations of which can non-enzymically generate H2O2 and delay peroxidase action on aromatic substrates. As DKG itself generates several by-products, we characterised these and their ability to generate H2O2 and delay peroxidase action. DKG preparations rapidly produced a by-product, compound (1), with λmax 271 and 251 nm at neutral and acidic pH respectively. On HPLC, (1) co-eluted with the major H2O2-generating and peroxidase-delaying principle. Compound (1) was slowly destroyed by ascorbate oxidase, and was less stable at pH 6 than at pH 1. Electrophoresis of an HPLC-enriched preparation of (1) suggested a strongly acidic (pKa ≈ 2.3) compound. Mass spectrometry suggested that un-ionised (1) has the formula C6H6O5, i.e. it is a reduction product of DKG (C6H8O7). In conclusion, compound (1) is the major H2O2-generating, peroxidase-delaying principle formed non-enzymically from DKG in the pathway ascorbate → dehydroascorbic acid → DKG → (1). We hypothesise that (1) generates apoplastic H2O2 (and consequently hydroxyl radicals) and delays cell-wall crosslinking - both these effects favouring wall loosening, and possibly playing a role in pathogen defence.


Gas-phase fragmentation of the Ag+-phenylalanine complex: cation-pi interactions and radical cation formation.
Collision-induced dissociation experiments on the Ag+-phenylalanine complex using several collision energies were shown to yield ten different fragment ions. Unambiguous assignment of these fragment ions were made by careful analysis of deuterium labeling experiments. The losses of H2O, CO, CO2, and AgH were commonly observed; also encountered were the losses of H2, Ag, and H. Deuterium labeling experiments and density functional calculations have been employed to probe fragmentation mechanisms that account for all experimental results.


Control in patients with advanced cancer: an interpretative phenomenological study.
In the context of life-threatening illness, loss of control is argued as a source of suffering and loss of perceived dignity, whereas having control over the dying process has been seen as a way of maintaining personal independence. Little is known about the meaning of control from the patients' perspectives. Thus, the aim of this study was to explore how patients with advanced cancer understand control, in terms of underlying beliefs, attitudes, and expectations consistent with self-efficacy, in different dimensions of their life, their illness, and their healthcare. We conducted semi-structured qualitative interviews using an interpretive phenomenological analysis approach. Patients with advanced cancer from an oncology unit and a palliative care unit from Barcelona (Spain) were recruited. The inclusion criteria were a) ≥ 18 years old; b) fluency in Spanish or Catalan; c) outpatients diagnosed with advanced cancer; d) Eastern Cooperative Oncology Group (ECOG) between 0 and 3; e) judged by their physician or nurse to be emotionally stable; f) considered to have control over their illness and circumstances according to their responsible physician; and g) signed informed consent. We interviewed eight participants (ages ranged from 29 to 70 years, six were female). Two themes were identified: 1) factors that influence the perception of control, with subthemes: uncertainty about future suffering, character traits underlying a need for control; sense of lack of care as a source of loss of control; and 2) perceiving control over an uncontrollable illness, explained by perceived control over subjective wellbeing and adjusting the focus of control. The data allowed us to identify strategies that promote a sense of control in these patients. The illness, according to the participants, was experienced as series of losses. However, attention was often focused on areas where they continued to have control. These findings selectively reflect experiences of those who see themselves able to effect outcomes in life, suggesting future research should address how both family members and healthcare professionals can help to empower all patients.


Sickness certification in primary care.
Sickness certification is a common task, which is however insufficiently studied. Our objective was to describe, prospectively, prescription practices in sickness certification by primary care physicians. We recorded patients receiving a sickness certificate during a six-week study period. The main outcome measures were: duration of sick-leave according to age, profession, diagnosis, nationality, somatic, or psychiatric comorbidity as well as co-factors related to the familial or professional environment. Out of a total of 6,433 consultations, 602 patients received a sickness certification, and in 56% of these, sick-leave duration was > or = 6 days. Multivariate analysis showed that presence of co-morbidity and co-factors, greater age and musculoskeletal, cardiovascular, psychiatric disease and injury were independently associated with a longer sickness certification duration. Sickness certification is a complex task which entails not only consideration of the diagnosis but also of other factors such as co-morbidity, as well as familial and professional environment. Physicians should be aware of these elements and of situations, which might lead to a longer sick-leave period.


Fast analysis of phthalates in freeze-dried baby foods by ultrasound-vortex-assisted liquid-liquid microextraction coupled with gas chromatography-ion trap/mass spectrometry.
This paper is focused on the determination of phthalates (PAEs), compounds "plausibly" endocrine disruptors, in baby food products by means of a method based on ultrasound-vortex-assisted liquid-liquid microextraction coupled with GC-IT/MS (UVALLME-GC-IT/MS). Particularly, the whole procedure allows the determination of six phthalates such as DMP, DEP, DBP, iBcEP, BBP and DEHP. After dissolution of 0.1g product sample and addition of anthracene as Internal Standard, 250μL of n-heptane are used as extraction solvent. The solution, held for 5min on the vortex mixer and for 6min in an ultrasonic bath at 100W for favoring the solvent dispersion and consequently the analyte extraction, is centrifuged at 4000rpm for 30min. About 100μL of heptane are recovered and 1μL is injected into the GC-IT/MS. All the analytical parameters investigated are deeply discussed: under the best conditions, the percentage recoveries range between 96.2 and 109.2% with an RSD ≤10.5% whereas the Limit of Detections (LODs) and the Limit of Quantifications (LOQs) are below 11 and 20ngg-1, respectively, for all the PAEs except for iBcEP (23 and 43ngg-1, respectively). The linear dynamic range of this procedure is between 10 and 5000ngg-1 with R2 ≥0.92. The method has been applied to real commercial freeze-dried samples (chicken and turkey meats) available on the Italian pharmaceutical market: three PAEs were preliminary identified, i.e. DEP (14ngg-1), DBP (11ngg-1) and DEHP (64ngg-1).


Illuminating the physics of dynamic friction through laboratory earthquakes on thrust faults.
Large, destructive earthquakes often propagate along thrust faults including megathrusts. The asymmetric interaction of thrust earthquake ruptures with the free surface leads to sudden variations in fault-normal stress, which affect fault friction. Here, we present full-field experimental measurements of displacements, particle velocities, and stresses that characterize the rupture interaction with the free surface, including the large normal stress reductions. We take advantage of these measurements to investigate the dependence of dynamic friction on transient changes in normal stress, demonstrate that the shear frictional resistance exhibits a significant lag in response to such normal stress variations, and identify a predictive frictional formulation that captures this effect. Properly accounting for this delay is important for simulations of fault slip, ground motion, and associated tsunami excitation.


Similarity of cardiovascular response to upper and lower body static contraction in endurance-trained and untrained males.
The purpose of this study was to investigate the cardiovascular response to upper and lower body static contraction in endurance-trained (ET) and untrained (UT) males (both groups N = 6). The groups were similar in age, height, and weight. However, the ET group exhibited a markedly higher (P less than 0.01) VO2 max during treadmill running than the UT group (65.4 +/- 4.8 vs 49.9 +/- 2.8 ml X kg-1 X min-1, mean +/- SD). Both groups performed static handgrip and leg extension in a randomly assigned order at 30% of maximal voluntary contraction for 3 min. Heart rate and mean intra-arterial blood pressure (MABP) were measured at rest and throughout contraction. At rest, differences between the two groups were not significant for heart rate (54 +/- 10 vs 66 +/- 8 beats X min-1) or MABP (93 +/- 4 vs 91 +/- 5 mm Hg). During handgrip, the increases in heart rate (24 +/- 12 vs 15 +/- 6) and MABP (24 +/- 10 vs 27 +/- 12) were not significantly different between the two groups. During leg extension, the magnitude of the increases in heart rate (44 +/- 21 vs 46 +/- 27) and MABP (37 +/- 11 vs 41 +/- 10) were again not different for the two groups. These results suggest that cardiovascular regulation during static contraction is similar in endurance-trained and untrained individuals, even during contraction involving the trained musculature.


