Major and trace element partitioning between dissolved and particulate phases in Antarctic surface snow.
In order to provide a new insight into the Antarctic snow chemistry, partitioning of major and trace elements between dissolved and particulate (i.e. insoluble particles, >0.45 μm) phases have been investigated in a number of coastal and inland snow samples, along with their total and acid-dissolvable (0.5% nitric acid) concentrations. Alkaline and alkaline-earth elements (Na, K, Ca, Mg, Sr) were mainly present in the dissolved phase, while Fe and Al were predominantly associated with the particulate matter, without any significant difference between inland and coastal samples. On the other hand, partitioning of trace elements depended on the sampling site position, showing a general decrease of the particulate fraction by moving from the coast to the plateau. Cd, Cu, Pb and Zn were for the most part in the dissolved phase, while Cr was mainly associated with the particulate fraction. Co, Mn and V were equally distributed between dissolved and particulate phases in the samples collected from the plateau and preferentially associated with the particulate in the coastal samples. The correlation between the elements and the inter-sample variability of their concentration significantly decreased for the plateau samples compared to the coastal ones, according to a change in the relative contribution of the metal sources and in good agreement with the estimated marine and crustal enrichment factors. In addition, samples from the plateau were characterised by higher enrichment factors of anthropogenic elements (Cd, Cr, Cu, Pb and Zn), compared to the coastal area. Finally, it was observed that the acid-dissolvable metal concentrations were generally lower than the total concentration values, showing that the acid treatment can dissolve only a given fraction of the metal associated with the particulate (<20% for iron and aluminium).


Advances in hormone replacement therapy: making the menopause manageable.
The importance of the results of some large, randomized controlled trials (RCTs) on Hormone Replacement Therapy (HRT) has modified the risk/benefit perception of HRT. Recent literature review supports a different management. The differences in age at initiation and the duration of HRT are key points. HRT appears to decrease coronary disease in younger women, near menopause; yet, in older women, HRT increases risk of a coronary event. Although HRT is a recognized method in the prevention and treatment of osteoporosis, it is not licensed for the prevention of osteoporosis as a first-line treatment. The effectiveness of low and ultra-low estrogen doses has been demonstrated for the treatment of vasomotor symptoms, genital atrophy and the prevention of bone loss, with fewer side-effects than the standard dose therapy. Further research, however, is needed to determine the effect both on fractures, as well as on cardiovascular and breast diseases. Newer progestins show effects that are remarkably different from those of other assays. The effectiveness of testosterone at improving both sexual desire and response in surgically and naturally postmenopausal women is shown by the testosterone patch. The intention, dose and regimen of HRT need to be individualized, based on the principle of choosing the lowest appropriate dose in relation to the severity of symptoms and the time and menopause age.


New functional identity for the DNA uptake sequence in transformation and its presence in transcriptional terminators.
The frequently occurring DNA uptake sequence (DUS), recognized as a 10-bp repeat, is required for efficient genetic transformation in the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae. Genome scanning for DUS occurrences in three different species of Neisseria demonstrated that 76% of the nearly 2,000 neisserial DUS were found to have two semiconserved base pairs extending from the 5' end of DUS to constitute a 12-mer repeat. Plasmids containing sequential variants of the neisserial DUS were tested for their ability to transform N. meningitidis and N. gonorrhoeae, and the 12-mer was found to outperform the 10-mer DUS in transformation efficiency. Assessment of meningococcal uptake of DNA confirmed the enhanced performance of the 12-mer compared to the 10-mer DUS. An inverted repeat DUS was not more efficient in transformation than DNA species containing a single or direct repeat DUS. Genome-wide analysis revealed that half of the nearly 1,500 12-mer DUS are arranged as inverted repeats predicted to be involved in rho-independent transcriptional termination or attenuation. The distribution of the uptake signal sequence required for transformation in the Pasteurellaceae was also biased towards transcriptional terminators, although to a lesser extent. In addition to assessing the intergenic location of DUS, we propose that the 10-mer identity of DUS should be extended and recognized as a 12-mer DUS. The dual role of DUS in transformation and as a structural component on RNA affecting transcription makes this a relevant model system for assessing significant roles of repeat sequences in biology.


Helical nanotube structures of MoS2 with intrinsic twisting: an objective molecular dynamics study.
Objective molecular dynamics combined with density-functional-based tight binding makes it possible to compute chiral nanotubes as axial-screw dislocations. This enables the surprising revelation of a large catalog of MoS2 nanotubes that lack the prescribed translational symmetry and exhibit chirality-dependent electronic band gaps and elastic constants. Helical symmetry is the natural property to rely on when studying quasi-one-dimensional nanomaterials formally derived or grown via screw dislocations.


The mystery of recurrent idiopathic cerebrovascular and coronary arterial thrombosis.
A 46-year-old man presented to our hospital with ST elevation myocardial infarction (STEMI). Previous records revealed a history of recurrent non-STEMI, stroke and transient ischaemic attacks. He was thoroughly investigated with coronary angiography, a cerebral CT angiography, thrombophilia panel and autoimmune screening tests, all of which proved negative. His current episode of STEMI resulted while on dual antiplatelet therapy; the patient was investigated for P2Y12 receptor resistance, which was also negative. A diagnosis of idiopathic recurrent arterial thrombosis was established and the patient was discharged home on aspirin and warfarin. Routine follow-up has revealed no recurrence of symptoms.


Resin-bound chiral derivatizing agents for assignment of configuration by NMR spectroscopy.
A general methodology for assigning the configuration of chiral mono- and polyfunctional compounds by NMR is presented. The approach is based on the use of polystyrene-bound chiral derivatizing agents (CDA-resins) specifically designed to achieve the high-yield formation of the covalent linkages (amide or ester bonds) between the substrate and the chiral auxiliary within the NMR tube, without the need for other manipulations, on a microscale level and in a short time. The deuterated NMR solvents (CDCl3, CD3CN, CS2/CD2Cl2) are also the reaction solvents and separations, purifications or workups of any kind are not necessary prior to recording the spectra. The CDA-resins prepared included MPA, 9-AMA, BPG, MTPA, and 2-NTBA as auxiliary agents incorporated either as single enantiomers or as mixed combinations of the (R)- and the (S)-enantiomers at unequal and known ratios. The high versatility of these systems was successfully demonstrated in a variety of ways based on double and single derivatization, low temperature experiments, or the formation of metal complexes. The approach allowed the absolute configurations of chiral primary amines, primary and secondary alcohols, cyanohydrins, thiols, diols, triols, and amino alcohols to be determined. Extensive high-resolution magic angle spinning (HR-MAS) NMR experiments allowed the characterization of the new CDA-resins and enabled the study of their stability and regioselectivity.


The use of evaporative cooling to extend the shelf life of reconstituted oral penicillin solutions.
The relationship between temperature and the degradation of reconstituted penicillin solutions was evaluated. In all cases storage at temperatures of 25 degrees C or less was sufficient to maintain penicillin stability within acceptable pharmacopoeial limits for 5 days. In addition, the relationship between humidity and dry bulb temperature was examined in order to assess the use of evaporative cooling in lowering the temperature of penicillin solutions in those areas of the country where temperatures commonly exceed 25 degrees C. The results of this study suggest that, with the use of evaporative cooling, penicillin solutions can be maintained in a stable state for a 5-day period without the need for refrigeration.


The effects of high-fat diet feeding over generations on body fat accumulation associated with lipoprotein lipase and leptin in rat adipose tissues.
The effects of high-fat diet feeding over generations on body fat accumulation were studied in rats. Male and female Sprague-Dawley rats fed a high-fat (HF) diet or a low-fat (LF) diet were mated in the same diet group at age 13 weeks, and the male pups (1st generation) obtained were used in this experiment. The 1st generation rats were nurtured by their own mothers (Experiment 1) or F344 foster mother rats (chow-fed) during pregnancy (Experiment 3) and the suckling period (Experiments 2 and 3). After weaning, rats with HF and LF dietary histories were fed a purified diet for 12-17 weeks. Body weights and abdominal adipose tissue weights were greater in rats with HF dietary histories than in those with LF dietary histories, even controlling for environmental backgrounds related to the mother rats during pregnancy and suckling periods. The levels of lipoprotein lipase and leptin mRNA in the perirenal adipose tissue were higher in rats with HF dietary histories. These results suggest that the effects on body fat accumulation of HF diet feeding over generations are not only associated with environmental factors but also with genetic factors. The obesogenous effects of HF diet feeding over generations may be associated with lipoprotein lipase and leptin gene expression on rat adipose tissues.


War injuries of the ureter.
During the 18 months of war in Croatia, from 1991 until 1992, 4,425 wounded patients were treated at Clinical Hospital Osijek. Urogenital injuries were present in 115 treated patients (2.6%), and among them ureteral injuries were present in 11 patients (9.5%). The ureteral injuries were discovered by chance during exploratory abdominal surgery performed for other accompanying injuries. Ureteroureteral anastomosis was done in three cases. In three cases ureterocystoneostomy was performed. Exploration only was performed in three cases and nephrectomy was performed in two cases. It is important to emphasize that in three cases with contusions of the ureter wall that were not surgically reconstructed, the final result was ureteral stenosis. Moreover, in one case the final result was complete obliteration of the ureteral lumen.


Family quality of life from the perspective of older parents.
Family quality of life is a relatively new field of study. Research has primarily concentrated on families of children and young adults with intellectual disability (ID). This project explored the concept of family quality of life from the perspective of older parents who had adult children with ID aged 40+. Focus groups, individual interviews and surveys investigated family issues related to maintaining or enhancing family quality of life. Parents reported positive aspects of lifelong caregiving and quality of family life. There were concerns for the health of all family members, the social lives of their adult child, long-term living arrangements and the role of siblings. Current family and service issues that need to be addressed are related to funding and finances, staffing, and the need to adapt to age-related needs.


