Comparison of treatment plans for hypofractionated high-dose prostate cancer radiotherapy using the Varian Halcyon and the Elekta Synergy platforms.
To compare radiotherapy plans between an O-ring and a conventional C-arm linac for hypofractionated high-dose prostate radiotherapy in terms of plan quality, dose distribution, and quality assurance in a multi-vendor environment. Twenty prostate cancer treatment plans were irradiated on the O-ring Varian Halcyon linac and were re-optimized for the C-arm Elekta Synergy Agility linac. Dose-volume histogram metrics for target coverage and organ at risk dose, quality assurance, and monitor units were retrospectively compared. Patient-specific quality assurance with ion chamber measurements, gamma index analysis, and portal dosimetry was performed using the Varian Portal Dosimetry system and the ArcCHECK® phantom (Sun Nuclear Corporation). Prostate-only radiotherapy was delivered with simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) in 20 fractions of 2.5/3.0 Gy each. For both linacs, target coverage was excellent and plan quality comparable. Homogeneity in PTVBoost was high for Synergy as well as Halcyon with a mean homogeneity index of 0.07 ± 0.01 and 0.05 ± 0.01, respectively. Mean dose for the organs at risk rectum and bladder differed not significantly between the linacs but were higher for the femoral heads and penile bulb for Halcyon. Quality assurance showed no significant differences in terms of ArcCHECK gamma pass rates. Median pass rate for 3%/2 mm was 99.3% (96.7 to 99.8%) for Synergy and 99.8% (95.6 to 100%) for Halcyon. Agreement between calculated and measured dose was high with a median deviation of -0.6% (-1.7 to 0.8%) for Synergy and 0.2% (-0.6 to 2.3%) for Halcyon. Monitor units were higher for the Halcyon by approximately 20% (p < 0.001). Hypofractionated high-dose prostate cancer SIB VMAT on the Halcyon system is feasible with comparable plan quality in reference to a standard C-arm Elekta Synergy linac.


Simultaneous determination of ZT-1 and its metabolite Huperzine A in plasma by high-performance liquid chromatography with ultraviolet detection.
ZT-1 is a novel acetylcholinesterase (AChE) inhibitor. It is rapidly transformed to Huperzine A (Hup A) in vitro. A simple and rapid HPLC-UV method for the simultaneous determination of ZT-1 and its metabolite Hup A in plasma is described. The chromatographic separations were achieved on a C(18) ODS column (250 mm x 4.6 mm ID) using methanol-1 mmol/L ammonium acetate (70:30,v/v) as mobile phase. The flow rate was 0.7 mL/min, the detection wavelength was 313 nm and the column temperature was kept at 35 degrees C. Plasma samples were prepared as rapidly as possible and extracted immediately with 5 mL of chloroform:iso-propyl alcohol mixture (v/v, 9:1). The retention times of ZT-1 and Huperzine A (Hup A) were 18.7 and 14.4 min, respectively. The mean absolute recoveries of two analytes were >90%. Quantification limits were all 0.02 nmol/mL for ZT-1 and Hup A. This analytical method was reliable and convenient procedure that meets the criteria for the pharmacokinetic evaluation of ZT-1 on experimental animals.


Utility of spiral CAT scan in the follow-up of patients with pulmonary Langerhans cell histiocytosis.
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease that occurs almost exclusively in smokers, generally young adults between 20 and 40 years old. Prognostic biomarkers of the disease are lacking. This study describes the clinical-radiological features of a group of PLCH patients and applies a semi-quantitative CT score of the chest to verify the prognostic value of radiological findings in this disease. Clinical-radiological and immunological data from 12 Caucasian patients (6M, 7 smokers and 5 ex-smokers, mean age 36±8 years) were recorded at onset and after a follow-up period of 4 years. Application of the semi-quantitative CT score revealed a prevalently cystic pattern at onset and follow-up in the majority of the patients. Patients with a prevalently nodular pattern developed cystic lesions during follow-up. Interestingly, significant correlations were found between the extent of cystic lesions and DLCO values at onset (time 0: p<0.05) and at the end of follow-up (time 1, p<0.05) and with FEV1 values at time 0 (p<0.05) and time 1 (p<0.05). Patients with progressive functional decline were those with CT evidence of severe cystic alterations. The results suggest that high resolution CT scan of the chest is mandatory for characterizing PLCH patients at diagnosis and during follow-up. The proposed CT score of the chest showed potential prognostic value.


Review on flavivirus vaccine development. Proceedings of a meeting jointly organised by the World Health Organization and the Thai Ministry of Public Health, 26-27 April 2004, Bangkok, Thailand.
In light of the continuous spread of human pathogenic flaviviruses, in particular the mosquito-transmitted species, vaccine development remains a high priority on the public health agenda. On 26-27 April 2004, a conference was held in Bangkok, Thailand, to review current status of flavivirus vaccine development and related issues, focussing on dengue (DEN) and Japanese encephalitis (JE). This event, co-sponsored by the World Health Organization (WHO) and the Thai Ministry of Public Health, reviewed the progress made with vaccine development, sero-epidemiological studies and other accompanying activities critical for vaccine development and vaccination. The considerable interest in and awareness of the flavivirus diseases and their prevention by public health decision makers, as well as the establishment of two dedicated programmes for dengue and Japanese encephalitis vaccine development raise hopes that new or improved vaccines will become available in the coming years.


Stilbene C-glucosides from Cissus repens.
Four new stilbene C-glucosides, namely trans-3-O-methyl-resveratrol-2-C-beta-glucoside (1), cis-3-O-methyl-resveratrol-2-C-beta-glucoside (2), trans-3-O-methyl-resveratrol-2-(2-p-coumaric)-C-beta-glucoside (cissuside A) (3), and trans-3-O-methyl-resveratrol-2-(3-p-coumaric)-C-beta-glucoside (cissuside B) (4), were isolated from the aerial parts of Cissus repens, along with known trans-resveratrol (5), trans-resveratrol-2-C-beta-glucoside (6) and cis-resveratrol-2-C-beta-glucoside (7). Their structures were established by spectroscopic methods. Stilbene C-glucosides were found in the genus Cissus for the first time.


Lipoxins, RevD1 and 9, 13 HODE as the most important derivatives after an early incident of ischemic stroke.
There is limited information available regarding the association of plasma free fatty acids (FFA) and inflammation mediators with ischemic stroke. At the same time, new treatment strategies are being pursued. The aim of this study was to carry out a thorough analysis of inflammation with multiple FFA-derivative mediators after and ischemic stroke and standard treatment. HPLC separations of 17 eicosanoids were performed using an Agilent Technologies 1,260 liquid chromatograph. The profiles of the esters of fatty acids were labelled by means of gas chromatography. FFA, and eicosanoid profiles in the group of patients after ischemic stroke significantly differed from the profile of the control group. Studies confirmed the involvement of derivative synthesis pathways responsible for the inflammation, especially palmitic acid (9 and 13 HODE), arachidonic acid, EPA and DHA. Arachidonic acid derivatives were synthesised on 5LOX, 15 LOX and COX pathways with the participation of prostaglandins while omega 3 derivatives strengthened the synthesis of resolvins, RevD1 in particular. The ability to accelerate the quenching of inflammation after ischemic stroke seems to be a promising strategy of stroke treatment in its early stage. In this context, our study points to lipoxins, RevD1, and 9, 13 HODE as the most important derivatives.


catena-Poly[[[(3,5-dimethyl-1H-pyrazole)-copper(II)]-μ-{N-[1-(2-oxidophen-yl)ethyl-idene]-l-valinato}] methanol monosolvate].
The asymmetric unit of the title compound, {[Cu(C(13)H(15)NO(3))(C(5)H(8)N(2))]·CH(3)OH}(n), contains two complex mol-ecules and two solvent mol-ecules. Each Cu(II) ion is in a distorted square-pyramidal coordination with one N and two O atoms from the Schiff base ligand and one N atom from the heterocycle in the basal positions and one carboxyl-ate O atom from a neighbouring ligand in the apical position. The apical Cu-O bonds are much longer than the basal Cu-O and Cu-N bonds. The carboxyl-ate groups of the Schiff base ligands bridge the Cu(II) ions, forming helical chains along [100]. The crystal packing is stabilized by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds.


Surgical hip dislocation for treatment of synovial chondromatosis of the hip.
In the present study, we aimed to evaluate the clinical outcomes of surgical hip dislocation in patients with synovial chondromatosis (SC) of the hip. Seven patients with primary SC of the hip treated with open synovectomy and removal of loose bodies by surgical hip dislocation from 2016 to 2019 were retrospectively reviewed. All patients had numerous and widespread loose bodies based on pre-operative images, including routine radiographs, CT, and MRI. The visual analog scale (VAS) score and Harris hip score (HHS) were collected and analyzed before and after surgery. The post-operative radiographs were reviewed to evaluate disease recurrence and osteoarthritis progression. The mean operative time was 61 minutes (range, 42-75 min). An average of 33 loose bodies in each patient (range, 16-67) was removed, and extra-articular pathology was found in one patient. Patients were followed up for a mean duration of 30 months (range, 18-42 months). The average VAS scores were decreased from 3.7 (range, 2-6) pre-operatively to 0.9 (range, 0-2) at the last follow-up, and the HHS was improved from 60.1 (range, 50-73) to 90.1 (range, 82-95). All results demonstrated significant improvements (P < 0.05). Post-operative radiographs showed no recurrence, osteoarthritis progression, or osteonecrosis of the femoral head in all hips. Surgical hip dislocation was a practical approach for managing both intra-articular and extra-articular pathologic lesions around the hip. It was an effective treatment for SC of the hip with short surgical time, good joint functions, a lower recurrence rate, and few complications.