Transmission line matrix modelling of thermal injuries to skin.
A numerical model based on the transmission line matrix method is presented for the quantitative prediction of skin burn resulting from exposure of a specific region of human skin surface to a high temperature heat source. Transient temperatures were numerically estimated by Pennes' bioheat equation, and the damage function denoting the extent of burn was calculated using the Arrhenius assumptions for protein damage rate. A two-dimensional transmission line matrix model was used to predict the effects of exposure time and structure thicknesses on the transient temperature distribution and damage extent. Compared with other numerical sources the transmission line matrix results revealed good agreement, suggesting that this method may be an effective tool for the thermal diagnostic of burns.


Guidelines for diagnosis, prevention, and treatment of hand eczema.
Hand eczema is a common inflammatory skin disorder. Health care providers need continuously updated information about the management of hand eczema to ensure best treatment for their patients. To update the European Society of Contact Dermatitis guideline on the diagnosis, prevention, and treatment on of hand eczema. The Guideline Development Group (GDG) was established on behalf of the ESCD. A call for interest was launched via the ESCD website and via the ESCD members' mailing list. Appraisal of the evidence for therapeutic and preventive interventions was applied and a structured method of developing consensus was used and moderated by an external methodologist. The final guideline was approved by the ESCD executive committee and was in external review on the ESCD webpage for 1 month. Consensus was achieved for several statements and management strategies. The updated guideline should improve management of hand eczema.


Effects of the G(-656)A variant on CREB1 promoter activity in a neuronal cell line: interactions with gonadal steroids and stress.
Major depressive disorder (MDD) constitutes a major public health problem worldwide and affects women twice as frequently as men. Previous genetic studies have revealed significant evidence of linkage of the cAMP-responsive element-binding protein 1 (CREB1) gene region (2q33-35) to mood disorders among women from families with recurrent, early-onset MDD (RE-MDD), a severe and familial subtype of MDD. A rare G-to-A transition at position -656 in the CREB1 promoter co-segregates with mood disorders in women from these families, implicating CREB1 as a sex-related susceptibility gene for unipolar mood disorders. In the current study, the functional significance of the CREB1 promoter variant was determined using transfection experiments that employed plasmid constructs containing the wild-type or variant CREB1 promoters coupled to a reporter gene. The results support the hypothesis that the A(-656) allele contributes to the development of MDD in women through selective alteration of CREB1 promoter activity by female gonadal steroids in noradrenergic neuronal cells. Furthermore, exaggeration of these effects during a simulated stress condition may be relevant to reported gene-environment interactions that contribute to the emergence of MDD in clinical populations.


Bromodomain containing protein represses the Ras/Raf/MEK/ERK pathway to attenuate human hepatoma cell proliferation during HCV infection.
Hepatitis C virus (HCV) infection facilitates the development of hepatocellular carcinoma (HCC). Activation of Ras/Raf/MEK/ERK pathway is found in more than 30% human cancers. Here, we revealed a novel mechanism underlying the regulation of hepatoma cell proliferation mediated by HCV. On one hand, hepatoma cell proliferation is facilitated by HCV infection through a positive feedback regulatory cycle. HCV promotes hepatoma cell proliferation by activating the Ras/Raf/MEK/ERK pathway, which in turn facilitates HCV replication to further enhance hepatoma cell proliferation. On the other hand, hepatoma cell proliferation is attenuated by the bromodomain containing 7 (BRD7), a tumor suppressor, through a negative feedback regulatory mechanism. After activation, the Ras/Raf/MEK/ERK pathway stimulates BRD7 production, which in turn represses the Ras/Raf/MEK/ERK pathway, leading to the attenuation of hepatoma cell proliferation. However, HCV persistent infection attenuates BRD7 gene expression and facilitates the protein degradation to release the Ras/Raf/MEK/ERK signaling, which results in the facilitation of hepatoma cell proliferation. Therefore, we proposed that the balance between BRD7 function and Ras/Raf/MEK/ERK activity is important for determining the outcomes of HCV infection and HCC development.


Lipid-induced DRAM recruits STOM to lysosomes and induces LMP to promote exosome release from hepatocytes in NAFLD.
The biogenesis and diagnostic value of exosomes in nonalcoholic fatty liver disease (NAFLD) are unclear. In this study, we revealed that the plasma exosome level was higher in patients with NAFLD than that in healthy controls. Damage-regulated autophagy modulator (DRAM) was identified as one of the genes related to exosome secretion in patients with NAFLD. Then, loss or knockdown of DRAM down-regulated exosome secretion from hepatic cells using a knockout mouse model and a knockdown cell model. DRAM knockout reversed high-fat diet–induced increase of secreted exosomes. Furthermore, DRAM knockdown inhibited fatty acid (FA)–induced lysosomal membrane permeabilization and lysosome inhibitor reversed the down-regulation of exosome release in DRAM knockout mice. Last, FA-induced DRAM interacted with stomatin and promoted its lysosomal localization to enhance exosome secretion from hepatic cells. We revealed a DRAM-mediated mechanism for exosome secretion and provided the foundation for plasma exosomes as a potential biomarker for NAFLD.


Treatment dropouts in hindsight: a follow-up study.
In a comprehensive rehabilitation center serving the mentally ill 64 dropouts and 42 successful terminees were interviewed monthly for 18 months following termination. The interview schedules elicited information about employment, heterosexual adjustment, living conditions, rent payment, social preferences, intimate friendships, and rehospitalization episodes. Analysis revealed that dropouts and successful terminees typically differed significantly on these variables for at least part of the follow-up period, but that by the end of the follow-up period there were no significant differences between the two groups on any of the variables, whether or not rehospitalization was controlled for. This hindsight examination of dropouts in comparison with successful terminees shows the concept of "dropping out" to be a time-limited concept.


The subcellular distribution of zinc in dog prostate studied by x-ray microanalysis.
X-ray microanalysis of zinc in ultrathin sections of dog prostate was performed by electron microscope microanalysis using the potassium pyroantimonate method of preparation. Prostates of both mature and immature dogs were examined and the metal was found to be localised primarily in the nucleolus, nuclear chromatin and secretory granules of epithelial cells. Differences in zinc concentrations were observed between mature and immature tissues, particularly in the nuclear chromatin. The metal was also incorporated into epithelial secretions, lysosomes and fibromuscular stroma. Variable binding of zinc to tissue components was revealed by a combination of histochemical precipitation and subcellular analysis.


Characterising contaminants distribution in marine-coastal sediments through multivariate and nonparametric statistical analyses: a complementary strategy supporting environmental monitoring and control.
This work investigates a statistical approach analysing data from monitoring activities on marine-coastal areas for environmental quality determination and surveillance. Analyses were performed on a database of the Environmental Protection and Prevention Agency of the Puglia Region. As, Cr, Ni, and Pb concentration values in marine sediments and biota from 2013 to 2015 and 2017 were processed to investigate different contaminant characteristics. Hierarchical cluster analysis identified three contaminant distribution classes with (1) highest Cr, Ni, and Pb concentrations, (2) highest As concentration, and (3) lowest contaminants concentration. The Kruskal-Wallis and Friedman tests showed that contaminant distributions were statistically different when considering the monitoring years and classes. However, statistical similarities resulted during the 2013-2017 and 2014-2015 periods. Spearman's coefficients displayed positive correlations among the pollutants in each matrix and mainly negative correlations for matrices comparison. This methodology aims to provide a practical support for monitoring to identify potential environmental deterioration over time and correlations with specific contamination sources.


Sex, drugs and chronic illness: health behaviours among chronically ill youth.
A growing body of literature indicates that adolescents with chronic conditions are as likely, or more likely, to take risky behaviours than their healthy peers. The objective of this research was to assess whether adolescents with chronic illness in Catalonia differ from their healthy peers in risk-taking behaviour. Data were drawn from the Catalonia Adolescent Health database, a survey including a random school-based sample of 6952 young people, aged 14-19 years. The index group (IG) included 665 adolescents (450 females) reporting several chronic conditions. The comparison group (CG) comprised 6287 healthy adolescents (3306 females). Personal, family and school-related variables were analysed to ensure comparability between groups. Sexual behaviour, drug use (tobacco, alcohol, cannabis, cocaine and synthetic drugs) and perception of drug use among peers and in school were compared. Analysis was carried out separately by gender. chi-square, Fisher's and Student's tests were used to compare categorical and continuous variables. The prevalence of chronic conditions was 9.6%, with females showing a higher prevalence than males. The IG showed similar or higher rates of sexual intercourse and risky sexual behaviour. For most studied drugs, IG males reported slightly lower rates of use than CG males, while IG females showed higher rates for every drug studied. No differences were found in the perceptions of drug use among peers or in their school. Similar to previous research, chronically ill adolescents in our sample are as likely, or more likely, to take risky behaviours than their healthy counterparts and should receive the same anticipatory guidance.