Development of a resource to help consumers select nutrition supplements.
In Canada, many people do not meet all the recommended nutrient intakes with food alone; the use of supplements may be one strategy to compensate for some of these inadequacies. Previous research has revealed several barriers to supplement use, including a lack of knowledge. In this qualitative study, we developed a resource to help inform and educate consumers on the selection of appropriate nutrition supplements. Three focus groups with participants residing in low-income neighbourhoods in Saskatoon, Saskatchewan, and seven key informant interviews were conducted using a semi-structured interview guide and four resource examples. After transcription of the discussion and interviews, thematic analysis was used to identify emergent themes. Analysis yielded three overarching themes: barriers to use, interdisciplinary issues, and resource expectations. Each overarching theme had several subthemes. Subthemes of the overarching theme of resource expectations were subsequently used to create a new tool to help consumers select an appropriate multivitamin. A tool was developed after available resources were explored and stakeholders were interviewed. The new resource was based on community members' and health care professionals' expressed needs, ideas, and beliefs.


Electrical transport in amorphous nanofilms embedded with crystalline grains at low temperatures.
Amorphous and ferromagnetic Al-Ni nanofilms have been grown by the magnetron-sputtering method with some nanosized crystalline grains embedded therein. Resistivity is demonstrated to transit from a positive temperature coefficient to a negative temperature coefficient (NTC) with increasing the fraction of Ni atoms in the Al-Ni nanofilms. The lattice disorder is deduced to induce the Anderson localization of electrons and the formation of polarons so that the NTC of the resistivity is driven in the Al-Ni nanofilms, different from that in the elemental Al and Ni nanofilms. The electron transport in the Al-Ni nanofilms is dominated by polaron hopping while it is also determined by electron-magnon and electron-phonon scatterings. The electron-magnon scatterings are further revealed to have a more important contribution to the electron transport at low temperatures than electron-phonon scatterings in the amorphous Al-Ni nanofilms. A so-called polaron-metal physical model has thus been proposed to well explain the electron transport in disorder lattices with crystalline grains embedded therein. This study may help to optimize the design of nano-engineered devices.


Precise inhibition is essential for microsecond interaural time difference coding.
Microsecond differences in the arrival time of a sound at the two ears (interaural time differences, ITDs) are the main cue for localizing low-frequency sounds in space. Traditionally, ITDs are thought to be encoded by an array of coincidence-detector neurons, receiving excitatory inputs from the two ears via axons of variable length ('delay lines'), to create a topographic map of azimuthal auditory space. Compelling evidence for the existence of such a map in the mammalian lTD detector, the medial superior olive (MSO), however, is lacking. Equally puzzling is the role of a--temporally very precise glycine--mediated inhibitory input to MSO neurons. Using in vivo recordings from the MSO of the Mongolian gerbil, we found the responses of ITD-sensitive neurons to be inconsistent with the idea of a topographic map of auditory space. Moreover, local application of glycine and its antagonist strychnine by iontophoresis (through glass pipette electrodes, by means of an electric current) revealed that precisely timed glycine-controlled inhibition is a critical part of the mechanism by which the physiologically relevant range of ITDs is encoded in the MSO. A computer model, simulating the response of a coincidence-detector neuron with bilateral excitatory inputs and a temporally precise contralateral inhibitory input, supports this conclusion.


Surgical treatment of tricuspid valve dysplasia in children.
Congenital tricuspid valve dysplasia (TVD) is a rare cardiac disease, often discussed in the same way as Ebstein's anomaly. Though the morphology of TVD is different, the clinical appearance is similar. The indication for surgical treatment depends on the morphology of the tricuspid valve (TV) and the clinical presentation. We reviewed all patients below 18 years of age who underwent TV repair between 2005 and 2019 and identified 9 with a TVD. The diagnosis was verified with the operative notes and patients were excluded if the septal leaflet was displaced as in Ebstein's anomaly. The aim of the study was to describe the morphology of the TV and analyse the surgical possibilities and their results. The median age at surgery was 2.3 years (5 days to 14 years), 3 patients were neonates with a duct-dependent pulmonary circulation. Morphology of the TV showed a tethering of at least 1 leaflet in all patients, a restrictive septal leaflet in 8, a large anterior leaflet in 7 and a small posterior leaflet in 4. Surgical techniques included an annuloplasty in 7 patients, a leaflet procedure in 6 patients, an edge-to-edge stitch in 5 patients and a primary Starnes procedure in 1 neonate. During a median follow-up time of 2.8 years (5 months to 15 years), 1 valve replacement and 1 conversion to univentricular palliation were necessary. Unequal leaflet size and tethering are the most common features of TVD. A variety of surgical techniques is available to achieve good results beyond the neonatal period.


Mechanical properties of dry and wet cellulosic and acrylic films prepared from aqueous colloidal polymer dispersions used in the coating of solid dosage forms.
The mechanical properties of dry and wet polymeric films prepared from various aqueous polymeric dispersions were evaluated by a puncture test. They were studied with respect to type of polymer dispersion [cellulosic: Aquacoat and Surelease; acrylic: Eudragit NE, L, RS, and RL 30 D], plasticizer type (water-soluble or water-insoluble), drying or curing conditions, method of film preparation (pseudolatex-vs solvent casting) and ratio of Eudragit RS/RL 30 D in mixed Eudragit RS/RL films. Dry and wet mechanical strengths of the polymeric films depended primarily on the types of the colloidal polymer dispersion and the plasticizer. Films prepared from ethylcellulose dispersions resulted in very weak and brittle films when compared to the acrylic films. Pseudolatex-cast ethylcellulose films showed lower puncture strength and elongation values when compared to those of the solvent-cast films. Curing of the pseudolatex-cast ethylcellulose films had minimal effects on their mechanical properties. Eudragit L 30D, an enteric polymer dispersion, resulted in brittle films in the dry state, but in very flexible films in the wet state because of the plasticization effect of water. Wet Eudragit RS 30 D polymer films plasticized with water-insoluble plasticizers were significantly more flexible than the corresponding wet films plasticized with water-soluble plasticizers. The water-soluble plasticizers leached from the films during exposure to the aqueous medium, while the water-insoluble plasticizers were almost completely retained within the wet films. The low permeability of a water-soluble drug, chlorpheniramine maleate, and the weak mechanical properties of Aquacoat films could suggest osmotic driven/rupturing effects as the release mechanisms from Aquacoat-coated dosage forms.


Influenza vaccination in pregnancy: current practices in a suburban community.
The Centers for Disease Control (CDC) identify women in their second and third trimesters as a high-risk population warranting influenza vaccination. This study attempted to characterize understanding of these guidelines and obstacles to their implementation in a suburban community. Family physicians and obstetricians with admitting privileges to a community-based hospital were surveyed regarding estimated vaccine availability and administration in their practices and regarding knowledge of indications and contraindications to influenza vaccination in pregnancy. Of the 20 obstetricians and 66 family physicians completing the survey, 68.4% of obstetricians and 90.5% of family physicians carried the vaccine in their offices (P =.027). Both obstetricians and family physicians incorrectly perceived multiple factors as contraindications to influenza vaccination in pregnancy. Obstetricians and family physicians reported similar proportions of their pregnant patients received the vaccine (35 versus 40%). In this study, more family physicians had the influenza vaccine available than obstetricians, but there was no difference in estimated rates of vaccination during pregnancy or in the understanding of its indications and contraindications. Finally, no physicians in our community reported providing influenza vaccination in pregnancy at recommended frequencies. Further research is needed to clarify methods of improving vaccination rates in both family practice and obstetric settings.


[The causes of instability of artificial mini-chromosomes in yeasts mutant for chl genes].
In mutants chl2, chl3, chl5, and chl6, which control mitotic chromosome transmission, the behaviour of the centromeric plasmids with various genes was analyzed. The main cause of chromosome instability in chl2, chl5, and chl6 is chromosome loss during cell division (1:0 segregation). The main cause of chromosome instability in chl3. is nondisjunction (2:0 segregation). According to this, the chl3 mutant, but not other chl's, cannot maintain the mini-chromosome with SUP11 gene. This gene causes cell death in high copy number. Chromosome nondisjunction in chl3 is also confirmed by the data on the mini-chromosome carrying CUP1 gene responsible for copper-resistance in yeast. The copper resistancy level in chl3 transformants is much higher than in chl5 or wild type transformants. Elevated copper resistance of chl3 transformants is caused by the transit accumulation of CUP1-carrying mini-chromosome in part of the cell population as a result of segregation mistakes upon cell divisions. Thus, the CHL3 gene is a new gene that controls the process of mitotic chromosome disjunction in yeast.


Adult and adolescent livestock productive asset transfer programmes to improve mental health, economic stability and family and community relationships in rural South Kivu Province, Democratic Republic of Congo: a protocol of a randomised controlled trial.
People living in poverty have limited access to traditional financial institutions. Microfinance programmes are designed to meet this gap and show promise in improving income, economic productivity and health. Our Congolese-US community academic research partnership developed two livestock productive asset transfer programmes, Pigs for Peace (PFP) and Rabbits for Resilience (RFR), to address the interlinked health, social and economic well-being of individuals, their families and communities. The community-based randomised controlled trials examine the effectiveness of PFP and RFR to improve health, economic stability, and family and community relationships among male and female adults and adolescents living in 10 rural, postconflict villages of eastern Democratic Republic of Congo. PFP participants include adult permanent residents of rural villages; adolescent participants in RFR include male and female adolescents 10-15 years old living in the selected rural villages. Participants were randomised to intervention or delayed control group. Participants in PFP completed baseline interview prior to intervention and follow-up interview at 6, 12 and 18 months postintervention. In RFR, participants completed baseline interview prior to intervention and follow-up interview at 6, 12 and 18 months postbaseline. The primary outcome of both trials, the change in baseline mental health distress at 18 months in the intervention group (adults, adolescents) compared to control group, is used to calculate sample size. The Johns Hopkins Medical Institute Internal Review Board approved this protocol. A committee of respected Congolese educators and community members (due to lack of local ethics review board) approved the study. The findings will provide important information on the potential for community-led sustainable development initiatives to build on traditional livelihood (livestock raising, agriculture) to have a sustained health, economic and social impact on the individual, family and community. NCT02008708, NCT02008695.