Tumor progression by DNA flow cytometry in human colorectal cancer.
We wished to better understand the role of aneuploidy during the progression of human colorectal cancer. Fresh or frozen multiple samples from 221 human colorectal adenomas, 93 carcinomas, and corresponding control mucosa were investigated using high-resolution DNA flow cytometry. A total number of 164 DNA abnormal clones were observed and characterized by a quantitative index of DNA aneuploidy (DI). In precancerous lesions the vast majority of DNA abnormal clones (almost 3/4 in adenomas with mild to moderate dysplasia) was hypo- and hyper-diploid with DI values from 0.8 to 1.2 (near-diploidy). In moderately to poorly differentiated carcinomas the vast majority of abnormal clones was near-triploid and hypotetraploid with DI values from 1.4 to 1.8 (near hypertriploidy) and only 12% were near-diploid. Adenomas with foci of carcinomas, a group of special interest since they represent a link in colorectal tumor progression, had median triploid DNA content. In addition to an increase in DI values, the carcinomas had a clear increase in the proportion of cells actively synthesizing DNA (S-phase fraction). These results are interpreted as evidence for a ploidy-evolution model according to which near-diploid clones in adenomas at early stages of dysplasia would derive from abnormal mitotic cells that divide their DNA unequally between two daughter cells. Tetrapolidization of these near-diploid cells and successive DNA loss would then lead in later stages of tumor progression to near-hypertriploid clones characterized by a balance of chromosomes bearing growth-promoting and growth-suppressing genes confering a selective proliferative advantage.


Keratinocyte Carcinoma and Risk for Another Type of Cancer: Assessment of a Dose-response Relationship.
Keratinocyte carcinoma (KC) is a marker of increased risk of other cancer types. To assess if this association exhibits a dose-response relationship, a case-control study was carried out. This was a clinic-based study of cases with KC plus another type of cancer matched by age, race (all Caucasian), sex and histologic type to controls with KC only (n=48 matched pairs). Compared with the KC only group, those with KC plus another cancer had a mean number of lesions that were 43%, 35%, and 41% greater for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and total KC, respectively. The odds ratio (OR) of developing another type of cancer increased from 1.0 to 1.09 (95% confidence interval (CI)=0.23-5.13) to 2.12 (95%CI=0.50-9.08) according to whether the patient had zero, one, or ≥two BCC lesions; for SCC, the corresponding ORs were 1.0, 1.24 (95%CI=0.48-3.24), and 1.39 (95%CI=0.29-6.61). A dose-response relationship seems to exist between the number of skin lesions and the risk of another type of cancer, but the lack of statistical significance weakens this evidence.


Open surgery induces a dramatic decrease in circulating intact IGFBP-3 in patients with colorectal cancer not seen with laparoscopic surgery.
As shown earlier by the authors via Western blot analysis, open (OS) but not laparoscopic surgery (LS) induces a qualitative decrease in plasma insulin-like growth factor-binding protein 3 (IGFBP-3) levels on postoperative day 1 (POD 1). Intact IGFBP-3 has tumor suppressive effects, but its degradation products do not. Enzyme linked immunoassay (ELISA) inevitably measures both. In this study, using a novel combined Western blot and ELISA analysis method, precise plasma levels of intact IGFBP-3 on POD2 after open and closed colorectal cancer resection (stage I-III) were determined. This study included 15 OS patients with a mean incision length of 26.7 +/- 15.5 cm and 16 LS patients with a mean incision length of 5.3 +/- 3.1 cm. Intact IGFBP-3 levels were determined via ELISA and Western blot analysis in plasma collected preoperatively and postoperatively. In the OS patients, the mean preoperative concentration of intact 43-45 kDa IGFBP-3 protein was 1920 +/- 1430 ng/ml. It decreased dramatically on POD2 to 355 +/- 545 ng/ml (p < 0.005). In the LS group, no significant difference was noted between the preoperative level (1305 +/- 807 ng/ml) and the POD2 level (922 + 714 ng/ml). Open cancer resection, unlike its minimally invasive alternative, induces a dramatic decrease in concentration of intact IGFBP-3, which may have important implications with regard to colon cancer recurrence.


Site-specific determination of lysine acetylation stoichiometries on the proteome-scale.
Posttranslational modification of proteins (PTMs) offers a versatile mechanism to fine-tune the structure, activity, and interactions of the target proteins. Understanding the dynamics and prevalence of the PTM at the site-specific level will provide mechanistic insight into the physiological significance of the modification pathway in cells and diseases. In this chapter, we describe a highly efficient chemical proteomic workflow for the absolute quantification of lysine acetylation stoichiometry. The strategy is capable of measuring the site-specific prevalence of acetylation in a system-wide and untargeted manner. We highlight the importance of validating the workflow using standard proteins and synthetic peptides. Detailed protocols for global stoichiometric analysis of lysine acetylation from cell lysate are presented.


The Potential Use of Saliva as a Biofluid for Systemic Inflammatory Response Monitoring in Children with Pneumonia.
To investigate the levels of C-reactive protein, procalcitonin, calprotectin, interleukin 1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) in both saliva and serum in children with community-acquired pneumonia and to compare the saliva response with the systemic response. Forty hospitalized children with community-acquired pneumonia aged between 1 mo and 15 y; and 40 healthy controls were included. Both serum and saliva samples were collected on admission and at the time of discharge. Calculated differences between values for each serum and salivary parameter on admission and before discharge named delta (Δ) values were used for correlation analysis. Salivary Δ values of each parameter were moderately/strongly correlated with their corresponding serum Δ levels [IL-1β ÷ (r = 0.554, p < 0.001); IL-6 ÷ (r = 0.484, p = 0.002); PCT ÷ (r = 0.737, p < 0.001); TNF-α ÷ (r = 0.587, p < 0.001); CRP ÷ (r = 0.703, p < 0.001); and calprotectin ÷ (r = 0.774, p < 0.001)]. This study will evaluate the reflection of systemic changes in saliva and the efficacy of saliva in pediatric patients with pneumonia. Results will highlight saliva potential use as a biofluid for systemic monitoring in this patient group.


CD33 expression on natural killer cells is a potential confounder for residual disease detection in acute myeloid leukemia by flow cytometry.
Detection of minimal/measurable residual disease (MRD) in acute myeloid leukemia (AML) is important for guiding patient-specific clinical management. Natural killer (NK) cells can express various markers not typically associated with NK lineage, potentially confounding the detection of MRD by flow cytometry. We have observed CD33 expression on NK cells when evaluating for AML MRD in routine clinical practice in multiple patient samples. To characterize CD33 expression on NK cells, 40 peripheral blood or bone marrow samples with NK cells present at >5% of lymphocytes were selected for further assessment of NK cell phenotype and CD33 expression. Seven of the 40 samples (17.5%) were found to have CD33 expression on at least 5% of the NK cells. The CD33-positive NK cell population accounted for an average of 11.4% of NK cells (median 11.9%, range 8.0-15.3%) and 2.2% of total white cells (median 1.1%, range 0.1-10.1%). This NK cell subset expressed bright CD2, bright CD56, and dim CD16. On average, CD33 expression on NK cells was dimmer than on monocytes (mean median fluorescence intensity ratio 0.4; range 0.1-1.0). This study characterizes expression of CD33 on NK cells. Recognition of this pattern of antigen expression is critical in evaluating samples for MRD in patients with myeloid neoplasms, particularly AML.


A study of risk factors for tuberculous meningitis among patients with tuberculosis in China: An analysis of data between 2012 and 2019.
The present study aimed to explore the risk factors for tuberculous meningitis (TBM) among patients with tuberculosis (TB). This retrospective study was conducted on patients with TB who were hospitalized in Beijing Chest Hospital between January 2012 and December 2019. Demographic and clinical data of patients with TB were extracted from electronic medical records using a standardized data collection system. Logistic regression was used to analyze the risk factors associated with TBM. Of the total number of 22,988 cases enrolled, 3.1% were cases of TBM, which included 127 definite and 581 probable TBM, respectively. Multivariate analysis showed that definite TBM was significantly associated with patients aged < 30 years [adjusted odds ratio (aOR) = 3.015, 95% confidence interval (CI): (1.451-6.266)], who were farmers [aOR = 1.490, 95%CI: (1.020-2.177)], with miliary pulmonary TB [aOR = 105.842, 95%CI: (71.704-156.235)], and with malnutrition [aOR = 2.466, 95%CI: (1.110-5.479)]. Additionally, probable TBM was significantly associated with patients aged < 30 years [aOR = 2.174, 95% CI: (1.450-3.261)], aged 30-59 years [aOR = 1.670, 95% CI: (1.222-2.282)], who were farmers [aOR = 1.482, 95%CI: (1.203-1.825)], with miliary pulmonary TB [aOR = 108.696, 95%CI: (87.122-135.613)], and with a digestive system TB [aOR = 2.906, 95%CI: (1.762-4.793)]. An age of < 30 years, being a farmer, and having miliary pulmonary TB were risk factors for TBM among patients with TB. Further screening of patients with TB with aforementioned characteristics could facilitate clinicians to identify patients with TBM at an early stage.