Management of postsurgical hyperhidrosis with direct current and tap water.
Excessive sweating, known as hyperhidrosis, involves the eccrine sweat glands of the axillae, soles, palms, and/or forehead. The use of iontophoresis to reduce or eliminate excessive sweating has been described since 1952. The purpose of this case report is to describe the use of tap water galvanism (TWG) using direct current (DC) with a patient who had postsurgical hyperhidrosis. The patient was a 36-year-old male electrician with traumatic phalangeal amputation and postsurgical development of hyperhidrosis. Tap water galvanism was administered using a DC generator, 2 to 3 times per week for 10 treatments. The patient's hands were individually submerged in 2 containers of tap water with the electrodes immersed directly into the containers. Each hand was treated with 30 minutes of TWG at 12 mA. Hyperhidrosis was measured by a 5-second imprint and subsequent tracing of the left hand placed on dry paper toweling. The patient's hyperhidrosis decreased from the full left palmar pad, with a surface area of 10.3x12.0 cm, to a reduced area of wetness that covered a 2.2-x2.7-cm area. The patient returned to work as an electrician without needing absorbent gloves, which had prevented him from performing electrical work. Following use of TWG, the patient's palmar hyperhidrosis returned to normhidrosis.


Transformation mechanisms of iopamidol by iron/sulfite systems: Involvement of multiple reactive species and efficiency in real water.
Although the ability of iron/sulfite system for decontamination purposes has been investigated, the complex reactive species generated and the underlying transformation mechanisms remain elusive. Here, we have comprehensively examined the transformation of iopamidol (IPM), a representative of iodinated X-ray contrast media, by iron catalyzed sulfite oxidation process under different water chemistry conditions. Multiple reactive intermediates including Fe(IV), SO4•-, and SO5•- were identified by conducting a series of experiments. Eight transformation products were detected by mass spectrometry analysis, and correlation with the nature of involved reactive species has been made. Further, the transformation pathways including amide hydrolysis, deiodination, amino and hydroxyl groups oxidation were proposed. Interestingly, these transformation products could be removed through adsorption to iron precipitates formed via pH adjustment. Combining Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, we revealed an effective way to reduce the amount of transformation products in the treated solutions. Since the iron/sulfite process appears to be less sensitive to natural organic matter, it exhibited very good efficiency for IPM removal in real water samples, even with a high organic carbon loading. These findings may have strong implications in the development of novel oxidation process based on the sulfite/iron systems for wastewater treatment.


Mechanisms for the synthesis of conjugated enynes from diphenylacetylene and trimethylsilylacetylene catalyzed by a nickel(0) complex: DFT study of ligand-controlled selectivity.
Density functional theory (DFT) was utilized to elucidate the reaction mechanisms of and the key factors that influence the Ni(0)-catalyzed cross-dimerization and -trimerization of trimethylsilylacetylene (R1) and diphenylacetylene (R2). Calculated results revealed that the electron-donating ability of the ligand plays a crucial role in determining the regionselectivity of this tandem reaction. The use of strongly electron-donating ligands favors the formation of cross-dimer intermediates, whereas cross-trimer products can easily be synthesized using weakly electron-donating ligands. A simple method of estimating the electron-donating abilities of different ligands based on the Mulliken charge distribution of the ligand-ligand pair was employed. The present theoretical results allow us to elucidate the reaction mechanisms for and to identify the factors that exert the greatest influence on the ligand-controlled cross-dimerization and -trimerization of trimethylsilylacetylene and diphenylacetylene. Guidelines for the design of novel ligand systems with Ni(0) catalysts are also proposed.


Author Correction: Self-assembled poly-catenanes from supramolecular toroidal building blocks.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Comparative analysis of mandibular anatomical variations between panoramic radiography and cone beam computed tomography.
The objective of this study is to compare the ability of panoramic radiography and cone beam computed tomography (CBCT) in detecting anatomical variations of the mandibular canal and mental foramen. One hundred twenty-seven preoperative panoramic and CBCT images were evaluated. Two oral and maxillofacial radiologists investigated the presence of bifid mandibular canals and/or additional mental foramina on the right, left, or both sides of the mandible. Intra- and interobserver reliability was determined using Cohen's kappa coefficient. McNemar's test compared the prevalence of mandibular anatomical variations between panoramic radiography and CBCT. The significance level was set at 0.05. Additional mental foramen and bifid mandibular canal were detected in 1.2 and 7.4 % of the panoramic radiographs and 7.4 and 9.8 % of the CBCT images, respectively. The incidence of anatomical variations on the mandibular canal was not significantly different between both imaging modalities (P > 0.05). Although CBCT provides better viewing of anatomical structures, including location, shape, and relationship with the surrounding area, panoramic radiography is a conventional imaging modality that can be used in the study of the bifid mandibular canals.


1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea.
1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PM2.5. We have found that this quinone is capable of causing a concentration-dependent contraction of tracheal smooth muscle in guinea pigs with EC50 value of 18.7 microM. The contraction required extracellular calcium and was suppressed by L-type calcium channel blockers nifedipine and diltiazem. It was found that 1,2-NQ activated phospholipase A2 (PLA2)/lipoxygenase (LO)/vanilloid receptor (VR1) signaling. Additionally, 1,2-NQ was capable of transactivating protein tyrosine kinases (PTKs) such as epidermal growth factor receptor (EGFR) in guinea pig trachea, suggesting that phosphorylation of PTKs contributes to 1,2-NQ-induced tracheal contraction. Consistent with this notion, this action was blocked by the PTKs inhibitor genistein and the EGFR antagonist PD153035, indicating that contraction was, at least in part, attributable to PTKs phosphorylation that activates VR1, resulting in increased intracellular calcium content in the smooth muscle cells.


Epithelial to mesenchymal transition in the liver field: the double face of Everolimus in vitro.
Everolimus (EVE), a mammalian target of rapamycin inhibitor, has been proposed as liver transplant immunosuppressive drug, gaining wide interest also for the treatment of cancer. Although an appropriate tolerance, it may induce several adverse effects, such as fibro-interstitial pneumonitis due to the acquisition of activated myofibroblasts. The exact molecular mechanism associated with epithelial to mesenchymal transition (EMT) may be crucial also in the liver context. This work examines the role and the molecular mediators of EMT in hepatic stellate cell (HSC) and human liver cancer cells (HepG2) and the potential role of EVE to maintain the epithelial phenotype rather than to act as a potential initiators of EMT. Real time-PCR and western blot have been used to assess the capability of EVE at low-therapeutic (10 nM) and high (100 nM) dose to induce an in vitro EMT in HSC and HepG2. Biomolecular experiments demonstrated that low concentration of EVE (10 nM) did not modify the gene expression of alpha-smooth muscle actin (α-SMA), Vimentin (VIM), Fibronectin (FN) in both HSC and HepG2 cells, whereas EVE at 100 nM induced a significant over-expression of all the three above-mentioned genes and an increment of α-SMA and FN protein levels. Additionally, 100 nM of EVE induced a significant phosphorylation of AKT and an up-regulation of TGF-β expression in HSC and HepG2 cells. Our data, although obtained in an in vitro model, revealed, for the first time, that high concentration of EVE may induce EMT in liver cells confirming previous published evidences obtained in renal cells. Additionally, they suggested that mTOR-I should be administered at the lowest dose able to maximize their important and specific therapeutic properties minimizing or avoiding fibrosis-related adverse effects. In summary, if confirmed by additional studies, our results could be useful for researchers to standardize new therapeutic immunosuppressive and anticancer drugs protocols.