[Real temperature of the continuous-wave pluggers].
To measure the real temperatures on the pluggers of three continuous-wave devices, and to provide theoretical reference to evaluate thermal damage and heat's influence on the filling materials. The dual channel K type thermocouple was contacted to various sizes' pluggers in three different continuous-wave devices (BeeFill, Elements, B&L), and the highest temperatures at different points (tip, and 2 mm, 5 mm, 10 mm from the tip) of the pluggers (preset temperature was 200 °C) were recorded. The measurements were performed 5 times. T-test was used to compare the real temperatures at the tips with that set on the display and one-way ANOVA was used to compare the temperatures of the pluggers in different devices, sizes and points. The highest temperature was at the tip of BeeFill 40/0.03 plugger (198.7±7.7) °C, but there was on statistical differences between that and the preset temperature 200 °C. The temperatures of the remaining pluggers were obviously lower than 200 °C (P<0.05). The lowest temperature of the pluggers was detected at 10 mm from the tip of BeeFill 60/0.06 plugger (69.9±4.0) °C. The highest temperature of each plugger was detected at the tip or 2 mm from the tip (112.1 to 198.7 °C,and the median was 140.8 °C). The real temperature of most continuous-wave pluggers included in this study is below the set temperature 200 °C.


Separation of Siamese twins in Bratislava.
At the pediatric surgical clinic in Bratislava, in the year 2000, we successfully carried out the separation of Siamese twins, which we classified as "ischiopagus tetrapus"+. The pelvic ring, the gastrointestinal tract and the urogenital system were all malformed. There was a common terminal ileum and only a short segment of the large intestine with a blind end. This was a case of non-developed anal segment and rectum. Each of the twins had two kidneys and two commonly shared urinary bladders. There were two uteruses, which were both bicornuate in nature with a fallopian tube arising from each of the horns as well as an ovary. The orifices of both urinary bladders and those of the two uteruses joined into a common urogenital sinus. The external ostia of this sinus represented a bizarre fissure with a single skin fold similar to the labium majus, located dorsally at the point of fusion of the pelvic structures. The act of separation was performed in two stages. Separation of the gastrointestinal tract was urgent due to the severe ileus caused by aplasia of the anus and the rectum. This first stage procedure was performed on the third day of admission (24.2.2000) after the babies had spent a month in other health institutions. The definitive separation was carried out a month after the first procedure (28.3.2000) following the optimal stabilization of the functions of the gastrointestinal tract. The uropoietic and genital systems were separated. A new pelvic ring and a pelvic floor were formed. The anterior abdominal wall was reconstructed and plastic correction of the skin in the gluteal and perineal regions was performed. The colostomies are functioning well and the twins pass well-formed stools. Lucia has long dry intervals between mictions. Andrea has shorter dry intervals. The girls have recently celebrated their third birthday. Their mental development is excellent; they speak Slovak and Hungarian languages. They have a well-developed locomotive apparatus, without any movement impairments. (Tab. 1, Fig. 16, Ref. 10.)


[Classification of heat illness].
In the type of heat illness, several medical terms such as heat syncope, heat cramp, heat exhaustion, heat stroke are included. But their Japanese medical terms are neither unified nor clearly defined. To eliminate this problem, the new classification for heat illness is proposed. By the severity of heat illness, they are divided into three grades. Grade I is corresponded to heat cramp and heat syncope. Grade III is corresponded to heat stroke, and used for any one of the three following clinical findings, (1) Central nervous system dysfunction, i.e., consciousness disturbance, seizure, ataxia. (2) Liver and kidney dysfunction. (3) Clotting disorder, i.e., DIC. This classification can be beneficial not only to the diagnosis in the hospital, but also to the early detection and management of heat illness in the field.


Treatment utilization and modality preference among veterans receiving outpatient substance use disorder treatment during a pandemic.
This study examines substance use disorder (SUD) treatment utilization patterns in response to a pandemic. Retrospective electronic medical record data were collected during three time periods (N = 390): "Pre-COVID-19" (12/02/2019-03/14/2020), "COVID-19" (03/15/2020-06/30/2020), and COVID-19 "Re-entry" (7/01/2020-10/01/2020). Number of visits in each time period, SUD diagnosis, treatment modality (video, telephone, none), demographic, and clinical variables were examined. One-way analyses of variance (ANOVA) and chi-square analyses tested the relationships between treatment modality, demographics, clinical variables, and psychiatric emergency room (PER) visits. Binary logistic regressions examined the effect of treatment modality on PER use during COVID-19 and Re-entry, controlling for alcohol, opioid, and cocaine use disorders, age, and past-year (pre-COVID-19) PER use. Treatment modality was associated with SUD (alcohol, cocaine, opioids), age, and PER visits. Veterans who primarily attended telephone appointments were more likely to require PER services compared to those attending video appointments. In the full model, alcohol use disorder (AUD), past-year PER visits, and treatment modality (telephone visits) continued to be significantly associated with COVID-19 PER use, while past-year PER visits correlated with Re-entry PER use. During COVID-19, veterans whose main treatment modality was telephone were more likely to require PER services than veterans who were seen by video, even after controlling for age, AUD, opioid use disorder, and past-year PER visits. This study is the first to have examined SUD treatment modality utilization patterns in response to COVID-19. Findings suggest that treatment modality during the initial phase of COVID-19 correlated with PER presentation.


Reduced expression of miR‑205‑5p promotes apoptosis and inhibits proliferation and invasion in lung cancer A549 cells by upregulation of ZEB2 and downregulation of erbB3.
Previous studies have demonstrated that microRNA (miR)-205-5p expression is significantly increased in non‑small cell lung cancer tissues and is associated with tumor differentiation grade. The aim of the present study was to explore the effects of miR‑205‑5p on viability, apoptosis and invasion of lung cancer A549 cells. The hsa‑miR‑205‑5p small interfering RNA (siRNA) inhibitor was transfected into A549 cells and expression of miR‑205‑5p was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Cell viability, apoptosis and invasion were assayed by Cell Counting kit‑8, Annexin V/propidium iodide double staining and Transwell assay, respectively. Target genes of miR‑205‑5p were predicted using bioinformatics analysis. Expression of mRNA and protein levels of candidate target genes following miR‑205‑5p inhibition were detected using RT‑qPCR and western blot analysis respectively. The results demonstrated that relative survival rates of A549 cells were significantly inhibited in miR‑205‑5p siRNA‑transfected cells at 24 and 48 h compared with control cells. Apoptosis was markedly increased in the miR‑205‑5p siRNA cells compared with control cells. The number of invaded cells following miR‑205‑5p siRNA silencing was significantly decreased compared with control cells. Bioinformatics analysis revealed that erb‑B2 receptor kinase 3 (erbB3), zinc finger E‑box binding homeobox 2 (ZEB2), clathrin heavy chain (CLTC) and mediator complex subunit 1 (MED1) may be potential target genes of miR‑205‑5p. Reduced expression of miR‑205‑5p significantly increased the expression of ZEB2 mRNA and protein, inhibited the expression of erbB3 protein, but had no significant effect on the expression levels of CLTC and MED1. In summary, reduced expression of miR‑205‑5p promoted apoptosis and inhibited proliferation and invasion in lung cancer A549 cells through upregulation of ZEB2 and downregulation of erbB3. The present results suggested that the increased miR‑205‑5p expression observed in non‑small cell lung cancer tissues may contribute to increased proliferation and invasion of lung cancer cells and thus to cancer progression.


Reinforcer quality matters: A test of the Mathematical Principles of Reinforcement with domestic hens (Gallus gallus domesticus).
This study evaluated the ability of Killeen's (1994) Mathematical Principles of Reinforcement to account for the effects of changes in reinforcer quality on hens' rates of responding on fixed-ratio schedules. Hens were trained to peck a key on a fixed-ratio schedule of reinforcement and then experienced an ascending series of ratio values in two separate conditions. In different conditions, the food reinforcer was either wheat or puffed wheat. Response rates initially increased with increases in ratio requirement before eventually decreasing at larger ratios. Quantitative fits of the model accounted for the data well. The fits revealed that different foods were systematically associated with changes in the specific activation parameter, a, and these were consistent with previous reports of preference for those food items.


Levetiracetam therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs.
The authors assessed the effect of concomitant antiepileptic therapy on steady-state plasma concentrations of the new anti-epileptic drug (AED) levetiracetam in a cohort of 100 adult patients with epilepsy. On the basis of concomitant AEDs, patients were divided into two groups, otherwise comparable for age, gender, weight-adjusted daily dose of levetiracetam, and dosing frequency: group A (n = 65), receiving levetiracetam plus AED inducers of cytochrome P450 (CYP) metabolism, such as carbamazepine, phenobarbital, and phenytoin; group B (n = 35), receiving levetiracetam plus AEDs without inducing properties of CYP metabolism, namely valproic acid and lamotrigine. Plasma levetiracetam concentrations were measured by HPLC with spectrophotometric detection. Median morning trough levetiracetam plasma concentrations were significantly lower in patients of group A than in patients of group B (10.4 microg/mL versus 14.7 microg/mL, P < 0.001). Median weight-normalized levetiracetam apparent oral clearance (CL/F) was 1.3-fold in patients receiving AED inducers compared with patients on AED noninducers (1.93 versus 1.45 mL x min(-1) x kg, P < 0.001). No gender-related difference was observed in CL/F values. Levetiracetam plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 500 to 5000 mg/d, although at a given daily dose an appreciable interpatient variability was observed in matched plasma drug concentrations. Concomitant AED inducers can contribute to variability in levetiracetam disposition in patients with epilepsy. The observed differences were moderate and possibly of minor clinical significance.