Dioxin uptake by Indian plant species.
Dioxins like various gaseous pollutants and aerosols can be scavenged by appropriate vegetative greenbelts. Based on their stomatal properties and the models for contaminant uptake, uptake of dioxin (2,3,7,8-TCDD) by three important Indian plant species, viz. Eugenia jambolana (Jamun), Azadirachta indica (Neem) and Ficus religiosa (Peepal), has been estimated. 2,3,7,8-TCDD is a contaminant with severe harmful ecological ramifications. Computations show that Ficus religiosa has highest uptake capacity. The present exercise has its utility in designing appropriate green-belts for mitigating adverse environmental and human health impacts due to dioxins. This can be an effective management option for mitigating the damages caused by dioxins.


Digital breast tomosynthesis (DBT) plus synthesised two-dimensional mammography (s2D) in breast cancer screening is associated with higher cancer detection and lower recalls compared to digital mammography (DM) alone: results of a systematic review and meta-analysis.
Digital breast tomosynthesis (DBT) plus digital mammography (DM) in screening is problematic due to increased radiation by the double exposure. Synthesised two-dimensional mammography (s2D) calculated from DBT datasets at no additional dose appears a sensible alternative compared to adding DM. This systematic review and meta-analysis focuses on screening performance outcomes in women screened with DBT plus s2D compared to DM alone. PubMed was searched from January 1, 2010, to September 2, 2020. Studies comparing DBT plus s2D to DM alone in breast cancer screening were included. Pooled risk ratios (RR) were estimated for cancer detection rates (CDR), recall rates, interval cancer rates (ICR), biopsy rates, and positive predictive values for recalls (PPV-1), for biopsies recommended (PPV-2), and for biopsies performed (PPV-3). Sensitivity analyses were performed using the leave-one-out approach. Risk of bias (RoB) was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Twelve papers covering 414,281 women were included from 766 records identified. CDR is increased ([RR, 95% CI] 1.35, 1.20-1.52), recall rates are decreased (0.79, 0.64-0.98), and PPV-1 is increased (1.69, 1.45-1.96) when using DBT plus s2D compared to DM alone. ICR and biopsy rates did not differ, but PPV-2 respectively PPV-3 increased with DBT plus s2D (1.57, 1.08-2.28 respectively 1.36, 1.17-1.58). Overall RoB of studies was assessed to be low. Results show improved diagnostic outcomes with DBT plus s2D compared to DM alone and underline the value of DBT in combination with s2D in breast cancer screening. • DBT plus s2D is associated with higher CDR, lower recall rates, and a higher PPV-1 compared to DM alone in breast cancer screening. • No differences in biopsy rates were found between screening modalities, but PPV-2 and PPV-3 were higher in women screened with DBT plus s2D compared to DM alone. • We identified inconsistent results of ICR in two studies comparing DBT plus s2D to DM alone-resulting in no differences when pooling ICR in meta-analysis.


Is systemic administration of local anesthetic agents effective for relieving neuropathic pain? A Cochrane Review summary with commentary.
The role of systemic use of local anesthetics in the treatment of neuropathic pain (NP) is still unclear. To assess the efficacy and safety of systemic local anesthetics for NP. To summarize and to discuss the rehabilitation perspective on the published Cochrane Systematic Review "Systemic administration of local anesthetic agents to relieve neuropathic pain" by Challapalli V et al.RESULTS:The review included 30 RCTs including patients with NP treated with iv lidocaine, oral mexiletine, lidocaine and mexiletine, or oral tocainide. Low-to-moderate quality of the evidence suggest that intravenous lidocaine or oral mexiletine may slightly reduce NP vs placebo, but the efficacy of these drugs is comparable to anticonvulsants or morphine. Systemic administration of local anesthetics is not supported by scientific evidence for pain relief as well as for functional improvement.


Intracellular retention and insulin-stimulated mobilization of GLUT4 glucose transporters.
GLUT4 glucose transporters are expressed nearly exclusively in adipose and muscle cells, where they cycle to and from the plasma membrane. In cells not stimulated with insulin, GLUT4 is targeted to specialized GLUT4 storage vesicles (GSVs), which sequester it away from the cell surface. Insulin acts within minutes to mobilize these vesicles, translocating GLUT4 to the plasma membrane to enhance glucose uptake. The mechanisms controlling GSV sequestration and mobilization are poorly understood. An insulin-regulated aminopeptidase that cotraffics with GLUT4, IRAP, is required for basal GSV retention and insulin-stimulated mobilization. TUG and Ubc9 bind GLUT4, and likely retain GSVs within unstimulated cells. These proteins may be components of a retention receptor, which sequesters GLUT4 and IRAP away from recycling vesicles. Insulin may then act on this protein complex to liberate GLUT4 and IRAP, discharging GSVs into a recycling pathway for fusion at the cell surface. How GSVs are anchored intracellularly, and how insulin mobilizes these vesicles, are the important topics for ongoing research. Regulation of GLUT4 trafficking is tissue-specific, perhaps in part because the formation of GSVs requires cell type-specific expression of sortilin. Proteins controlling GSV retention and mobilization can then be more widely expressed. Indeed, GLUT4 likely participates in a general mechanism by which the cell surface delivery of various membrane proteins can be controlled by extracellular stimuli. Finally, it is not known if defects in the formation or intracellular retention of GSVs contribute to human insulin resistance, or play a role in the pathogenesis of type 2 diabetes.


Removal of lead from acidic wastewater by bio-mineralized bacteria with pH self-regulation.
Microorganisms with the function of bio-mineralization were isolated from a soil. They were identified as urease-producing bacteria and phosphate-solubilizing bacteria. These two kinds of bacteria belong to the eosinophilic bacteria, which regulated the pH of solution and removed Pb2+ the best at the initial solution pH of 4. The Pb2+ removal mechanism was further explored using various techniques including zeta potential measurement, three-dimensional fluorescence, FTIR, XRD, and TEM-EDS. The results showed that extracellular adsorption, intracellular accumulation and bio-mineralization occurred at the same time and converted to each other. The extracellular adsorption of urease-producing bacteria was through electrostatic adsorption and gradually decomposed urea to produce PbCO3 minerals. The extracellular adsorption of phosphate-solubilizing bacteria was controlled by extracellular polymeric substances (EPS) and rapidly formation of Pb3(PO4)2 stable minerals. In addition, the stabilities of Lead minerals of the two strains were compared. The results showed that the precipitates of phosphate-solubilizing bacteria were more stable. While phosphate-solubilizing bacteria have some advantages, both strains can play important roles in bio-mineralization of HMs in acidic wastewater.


Feeling-of-knowing in fact retrieval: further evidence for preservation in early Alzheimer's disease.
The ability to retrieve and monitor factual information varying in datedness (i.e., dated vs. contemporary) was examined in healthy older adults and patients in an early phase of Alzheimer's disease (AD). Subjects were given free recall and multiple-choice recognition tests of 48 general knowledge questions. For all questions not responded to in recall, subjects made feeling-of-knowing (FOK) judgments. Results indicated dementia-related deficits in both recall and recognition, although both groups showed better recall and recognition with the dated compared with the contemporary questions. Importantly, despite deficits in fact retrieval, the AD patients showed intact monitoring of stored knowledge, as indicated by equivalent FOK accuracy for both groups. In addition, FOK accuracy was similar for the dated and the contemporary information in both groups, suggesting independence between level of general knowledge and the ability to supervise information stored in memory.


Concentrations of some legacy pollutants have increased in South Australian bottlenose dolphins from 1989 to 2014.
Information about pollution and its potential impact in Australian marine wildlife is scarce. To fill this knowledge gap, our study investigated concentrations of legacy pollutants as well as naturally produced methoxylated polybrominated diphenyl ethers (MeO-PBDEs) in blubber, liver, kidney and muscle of Indo-Pacific bottlenose dolphins (Tursiops aduncus) from two large inverse estuaries in South Australia from 1989 to 1995 and 2009-2014. Our results show that concentrations of most pollutant classes are relatively low compared to the literature but at the higher end of the ranges reported for marine mammals in Australia. Results for some individuals exceed toxicity thresholds indicative of immunotoxicity in marine mammals. It is important to note that concentrations of some compound classes, particularly PBDEs and polychlorinated biphenyls (PCBs), increased over a time interval of 20 years thereby placing more individuals at risk in recent years. Some of the highest concentrations of persistent organic pollutants (POPs) were measured in juveniles, which may jeopardize their development and the success of future generations. These results indicate that legacy pollutants may play a role in the long-term health of T. aduncus and should be included in biomonitoring efforts.


Identification of key genes contributing to amino acid biosynthesis in Torreya grandis using transcriptome and metabolome analysis.
Torreya grandis has high economic and nutritional value due to the high nutrients in its kernels. The kernels of different development stages vary enormously in their amino acids content. However, the molecular basis and the regulatory mechanism of amino acid biosynthesis remain unclear. Here, transcriptome and metabolome analysis were performed. Correlation analysis result showed that 4 unigenes were significantly and positively correlated with at least 10 amino acids. The full length CDS of 2 unigenes (TgDAHP2 and TgASA1) were successfully cloned from the 4 unigenes for DAHP, ASA and CITS. Subcelluar localization analysis showed that both TgDAHP2 and TgASA1 were localized to the chloroplast. Overexpression of TgDAHP2 and TgASA1 in Arabidopsis can greatly increase the content of most amino acids. Moreover, 3 transcription factors were found to positively regulate the expression of TgASA1. This research contributes to understand the molecular regulatory mechanisms of amino acid biosynthesis in T. grandis.


Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways.
The discovery and clinical implementation of immune-checkpoint inhibitors (ICIs) targeting CTLA4, PD-1 and PD-L1 has revolutionized the treatment of cancer, as recognized by the 2018 Nobel Prize for Medicine and Physiology. This groundbreaking new approach has improved the outcomes of patients with various forms of advanced-stage cancer; however, the majority of patients receiving these therapies, even in combination, do not derive clinical benefit. Further development of agents targeting additional immune checkpoints, co-stimulatory receptors and/or co-inhibitory receptors that control T cell function is therefore critical. In this Review, we discuss the translational potential and clinical development of agents targeting both co-stimulatory and co-inhibitory T cell receptors. Specifically, we describe their mechanisms of action, and provide an overview of ongoing clinical trials involving novel ICIs including those targeting LAG3, TIM3, TIGIT and BTLA as well as agonists of the co-stimulatory receptors GITR, OX40, 41BB and ICOS. We also discuss several additional approaches, such as harnessing T cell metabolism, in particular via adenosine signalling, inhibition of IDO1, and targeting changes in glucose and fatty acid metabolism. We conclude that further efforts are needed to optimize the timing of combination ICI approaches and, most importantly, to individualize immunotherapy based on both patient-specific and tumour-specific characteristics.


Impact of preoperative hyponatraemia on paediatric perioperative mortality.
Preoperative hyponatraemia is an independent risk factor for postoperative mortality in adults. To our knowledge, this has not been investigated in children. Using data from the 2014 and 2015 data sets of the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P), we conducted a retrospective study of children undergoing surgery. The primary outcome was 30-day all-cause mortality. The secondary outcomes of interest were postoperative seizure within 30 days and prolonged length of stay. To identify any independent association between preoperative hyponatraemia, defined as mild (serum sodium of 131-135 mEq L-1) or severe (≤130 mEq L-1), and death, postoperative seizures, or prolonged length of stay, multivariable logistic regression models were generated. A total of 152 894 patients were identified, and of these 35 291 were included in the final analysis. Preoperative hyponatraemia was present in 5422 patients or 15.4% of the final cohort. There were 432 (0.80%) deaths at 30 days. Compared with patients with a normal preoperative sodium concentration, those with mild (P=0.003; odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.17-2.18) and severe (P=0.002; OR: 2.16; 95% CI: 1.32-3.54) hyponatraemia had increased rates of death, after adjusting for co-morbidity and procedural complexity. Both mild (P<0.001; OR: 1.53; 95% CI: 1.42-1.65) and severe (P<0.001; OR: 1.51; 95% CI: 1.19-1.93) hyponatraemia were independently associated with prolonged length of stay, after adjusting for relevant co-variates. This retrospective analysis identified an association between preoperative hyponatraemia and perioperative mortality and length of stay in paediatric patients.


A Pilot Study of 18F-Alfatide PET/CT Imaging for Detecting Lymph Node Metastases in Patients with Non-Small Cell Lung Cancer.
Angiogenesis plays a key role in tumor development and αvβ3 integrin are overexpressed on the endothelial cell surface of newly forming vessels. 18F-Alfatide has favorable properties for αvβ3 integrin targeting and showed potential for imaging angiogenesis with Positron Emission Tomography (PET)/computed tomography (CT). In this study, 13 patients with non-small cell lung cancer (NSCLC) who underwent 18F-Alfatide PET/CT before surgery were enrolled. The uptake of all dissected lymph nodes (LNs) of 18F-Alfatide were assessed visually and analyzed with a maximum and mean standard uptake value (SUVmax, SUVmean) and SUV ratios. LN metastases were pathologically confirmed and 20 of 196 LNs were malignant. All malignant LNs were successfully visualized on 18F-Alfatide PET/CT in patients and the sensitivity, specificity and accuracy was 100.0%, 94.9% and 95.4%, respectively. SUVmax, SUVmean and SUV ratios in malignant LNs were significantly higher than in benign LNs for NSCLC patients (P < 0.001). The same result was observed in patients with adenocarcinoma and squamous cell carcinoma (P < 0.001). The 18F-Alfatide parameter shows high sensitivity (83.9-100%), specificity (78.6-96.7%) and accuracy (81.7-96.9%) according to thresholds calculated from receiver operating characteristic curve. Our results suggest that 18F-Alfatide PET/CT is valuable in the diagnosis of metastatic LNs for NSCLC patients.


Antimicrobial activity of a silver-microfibrillated cellulose biocomposite against susceptible and resistant bacteria.
Antibiotic Microbial Resistance (AMR) is a major global challenge as it constitutes a severe threat to global public health if not addressed. To fight against AMR bacteria, new antimicrobial agents are continually needed, and their efficacy must be tested. Historically, many transition metals have been employed, but their cytotoxicity is an issue and hence must be reduced, typically by combination with organic polymers. Cellulose of natural origin, especially those derived from unavoidable residues in the food supply chain, appears to be a good capping agent for the green synthesis of silver nanoparticles. Herein, we describe a green synthesis method to produce a novel biocomposite, using ascorbic acid as reducing agent and microfibrillated cellulose as a capping agent and demonstrate this material to be an efficient antimicrobial agent. Silver nanoparticles were obtained in the cellulose matrix with an average size of 140 nm and with antimicrobial activity against both sensitive and resistant Gram positive (using 1500 ppm) as well as sensitive and resistant Gram negative (using 125 ppm) bacteria. Also, an inverted disk-diffusion methodology was applied to overcome the low-solubility of cellulose compounds. This novel silver nanoparticle-cellulose biocomposite synthesized by a green methodology shows the potential to be applied in the future development of biomedical instruments and therapeutics.


Cell-to-substratum contacts in living cells: a direct correlation between interference-reflexion and indirect-immunofluorescence microscopy using antibodies against actin and alpha-actinin.
Rat mammary cells growing on glass coverslips were photographed first using interference-reflexion microscopy and then after processing for indirect-immunofluorescence microscopy with antibodies to actin or to alpha-actinin. A comparison of the images of the same cell given by the 2 microscopical procedures indicates that the focal contacts between the cell and the substratum correspond to distal ends of microfilament bundles, and the these bundles are only in limited areas close to the substratum. The focal contracts are rich in alpha-actinin which has been proposed as a membrane-anchorage protein for microfilament bundles. Use of stereo immunofluorescence microscopy allows a direct comparison between the interference-reflexion image, and the underside of the cell after staining with antibodies to actin or alpha-actinin.


Are critical shoulder angle and acromion index correlated to the size of a rotator cuff tear.
Scapular morphology is an extrinsic factor playing role in rotator cuff tear (RCT) etiology. The objective of this study was to evaluate the relationship between critical shoulder angle (CSA) and acromion index (AI) with partial-bursal side and full thickness RCT and the size of the RCT. The hypothesis was that CSA and AI would be greater in partial bursal-side RCT and full-thickness RCT patients and would increase with the size of the RCT. This retrospective study assessed 218 patients who had standard shoulder radiographs and magnetic resonance imaging. Patients were divided into three groups: intact rotator cuff (68), partial bursal-side RCT (34) and full-thickness RCT (116). In the second part, full-thickness RCT patients were divided into four groups according to RCT size; small (<1cm), medium (1-3cm), large (3-5cm) and massive (>5cm). AI and CSA measurements were evaluated from radiographs. The mean CSA was 32.8̊ in control group, 34.3̊ in partial group and 36.9̊ in full-thickness group. The mean AI was 0.66, 0.68 and 0.72 respectively. Significant difference was found in AI and CSA between full thickness RCT and intact RC group (p<0.01), and partial RCT and full thickness RCT group (p<0.05) in paired comparisons. In full thickness RCT size groups the mean CSA was 34.2̊, 36.4̊, 39.0̊ and 40.8̊ and mean AI was 0.70, 0.71, 0.73 and 0.79 respectively. Significant difference was found between small-large, small-massive, medium-massive groups for CSA in paired comparisons and between small-massive, medium-massive groups for AI. CSA and AI were significantly greater in full-thickness RCT patients and the size of the RCT increased with CSA and AI. The greater CSA and AI could be predictors for larger RCT. III; Cross-Sectional Design; Prognosis Study.


β-Catenin is required for optimal exercise- and contraction-stimulated skeletal muscle glucose uptake.
Loss of β-catenin impairs in vivo and isolated muscle exercise/contraction-stimulated glucose uptake. β-Catenin is required for exercise-induced skeletal muscle actin cytoskeleton remodelling. β-Catenin675 phosphorylation during exercise may be intensity dependent. The conserved structural protein β-catenin is an emerging regulator of vesicle trafficking in multiple tissues and supports insulin-stimulated glucose transporter 4 (GLUT4) translocation in skeletal muscle by facilitating cortical actin remodelling. Actin remodelling may be a convergence point between insulin and exercise/contraction-stimulated glucose uptake. Here we investigated whether β-catenin is involved in regulating exercise/contraction-stimulated glucose uptake. We report that the muscle-specific deletion of β-catenin induced in adult mice (BCAT-mKO) impairs both exercise- and contraction (isolated muscle)-induced glucose uptake without affecting running performance or canonical exercise signalling pathways. Furthermore, high intensity exercise in mice and contraction of myotubes and isolated muscles led to the phosphorylation of β-cateninS675 , and this was impaired by Rac1 inhibition. Moderate intensity exercise in control and Rac1 muscle-specific knockout mice did not induce muscle β-cateninS675 phosphorylation, suggesting exercise intensity-dependent regulation of β-cateninS675 . Introduction of a non-phosphorylatable S675A mutant of β-catenin into myoblasts impaired GLUT4 translocation and actin remodelling stimulated by carbachol, a Rac1 and RhoA activator. Exercise-induced increases in cross-sectional phalloidin staining (F-actin marker) of gastrocnemius muscle was impaired in muscle from BCAT-mKO mice. Collectively our findings suggest that β-catenin is required for optimal glucose transport in muscle during exercise/contraction, potentially via facilitating actin cytoskeleton remodelling.