Legal cannabis market shares during Canada's first year of recreational legalisation.
This study estimated legal products' share of Canada's total cannabis consumption during the first year of recreational legalisation, October 2018 to September 2019. Government data was used to estimate monthly recreational sales in dollars per capita, grams per user, and percentage share of kilograms or litres consumed. As explanatory factors, the analysis considered provincial differences in retail pricing (percentage mark-ups) and store density (stores per million users), as well as national monthly production of dry cannabis (kilograms) and cannabis oil (litres) finished products. Legal recreational products' share of Canada's overall cannabis consumption began at 7.8% in October 2018 and grew to 23.7% by September 2019, with an average of 14.5% over the first 12 months. Sales growth was delayed by shortages of both dry cannabis products and licensed stores, but not cannabis oils. Across the 10 provinces, legal recreational shares in September 2019 varied from 13% to 70%; differences in store densities and retail prices partly explained the variation. Prince Edward Island's large 70% share seemed due to it having minimal product shortages, high store densities, and low prices. Legal recreational products captured market share to the extent they were available, accessible, and low-priced. Problems with those factors slowed the initial expansion of legal product sales but also suggested ways to gradually increase their market share.


Probing three-way interactions in moderated multiple regression: development and application of a slope difference test.
Researchers often use 3-way interactions in moderated multiple regression analysis to test the joint effect of 3 independent variables on a dependent variable. However, further probing of significant interaction terms varies considerably and is sometimes error prone. The authors developed a significance test for slope differences in 3-way interactions and illustrate its importance for testing psychological hypotheses. Monte Carlo simulations revealed that sample size, magnitude of the slope difference, and data reliability affected test power. Application of the test to published data yielded detection of some slope differences that were undetected by alternative probing techniques and led to changes of results and conclusions. The authors conclude by discussing the test's applicability for psychological research.


Prevalence of abnormalities in dental structure, position, and eruption pattern in a population of unilateral and bilateral cleft lip and palate patients.
To evaluate the dental characteristics of patients subjected to a protocol that included early secondary gingivoalveoloplasty (ESGAP). Panoramic radiographs of 87 patients with unilateral cleft lip and palate (UCLP) and 29 with bilateral cleft lip and palate (BCLP) were evaluated. Missing and supernumerary teeth were also quantified on the cleft and noncleft side and in the maxilla and mandible. Crown and root malformations and tooth rotations were quantified. A subsample in permanent dentition was extrapolated to analyze canine eruption patterns. A total of 48.8% of the UCLP patients presented with missing permanent lateral incisors in the cleft area and 6.1% contralaterally. A total of 4.9% presented with missing second maxillary premolars on the cleft site and 1.2% contralaterally. A total of 7.3% presented with supernumerary lateral incisors, and 45% of the BCLP cleft sites presented with missing lateral incisors, while 25% of the cleft sites presented second maxillary premolars agenesis. Five percent of the cleft sites presented with supernumerary lateral incisors. Evaluation of the subsample in permanent dentition showed that 15.5% had a canine retention and 4.4% of the canines had to be surgically exposed. A significant association was observed between canine inclination and retention but not with absence of the lateral incisor. The frequency of dental anomalies in this sample was similar to other cleft populations. As surgical trauma has been suggested to damage forming teeth, the results of this study indicated that ESGAP has no detrimental influence on subsequent dental development.


Molecular cloning of the rat vascular smooth muscle thrombin receptor. Evidence for in vitro regulation by basic fibroblast growth factor.
To study thrombin's receptor-mediated effects on vascular cells, we cloned and characterized a cDNA encoding a rat smooth muscle cell thrombin receptor. A rat aortic smooth muscle (RASM) cell cDNA library was screened with a 500-base pair (bp) sequence from the human thrombin receptor, obtained by polymerase chain reaction (PCR) amplification of cDNA synthesized from human erythropoietic leukemia (HEL) cell mRNA with PCR primers based on the published human thrombin receptor sequence. Clone pRTHR17 contains a 3418-bp insert that includes 50 bp of the 5'-untranslated region and the entire coding and 3'-untranslated regions of the RASM cell thrombin receptor. The sequence of pRTHR17 is 85% similar, at the nucleotide level, and 78% similar, at the deduced amino acid level, to the human thrombin receptor. Although the putative thrombin cleavage and binding sites are present, there are significant differences between the rat and human receptors in their amino-terminal sequences. Detectable signals (consisting of a single band of 3.45 kb) are present by Northern analysis of mRNA from RASM cells, and rat lung, kidney, and testes, but not in aorta or other tissues probed. The results of Southern analysis of rat genomic DNA are consistent with the existence of a single copy of the gene encoding this receptor. The steady state thrombin receptor mRNA level is low in cultured growth-arrested RASM cells and not detectable in rat aorta. To determine whether regulation of the RASM cell thrombin receptor occurs under growth-stimulating conditions, growth-arrested RASM cells were treated with basic fibroblast growth factor (bFGF, recently proposed to be a major mitogen controlling vascular smooth muscle cell growth following injury (Lindner, V., and Reidy, M. A. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 3739-3743)). There was a significant increase in thrombin receptor mRNA following the addition of bFGF. These data demonstrate that: 1) mRNA for a thrombin receptor similar to that reported from human megakaryocyte and hamster fibroblast cell lines is present in proliferating primary culture rat smooth muscle cells, 2) the most significant sequence differences are present in the amino-terminal tail of the thrombin receptor, and 3) the mRNA level for this receptor is regulated under growth-stimulating conditions in vitro.


Direct visualization of serotonin1D receptors in the human brain using a new iodinated radioligand.
The development of the new ligand serotonin-5-O-carboxymethyl-glycyl [125I]tyrosinamide (abbreviated [125I]GTI) allows for the direct visualization of serotonin1B and serotonin1D (5-HT1B/1D) sites. Autoradiographic techniques were used to demonstrate the selective binding of this ligand to 5-HT1D sites in human post-mortem brain materials. The distribution of [125I]GTI binding sites was compared to [3H]5-HT sites in the presence of different displacers. The results show the selective binding of [125I]GTI to sites in the basal ganglia and substantia nigra which corresponds to 5-HT1D receptors.


A question of class.
Fundamental misunderstandings about classification can lead scientists down unproductive or dangerous paths, argue Jeffrey Parsons and Yair Wand.


Stability and surface properties of selenium nanoparticles coated with chitosan and sodium carboxymethyl cellulose.
The effect of polysaccharide coatings on the stability and release characteristics of selenium nanoparticles (SeNPs) was evaluated by comparing the characteristics of chitosan-coated SeNPs (CS-SeNPs) and sodium carboxymethyl cellulose-coated SeNPs (CMC-SeNPs). The release characteristics of SeNPs were investigated in storage conditions, gastrointestinal conditions, and free radical systems. CMC-SeNPs formed dimers or trimers, whereas CS-SeNPs were monodispersed but formed large aggregates in a pH range of 7.4-8.25. Upon 50 days of storage at 30 °C, both CMC-SeNPs and CS-SeNPs were converted to Se4+. SeNPs exhibited a lower release rate in simulated gastrointestinal conditions than in free radical systems. SeNPs release in ABTS and superoxide anion free radical systems followed the first-order and Korsmeyer-Peppas models, respectively, indicating that SeNP release is mainly governed by dissolution mechanisms. Additional studies are needed to examine the potential environmental effects and biological activity of the Se4+ released from SeNPs.


Extreme lithium-metal cycling enabled by a mixed ion- and electron-conducting garnet three-dimensional architecture.
The development of solid-state Li-metal batteries has been limited by the Li-metal plating and stripping rates and the tendency for dendrite shorts to form at commercially relevant current densities. To address this, we developed a single-phase mixed ion- and electron-conducting (MIEC) garnet with comparable Li-ion and electronic conductivities. We demonstrate that in a trilayer architecture with a porous MIEC framework supporting a thin, dense, garnet electrolyte, the critical current density can be increased to a previously unheard of 100 mA cm-2, with no dendrite-shorting. Additionally, we demonstrate that symmetric Li cells can be continuously cycled at a current density of 60 mA cm-2 with a maximum per-cycle Li plating and stripping capacity of 30 mAh cm-2, which is 6× the capacity of state-of-the-art cathodes. Moreover, a cumulative Li plating capacity of 18.5 Ah cm-2 was achieved with the MIEC/electrolyte/MIEC architecture, which if paired with a state-of-the-art cathode areal capacity of 5 mAh cm-2 would yield a projected 3,700 cycles, significantly surpassing requirements for commercial electric vehicle battery lifetimes.