The use of quantitative sterile brush culture and gram stain analysis in the diagnosis of lower respiratory tract infection.
We prospectively evaluated 55 patients (58 studies) who presented for diagnostic fiberoptic bronchoscopy for the presence of lower respiratory tract infection. A sheathed, nonplugged, sterile brush passed transbronchoscopically under fluoroscopic control was used to retrieve bronchial secretions. These were evaluated using Gram stains, Wright-Giemsa stains, and quantitative bacterial cultures. In 18 studies of patients with known or suspected infection, polymorphonuclear leukocytes and bacterial were easily identifiable on Gram stain, and potential lower respiratory pathogens were recovered in concentrations greater than or equal to 10(6) colony-forming units (cfu)/ml. In 15 control studies of patients with noninfectious lung disease and in 17 studies of patients with suspected lung infection (nine with prior antibiotic therapy), organisms were not seen on Gram stain and in 28/32 studies bacteria were present in concentrations of less than or equal to 10(4) cfu/ml. The remaining eight studies were in patients proved to have active granulomatous disease. These studies establish the ability of a fiberoptic bronchoscopic technique to diagnose bacterial infection in a group of patients presenting difficult diagnostic problems.


MicroRNA-610 is downregulated in glioma cells, and inhibits proliferation and motility by directly targeting MDM2.
The expression of microRNA (miR)-610 has previously been reported to be downregulated in gastric cancer and hepatocellular carcinoma. However, miR-610 has yet to be investigated in human glioma. In the present study, miR-610 expression was analyzed by reverse transcription-quantitative polymerase chain reaction. Post‑transfection with miR‑610 mimics and inhibitors, MTT assay, cell migration and invasion assays, western blot analysis and a luciferase assay were performed in glioma cell lines. The results demonstrated that miR‑610 was downregulated in glioma tissues compared with their normal adjacent tissues and normal brain tissues (P<0.05). The reduced expression levels of miR‑610 were associated with World Health Organization grade and the Karnofsky performance status of patients with glioma. Furthermore, the present study revealed that miR‑610 inhibited cell growth, migration and invasion in glioma cells. To the best of our knowledge, the present study is the first to provide evidence suggesting that miR‑610 directly targets MDM2 proto-oncogene E3 ubiquitin protein ligase to function as a tumor suppressor in glioma. These results indicate that miR‑610 may be investigated as a target for therapeutic drugs designed to treat glioma.


Fast and flexible simulation of DNA sequence data.
Simulation of genomic sequences under the coalescent with recombination has conventionally been impractical for regions beyond tens of megabases. This work presents an algorithm, implemented as the program MaCS (Markovian Coalescent Simulator), that can efficiently simulate haplotypes under any arbitrary model of population history. We present several metrics comparing the performance of MaCS with other available simulation programs. Practical usage of MaCS is demonstrated through a comparison of measures of linkage disequilibrium between generated program output and real genotype data from populations considered to be structured.


Current and planned shared service arrangements in Wisconsin local and tribal health departments.
The objective of this study was to explore current and future use of shared service arrangements as a management strategy to increase capacity to provide public health essential services in Wisconsin. An online cross-sectional survey of 99 local and tribal health departments in Wisconsin was conducted. Select variables from the 2010 Wisconsin Local Health Department Survey were merged. Other data sources included results from a Board of Health governance analysis and the Wisconsin Department of Health Services region data. Descriptive analysis was performed of current and future shared service arrangements and the characteristics of the types of arrangements and agreements in place. Ninety-one of 99 Wisconsin local and tribal health departments responded, yielding a 92% response rate. Seventy-one percent of respondents currently share services with 1 or more other health departments. More frequent arrangements were present in programmatic areas than in departmental operations. Most frequently reported motivators include making better use of resources, providing better services, and responding to program requirements. Extensive qualitative comments indicate arrangements accomplished what the local health department hoped it would with perceived gains in efficiency and effectiveness. There is widespread use of shared services among health departments in Wisconsin. Extensive qualitative comments suggest participant satisfaction with what the arrangements have accomplished. Motivating factors in developing the arrangements and limited mention of expiration dates suggest continued study of how these arrangements may evolve. Further examination of shared services as a potential mechanism to advance service effectiveness and efficiency is needed.


Caught between a rock and a hard place: mental health of migrant live-in caregivers in Canada.
Canada depends on Temporary Foreign Workers (TFWs), also known as migrant workers, to fill labour shortage in agriculture, hospitality, construction, child/senior care, and other low-skilled occupations. Evidence shows that TFWs, especially women live-in caregivers (LC), constitute a vulnerable population. Their health is compromised by the precarious and harsh working and living conditions they encounter. There is a paucity of research on the mental health of LCs, their support systems and access to mental health services. In this community-based exploratory study, we used mixed methods of survey and focus groups to explore the work related experiences and mental health of migrant live-in caregivers in the Greater Toronto Area in Ontario, Canada. Convenience and snowball sampling were used to recruit participants. The inclusion criteria were: being 18 years or older, initially migrated to Canada as TFWs under LC program, resided in the Greater Toronto Area, and able to understand and converse in English based on self-report. This paper reports on the focus group results derived from inductive thematic analysis. A total of 30 women LCs participated in the study. Most of them were from the Philippines. A number of key themes emerged from the participants' narratives: (1) precarious migration-employment status (re)produces exploitation; (2) deskilling and downward social mobility reinforce alienation; (3) endurance of hardship for family back home; (4) double lives of public cheerfulness and private anguish; and (4) unrecognized mental health needs. The study results reflected gross injustices experienced by these women. A multi-faceted approach is required to improve the working and living conditions of this vulnerable group and ultimately their health outcomes. We recommend the following: government inspection to ensure employer compliance with the labour standards and provision of safe working and living conditions; change immigration policy to allow migrant caregivers to apply for permanent residence upon arrival; the TFWs Program to establish fair wages and subsidized housing so that caregivers can truly access the live-out option; and local ethno-specific, settlement and faith organizations be leveraged to provide TFWs with social support as well as information about their rights and how to access health and social care.


Probit analysis of comparative assays on toxicities of lead chloride and lead acetate to in vitro cultured human umbilical cord blood lymphocytes.
This work describes that cytotoxicity of lead chloride and lead acetate to in vitro cultured lymphocytes from human umbilical cord blood, using four monitoring methods namely, trypan blue staining, acridine orange/ethidium bromide staining, 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide (MTT) and neutral red uptake assays; lead genotoxicity to lymphocytes was monitored by comet assay. The MIC value in each method was invariably 300 mg/L for PbCl2. Lethal concentration25 (LC25) values were almost in an agreeable range: 691.83 to 831.76 mg/L; LC50 values in each method were almost in the range: 1174.9 to 1348.9 mg/L; LC100 values were in the range: 3000 to 3300 mg/L, for lead chloride. Similarly, The MIC value in each method were invariably 150 mg/L; LC25 values were almost in the range: 295.12 to 371.53 mg/L; LC50 values were in the range: 501.18 to 588.84 mg/L; LC100 value was 1500 mg/L in all assays, for lead acetate. The comet assay also indicated that the LC100 values were 3300 mg/L lead chloride and 1500 mg/L lead acetate. Thus, both cytotoxicity and genotoxicity were recorded at 3300 mg/L lead chloride and 1500 mg/L lead acetate with lymphocytes.


Atomic force microscopy of chromatin arrays reveal non-monotonic salt dependence of array compaction in solution.
Compaction of DNA in chromatin is a hallmark of the eukaryotic cell and unravelling its structure is required for an understanding of DNA involving processes. Despite strong experimental efforts, many questions concerning the DNA packing are open. In particular, it is heavily debated whether an ordered structure referred to as the "30 nm fibre" exist in vivo. Scanning probe microscopy has become a cutting edge technology for the high-resolution imaging of DNA- protein complexes. Here, we perform high-resolution atomic force microscopy of non-cross-linked chromatin arrays in liquid, under different salt conditions. A statistical analysis of the data reveals that array compaction is salt dependent in a non-monotonic fashion. A simple physical model can qualitatively explain the observed findings due to the opposing effects of salt dependent stiffening of DNA, nucleosome stability and histone-histone interactions. While for different salt concentrations different compaction states are observed, our data do not provide support for the existence of regular chromatin fibres. Our studies add new insights into chromatin structure, and with that contribute to a further understanding of the DNA condensation.


Consent and care go hand in hand.
During my placement in a busy emergency department, a woman was admitted with heavy vaginal bleeding. She had undergone a scan at six weeks' pregnant and been told that she was miscarrying. Medical staff had advised her to go home and wait, as she wanted the process to occur naturally. But this was five weeks later, and she still had no signs that she had miscarried fully.


Risk Factors for Recalcitrant Chronic Rhinosinusitis in Organ Transplant Recipients.
Studies suggest that transplant patients are at risk for chronic rhinosinusitis (CRS). However, there is limited information in the literature regarding frequency and reasons for failure of adequate medical therapy. We aim to determine the risk factors associated with the development of medically recalcitrant CRS requiring endoscopic sinus surgery (ESS). Retrospective cohort. Mayo Clinic. This is a retrospective chart review of 925 transplant recipients seen at Mayo Clinic between 2017 and 2022. (1) a rhinologic consultation after transplant and (2) clinical diagnosis of CRS. A total of 549 patients met the inclusion criteria and were divided based on the need for ESS versus successful treatment with medical therapy. Univariate and logistic regression analyses were performed to identify risk factors and predictive variables related to failure of medical therapy. Of the 549 patients, 201/549 (37%) had medically recalcitrant disease requiring ESS, while 348/549 (63%) were successfully treated with medical therapy Based on logistic regression, patients with recurrent acute rhinosinusitis in the pretransplant period were 8.68 more likely to have a recalcitrant disease (95% confidence interval, 3.72-20.28, p < 0.0001). Some of the largest determinants of medical therapy failure in the posttransplant period were CRS with nasal polyps, odontogenic CRS, and noninvasive fungal sinusitis. The presence of neutropenia, aplastic anemia, and living transplant were also associated with medically recalcitrant CRS requiring ESS. Our predictive model identifies with high accuracy the patients who may be at risk of developing recalcitrant CRS in the organ transplant population.