Immunoglobulins attached to and in the integument of adult Schistosoma mansoni Sambon 1907, from first infection of CF mice.
7Sgamma2b antibody was found attached to and in the integument of adult Schistosoma mansoni removed from CF1 white mice. With the techniques used, IgA, IgM, 7Sgamma1, 7Sgamma2a, 7Sgamma3, and C3 complement were not found to be attached to the integumental surfaces. 7Sgamma2b does not seem to fix C3, and it is suggested this antibody may be acting in enhancing and blocking roles which protect the worms from the host.


Peripheral intravenous cannulation in nursing: performance predictors.
This study examined the impact of nurses' education and experience and the characteristics of their patients on their performance of peripheral intravenous cannulation. A researcher-developed peripheral intravenous cannulation assessment tool was used to assess nurses' behavior during cannulation. Results from a hierarchical multiple regression indicated that patient demographic variables did not significantly predict overall ratings of peripheral intravenous cannulation performance. Nurses' education and experience significantly predicted overall ratings of peripheral intravenous cannulation. Educational preparation at a postgraduate level was a significant positive predictor, and the years of experience in general nursing were a significant negative predictor of overall ratings of peripheral intravenous cannulation. The results from the current study highlight the importance of applied education, such as that indicated by a graduate degree, in providing and maintaining advanced clinical skills for specialty practice.


Functional recovery from spinal cord trauma following dexamethazone and chlorpromazine therapy in dogs.
The spinal cords of 20 normal dogs were exposed via dorsal laminectomies and damaged with a known impact force. Ten dogs were treated with dexamethazone and 10 dogs with chlorpromazine for five days after surgery. The results showed that neither drug had a significantly beneficial effect on the functional recovery of the spinal cords, when compared to a control group of similarly traumatised dogs.


Electrochemical Synthesis of Substituted Morpholines via a Decarboxylative Intramolecular Etherification.
An efficient method for the synthesis of 2,6-multisubstituted morpholines via an electrochemical intramolecular etherification has been developed. The method, which is operationally simple and easy to scale up, provides various substituted morpholine derivatives in high yields. The utility of this method is showcased by the synthesis of 2,2,6,6-tetrasubstituted morpholines, which are difficult to synthesize efficiently using previously reported strategies.


Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder.
To test whether change in motor evoked potential (ΔMEP) induced by continuous theta-burst stimulation (cTBS) of motor cortex (M1) distinguishes adults with autism spectrum disorder (ASD) from neurotypicals, and to explore the contribution of two common polymorphisms related to neuroplasticity. 44 adult neurotypical (NT) participants (age 21-65, 34 males) and 19 adults with ASD (age 21-58, 17 males) prospectively underwent M1 cTBS. Their data were combined with previously obtained results from 35 NT and 35 ASD adults. ΔMEP at 15 minutes post-cTBS (T15) was a significant predictor of diagnosis (p = 0.04) in the present sample (n=63). T15 remained a significant predictor in a larger sample (n=91) and when partially imputed based on T10-T20 from a yet-greater sample (N=133). T15 also remained a significant predictor of diagnosis among brain-derived neurotrophic factor (BDNF) Met+ and apolipoprotein E (APOE) ε4- subjects (p's < 0.05), but not among Met- or ε4+ subjects (p's > 0.19). ΔMEP at T15 post-cTBS is a significant biomarker for adults with ASD, and its utility is modulated by BDNF and APOE polymorphisms. M1 cTBS response is a physiologic biomarker for adults with ASD in large samples, and controlling for BDNF and APOE polymorphisms can improve its diagnostic utility.


Family status and women's career mobility during urban China's economic transition.
In contrast to the historical experience of Western welfare states, where social and family policies help create more integrated public-private spheres, marketization in China has presented a case of sphere separation. This phenomenon has important implications for the dynamics of gender inequality in economic transition. This article examines how family status is associated with women's career mobility in reform-era urban China and the impact of family on women's career choices across different reform stages. Based on retrospective data from the Chinese General Social Survey (CGSS) in 2008, we adopt discrete-time logit models to examine the effects of marriage and childbearing on women's upward mobility, the risk of labor market exit, and how the effects vary over time. Chinese women in the workforce are adversely affected by marriage and having dependent children. They are more likely than men to experience (involuntary, in particular) job exit to fulfill their roles as wives and mothers and less likely to move up in the career ladder. This pattern is more prominent as the economic reform proceeds. Marketization has adversely affected Chinese women's career outcomes by increasing work-family tension after the work unit (danwei) system and socialist programs that supported working women were scrapped. This study is one of the few empirical studies to attempt to explain the widening gender gap in China's job market from the perspective of family using the two-sphere separation framework. The framework originated in Western family studies but has been adapted to suit the context of urban China.


Imaging of Cartilage in the Athlete.
MRI remains the optimal imaging modality to evaluate cartilage injuries in the athlete. As these injuries have no intrinsic healing capacity, early and accurate noninvasive diagnosis remains integral to determining the most appropriate treatment option in this class of patients. Although surgical success depends primarily on clinical outcomes, MRI evaluation can provide pertinent information regarding the status of the surgical repair and the progression of cartilage disease.


New record of Arcella gandalfi (Amoebozoa: Arcellinida) from Colombia.
The reports of testate amoebae species in Colombia are limited to a few studies in lentic and peat bog systems; however, the diversity in lotic systems has been poorly investigated. Zooplankton sampling was performed in lotic environments of the Piedemonte Llanero in Colombia. Ten individuals of the species Arcella gandalfi were identified to document the first record of A. gandalfi from the Piedemonte Llanero in Colombia, expanding its distribution from Brazil to Colombia. This finding corroborates the status of A. gandalfi as a flagship species from the South America continent.


NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.
The purpose of the study was to describe a pedigree with NEFL E396K mutation associated with a novel dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) phenotype. The pedigree comprised four patients over two generations, aged between 35 and 59 years, who have been serially evaluated since 1993. Their clinical picture was characterized by pes cavus, sensorimotor neuropathy and spastic gait. Both older patients showed ascending leg weakness to involve pelvic musculature. CMT neuropathy score ranged from 14 to 26 (moderate to severe disease). Electrophysiology showed uniform nerve conduction slowing in the intermediate range, both in distal and proximal nerve segments. Multimodal evoked potential and blink reflex studies revealed abnormalities indicative of central sensorimotor pathway dysfunction. On imaging studies of lower-limb musculature, there was massive atrophy of intrinsic foot muscles and to a lesser degree of calves and thighs predominating in muscles innervated by tibial and sciatic nerves. In both patients exhibiting waddling gait, there was atrophy of pelvic muscles mainly involving gluteus medius, gluteus minimus and piriformis. We conclude that NEFL E396K mutation may manifest with a novel DI-CMT phenotype, characterized by simultaneous involvement of the peripheral and central nervous system.


My problem or yours? Interpersonal problems and marital quality.
Research has consistently illustrated the impact of personality on marital quality. Given the inherent dyadic nature of relationships, recent investigations have integrated spouse-rated personality to account for both spouses' perspectives. Grounded in Contemporary Integrative Interpersonal Theory, we viewed personality through an interpersonal lens and conceptualized maladaptive interpersonal functioning as interpersonal problems. The present study examined the incremental validity of spouse-rated interpersonal problems beyond self-reported interpersonal problems to predict marital quality within an expanded actor-partner interdependence model (APIM). Within a community sample of heterosexual, married couples (N = 110), we used expanded APIMs, integrating both self-report and spouse-rating, to test the incremental validity of spouse-perceived interpersonal problems over self-perceived interpersonal problems on marital quality through a model comparison approach. We tested for possible gender differences in effects. Spouse perception, notably spouse-rated partner effects, appears to be the most frequent predictor of marital quality, and self-perception had less impact. Given the implications marital quality has on health and well-being, intervention efforts capitalizing on acceptance of spouses' perspectives are likely to lead to greater improvements in quality and overall health.


Selective chemiluminescent TURN-ON quantitative bioassay and imaging of intracellular hydrogen peroxide in human living cells.
Hydrogen peroxide is an unavoidable by-product of cell metabolism, but when it is not properly managed by the body it can lead to several pathologies (e.g., premature aging, cardiovascular and neurodegenerative diseases, cancer). Several methods have been proposed for the measurement of intracellular H2O2 but none of them has proven to be selective. We developed a rapid all-in-one chemiluminescent bioassay for the quantification of H2O2 in living cells with a low limit of detection (0.15 μM). The method relies on an adamantylidene-1,2-dioxetane lipophilic probe containing an arylboronate moiety; upon reaction with H2O2 the arylboronate moiety is converted to the correspondent phenol and the molecule decomposes leading to an excited-state fragment that emits light. The probe has been successfully employed for quantifying intracellular H2O2 in living human endothelial, colon and keratinocyte cells exposed to different pro-oxidant stimuli (i.e., menadione, phorbol myristate acetate and lipopolysaccharide). Imaging experiments clearly localize the chemiluminescence emission inside the cells. Treatment of cells with antioxidant molecules leads to a dose-dependent decrease of intracellular H2O2 levels. As a proof of concept, the bioassay has been used to measure the antioxidant activity of extracts from Brassica juncea wastes, which contain glucosinolates, isothiocyanates and other antioxidant molecules.