The hyper-reactive malarial splenomegaly: a systematic review of the literature.
The hyper-reactive malarial splenomegaly syndrome (HMS) is a leading cause of massive splenomegaly in malaria-endemic countries. HMS is caused by a chronic antigenic stimulation derived from the malaria parasite. Classic Fakunle's major criteria for case definition are: persistent gross splenomegaly, elevated anti-malarial antibodies, IgM titre >2 SD above the local mean value and favourable response to long-term malaria prophylaxis. The syndrome is fatal if left untreated. The aim of this study is to systematically review the literature about HMS, particularly focussing on case definition, epidemiology and management. The search strategy was based on the following database sources: Pubmed, EmBase, Scopus. Search was done in March, 2014 and limited to English, Spanish, Italian, French, and Portuguese. Papers detected were 149, of which 89 were included. Splenomegaly was variably defined and the criterion of increased IgM was not always respected. The highest prevalence was reported in Papua New Guinea (up to 80%). In different African countries, 31 to 76% of all splenomegalies were caused by HMS. Fatality rate reached 36% in three years. The most frequent anti-malarial treatments administered were weekly chloroquine or daily proguanil from a minimum of one month to lifelong. In non-endemic countries, a few authors opted for a single, short anti-malarial treatment. All treated patients with no further exposure improved. Cases not completely fulfilling Fakunle's criteria and therefore untreated, subsequently evolved into HMS. It seems thus appropriate to treat incomplete or 'early' HMS, too. For patients not re-exposed to endemic areas, a short course of treatment is sufficient, showing that eradicating the infection is sufficient to cure HMS. Longer (probably lifelong) courses, or intermittent treatments, are required for those who remain exposed. Splenectomy, associated with high mortality, should be strictly limited to cases not responding to medical treatment.


Transparent Bendable Secondary Zinc-Air Batteries by Controlled Void Ionic Separators.
First ever transparent bendable secondary zinc-air batteries were fabricated. Transparent stainless-steel mesh was utilized as the current collector for the electrodes due to its reliable mechanical stability and electrical conductivity. After which separate methods were used to apply the active redox species. For the preparation of the anode, zinc was loaded by an electroplating process to the mesh. For the cathode, catalyst ink solution was spray coated with an airbrush for desired dimensions. An alkaline gel electrolyte layer was used for the electrolyte. Microscale domain control of the materials becomes a crucial factor for fabricating transparent batteries. As for the presented cell, anionic exchange polymer layer has been uniquely incorporated on to the cathode mesh as the separator which becomes a key procedure in the fabrication process for obtaining the desired optical properties of the battery. The ionic resin is applied in a fashion where controlled voids exist between the openings of the grid which facilitates light passage while guaranteeing electrical insulation between the electrodes. Further analysis correlates the electrode dimensions to the transparency of the system. Recorded average light transmittance is 48.8% in the visible light region and exhibited a maximum power density of 9.77 mW/cm2. The produced battery shows both transparent and flexible properties while maintaining a stable discharge/charge operation.


NF-kappaB in tracheal lavage fluid from intubated premature infants: association with inflammation, oxygen, and outcome.
To determine if tracheal lavage concentrations of the transcription factor NF-kappaB, which is activated by risk factors associated with bronchopulmonary dysplasia (BPD) and induces expression of cytokines associated with BPD, is related to BPD in premature infants. Serial tracheal lavage samples from intubated premature infants were analysed for cell count and concentrations of interleukin (IL)8 and NF-kappaB, corrected for dilution by secretory component concentrations. Level III university hospital neonatal intensive care unit. Thirty three intubated infants (mean (SD) birth weight 903 (258) g, median gestation 27 weeks (range 24-31)) in the first 14 days of life. Tracheal effluent NF-kappaB, IL8, and cell counts, corrected for dilution by secretory component measurement. Square root transformed NF-kappaB concentrations were significantly related to signs of inflammation (cell count, p = 0.002; IL8, p = 0.019) and to simultaneous fraction of inspired oxygen in samples from the first 3 days of life (r = 0.512, p<0.003). Of the 32 subjects with samples in the first 3 days of life, the half who either died or had BPD had higher NF-kappaB concentrations than those without BPD (square root concentration 0.097 (0.043) v 0.062 (0.036) microg/microg protein/microg secretory component, p = 0.018). Tracheobronchial lavage NF-kappaB concentrations are related to lung inflammation, oxygen exposure, and pulmonary outcome in intubated preterm infants. NF-kappaB activation may be an early critical step leading to BPD.


Anthocephaline, a new indole alkaloid and cadambine, a potent inhibitor of DNA topoisomerase IB of Leishmania donovani (LdTOP1LS), isolated from Anthocephalus cadamba.
Chemical investigation of the stem bark of Anthocephalus cadamba has resulted in the isolation of anthocephaline (1), a new indole alkaloid, along with strictosamide (2), vincosamide (3) and cadambine (4). The structures of the isolated alkaloids (1-4) were established by detailed 2D NMR spectral analysis. Cadambine (4) exhibited potent DNA topoisomerase IB inhibitory activity.


Effects of magnesium and ATP on pre-steady-state phosphorylation kinetics of the Na+,K(+)-ATPase.
The aim of the present work was to elucidate the role played by ATP and Mg2+ ions in the early steps of the Na+,K(+)-ATPase cycle. The approach was to follow pre-steady-state phosphorylation kinetics in Na(+)-containing K(+)-free solutions under variable ATP and MgCl2 concentrations. The experiments were performed with a rapid mixing apparatus at 20 +/- 2 degrees C. The concentrations of free and complexes species of Mg2+ and ATP were calculated on the basis of a dissociation constant of 0.091 +/- 0.004 mM, estimated with Arsenazo III under identical conditions. A simplified scheme were ATP binds to the ENa enzyme, which is phosphorylated to MgEPNa and consequently dephosphorylated returning to the ENa form, was used. In the absence of ADP and phosphate four rate constants are relevant: k1 and k-1, the on and off rate constants for ATP binding; k2, the transphosphorylation rate constant and k3, the constant that governs the dephosphorylation rate. The values obtained were: k1 = 0.025 +/- 0.003 microM-1 ms-1 for both free ATP and ATPMg; k-1 = 0.038 +/- 0.004 ms-1 for free ATP and 0.009 +/- 0.002 ms-1 for ATPMg; k2 = 0.199 +/- 0.005 ms-1; k3 = 0.0019 +/- 0.0002 ms-1. The model that seems best to explain the data is one where (i) the role of true substrate can be played equally well by free ATP or ATPMg, and (ii) free Mg2+, an essential activator, acts by binding to a specific Mg2+ site on the enzyme molecule.


Protocols for hyperlactatemia induction in the lactate minimum test adapted to swimming rats.
The lactate minimum test (LACmin) has been considered an important indicator of endurance exercise capacity and a single session protocol can predict the maximal steady state lactate (MLSS). The objective of this study was to determine the best swimming protocol to induce hyperlactatemia in order to assure the LACmin in rats (Rattus norvegicus), standardized to four different protocols (P) of lactate elevation. The protocols were P1: 6 min of intermittent jumping exercise in water (load of 50% of the body weight - bw); P2: two 13% bw load swimming bouts until exhaustion (tlim); P3: one tlim 13% bw load swimming bout; and P4: two 13% bw load swimming bouts (1st 30 s, 2nd to tlim), separated by a 30 s interval. The incremental phase of LACmin beginning with initial loads of 4% bw, increased in 0.5% at each 5 min. Peak lactate concentration was collected after 5, 7 and 9 min (mmol L(-1)) and differed among the protocols P1 (15.2+/-0.4, 14.9+/-0.7, 14.8+/-0.6) and P2 (14.0+/-0.4, 14.9+/-0.4, 15.5+/-0.5) compared to P3 (5.1+/-0.1, 5.6+/-0.3, 5.6+/-0.3) and P4 (4.7+/-0.2, 6.8+/-0.2, 7.1+/-0.2). The LACmin determination success rates were 58%, 55%, 80% and 91% in P1, P2, P3 and P4 protocols, respectively. The MLSS did not differ from LACmin in any protocol. The LACmin obtained from P4 protocol showed better assurance for the MLSS identification in most of the tested rats.