Evaluation of accuracy and repeatability using CBCT and a dental scanner by means of 3D software.
The objective of the present study was to compare and evaluate the accuracy of three-dimensional (3D) image data acquired from cone beam computed tomography (CBCT) and a dental scanner using 3D software. After selecting the full-arch forms of the maxilla and mandible as the master cast, the master cast was scanned via a high-precision optical scanner for use as master model data. The model was scanned 12 times each using CBCT and a dental scanner. Scanned data were superimposed onto the master cast data for evaluation of accuracy and repeatability. Although significant differences in both accuracy and repeatability were seen between CBCT and dental scanner (P < 0.05), repeatability of the maxillary arch showed little difference, with CBCT and scanner having values of 17 ± 2 µm and 22 ± 5 µm, respectively. Meanwhile, repeatability of the mandibular arch with CBCT and scanner was 15 ± 0 µm and 19 ± 3 µm, respectively. Since good repeatability was shown, this demonstrated that data can be stably acquired. The present study demonstrated the feasibility of using a dental scanner to create a digital model as a substitute for a plaster model for use in orthodontic diagnosis and device fabrication.


Factors affecting direct and correlated responses in a White Leghorn population under long-term selection for egg number.
1. Data on 13,773 pullets, the progeny of 30 to 50 sires and about 135 to 220 dams per generation of a strain of White Leghorn under long-term selection for part period egg production over 16 generations, were examined. 2. Realised genetic gain per generation was highly significant for egg production (2.55 eggs), egg weight (-0.51 g), age at sexual maturity (-2.30 d) and 40 week body weight (-11.73 g). 3. The significant genetic response of 4.46 to 4.72 eggs per generation was realised in the first 8 generations only, which was accompanied by a marked decline in egg weight (-1.67 and -0.79 g per generation) and in age at sexual maturity (-4.63 and -6.39 d per generation). The 20 and 40 week body weights showed significant improvement in the last 4 generations. 4. Realised heritabilities were much lower in the last 8 than in the first 8 generation. 5. The additive genetic variance for most traits, except 20 week body weight and genetic covariances of egg production with egg weight and age at sexual maturity, declined significantly. 6. Natural selection did not seem to play any major role. No appreciable change in fitness traits was observed in the selected line. 7. The time trends were non-significant for all the traits in the control line, indicating its stability over generations.


Synthesis of genetic association studies on autism spectrum disorders using a genetic model-free approach.
Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous group of neurodevelopmental disorders. Despite the extensive efforts of scientists, the etiology of ASD is far from completely elucidated. In an effort to enlighten the genetic architecture of ASDs, a meta-analysis of all available genetic association studies (GAS) was conducted. We searched in the Human Genome Epidemiology Navigator (HuGE Navigator) and PubMed for available case-control GAS of ASDs. The threshold for meta-analysis was two studies per genetic variant. The association between genotype distribution and ASDs was examined using the generalized linear odds ratio (ORG). For variants with available allele frequencies, the examined model was the allele contrast. Overall, 57 candidate genes and 128 polymorphisms were investigated in 159 articles. In total 28 genetic polymorphisms have been shown to be associated with ASDs, that are harbored in 19 genes. Statistically significant results were revealed for the variants of the following genes adenosine deaminase (ADA), bone marrow stromal cell antigen-1 (CD157/BST1), Dopamine receptor D1 (DRD1), engrailed homolog 2 (EN2), met proto-oncogene (MET), methylenetetrahydrofolate reductase (MTHFR), solute carrier family 6 member 4 (SLC6A4), Synaptosomal-associated protein, 25kDa (SNAP-25) and vitamin D receptor (VDR). In the allele contrast model of cases versus healthy controls, significant associations were observed for Adrenoceptor Alpha 1B (ADRA1B), acetyl serotonin O - methyltransferase (ASMT), complement component 4B (C4B), dopamine receptor D3 (DRD3), met proto-oncogene (MET), neuroligin 4, X-linked (NLGN4), neurexin 1 (NRXN1), oxytocin receptor (OXTR), Serine/Threonine-Protein Kinase PFTAIRE-1 (PFTK1), Reelin (RELN) and Ras-like without CAAX 2 (RIT2). These significant findings provide further evidence for genetic factors' implication in ASDs offering new perspectives in means of prevention and prognosis.


Nodular Regenerative Hyperplasia in HIV-positive patients : a case series and review of the literature.
Nodular regenerative hyperplasia (NRH) is a well-described condition that leads to non-cirrhotic portal hypertension and is histologically characterised by a nodular transformation of the liver without fibrosis. It seems to be a consequence of obliterative portal venopathy of small hepatic veins. Its precise aetiology remains to be clearly determined. NRH was reported to occur in HIV-positive patients ten years ago. In this article, three consecutive clinical cases of HIV-related NRH were identified in a high volume reference centre of HIV positive patients and are presented. Clinical, diagnostic aspects and strategies for management of this under-diagnosed medical condition in the HIV population are also developed.


Micro enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of New World leishmaniasis.
Of 21 confirmed cases of New World leishmaniasis, 16 exhibited antibody to antigens of the promastigote of Leishmania braziliensis panamensis by the enzyme-linked immunosorbent assay (ELISA). Comparison of antibody titers obtained by ELISA with titers obtained by indirect immunofluorescence using an amastigote substrate confirmed that the sensitivities of the two techniques were within the same range (r = 0.80). Although sera from patients with New World leishmaniasis failed to react with antigens extracted from epimastigotes of Trypanosoma cruzi, sera from 39 cases of Chagas' disease were reactive with promastigotes of L. braziliensis panamensis. This apparent unidirectional cross-reactivity has been attributed to differences in potency of the antigenic stimulus presented in the two diseases.


Exercise and the Hallmarks of Cancer.
A wealth of evidence supports an association between regular physical activity (PA) and decreased risk for cancer and cancer mortality. This is clearly an important issue given the growing worldwide incidence of both cancer and physical inactivity. Of further importance is unraveling the biological mechanisms that explain the potential preventive effects of PA against the development of cancer, as this might improve our understanding of cancer biology and assist researchers exploring novel treatment strategies. Here we review mechanistic studies that help explain the anticancer effects of exercise based on how exercise impacts hallmark features of cancer. We also discuss the emerging role of myokines, methodological caveats in the field, and potential questions that remain to be addressed in future research.


Curious case of extraskeletal myxoid chondrosarcoma.
Extraskeletal myxoid chondrosarcomas (EMC) are a rare entity of soft tissue tumors that have slow growth with metastatic potential. We discuss here a case of EMC presenting with right upper extremity pain and hemoptysis. Computed tomography scans chest showed diffuse metastatic numerous lung nodules bilaterally. Biopsy confirmed the diagnosis of the tumor. Chemotherapy was a bigger challenge for our patient due to sparse research and data in the literature about the disease.


The immediate treatment of heatstroke.
The nature, diagnosis and treatment of heatstroke has been discussed. The importance of prevention, recognition and active and early treatment has been emphasised.


Kupffer cells in immune activation and tolerance toward HBV/HCV infection.
Kupffer cells (KCs) are macrophages that are found in the sinusoids of the liver. KCs are a crucial part of the innate immune system, acting as scavengers and phagocytes. KCs and sinusoidal endothelial cells together form the first immune barrier of the portal system. Studies show that KCs can not only maintain homeostasis in the immune response, but also facilitate the pathogenesis of type B and type C hepatitis (HBV/HCV) through their antigen-presenting function and secretion of soluble mediators. KCs can express toll-like receptors (TLRs), Fas ligand (FasL) and programmed cell death ligand 1 (PD-L1), and secrete large amounts of inflammatory factors leading to immune tolerance toward HBV/HCV. On the one hand, KCs contribute to the clearance of HBV/HCV due to their nature as innate immune cells. At the same time, KCs induce immune tolerance toward HBV/HCV, which leads to chronicity of the infection. The dual role of KCs in the immune response toward HBV/HCV means it is a gigantic challenge for scientists to illuminate the detailed mechanisms involved, but it also offers important potential therapeutic targets.


Pharmacokinetics of Ceftolozane-Tazobactam during Prolonged Intermittent Renal Replacement Therapy.
Prolonged intermittent renal replacement therapy (PIRRT) eliminates many drugs, and without dosing data, for new antibiotics like ceftolozane/tazobactam, suboptimal concentrations and treatment failure are likely. Herein, we describe the effect of PIRRT on the plasma pharmacokinetics of ceftolozane/tazobactam ad-ministered in a critically ill 55-year-old patient with a polymicrobial sternal wound osteomyelitis, including a multiresistant Pseudomonas aeruginosa. Blood samples were taken over 4 days where the patient received a 7.5-h PIRRT treatment. One- and 2-compartment models were tested for ceftolozane and tazobactam separately, and the log-likelihood ratio and goodness-of-fit plots were used to select the final model. Two-compartment models were developed for ceftolozane and tazobactam separately and described significant differences in clearance of ceftolozane and tazobactam with and without PIRRT (8.273 vs. 0.393 and 8.020 vs. 0.767 L/h, respectively). A ceftolozane/tazobactam dose of 500 mg/250 mg appears to be sufficient to attain pharmacokinetic/pharmacodynamic targets during PIRRT while the manufacturer's recommended dosing of 100 mg/50 mg every 8 h was sufficient during non-PIRRT periods.


Pharmacological studies on mechanisms of aminophylline-induced seizures in rats.
In the present study, the possible role of free radicals in aminophylline-induced seizures was evaluated in albino rats. Aminophylline (theophylline in ethylene diamine; 50 - 300 mg/kg) induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg. Conventional anti-epileptics, diphenylhydantoin and dizocilpine, as well as adenosine agonists were ineffective in antagonizing these seizures. On the other hand, phosphodiesterase inhibitors, pentoxyphylline and rolipram, showed insignificant seizurogenic effects. Pretreatment with antioxidants (ascorbic acid, alpha-tocopherol, and melatonin) showed differential attenuating effects on aminophylline seizures and lethality. Further, prior administration of 1-buthionine sulfoxamine (BSO, glutathione depletor) and triethyltetramine (TETA, superoxide dismutase inhibitor), precipitated seizures and enhanced lethality in response to subthreshold doses of aminophylline. The present results suggested of the possible involvement of oxidative stress during aminophylline-induced seizures.