Application of a Robotic Tele-Echography System for COVID-19 Pneumonia.
To date, coronavirus disease 2019 (COVID-19) has infected millions of people worldwide. Ultrasound plays an indispensable role in the diagnosis, monitoring, and follow-up of patients with COVID-19. In this study, we used a robotic tele-echography system based on a 5G communication network for remote diagnosis. The system has great potential for lung, heart, and vasculature information, medical staff protection, and resource sharing, can be a valuable tool for treating patients during the pandemic, and can be expected to expand to more specialized fields.


Are partner's features important to understand health at older ages? The Spanish case.
To analyse health differences among partnered individuals in Spain aged 65-81 considering their combined (education of both partners and age gap) and household (economic capacity of the household) characteristics. A cross-sectional study of the 2015 Spanish sample of the European Union Statistics on Income and Living Conditions survey (EU-SILC) on partnered individuals aged 65-81 years (N=1787). Using logistic regression models separately for women and men we obtained odds and predicted probabilities of having less than good health (95% confidence intervals) according to combined information from both partners on education and age, the household's economic capacity and partner's health status. Probabilities of not having good health are significantly less among lower educated women whose partners are more highly educated (compared to both partners being lower educated) and among women whose partner is younger or has good health status. The latter also applies to men. Living in a household without economic difficulties also favours health (both sexes). For both sexes a partner's health status is the variable that shows the largest effect on elderly partnered Spanish people's health but women's health appears to be more sensitive to their partner's educational attainment and the household's economic situation.


Preparation and characterization of novel fast disintegrating capsules (Fastcaps) for administration in the oral cavity.
The objective of this study was to prepare novel capsule-based fast disintegrating dosage forms for the oral cavity (Fastcaps). First, cast films were prepared from various additive-containing gelatin solutions and evaluated with respect to disintegration time and mechanical properties in order to identify suitable formulations for the capsule preparation. The disintegration time of films decreased with decreasing bloom strength and could be further decreased by the addition of sugars or PEGs. Fast disintegrating capsules were successfully prepared by a dipping process, whereby parameters such as the viscosity and temperature of the dipping solution and the dipping velocity of the steel pins were optimized. The required viscosity range of the dipping solution for Fastcap manufacturing was 500-600 cP. The addition of the hydrophilic additives (xylitol, sorbitol or PEG 1500) did not significantly affect the viscosity and gelation temperature of the dipping solution. The in vitro disintegration of Fastcaps (30-45 s) was twice as rapid as the one of regular hard gelatin capsules. In vivo, Fastcaps disintegrated rapidly (9-13 s) and their content was spread throughout the oral cavity within seconds. Lactose and/or microcrystalline cellulose were suitable fillers for Fastcaps. The mechanical properties of Fastcaps were similar to commercially available gelatin capsules, which assures good processability and handling.


Pragmatic trial of a Study Navigator Model (NAU) vs. Ambassador Model (N+) to increase enrollment to health research among community members who use illicit drugs.
Although drug use is common in the population, drug users are sometimes excluded from research without justification. Two models of individualized study matching were compared for effectiveness in enrolling people who "endorsed current drug use" and those who "did not" into appropriate research. Participants in the NIDA-funded Transformative Approach to Reduce Research Disparities Towards Drug Users study (Navigation Study) were recruited through a Clinical and Translational Science Award (CTSA) community engagement model. Of the 614 community-recruited adults, 326 endorsed current drug use (cases); 288 did not (controls). Participants were randomized to one of two intervention groups: Navigation as Usual (NAU) [individualized study matching through a Study Navigator] or Enhanced Navigation (N+) [individualized study matching plus transportation and other assistance through an Ambassador]. Rates of enrollment into research studies were compared. At 90 days, N+ vs. the NAU intervention was associated with higher enrollment among both drug users (36.0% N+ vs. 24.9% NAU) and non-drug users (45.5% N+ vs. 25.2% NAU). NAU attained the same rate of enrollment for users of drugs (24.9%) and non-users (25.2%); N+ had similar rates as well (36.0% drug users vs. 45.5% non-drug users). In addition, high rates of enrollment were achieved among all groups of participants, from 24.9% (drug users in NAU) to 45.5% (non-drug users in N+). Both the NAU and N+ methods can reduce barriers and help users and non-users become part of the population that participates in research. Working with the local CTSA adds significant value to the research enterprise.


Headache among mesial temporal lobe epilepsy patients: a case-control study.
Epilepsy and headache are two chronic disorders that are characterized by recurrent attacks, but the relationship between them is not completely understood. Using a structured questionnaire, we investigated the prevalence of headache during the previous year in a homogeneous group of 100 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The control group consisted of 100 age-matched individuals who were randomized from a nationwide Brazilian headache database. There was a significantly higher prevalence of headache (92%) among the MTLE-HS patients when compared with the controls (73%; p=0.001). Chronic daily headache (CDH) was significantly associated with MTLE-HS (OR 6.1, CI 95% 1.7-22, p=0.005). We did not find any association between the diagnosis of migraine or tension-type headache and MTLE-HS. This study showed that MTLE-HS increases the likelihood of a headache diagnosis. In addition, CDH was more prevalent among the MTLE-HS patients, which supports a common pathophysiological mechanism for epilepsy and headache.


Gamma Knife Radiosurgery for Short Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Syndrome: Targeting the Trigeminal Nerve and the Sphenopalatine Ganglion. Case Report and Literature Review.
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a primary headache syndrome with an unclear pathogenesis, and only in very few cases, SUNCT is secondary to known lesions (secondary SUNCT). Several pharmacological as well as interventional and invasive treatments have been used to treat SUNT cases, with no definitive results. We describe a patient with idiopathic SUNCT syndrome, successfully treated with gamma knife radiosurgery and we report a review of the cases of the literature treated with radiosurgery. A 63-year-old woman complained of episodes of intense and regular paroxysmal facial pain in the territory of the maxillary branch of the trigeminal nerve accompanied by inflammation of conjunctiva and involuntary lacrimation from 2006. During the following years, she received several treatments: combination of drugs, acupuncture, and endonasal infiltration of the sphenopalatine ganglion. The frequency of the painful attacks increased progressively and it was impossible for her to have a normal active life. Combined gamma knife radiosurgery treatment, targeting the trigeminal nerve (80 Gy maximum dose) and the sphenopalatine ganglion (80 Gy maximum dose) was performed in April 2016 (visual analog score before treatment = 6). Pain gradually reduced in the following months, as well as frequency and severity of the attacks. No sensory deficit developed. The follow-up length of our patient is 37 months: she is nearly pain free (visual analog score = 2) and has resumed a normal life. Patients with idiopathic SUNCT have few therapeutic options. Our case demonstrates that gamma knife radiosurgery is a feasible and effective noninvasive option to treat patients with medically refractory idiopathic SUNCT.


1H, 13C, 15N NMR analysis of sildenafil base and citrate (Viagra) in solution, solid state and pharmaceutical dosage forms.
Sildenafil citrate (SC) (Viagra) and sildenafil base in pure form are easily and unequivocally characterized by multinuclear NMR spectroscopy. Analysis of chemical shifts indicates that: (i) N6-H forms intramolecular hydrogen bonds, (ii) N25 is protonated in the salt and (iii) intermolecular OH...N hydrogen bonds involving N2 and N4 are present in the solid sildenafil citrate. 13C CPMAS NMR method has been proposed for the identification and quantitation of Viagra in its pharmaceutical formulations.


'A level playing field': Young people's experiences of wheelchair basketball as an enabling place.
Using a novel case-study of a youth wheelchair basketball team in Auckland, New Zealand, we investigate the experiences of young people with physical disabilities in recreational sports places. We consider the 'enabling places' created by this sport, which can enhance disabled young people's wellbeing and social inclusion. Semi-structured interviews with the team's players and coordinators revealed logistical and societal challenges associated with facilitating youth-oriented sports, as well as those encountered by team members personally. They also identified physical health and social benefits experienced through involvement in wheelchair basketball. The material, social and affective dimensions of participants' experiences of wheelchair basketball elucidate the capacity for the sport, and its team members and settings, to affirm young people's identity and place-in-the-world. We conclude that youth-specific, inclusive sports generate enabling places that enhance young people's social inclusion, wellbeing and life enjoyment.


Successful memory response following a booster dose with a virosome-formulated hepatitis a vaccine delayed up to 11 years.
Boosting adult travelers with the virosome-formulated, aluminum-free hepatitis A vaccine Epaxal up to 128 months after a single primary dose confers full protection against hepatitis A, even in travelers aged 50 years and above. Delaying the booster dose did not influence the immune memory response to Epaxal.