Pseudoseizure manifestations in two preschool age children.
We report two patients with epilepsy with pseudoseizures at age 6 years. Both presented with intractable staring spells. Pseudoseizures were provoked and aborted by suggestion, leading to the diagnosis. In both patients, evidence of a neuropsychological disturbance was later found and psychotherapy started. Monitoring of intractable staring episodes is recommended prior to escalating antiepileptic drug levels or resorting to polytherapy. In addition, differentiation from other non-epileptic phenomena is necessary to initiate proper therapy.


The genetic variability of MDR1 C3435T polymorphisms in four Southern Chinese populations.
To investigate the genetic variability of multiple drug resistant 1 (MDR1) gene C3435T polymorphism in four Southern Chinese populations. Using discrimination real-time PCR, we determined the MDR1 C3435T polymorphism in three ethnic minority groups Lahu (n=104), Wa (n=101) and Bulang (n=100) in Yunnan Province, and Han Chinese (n=199) in Hong Kong. All of them were residents in Southern China. For 3435 CC genotype, the frequency in Han Chinese in Hong Kong (44.7%) is significantly higher than in Lahu (16.3%) and Wa (29.7%) minorities, P<0.05. For 3435 CT genotype, the frequency in Han Chinese in Hong Kong (44.2%) is lower than in Lahu (58.7%), P<0.05. For 3435 TT genotype, frequency in Han Chinese in Hong Kong (11.1%) is lower than in Lahu (25%) and Wa (20.8%), P<0.05. For 3435 C allele, frequency in Han Chinese in Hong Kong (66.8%) is higher than in Lahu (45.7%) and Wa (54.5%), P<0.01. For 3435T allele, frequency in Han Chinese in Hong Kong (33.2%) is lower than in Lahu (54.3%) and Wa (45.5%), P<0.01. For MDR1 3435T allele, the frequencies are significantly higher in our four Southern Chinese populations than in African population (P<0.001) and significantly lower than in South-west Asians (P<0.05); Han Chinese in Hong Kong displayed significant difference from all the other ethnic populations except Japanese (P<0.05); compared with Caucasian and other ethnic Asians, Lahu minority showed no frequency difference (P>0.05) between Caucasian and other Asians (except Japanese). This is the first study to show the C3435T polymorphism of MDR1 in Southern Chinese populations. The frequency of C3435T, an important determinant for multidrug resistance, displays significant difference in ethnics. It may help for individualizing therapy for cancer, HIV and other common diseases.


Frequency of revision orchidopexy in Australia 1995-2014.
International criteria currently suggest orchidopexy at 6-12months for congenital undescended testis (UDT). Some children require repeat orchidopexy for recurrent UDT. This study aimed to assess practice in Australia over a 20-year period. We examined 20years of Australian orchidopexy data (1995-2014) from the Department of Human Services to explore the national revision orchidopexy rates over time. The total number of orchidopexy revisions was 890 over 20years compared with 25,984 primary operations. More than 50% of all primary and revision orchidopexies in 0-14year-old boys were performed in major population centers of NSW and Victoria (which hold 52% male population of same age), with a small number of revisions on 15-24year-old males. The incidence of revision orchidopexy significantly decreased over the 20-year period in boys ages 0-14years old, from 276 operations between 1995 and 1999 decreasing to 165 operations between 2010 and 2014 (-53%), compared to a population increase of +15% (p<0.05). These data demonstrate a decrease in revision orchidopexy since 1995, which may be related to change in referral practice with more children undergoing orchidopexy (primary and revision) by pediatric surgeons over the 20-year period. Level IV. Therapeutic Case Series with no Comparison Group.


Principles and Recommendations for Standardizing the Use of the Next-Generation Sequencing Variant File in Clinical Settings.
A national workgroup convened by the Centers for Disease Control and Prevention identified principles and made recommendations for standardizing the description of sequence data contained within the variant file generated during the course of clinical next-generation sequence analysis for diagnosing human heritable conditions. The specifications for variant files were initially developed to be flexible with regard to content representation to support a variety of research applications. This flexibility permits variation with regard to how sequence findings are described and this depends, in part, on the conventions used. For clinical laboratory testing, this poses a problem because these differences can compromise the capability to compare sequence findings among laboratories to confirm results and to query databases to identify clinically relevant variants. To provide for a more consistent representation of sequence findings described within variant files, the workgroup made several recommendations that considered alignment to a common reference sequence, variant caller settings, use of genomic coordinates, and gene and variant naming conventions. These recommendations were considered with regard to the existing variant file specifications presently used in the clinical setting. Adoption of these recommendations is anticipated to reduce the potential for ambiguity in describing sequence findings and facilitate the sharing of genomic data among clinical laboratories and other entities.


Electrophysiologically identified piriformis syndrome is successfully treated with incobotulinum toxin a and physical therapy.
Piriformis syndrome is entrapment of the sciatic nerve by the piriformis muscle. In this article we describe a 56-person randomized, double-blind, controlled study involving physical therapy and incobotulinum toxin A or placebo. Inclusion criteria were 3-SD delay of posterior tibial (PT) or fibular (FN) H-reflexes on flexion, adduction, and internal rotation (FAIR) testing, and normal paraspinal electromyographic findings. Outcome measures included adverse side effects, visual analog scale (VAS) findings, and H-reflex delay on the FAIR test. Mean intervention VAS score decreased significantly more compared with placebo at 2, 4, 6, 8, 10, and 12 weeks post-injection (P < 0.0001). FAIR test scores for PT, but not FN, decreased significantly more compared with placebo at 2, 4, 6, and 8 weeks post-injection (PT: P = 0.038, 0.003, 0.003, and 0.046). Adverse effects were minimal. VAS slope and PT FAIR test results varied significantly (P < 0.0001). Incobotulinum toxin A chemodenervation may be useful for treating piriformis syndrome as identified by the FAIR test. Muscle Nerve 56: 258-263, 2017.


A smartphone-based online tool for prehospital self-triage of COVID-19.
The COVID-19 epidemic has swept across China and spread to other countries. The rapid spreading of COVID-19 and panic combined with the lack of a hierarchical medical system in China have resulted in a huge number of hospital visiting which are overwhelming local medical system and increasing the incidence of cross infection. To meliorate this situation, we adopted the management concept of the system of Tiered Diagnosis and Treatment and developed an online tool for self-triage based on the mostly used multi-purpose smartphone app Wechat in China. This online tool helps people perform self-triage so that they can decide whether to quarantine at home or visit hospital. This tool further provides instructions for home quarantine and help patients make an appointment online if hospital visiting suggested. This smartphone application can reduce the burden on hospitals without losing the truly COVID-19 patients and protect people from the danger of cross infection.


cis-Diaminechloroplatinum in the treatment of advanced primary squamous cell carcinoma of the vaginal wall: a case report.
A 34-year-old patient with advanced primary squamocellular vaginal carcinoma was treated with external radiation (4000 cGy to the pelvis) and a line source Cesium application delivering 4000 cGy to the vaginal wall. During this treatment the patient developed a lesion on her back that proved to be a metastasis of a squamocellular cancer. The patient was started on six courses of cisplatin as a single agent. After the fourth course a complete remission was reached lasting for 4 months. By that time the metastasis recurred and was surgically excised. Sixteen months after diagnosis and 9 months after chemotherapeutic treatment there is no evidence of disease.