Hypersensitive Response of Plasmid-Encoded AHL Synthase Gene to Lifestyle and Nutrient by Ensifer adhaerens X097.
It is known that some bacteria, especially members of the family Rhizobiaceae, have multiple N-acyl homoserine lactones (AHL) synthase genes and produce multiple AHL signals. However, how bacteria selectively utilize these multiple genes and signals to cope with changing environments is poorly understood. Ensifer adhaerens is an important microorganism in terms of biotechnology, ecology and evolutionary. In this study, we investigated the AHL-based QS system of E. adhaerens X097 and its response to different lifestyles or nutrients. Draft genome sequence data indicated that X097 harbored three distinct AHL synthase genes (ensI1, 2, 3) and seven luxR homologs, which was different from other E. adhaerens strains. In vitro expression indicated that plasmid-encoded ensI1 and ensI2 directed production of multiple AHLs, while chromosome-encoded ensI3 only directed production of C14-HSL. Predicted three dimensional structure of EnsI3 was quite different from that of EnsI1 and EnsI2. X097 produced different AHL profiles in Luria-Bertani (LB) and NFB medium, under biofilm and planktonic lifestyle, respectively. Notably, expression of ensI1 and ensI2 but not ensI3 is hypersensitive to different lifestyles and nutrients. The hypersensitive response of plasmid-encoded AHL synthase genes to different culture conditions may shed a light on the phylogenetic development of AHL synthase genes in Rhizobiaceae family.


Cosmological implications of a large complete quasar sample.
Objective and reproducible determinations of the probabilistic significance levels of the deviations between theoretical cosmological prediction and direct model-independent observation are made for the Large Bright Quasar Sample [Foltz, C., Chaffee, F. H., Hewett, P. C., MacAlpine, G. M., Turnshek, D. A., et al. (1987) Astron. J. 94, 1423-1460]. The Expanding Universe model as represented by the Friedman-Lemaitre cosmology with parameters qo = 0, Lambda = 0 denoted as C1 and chronometric cosmology (no relevant adjustable parameters) denoted as C2 are the cosmologies considered. The mean and the dispersion of the apparent magnitudes and the slope of the apparent magnitude-redshift relation are the directly observed statistics predicted. The C1 predictions of these cosmology-independent quantities are deviant by as much as 11sigma from direct observation; none of the C2 predictions deviate by >2sigma. The C1 deviations may be reconciled with theory by the hypothesis of quasar "evolution," which, however, appears incapable of being substantiated through direct observation. The excellent quantitative agreement of the C1 deviations with those predicted by C2 without adjustable parameters for the results of analysis predicated on C1 indicates that the evolution hypothesis may well be a theoretical artifact.


The Biochemistry and Physiology of Mitochondrial Fatty Acid β-Oxidation and Its Genetic Disorders.
Mitochondrial fatty acid β-oxidation (FAO) is the major pathway for the degradation of fatty acids and is essential for maintaining energy homeostasis in the human body. Fatty acids are a crucial energy source in the postabsorptive and fasted states when glucose supply is limiting. But even when glucose is abundantly available, FAO is a main energy source for the heart, skeletal muscle, and kidney. A series of enzymes, transporters, and other facilitating proteins are involved in FAO. Recessively inherited defects are known for most of the genes encoding these proteins. The clinical presentation of these disorders may include hypoketotic hypoglycemia, (cardio)myopathy, arrhythmia, and rhabdomyolysis and illustrates the importance of FAO during fasting and in hepatic and (cardio)muscular function. In this review, we present the current state of knowledge on the biochemistry and physiological functions of FAO and discuss the pathophysiological processes associated with FAO disorders.


Glucose affects in vitro maturation of fetal rat islets.
Fetal pancreatic islets (21.5 days old) were cultured in RPMI 1640 containing either 2.8 or 11.1 mM glucose for 7 days. After the 7-day culture period, islets cultured in 2.8 mM glucose demonstrated a minimal first phase of insulin secretion in response to acute glucose stimulation, whereas islets cultured in 11.1 mM glucose demonstrated a biphasic insulin secretory pattern. Islets cultured in 11.1 mM glucose initiated insulin secretion at 4.4 +/- 0.1 mM glucose and plateaued at 11.6 mM glucose when exposed to a linear gradient. In addition, culture in 11.1 mM glucose increased DNA content (P less than 0.01) and [3H]thymidine incorporation (P less than 0.05) in fetal islets. However, ultrastructural morphometric analysis indicated that the actual number of beta-cells within islets cultured in either 2.8 or 11.1 mM glucose did not increase. The insulin contents of islets cultured in 2.8 and 11.1 mM glucose were 0.46 +/- 0.06 and 1.14 +/- 0.10 mU/islet, respectively. During subsequent glucose stimulation, islets cultured in 2.8 and 11.1 mM glucose released 3% and 5.6% of their total insulin content, respectively. Ultrastructural morphometric analysis indicated that 11.1 mM glucose stimulated an increase in the volume of individual beta-cells, i.e. hypertrophy. The hypertrophy of beta-cells within islets cultured in 11.1 mM glucose resulted in a concomitant increase in islet volume. Finally, the hypertrophy of beta-cells within islets cultured in 11.1 mM glucose was a result of increased volumes of mitochondria, secretory granules, and, to the greatest extent, endoplasmic reticulum. These findings indicate that glucose is a potent factor in the maturation of cultured fetal rat islets.


Acupotomy for the treatment of lumbar spinal stenosis: A protocol for a systematic review and meta-analysis.
This systematic review protocol describes the methods that will be used to evaluate the efficacy and safety of acupotomy for the treatment of lumbar spinal stenosis. The following electronic databases will be searched until December 2018 without language or publication status restrictions: five English databases, that is Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine Database (AMED), and Cumulative Index to Nursing and Allied Health Literature (CINAHL); three Korean databases, that is Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Service System (RISS), and Korea Citation Index (KCI); and three Chinese databases, that is China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP. Any clinical, randomized controlled trials using acupotomy for lumbar spinal stenosis treatment will be included. Changes in the degrees of pain and function will be assessed as primary outcomes. The total effective rate, changes in quality of life, adverse events, and amount of rescue medication used will be evaluated as secondary outcomes. Two independent researchers will perform study selection, data extraction, and risk of bias assessment. If applicable, a meta-analysis will be performed using RevMan version 5.3, with the results expressed as risk ratios or mean differences with 95% confidence intervals. According to a heterogeneity test or the number of studies included, fixed effects or random effects model will be used. The risk of bias tool from the Cochrane group will be used to evaluate the methodological quality of the included studies. Ethical approval is not required because individual patient data will not be included in this study. The findings of this systematic review will be disseminated through a peer-reviewed publication or conference presentations. CRD42018116567.


Interaction of the orally active dianionic cephalosporin cefixime with the uptake system for oligopeptides and alpha-amino-beta-lactam antibiotics in rabbit small intestine.
The uptake of two orally active beta-lactam antibiotics of different chemical structure, the zwitterionic alpha-aminocephalosporin cephalexin and the dianionic carboxymethoxyimino-cephalosporin cefixime, by brush border membrane vesicles obtained from rabbit small intestine and their molecular interaction with the H+/oligopeptide transport system were investigated. The uptake of both compounds was stimulated by an inwardly directed H(+)-gradient with a profound pH-maximum for cephalexin at pH 6outside and pH 7.4inside whereas cefixime uptake was maximal below pH 5outside. Modification of histidyl residues of membrane proteins led to a complete loss of pH dependence of transport of both cephalosporins. The uptake of cephalexin was competitively inhibited by cefixime and dipeptides and vice versa that of cefixime by cephalexin and dipeptides. The uptake of cefixime was trans-stimulated by cephalexin and glycyl-L-proline whereas cephalexin uptake could only be trans-stimulated by glycyl-L-proline, not by cefixime. Photoaffinity labeling with [3H]benzylpenicillin as a direct photoaffinity probe of the H+/oligopeptide transport system demonstrated a direct molecular interaction of both cephalexin and cefixime with this transporter in the pH range of 5-8. Thermal pretreatment of membrane vesicles inhibited the cephalexin transport system temperature-dependently, whereas cefixime uptake was not inhibited, but stimulated. Taken together we conclude that dianionic cephalosporins like cefixime bind to the transport system shared by oligopeptides and alpha-amino-beta-lactam antibiotics. Their transport across the enterocyte brush border membrane, however, may occur to a significant extent by a different transport system.


Fingerprints of resistant Escherichia coli O157:H7 from vegetables and environmental samples.
Some routes of transmission of Escherichia coli O157:H7 to fresh produce include contaminated irrigation water and manure polluted soils. The aim of the present study was to determine the genetic relationships of E. coli O157:H7 isolated from some produce growing region in Nigeria using enterobacterial repetitive intergenic consensus (ERIC) DNA fingerprinting analysis. A total of 440 samples comprising leafy greens, irrigation water, manure and soil were obtained from vegetable producing regions in Kano and Plateau States, Nigeria. Genes coding for the quinolone resistance-determinant (gyrA) and plasmid (pCT) coding for multidrug resistance (MDR) were determined using polymerase chain reaction (PCR) in 16 isolates that showed MDR. Cluster analysis of the ERIC-PCR profiles based on band sizes revealed six main clusters from the sixteen isolates analysed. The largest cluster (cluster 3) grouped isolates from vegetables and manure at a similarity coefficient of 0.72. The present study provides data that support the potential transmission of resistant strains of E. coli O157:H7 from vegetables and environmental sources to humans with potential public health implications, especially in developing countries. © 2017 Society of Chemical Industry.