Evaluation of partial tef1, rpb2, and nLSU sequences for identification of isolates representing Armillaria calvescens and Armillaria gallica from northeastern North America.
Armillaria calvescens and Armillaria gallica are two of the most closely-related species of Armillaria in North America and have been difficult to distinguish from one another using morphological and molecular techniques. In an attempt to better distinguish these two species, partial sequences of the elongation factor-1 alpha (tef1), RNA polymerase II (rpb2), and nuclear large subunit (nLSU) genes were generated for 32 total isolates; 12 isolates each for A. calvescens and A. gallica, along with two isolates each of Armillaria gemina, Armillaria mellea, Armillaria sinapina, and Armillaria solidipes. Within the tef1 amplicon, five single nucleotide polymorphisms (SNPs) were present between A. calvescens and A. gallica. Phylogenetic reconstruction using the maximum likelihood (ML) and maximum parsimony (MP) methods showed that tef1 was the only gene capable of distinguishing A. calvescens from A. gallica, and additionally, all isolates representing the six northeastern North American species. Partial tef1 sequences grouped A. calvescens into a strongly-supported, monophyletic clade with bootstrap support (BS) values of 98/98% (ML/MP), while A. gallica was grouped into a monophyletic clade with lower BS support (76/59%). The results illustrate the utility of partial tef1 sequences for the identification of field isolates of Armillaria from northeastern North America.


Effects of artificial cryptorchidism on sperm morphology.
In a diurnal artificial cryptorchidism (AC) experiment intended to provide a male contraceptive method, oligoasthenozoospermia was found as early as the fourth month, accompanied by an increase in the mean percentage of abnormally shaped spermatozoa. A detailed morphologic study concerning 19 volunteers exposed for 6 to 24 months demonstrated that the overall increase of the mean percentage of abnormally shaped spermatozoa resulted from the percentage increase of elongated, thin, and irregular heads and of bent tails. This increase is probably caused by the rise in environmental testicular temperature induced by AC. A return to baseline values was observed within 12 months after the end of the experiment.


Distribution of PCP4 protein in the forebrain of adult mice.
Purkinje-cell protein 4 (PCP4) is a small calmodulin (CaM)-binding protein that has been discovered to be selectively expressed by cerebellar Purkinje cells in the adult rodent brain. In addition, expression of PCP4 mRNA has been detected in the hippocampus and in the cortex. In order to determine the expression of PCP4 protein in the brain, we performed an immunohistochemical analysis using adult mice. We could demonstrate that PCP4 is expressed in neocortical structures, especially in the deep layers, as well as in other cortical structures and parts of the hippocampal formation. Moreover, PCP4 protein is highly expressed in the olfactory bulb and caudate putamen. PCP4 positive cells were also detected in specific areas of the amygdala, thalamus (especially dorsal lateral geniculate nucleus) and hypothalamus. By performing double-labeling experiments together with NeuN (a neuronal marker), we could demonstrate that PCP4 expressing cells in the brain are of neuronal origin.


Craniocerebral missile injuries in a combat zone: spectrum of injuries and lessons learnt.
High-velocity missile injuries are commonly encountered in war or war-like situations. Aggressive resuscitation, early evacuation to neurosurgical center, and application of neurosurgical principles remain tenets of success. The spectrum of injuries and clinical profile of 14 such cases with craniocerebral missile injuries managed at our center in the northern sector were included. Site of injury, GCS at presentation, associated injuries, surgical intervention, duration of hospitalization, and recovery of the patient were analyzed. Five patients had sustained gunshot wounds, and nine patients had sustained shrapnel injuries. Thirteen patients were deeply comatose, and one patient was conscious. The entry wound was in frontal lobe in eight patients, and in four patients, it was in the faciocranial area. Ten patients had Glasgow Coma Scale (GCS) less than 8 at presentation. Surgical intervention was required in 13 patients, including 11 decompressive craniectomies and anterior skull base repair in four patients with faciocranial entry wound. One patient expired during initial resuscitation, and one patient died in the postoperative period. Location of injury was the single most important determinant of outcome. An early decompressive craniectomy provides a reasonable chance of recovery. Aggressive debridement involving track explorations, lobectomies, or removal of retained shrapnels is not beneficial. Injuries to the skull base and violation of sinus spaces predispose these patients to cerebrospinal fluid leaks and infective sequelae. All these patients require aggressive postoperative intensive care and rehabilitation.


Genomic Diversity of Bacteriophages Infecting the Genus Acinetobacter.
The number of sequenced Acinetobacter phage genomes in the International Nucleotide Sequence Database Collaboration has increased significantly in recent years, from 37 in 2017 to a total of 139 as of January 2021 with genome sizes ranging from 31 to 378 kb. Here, we explored the genetic diversity of the Acinetobacter phages using comparative genomics approaches that included assessment of nucleotide similarity, shared gene content, single gene phylogeny, and the network-based classification tool vConTACT2. Phages infecting Acinetobacter sp. are genetically diverse and can be grouped into 8 clusters (subfamilies) and 46 sub-clusters (genera), of which 8 represent genomic singletons (additional genera). We propose the creation of five new subfamilies and suggest a reorganisation of the genus Obolenskvirus. These results provide an updated view of the viruses infecting Acinetobacter species, providing insights into their diversity.


Theoretical Studies on the Isomerization Kinetics of Low-Lying Isomers of the SiC4H2 System.
The low-lying isomers of SiC4H2 are investigated to understand the kinetics of isomerization pathways using density functional theory. In our earlier work, we studied the various possible isomers (J. Phys. Chem. A, 2020, 124, 987-1002) and the chemical bonding of low-lying isomers of SiC4H2 (J. Phys. Chem. A, 2022, 126, 9366-9374). Among them, four isomers, 1-ethynyl-3-silacycloprop-1-en-3-ylidene (1), 3-silapent-1,4-diyn-3-ylidene (2), 1-silapent-1,2,3,4-tetraen-1-ylidene (4), and 1-silapent-2,4-diyn-1-ylidene (5) have already been identified in the laboratory. The previously known theoretical isomer 2-methylene-1-silabicyclo[1.1.0]but-1(3)-en-4-ylidene (3) and the newly identified unknown isomer through the present kinetic studies 5-silabicyclo[2.1.0]pent-1(4),2-dien-5-ylidene (N6) remain elusive in the laboratory to date. The isomerization pathways of the low-lying isomers of SiC4H2 are predicted through the transition state structures. Intrinsic reaction coordinate analysis identifies the minimum energy reaction pathways connecting the transition state from one isomer to another of the investigated system. The present kinetic data reveal the isomerization of global minimum energy isomer 1 to thermodynamically stable low-lying isomers, 2 and 5. Interestingly, isomer 3 interconverts to the experimentally known low-energy isomer 4, the second most thermodynamically stable isomer among them. The thermodynamic and kinetic parameters of the low-lying isomers of SiC4H2 are also documented in this work. The rate coefficient and equilibrium constant for isomerization reactions are calculated using the Rice-Ramsperger-Kassel-Marcus theory. The equilibrium constant delineates the difficulties in forming N6 and 3 through the isomerization pathways. Furthermore, ab initio molecular dynamics studies dictate the stability of low-lying isomers of SiC4H2 within the time scale of the simulation.


Symptomatic internal hernias after laparoscopic bariatric surgery.
The aim of this study was to describe the occurrence and clinical characteristics of symptomatic internal hernias (IH) after laparoscopic bariatric procedures. We conducted a retrospective review of cases of IH after 1,064 laparoscopic gastric bypasses (LGB) and biliopancreatic diversions with duodenal switch (LBPD-DS) performed from September 1998 to August 2002. We documented 35 cases of IH (overall incidence of 3.3%). The IH occurred in 6.0% of patients with retrocolic procedures and 3.3% of patients with antecolic procedures. Most were in the Petersen defect (55.9%) and at the enteroenterostomy site (35.3%). A bimodal presentation was observed, with 22.9% of patients with IH diagnosed in the early postoperative period (2-58 days) and 77.1% in a delayed fashion (187-1,109 days). A laparoscopic approach to the repair of IH was possible in 60.0% of patients. Complications occurred in 18.8% of patients, including one death (2.9%). Complete closure of all mesenteric defects is strongly recommended during laparoscopic bariatric procedures to avoid IH and their associated complications.


Seed and Soil: Psychological Affordances in Contexts Help to Explain Where Wise Interventions Succeed or Fail.
Psychologically "wise" interventions can cause lasting improvement in key aspects of people's lives, but where will they work and where will they not? We consider the psychological affordance of the social context: Does the context in which the intervention is delivered afford the way of thinking offered by the intervention? If not, treatment effects are unlikely to persist. Change requires planting good seeds (a more adaptive perspective) in fertile soil in which that seed can grow (a context with appropriate affordances). We illustrate the role of psychological affordances in diverse problem spaces, including recent large-scale trials of growth-mindset and social-belonging interventions designed specifically to understand heterogeneity across contexts. We highlight how the study of psychological affordances can advance theory about social contexts and inform debates about replicability.


[The vascularized articular transfers from the foot].
Complete destruction of the PIP or MCP joint space can be treated by a vascularized transfer from the foot in selected patients. The surgical technique for PIP and MTP vascularised transplantation is described with special emphasis on recent improvements (use of a short vascular pedicle, refinements in donor site reconstruction). Results of a series of 50 transfers performed between 1992 and 2009 are presented. PIP transfer was performed in 37 patients, at an average age of 18.3 years (range 3 to 40) leading to an average active ROM of 44° (0-80), with a lag of extension of 34.2° (0-80). MCP transfer was performed in 12 patients (13 transfers), at an average age of 21.3 years (range 3 to 40) leading to an average range of motion of 60° (35-80), with a lag of extension of 18.6° (0-30). None of the reconstructed articulations was painful. On the plain radiographs, no degradation of the joint space of the transferred articulations was noted. Within the pediatric population, the growth potential was preserved, signing the perenniality of the vascularization of the transfers. When faced to a complete joint destruction involving either the PIP or the MCP of the long fingers, reconstruction can be achieved by the mean of a vascularized joint transfer. The range of motion obtained with these transfers is not superior to what is observed after arthroplasty but it will persist with time. Therefore, even it is a technically demanding option, it should remain in our armamentarium as an alternative to joint fusion or joint arthroplasty.