Microalgal sensitivity varies between a diuron-resistant strain and two wild strains when exposed to diuron and irgarol, alone and in mixtures.
A wild strain of Chaetoceros calcitrans and wild and diuron-resistant strains of Tetraselmis suecica, were exposed to the PSII inhibitor herbicides diuron and irgarol, individually and in mixtures. The effects of three concentrations of diuron and irgarol and four binary mixtures were evaluated on doubling time, relative reactive oxygen species and lipid content by flow cytometry, and on photosynthetic efficiency by pulse amplitude modulated fluorescence. In both wild strains, significant effects were observed for each molecule at the highest concentration tested: at irgarol 0.5 μg L(-1), C. calcitrans was shown to be more sensitive than T. suecica (+52% and +19% in doubling time, respectively), whereas at diuron 5 μg L(-1), T. suecica was more affected (+125% in doubling time) than C. calcitrans (+21%). Overall, irgarol had a higher toxicity at a lower concentration than diuron (no effect at diuron 0.5 μg L(-1)) for both wild strains. The strongest mixture (irgarol 0.5 μg L(-1) + diuron 5 μg L(-1)) increased doubling time by 356% for T. suecica, thus showing amplified effects when the two compounds were mixed. Sequencing of the diuron-resistant strain demonstrated a single mutation in the psbA gene coding sequence. Although resistance of this strain to diuron was confirmed with no effect at the highest diuron concentration, no resistance to irgarol was shown. In addition, the mutant strain exposed to the strongest mixture showed a 3.5-fold increase in doubling time compared with irgarol alone, thereby supporting the hypothesis of a biochemical interaction between these two compounds.


Statistical reasoning in clinical trials: hypothesis testing.
Hypothesis testing is based on certain statistical and mathematical principles that allow investigators to evaluate data by making decisions based on the probability or implausibility of observing the results obtained. However, classic hypothesis testing has its limitations, and probabilities mathematically calculated are inextricably linked to sample size. Furthermore, the meaning of the p value frequently is misconstrued as indicating that the findings are also of clinical significance. Finally, hypothesis testing allows for four possible outcomes, two of which are errors that can lead to erroneous adoption of certain hypotheses: 1. The null hypothesis is rejected when, in fact, it is false. 2. The null hypothesis is rejected when, in fact, it is true (type I or alpha error). 3. The null hypothesis is conceded when, in fact, it is true. 4. The null hypothesis is conceded when, in fact, it is false (type II or beta error). The implications of these errors, their relation to sample size, the interpretation of negative trials, and strategies related to the planning of clinical trials will be explored in a future article in this journal.


A randomized outcomes trial of ureteral stents for extracorporeal shock wave lithotripsy of solitary kidney or proximal ureteral stones.
Routine use of ureteral stents before extracorporeal shock wave lithotripsy of kidney stones between 10 and 20 mm. is controversial. We conducted a prospective randomized clinical trial to evaluate the outcome of ureteral stents for treating solitary kidney stones between 10 and 20 mm. or solitary proximal ureteral stones less than 20 mm. with shock wave lithotripsy. A total of 97 patients who met the aforementioned criteria were randomized between March 1994 to July 1997 into group 1-no stent, group 2-a 4.7Fr multi-length stent and group 3-a 7Fr multi-length stent. The patients were treated with the Dornier HM3 lithotriptor (Dornier Medical Systems, Inc., Marietta, Georgia) and monitored for stone-free rate, number of days lost from work, number of patients requiring rehospitalization, emergency room visits, irritative voiding symptom score and pain symptom score. Objective outcome was obtained from 91 patients based on a followup of at least 3 months. The overall stone-free rate was 80%, with a re-treatment rate of 7%. The number of days lost from work was approximately 2, with no significant differences among individual groups or subgroups. The hospitalization rate and number of emergency room visits in group 1 (22%) were statistically higher compared to groups 2 (7%) and 3 (7%). The irritative voiding symptom score was statistically higher in the stented groups 2 and 3 compared to the nonstented group 1. Although ureteral stents are associated with more irritative symptoms, their use resulted in fewer hospital readmissions and emergency room visits compared to when no stent was used to treat solitary kidney stones of 10 to 20 mm. or solitary proximal ureteral stones less than 20 mm. Size 4.7Fr stents may be preferable over 7Fr stents when used in conjunction with shock wave lithotripsy.


13C NMR studies of carboxylate inhibitor binding to cobalt(II) carboxypeptidase A.
Both 13C NMR and electronic absorption spectral studies on cobalt(II) carboxypeptidase A in the presence of acetate and phenylacetate provide evidence for two binding sites for each of these agents. The transverse relaxation rate T2-1 for the 13C-enriched carboxyl groups of the inhibitors is significantly increased when bound to the paramagnetic cobalt carboxypeptidase as compared to the diamagnetic zinc enzyme. The acetate concentration dependence of T2p-1 shows two inflections indicative of sequential binding of two inhibitor molecules. The cobalt-13C distances, calculated by means of the Solomon equation, indicate that the second acetate molecule binds directly to the metal ion while the first acetate molecule binds to a protein group at a distance 0.5-0.8 nm for the metal ion, consistent with it binding to one or more of the arginyl residues (Arg-145, Arg-127, or Arg-71). In the case of phenylacetate, perturbation of the cobalt electronic absorption spectrum shows that binding occurs stepwise. 13C NMR distance measurements indicate that one of the two phenylacetates is bound to the metal in the EI2 complex. These binding sites may correspond to those identified previously by kinetic means (one of which is competitive, the other noncompetitive) with peptide binding. The studies further indicate that it should be possible to map the protein interactions of the carbonyl groups of both substrate and noncompetitive inhibitors during catalysis by means of 13C NMR studies with suitably labeled substrates and inhibitors.


Injury patterns in patients with severe traumatic brain injuries from motor crashes admitted to Mulago hospital accidents & emergency unit.
The global burden of Road Traffic Crashes (RTC) is increasing. Uganda has one of the highest rates of RTCs in Sub-Sahara. Victims of RTCs sustain varying degrees of injuries depending on factors including the velocity at time of impact, protective gear; and if it was a motorcycle-motorcycle or motorcycle-vehicle crash. High speed collisions can result in severe forms of injuries and polytrauma. Some injuries are undetected. A cross sectional study was carried at Mulago Hospital Accidents & Emergency Unit, between November 2021 and February 2022; on all adult patients (≥18 years) with severe head injury from motor road traffic crashes. The study looked at injury patterns and assessed the relationship of polytrauma in patients with severe head injury to the mechanism of injury (motorcycles versus vehicles). Data were extracted from patient charts using a validated data abstraction tool and complete head to toe physical examination was carried out and injuries recorded. Data were analysed to determine the relationship of polytrauma in patients with severe head injury to the mechanism of injury. The participants were predominantly males with a population median age of 32 (25-39). The commonest modes of transportation of patients to the hospital were Police Pickup trucks (40%) and ambulance (36.1%). Among motorcycle RTCs, (19.2%) wore helmets; 21.2% had protective gear; with injury identified mainly in; the limbs (84.8%), neck (76.8%), chest (39.4%), and abdomen (26.3%). Patients from vehicle RTCs were 19% more likely to have polytrauma compared to patients from motorcycle RTCs. This study showed that patients who sustain severe traumatic brain injuries from vehicle crashes have an increased likelihood of having multiple injuries, compared to patients from motorcycle RTCs. For motorcycle users, injuries mostly affect the limbs. At particular risk are motorcyclists who do not wear helmets and protective coveralls.


Study on immunostimulatory activity and extraction process optimization of polysaccharides from Caulerpa lentillifera.
The process of extracting polysaccharides from the green algae Caulerpa lentillifera was studied by single factor experiments and response surface methodology. Additionally, the immunostimulatory activity of Caulerpa lentillifera polysaccharides (CLP) on RAW264.7 mouse macrophage was evaluated by in vitro cell experiments. The results showed that the optimal extraction conditions consisted of ultrasonification for 30 min, extraction time of 9 h, extraction temperature of 100 °C, and a ratio of water to raw material of 40:1. RAW264.7 macrophage exhibited enhanced phagocytosis with no toxic effects after treatment with CLP. In addition, CLP effectively increased the synthesis and secretion of cytokines (IL-6, TNF-α, IL-1β, and NO), whereby the secretion levels of IL-6, TNF-α, and IL-1β were 1,840.32 ± 21.03 pg/mL (50 μg/mL), 197.17 ± 3.13 ng/mL (50 μg/mL), and 1,178.35 ± 78.82 pg/mL (25 μg/mL), respectively. The polysaccharides contained in Caulerpa lentillifera have potential value for further development due to their immunological activity.