Exploring the pharmacology of the pro-convulsant effects of alpha 2-adrenoceptor antagonists in mice.
The effects of selective and specific alpha 2-adrenoceptor antagonists on electroshock seizure threshold in mice were investigated. Idazoxan, at low doses, efaroxan, RX811059 and RX821002 significantly lowered seizure threshold. The alpha 1-agonist St 587 and the beta-agonist isoprenaline were also pro-convulsant. On the other hand the alpha 2-agonists clonidine and UK 14,304 produced small increases in seizure threshold. Anticonvulsant effects were also produced by low doses of the noradrenaline uptake inhibitor desipramine. This compound increases levels of noradrenaline in the synaptic cleft which could subsequently act at post-synaptic alpha 2-adrenoceptors. The pro-convulsant action of alpha 2-adrenoceptor antagonists could be explained in terms of two mechanisms: a) blockade of endogenous noradrenaline which may normally exert a tonic anti-convulsant influence on seizure threshold, through post-synaptic alpha 2-receptors and/or b) increased activation of alpha 1- and beta-adrenoceptors by elevated synaptic noradrenaline levels following blockade of pre-synaptic alpha 2-adrenoceptors. Of the alpha 2-antagonists tested, idazoxan was unusual in that high doses were not pro-convulsant; this difference may be explained by alpha 1-adrenoceptor mediated actions or be related to its recently described affinity at a non-adrenoceptor site--a function for which is currently unknown.


Stability of different zinc(II)-diamine complexes in aqueous solution with respect to structure and dynamics: a QM/MM MD study.
In the context of our detailed study of the chemical behavior of aquo- and ammine-Zn(II) complexes, ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations were performed at the Hartree-Fock (HF) level for the zinc(II)-diamine complexes in aqueous solution. The initial structures of cis and trans isomers of the tetraaquodiamminezinc(II) complex were found to transform into the triaquodiamminezinc(II) complex by releasing one water ligand after approximately 6 and approximately 22 ps of simulation time, respectively. The structural and dynamical properties of these three zinc complexes, i.e., cis-[Zn(NH3)2(H2O)4]2+, trans-[Zn(NH3)2(H2O)4]2+, and [Zn(NH3)2(H2O)3]2+, were analyzed in terms of radial distribution functions (RDF), coordination number distributions (CND), angular distribution functions (ADF), tilt and theta angle distributions, ligands' mean residence times (MRTs), and ion-ligand stretching frequencies. One considerably elongated Zn-O bond of 2.43 A was observed in the case of the cis isomer for one of the water ligands located in the trans position to an ammonia ligand. In the trans isomer the average Zn-O bond length was observed to be 2.23 A, while in the triaquodiamminezinc(II) complex two distinct Zn-O bonds, namely 2.12 A for the ligands in the trigonal plane and 2.26 A for axial water molecules, were observed. As both of the octahedral isomers are transformed into the pentacoordinated structure within the picosecond range, they might be regarded as "metastable species or intermediates", while the triaquodiamminezinc(II) complex is the most stable species of the zinc(II)-diamine complex in aqueous solution.


In situ FT-IR studies on the mechanism of selective catalytic reduction of NOx by propene over SnO2/Al2O3 catalyst.
The mechanism of the selective catalytic reduction (SCR) of NOx by propene over SnO2/Al2O3 catalyst in the presence of oxygen has been investigated using in situ Fourier transform infrared (FT-IR) spectroscopy. In situ IR measurements indicate that acetate and formate, which are the derivatives of the partial oxidation of propene, play a crucial role in the formation of NCO by reacting with the reactive monodentate nitrate species. The resulting NCO species subsequently reacts with NOx to form N2. The presence of oxygen substantially contributes to the partial oxidation of propene and thus shows a promoting effect for the NOx reduction.


[Application progress of implementation research on diabetes management].
Diabetes is one of the most important non-communicable chronic diseases. Although a large amount of clinical evidence on the effectiveness of diabetes prevention and treatment interventions has been established, the current quality of care and results are still insufficient. Implementation Research can bridge the gap between research and practice. Implementation Research on diabetes management can clarify what is effective and what is ineffective in management, and promote the transformation of complex, multi-component interventions into medical practice faster and more effectively. This paper reviews the main research contents and application of implementation research of diabetes management at home and abroad, aiming to provide reference for related research and promote the application of implementation research in diabetes management in China.


Obesity in a Somerset town: prevalence and relationship to morbidity.
Body mass index was determined for 953 subjects, randomly selected from the electoral roll of a town in south-west England. Morbidity was estimated using a questionnaire.The prevalence of obesity (body mass index < 28) was 21 per cent for males and 22 per cent for females. Overall morbidity was significantly increased in obese females. The three main disease groups that were more prevalent in both the obese males and females were hypertension, cardiovascular disease and musculoskeletal disorders.


Response and acquired resistance to everolimus in anaplastic thyroid cancer.
Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed a nonsense mutation in TSC2, a negative regulator of mTOR, suggesting a mechanism for exquisite sensitivity to everolimus. The resistant tumor also harbored a mutation in MTOR that confers resistance to allosteric mTOR inhibition. The mutation remains sensitive to mTOR kinase inhibitors.


Going Global: Toward Competency-Based Best Practices for Global Health in Dental Education.
The Global Oral Health Interest Group of the Consortium of Universities for Global Health (GOHIG-CUGH) published recommended competencies to support development of competency-based global health education in dental schools. However, there has been no comprehensive, systematically derived, or broadly accepted framework for creating and delivering competency-based global health education to dental students. This article describes the results of a collaborative workshop held at the 2016 American Dental Education Association (ADEA) Annual Session & Exhibition designed to build on the GOHIG-CUGH competencies and start to develop systematic approaches for their practical application. Workshop organizers developed a preliminary theoretical framework for guiding the development of global health in dental education, grounded in published research. Collectively, workshop participants developed detailed outcomes for the theoretical framework with a focus on three educational practices: didactic, experiential, and research learning and how each can meet the competencies. Participants discussed learning objectives, keys to implementation, ethical considerations, challenges, and examples of success. Outcomes demonstrated that no educational practice on its own meets all 33 recommended competencies for dental students; however, the three educational practices combined may potentially cover all 33. Participants emphasized the significance of sustainable approaches to student learning for both students and communities, with identified partners in the communities to collaborate on the development, implementation, evaluation, and long-term maintenance of any student global health activity. These findings may represent early steps toward professional consensus and best practices for global health in dental education in the United States.


The effect of hyoscine butylbromide on the duration and progress of labor in primigravidae: a randomized controlled trial.
To assess the effect of hyoscine butylbromide (HBB) on duration of the first stage of labor in primigravdae. A case-control study conducted on 120 primigravida at term admitted in active labor were divided into three equal groups. A single dose of the drug (placebo or HBB 20 mg or HBB 40 mg) was injected intravenously slowly to groups A, B, and C. The duration of the first stage was calculated from the time of cervical dilatation of three to four centimeters in active labor until a fully dilated cervix was observed. The duration of first stage was significantly shorter in women receiving 20 and 40 mg of HBB when controlled to control women (187.73 ± 20.92, 186.41 ± 19.40 versus 231.39 ± 33.14 min). There was no significant difference between the three study groups regarding duration of the second stage (36.76 ± 9.98, 35.72 ± 9.97 and 37.55 ± 10.57, respectively, p > .05), number of cases delivered by cesarean section (12.5%, 12.5%, and 15%, respectively, p > .05) and Apgar score of the neonates (p > .05). There was no significant difference between the three study groups regarding occurrence of side effects named dry mouth (7.5%, 12.5%, and 5%, p > .05), flushing (2.5%, 5% and 0%, p > .05), tachycardia (2.5%, 2.5%, and 2.5%, p > .05), or urinary retention (2.5%, 0%, and 0%, p > .05). Intravenous injection of HBB decreases the duration of active phase of labor in primigravidae with no side effects.


Differences in prevalence of seasonal affective disorder that are not explained by either genetic or latitude differences.
The prevalence of winter SAD was measured in two groups of a(lult Manitobans of wholly Icelandic (lescent, 210 resident in Winnipeg (50 degrees N) and 252 resident in the nearby Interlake district (50.5 degrees N), using the Seasonal Pattern Assessment Questionnaire (SPAQ). These groups live practically at the same latitude and are according to all indications genetically identical. The age-and-sex-standardized prevalence rates of winter SAD proved to be markedly higher in the Winnipeg population than in the Interlake population: 4.8% and 1.2% (p<0.001), respectively. This four-fold dif ference is evidently unexplained by genetic factors or a difference in latitude; its causes have yet to be discovered.


Patterning the nervous system through development and evolution.
We report presentations and discussions at a meeting held in May 2010 in the small village of Minerve, in the south of France. The meeting was devoted mostly but not exclusively to patterning in the nervous system, with an emphasis on two model organisms, Drosophila Melanogaster and Danio rerio. Among the major issues presented were fear and its neuroanatomy, life in darkness, patterning of sensory systems, as well as fundamental issues of neural connectivity, including the role of lineage in neural development. Talks on large-scale patterning and re-patterning, and on the mouse as a third model system, concluded the meeting.


A Janus-ROS Healing System Promoting Infectious Bone Regeneration via Sono-Epigenetic Modulation.
Elimination of bacterial infections and simultaneously promoting osteogenic differentiation are highly required for infectious bone diseases. Massive reactive oxygen species (ROS) can damage cells, while low ROS concentrations as a molecular signal can regulate cellular fate. In this study, a Janus-ROS healing system is developed for infectious bone regeneration. An alendronate (ALN)-mediated defective metal-organic framework (MOF) sonosensitizer is prepared, which can effectively clear Methicillin-resistant Staphylococcus aureus (MRSA) infections and promote osteogenic differentiation under differential ultrasonic irradiation. In the presence of zirconium-phosphate coordination, the ALN-mediated porphyrin-based MOF (HN25) with a proper defect has great sonodynamic antibacterial efficiency (98.97%, 15 min) and bone-targeting ability. Notably, under low-power ultrasound irradiation, HN25 can increase the chromatin accessibility of ossification-related genes and FOXO1 to promote bone repair through low ROS concentrations. Animal models of paravertebral infection, fracture with infection, and osteomyelitis demonstrate that HN25 successfully realizes the targeted and potent repair of various infectious bone tissues through rapid MRSA elimination, inhibiting osteoclast activity and promoting bone regeneration. The results show that high catalytic efficiency and bioactive MOF can be constructed using pharmaceutical-mediated defect engineering. The Janus-ROS treatment is also a promising therapeutic mode for infectious tissue regeneration.