Experimental design approach for the optimisation of a HPLC-fluorimetric method for the quantitation of the angiotensin II receptor antagonist telmisartan in urine.
A high performance liquid chromatographic method with fluorimetric detection has been developed for the quantitation of the angiotensin II receptor antagonist (ARA II) 4-((2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl)methyl)biphenyl-2-carboxylic acid (telmisartan) in urine, using a Novapak C18 column 3.9 x 150 mm, 4 microm. The mobile phase consisted of a mixture acetonitrile-phosphate buffer (pH 6.0, 5 mM) (45:55, v/v) pumped at a flow rate of 0.5 ml min(-1). Effluent was monitored at excitation and emission wavelengths of 305 and 365 nm, respectively. Separation was carried out at room temperature. Chromatographic variables were optimised by means of experimental design. A clean-up step was used for urine samples consisting of a solid-phase extraction procedure with C8 cartridges and methanol as eluent. This method proved to be accurate (RE from -12 to 6%), precise (intra- and inter-day coefficients of variation (CV) were lower than 8%) and sensitive enough (limit of quantitation (LOQ), ca. 1 microg l(-1)) to be applied to the determination of the active drug in urine samples obtained from hypertensive patients. Concentration levels of telmisartan at different time intervals (from 0 up to 36 h after oral intake) were monitored.


DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose.
Diabetes mellitus, characterized by abnormally high blood glucose levels, gives rise to impaired bone remodeling. In response to high glucose (HG), the attenuated osteogenic differentiation capacity of human periodontal ligament stem cells (hPDLSCs) is associated with the loss of alveolar bone. Recently, DNA methylation was reported to affect osteogenic differentiation of stem cells in pathological states. However, the intrinsic mechanism linking DNA methylation to osteogenic differentiation ability in the presence of HG is still unclear. In this study, we found that diabetic rats with increased DNA methylation levels in periodontal ligaments exhibited reduced bone mass and density. In vitro application of 5-aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to decrease DNA methylation levels in hPDLSCs, rescued the osteogenic differentiation capacity of hPDLSCs under HG conditions. Moreover, we demonstrated that the canonical Wnt signaling pathway was activated during this process and, under HG circumstances, the 5-aza-dC-rescued osteogenic differentiation capacity was blocked by Dickkopf-1, an effective antagonist of the canonical Wnt signaling pathway. Taken together, these results demonstrate for the first time that suppression of DNA methylation is able to facilitate the osteogenic differentiation capacity of hPDLSCs exposed to HG, through activation of the canonical Wnt signaling pathway.


Precursor of the nuclear-encoded extrinsic 30 kDa protein in photosystem II of Euglena gracilis Z is not a polyprotein.
Polyprotein-type precursors have been reported for the nuclear-encoded proteins such as the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and the apoproteins of light-harvesting chlorophyll-protein (LHC) in Euglena. We report here that the precursor of the extrinsic 30 kDa protein of photosystem II (PS II) encoded by nuclear DNA is not a polyprotein. The precursor was identified as a 45 kDa protein by immunoprecipitation of in vitro translation products of mRNA and by a pulse-chase experiment. It is probable that the structure of the precursor of the nuclear-encoded protein in Euglena chloroplast is closely related to the feature of assembly, as well as of transport, of the protein in chloroplast.


The multiple sclerosis self-concept change scale: Development and validation of a new measure.
Self-concept change may impact psychological wellbeing and functioning in people with MS (pwMS). However, the extent and nature of change in self-concept that pwMS experience is poorly understood, owing to the lack of quantitative measures available to assess this construct. To examine the factor structure, validity, and internal consistency of the newly developed Multiple Sclerosis Self-Concept Change Scale (MSSCCS). Items measuring self-concept change were created, reviewed by a panel of experts and pre-tested in a sample of 135 pwMS. A revised list of 51 items were then administered to 1307 pwMS (80.3% female; Age M = 59.21 years, SD = 11.40), together with measures of disease impact and psychosocial functioning. Exploratory factor analysis using principal axis factor extraction in 643 randomly selected participants yielded 23-items measuring 5 latent factors for the final MSSCCS. Confirmatory factor analysis involving the remaining participants supported the 5-factor model, as well as a 2nd order model of "global change". Internal consistency of the total scale was good (α = 0.89). The MSSCCS also demonstrated evidence of concurrent and construct validity. The MSSCCS is a reliable and valid assessment, which may assist in enhancing understanding of self-concept change in pwMS.


A pre-experimental design evaluation of brief harm reduction interventions to improve coping self-efficacy of carers of people with substance use disorder.
Globally, the rise in the number of people living with a substance use disorder (SUD) carries a multitude of individual and social health implications for carers and their families, often impacting negatively on their quality of life. Considered from a harm reduction approach, SUD is understood as a chronic protracted, complex health and social condition. From the extant literature, there is no evidence of the harm reduction approach being applied to address the needs of carers/family members who carry the burden of SUD care. This study preliminarily evaluated the Care4Carers Programme. It is a purposively designed set of brief interventions to improve the coping self-efficacy of carers of people with SUD (PwSUD carers) by equipping them to think about ways to exert control over their motivation, behaviours and social environment. A pre-experimental, one group pretest-posttest design was implemented with 15 purposively selected participants in the Gauteng Province of South Africa. The intervention was conducted by the lead researcher, a registered social worker. Eight brief intervention sessions were held, over 5-6 weeks at research sites where the participants were identified. The coping self-efficacy scale was completed before and directly after exposure to the programme. Results were analysed using paired t-tests. There were statistically significant (p < .05) improvements in carers' coping self-efficacy, both overall and in respect of each of its constituent components: problem-focused coping, emotion-focused coping and social support strategies. The Care4Carers Programme improved the coping self-efficacy of carers of people living with SUDs. The application of this programmatic harm reduction intervention to support PwSUD carers should be tested on a larger scale across South Africa.


Quality of word and concept embeddings in targetted biomedical domains.
Embeddings are fundamental resources often reused for building intelligent systems in the biomedical context. As a result, evaluating the quality of previously trained embeddings and ensuring they cover the desired information is critical for the success of applications. This paper proposes a new evaluation methodology to test the coverage of embeddings against a targetted domain of interest. It defines measures to assess the terminology, similarity, and analogy coverage, which are core aspects of the embeddings. Then, it discusses the experimentation carried out on existing biomedical embeddings in the specific context of pulmonary diseases. The proposed methodology and measures are general and may be applied to any application domain.


Structural and functional characterization of solute binding proteins for aromatic compounds derived from lignin: p-coumaric acid and related aromatic acids.
Lignin comprises 15-25% of plant biomass and represents a major environmental carbon source for utilization by soil microorganisms. Access to this energy resource requires the action of fungal and bacterial enzymes to break down the lignin polymer into a complex assortment of aromatic compounds that can be transported into the cells. To improve our understanding of the utilization of lignin by microorganisms, we characterized the molecular properties of solute binding proteins of ATP-binding cassette transporter proteins that interact with these compounds. A combination of functional screens and structural studies characterized the binding specificity of the solute binding proteins for aromatic compounds derived from lignin such as p-coumarate, 3-phenylpropionic acid and compounds with more complex ring substitutions. A ligand screen based on thermal stabilization identified several binding protein clusters that exhibit preferences based on the size or number of aromatic ring substituents. Multiple X-ray crystal structures of protein-ligand complexes for these clusters identified the molecular basis of the binding specificity for the lignin-derived aromatic compounds. The screens and structural data provide new functional assignments for these solute-binding proteins which can be used to infer their transport specificity. This knowledge of the functional roles and molecular binding specificity of these proteins will support the identification of the specific enzymes and regulatory proteins of peripheral pathways that funnel these compounds to central metabolic pathways and will improve the predictive power of sequence-based functional annotation methods for this family of proteins.