Synergistic Effect of Sulindac and Simvastatin on Apoptosis in Lung Cancer A549 Cells through AKT-Dependent Downregulation of Survivin.
Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventive or chemotherapeutic agents. The mechanism underlying the deregulation of survivin by NSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. In this study, we investigated the synergistic interaction of sulindac and simvastatin in lung cancer A549 cells. Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells. Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDA and MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. The effects of AKT on survivin expression in sulindac- and simvastatin-treated cells were assessed. Survivin was knocked down or overexpressed to determine its role in apoptosis induced by sulindac and simvastatin. Sulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROS production in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, while AKT overexpression markedly increased survivin expression, even in the presence of sulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininduced apoptosis. In contrast, survivin upregulation protected against sulindac- and simvastatin-induced apoptosis. Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. These results indicate that sulindac and simvastatin may be clinically promising therapies for the prevention of lung cancer.


Transient receptor potential ankyrin-1 participates in visceral hyperalgesia following experimental colitis.
Transient receptor potential ankyrin-1 (TRPA1) is an important receptor that contributes to inflammatory pain. However, previous studies were mainly concerned with its function in somatic hyperalgesia while few referred to visceral, especially colonic inflammatory hyperalgesia. The present study was aimed to investigate the role of TRPA1 in visceral hyperalgesia after trinitrobenzene sulfonic acid (TNBS)-induced colitis. Results indicate that TNBS induced a significant increase in visceral sensitivity to colonic distension and chemical irritation accompanied by up-regulation of TRPA1 in colonic afferent dorsal root ganglia (DRG). Intrathecal administration of TRPA1 antisense (AS) oligodeoxynucleotide (ODN) reduced the TRPA1 expression in DRG as well as suppressed the colitis-induced hyperalgesia to nociceptive colonic distension and intracolonic allyl isothiocyanate (AITC). Meanwhile the TRPA1 antisense ODN had no effect on transient receptor potential vanilloid-1 (TRPV1) expression, which was proposed to highly co-express with TRPA1, and no effect on the response to TRPV1 agonist, capsaicin. These data suggest an apparent role of TRPA1 in visceral hyperalgesia following colitis that might provide a novel therapeutic target for the relief of pain.


The use of a metabolically structured model in the study of growth, nitrification, and denitrification by Thiosphaera pantotropha.
Thiosphaera pantotropha is capable of aerobic heterotrophic nitrification and both aerobic and anaerobic denitrification. These phenomena have been studied in acetate-limited aerobic and anaerobic continuous cultures supplied with ammonia and nitrate. The internal reaction rates were defined, based on biochemical knowledge. The observable external conversion rates are related through a linear equation on the basis of the specified internal reaction rates. The linear equation is a Pirt relation extended for microbial systems with multiple electron donors (acetate and ammonia) and electron acceptors (oxygen and nitrate). The coefficients in this equation were estimated from the continuous culture measurements, and are composed of parameters involved in ATP production and consumption by the microorganism. It is shown that with realistic values for these parameters, the metabolically structured model describes the aerobic as well as the anaerobic experiments.


Unsaturated nitriles: stereoselective MgO eliminations.
Alpha,beta-unsaturated nitriles are readily synthesized by eliminating MgO from beta-hydroxynitriles. Deprotonating acyclic, and cyclic, beta-hydroxynitriles with excess MeMgCl smoothly generates dianion intermediates that eject MgO with concurrent formation of alpha,beta-unsaturated nitriles. Alternatively, sequential addition of lithioacetonitrile and MgBr(2) to aldehydes and ketones generates magnesium alkoxides in situ that eliminate MgO upon addition of MeMgCl. The MeMgCl-induced MgO eliminations smoothly generate alpha,beta-unsaturated nitriles from hindered ketones that are otherwise difficult to synthesize.


Efficient Simultaneous Detection of Metabolites Based on Electroenzymatic Assembly Strategy.
Objective and Impact Statement: We describe an electroenzymatic mediator (EM) sensor based on an electroenzymatic assembly peak separation strategy, which can efficiently realize the simultaneous detection of 3 typical cardiovascular disease (CVD) metabolites in 5 μl of plasma under one test. This work has substantial implications toward improving the efficiency of chronic CVD assessment. Introduction: Monitoring CVD of metabolites is strongly associated with disease risk. Independent and time-consuming detection in hospitals is unfavorable for chronic CVD management. Methods: The EM was flexibly designed by the cross-linking of electron mediators and enzymes, and 3 EM layers with different characteristics were assembled on one electrode. Electrons were transferred under tunable potential; 3 metabolites were quantitatively detected by 3 peak currents that correlated with metabolite concentrations. Results: In this study, the EM sensor showed high sensitivity for the simultaneous detection of 3 metabolites with a lower limit of 0.01 mM. The linear correlation between the sensor and clinical was greater than 0.980 for 242 patients, and the consistency of risk assessment was 94.6%. Conclusion: Metabolites could be expanded by the EM, and the sensor could be a promising candidate as a home healthcare tool for CVD risk assessment.


Value of fluoroscopic assistance during transpyloric intubation.
Blind insertion of a weighted nasoenteric tube (NET) has a low chance of immediate duodenal intubation and may cause serious complications. This study used fluoroscopic assistance to facilitate the passage of an NET to the duodenum. The success rate and complications were compared to those for NET insertion without fluoroscopy. Blind passage of a weighted feeding tube was associated with a 15% success rate in 13 patients; by contrast, fluoroscopic assistance allowed 95% of 20 patients to be intubated successfully in an average of 14 +/- 12 min. Although blind insertion caused intrabronchial intubation in two patients, there were no complications associated with fluoroscopy.


Co-Polymers based on Poly(1,4-butylene 2,5-furandicarboxylate) and Poly(propylene oxide) with Tuneable Thermal Properties: Synthesis and Characterization.
Poly(ether ester)s (PEEs) represent a promising class of segmented co-polymers, nevertheless the synthesis of PEEs based on renewable 2,5-furandicarboxylic acid (FDCA) is still scarce. In this context, a series of poly(1,4-butylene 2,5-furandicarboxylate)-co-poly(poly(propylene oxide) 2,5-furandicarboxylate) co-polyesters with different composition of stiff poly(1,4-butylene 2,5-furandicarboxylate) (PBF) and soft poly(poly(propylene oxide) 2,5-furandicarboxylate) (PPOF) moieties were synthesized, via a two-step bulk polytransesterification reaction. The molar ratio of PBF/PPOF incorporated was varied (10 to 50 mol%) in order to prepare several novel materials with tuned properties. The materials were characterised in detail through several techniques, namely ATR FTIR, ¹H and 13C NMR, TGA, DSC, DMTA and XRD. Their hydrolytic and enzymatic degradation evaluation was also assessed. These new co-polymers showed either a semi-crystalline nature when higher PBF/PPOF ratios were used, and for approximately equal amounts of PBF and PPOF an amorphous co-polyester was obtained instead.


Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma.
Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH) but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS) melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient's disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.


Insulin fibril nucleation: the role of prefibrillar aggregates.
Dynamic light scattering and Fourier transform infrared spectroscopy were used to study the formation of prefibrillar aggregates and fibrils of bovine pancreatic insulin at 60 degrees C and at pH 1. The kinetics of disintegration of the prefibrillar aggregates were also studied using these techniques after a quench to 25 degrees C. These experiments reveal that formation of prefibrillar aggregates is reversible under the solution conditions studied and show that it is possible to significantly reduce the nucleation (lag) times associated with the onset of fibril growth in bovine pancreatic insulin solutions by increasing the concentration of prefibrillar aggregates in solution. These results provide convincing evidence that less structured prefibrillar aggregates can act as fibril-forming intermediates.


Luminescent Mycena: new and noteworthy species.
Seven species of Mycena are reported as luminescent, representing specimens collected in Belize, Brazil, Dominican Republic, Jamaica, Japan (Bonin Islands), Malaysia (Borneo) and Puerto Rico. Four of them represent new species (Mycena luxaeterna, M. luxarboricola, M. luxperpetua, M. silvaelucens) and three represent new reports of luminescence in previously described species (M. aff. abieticola, M. aspratilis, M. margarita). Mycena subepipterygia is synonymized with M. margarita, and M. chlorinosma is proposed as a possible synonym. Comprehensive descriptions, illustrations, photographs and comparisons with phenetically similar species are provided. A redescription of M. chlorophos, based on analyses of type specimens and recently collected topotypical material, is provided. The addition of these seven new or newly reported luminescent species of Mycena brings the total to 71 known bioluminescent species of fungi.


Black Tea Source, Production, and Consumption: Assessment of Health Risks of Fluoride Intake in New Zealand.
In countries with fluoridation of public water, it is imperative to determine other dietary sources of fluoride intake to reduce the public health risk of chronic exposure. New Zealand has one of the highest per capita consumption rates of black tea internationally and is one of the few countries to artificially fluoridate public water; yet no information is available to consumers on the fluoride levels in tea products. In this study, we determined the contribution of black tea as a source of dietary fluoride intake by measuring the fluoride content in 18 brands of commercially available products in New Zealand. Fluoride concentrations were measured by potentiometric method with a fluoride ion-selective electrode and the contribution of black tea to Adequate Intake (AI) and Tolerable Upper Intake Level (UL) was calculated for a range of consumption scenarios. We examined factors that influence the fluoride content in manufactured tea and tea infusions, as well as temporal changes in fluoride exposure from black tea. We review the international evidence regarding chronic fluoride intake and its association with chronic pain, arthritic disease, and musculoskeletal disorders and provide insights into possible association between fluoride intake and the high prevalence of these disorders in New Zealand.