Development and pharmacokinetic evaluation of erythromycin lipidic formulations for oral administration in rainbow trout (Oncorhynchus mykiss).
The aim of this work was to enhance the bioavailability of erythromycin base when administered orally in rainbow trout (Oncorhynchus mykiss). Since erythromycin is normally given in the form of medicated feed, in this study three new types of feed formulation were developed. A self-emulsifying system and two types of double microemulsions (O/W/O) were prepared, characterized and adsorbed on a commercial extruded diet for fish. The emulsified systems were based on saturated polyglycolized glycerides and mono- and diglycerides of medium-chain fatty acids (as oily phase), Tween 80 (as surfactant) and, in the case of double microemulsions, distilled water. The systems differed in percentage composition and for the amount and position of erythromycin in different phases. The three medicated feed were then administered orally by means of a gastric probe to rainbow trout and their relative bioavailability was estimated in comparison with that obtained after oral administration of feed with erythromycin powder. For each medicated feed, 80 fish were tested. Finally, plasma profiles of erythromycin after single administration of medicated feeds were used to predict profiles obtainable by administering once-daily medicated feeds for 7 consecutive days. The results proved that the feeds containing microemulsified erythromycin provided largely superior oral bioavailability and the advantage of obtaining the same efficacy against bacterial infections with a much lower dose of drug.


Increased risk of chronic obstructive pulmonary disease in patients with bipolar disorder: A population-based study.
We conducted this nationwide study to examine the prevalence and incidence of chronic obstructive pulmonary disease (COPD) among patients with bipolar disorder in Taiwan. We used a random sample of 766,427 subjects who were aged ≥18 years in 2005. Patients with at least one primary diagnosis of bipolar disorder were identified. Study participants with one primary or secondary diagnosis of COPD for either ambulatory or inpatient care were also identified. We compared the prevalence of COPD in patients with bipolar disorder and the general population in 2005. In addition, we further investigated this cohort from 2006 to 2010 to detect incident cases of COPD in patients with bipolar disorder compared with the general population. The factors associated with COPD among patients with bipolar disorder were also analyzed. The prevalence of COPD in patients with bipolar disorder was higher than in the general population in 2005 (5.68% vs. 2.88%, odds ratio 2.03; 95% confidence interval, 1.53-2.67). The average annual incidence of COPD in patients with bipolar disorder was also higher than in the general population (2.03% vs. 1.03%, risk ratio 1.94; 95% confidence interval, 1.65-2.29) from 2006 to 2010. Some risk factors for COPD such as substance use, obesity, or lifestyle pattern were not available in this study. Patients with bipolar disorder had a higher prevalence and incidence of COPD compared with the general population. Higher prevalence of COPD among bipolar patients was associated with increased age, males, hypertension, and second-generation antidepressant use.


Pygoscelis antarcticus feathers as bioindicator of trace element risk in marine environments from Barton Peninsula, 25 de Mayo (King George) Island, Antarctica.
We report the contents of elements in feathers of Chinstrap penguin (Pygoscelis antarcticus), which had not been informed up to now, such as silver and bromine and others listed as hazardous by the United States Environmental Protection Agency as arsenic, cobalt, chromium, and mercury. Analyses of the element concentrations in feathers, adult and chicken, from Barton Peninsulas at 25 de Mayo (King George) Island, South Shetlands, were made by Instrumental Neutron Activation Analysis. Samarium, lanthanum a, thorium, and uranium concentrations in Chinstrap penguin feathers were below 0.1 mg/kg. This suggests that the elements in feather do not come from atmospheric particles surface deposition. Arsenic (0.120 ± 0.050 mg/kg) and cobalt (0.030 ± 0.020 mg/kg) concentrations were lower than the reports for other colony of Chinstrap penguins, and essential elements as iron (26 ± 12 mg/kg), zinc (78.0 ± 5.3 mg/kg), and chromium (0.51 ± 0.27 mg/kg) were in the same range while Se (2.90 ± 0.65 mg/kg) content were the lowest reported. Mercury (0.43 ± 0.21 mg/kg), chromium (0.210 ± 0.060 mg/kg), and silver (0.083 ± 0.003 mg/kg) in chicks tended to be lower than in adults. Iron, cobalt, and arsenic concentrations in feathers found in this study were the lowest compared to measurements were in several penguin species in Antarctica. These results confirm to feathers like effective indicators for the trace elements incorporated in the penguins and it provide a data set which can adds to the baseline for bioindication studies using feathers.


Antibiotic resistance: a view from the prescriber.
Antibiotic resistance is increasingly affecting the management of infectious diseases. The prescribing clinician is not only important to the development of the problem but also central to its solution. This article addresses the current weaknesses in the information systems and the evidence base that support prescribing. Remedies necessary for improvements in prudent prescribing include better guidance in managing specific diseases where resistance is of prognostic significance and also increasing diagnostic precision.


The New Zealand Neuromuscular Disease Registry: rate of diagnoses confirmed by molecular testing.
The New Zealand Neuromuscular Disease Registry (NZ NMD Registry) is part of the TREAT NMD Alliance, an international network that provides infrastructure ensuring the most promising new therapies reach neuromuscular patients as quickly as possible. Its main aim is to ensure that the most promising new therapies reach patients as quickly as possible. From the perspective of researchers interested in trialling treatments it is useful to have data on the pool of potential research participants. From a patient's perspective it is important to know what trials they can take part in. Both of these require a confirmed molecular diagnosis in the patient. Some therapeutic strategies not only require knowledge of which gene is affected but are targeted at specific mutations within the gene. In reviewing data held in the NZ NMD Registry it was noted that, of those diagnosed with a genetic condition, only 51% have a confirmed molecular genetic diagnosis. This low rate of genetic diagnosis is a potential barrier to research participation but can be removed with improved genetic technology and with changes in knowledge about and attitudes towards genetic testing.


Lower Center Edge Angle and Bioipolar Cartilage Lesions Are Associated With Conversion to Hip Arthroplasty Within 2 Years Following Hip Arthroscopy: A Matched Cohort Analysis.
The purpose of this study was to determine whether radiographic parameters, intraoperative findings, patient-reported outcome measures, or intraoperative interventions that were performed differentiate those patients with >2 mm of joint space who convert under two years to total hip arthroplasty (THA) after undergoing hip arthroscopy for femoroacetabular impingement (FAI) when compared to those converting after 2 years. Included in this study were patients who underwent conversion to THA within 2 years of primary hip arthroscopy from a prospectively collected patient registry from 2007 to 2017. Patients who underwent early conversions to arthroplasty were matched 1:1 with patients who converted after 2 years, based upon age and gender. Preoperative outcome scores were collected, including Short Form-12, modified Harris Hip Score, and Hip Outcome Score. Additionally, variables from the preoperative radiographic evaluation, surgical findings, and procedures performed were also compared. Forty-nine patients were included in the early conversion group and were matched with 49 patients in the later conversion group. Patients with lateral center edge angles of less than 25° were more likely to be in the early failure group [OR: 3.9; 95% CI: 1.01 to 15]. Patients with unipolar chondral defects on either the femoral (P = .128) or acetabular side (P = .656) were not at increased odds for early conversion compared to later conversion; however, those with bipolar chondral lesions at the time of surgery had increased odds of early conversions [OR: 3.3; 95% CI: 1.4 to 8] (P = .01). Neither surgical treatment nor preoperative patient-reported outcome measures were associated with early conversion. In patient with >2 mm of joint space, lateral center edge angles of less than 25° and those with bipolar articular cartilage lesions seen at the time of hip arthroscopy are at increased risk for conversion to total hip arthroplasty within two years. Level III, retrospective comparison study.


Genomic structure and mapping of the chromosomal gene for transcobalamin I (TCN1): comparison to human intrinsic factor.
Transcobalamin I (TCI) is a vitamin B12 binding protein that is found in the secondary granules of mature neutrophils. The expression of the gene for TCI (TCN1) within neutrophils has been shown to be restricted to the later stages of myeloid development and can therefore be used as a marker for granulocyte differentiation. To study transcriptional control regions important in late stage myeloid gene regulation the genomic sequence for TCN1 has been cloned. Clones were isolated from a genomic library constructed in Charon 4A using homologous full-length cDNA probes. Southern blot analysis showed the gene to reside on five EcoRI fragments totaling 14 kb in length. Two overlapping phage clones, containing the entire 14 kb, were isolated and the introns and exons were mapped using Southern blotting and dideoxy sequencing of subclones. The cDNA is represented by nine exons contained within 12 kb of genomic DNA. Comparison of the genomic structure to gastric intrinsic factor (GIF), another vitamin B12 binding protein, revealed a strikingly similar intron/exon structure, with several positionally conserved splice sites. The gene was localized to chromosome 11 using in situ hybridization.


Improved mechanical performance of self-adhesive resin cement filled with hybrid nanofibers-embedded with niobium pentoxide.
In this study hybrid nanofibers embedded with niobium pentoxide (Nb2O5) were synthesized, incorporated in self-adhesive resin cement, and their influence on physical-properties was evaluated. Poly(D,L-lactide), PDLLA cotton-wool-like nanofibers with and without silica-based sol-gel precursors were formulated and spun into submicron fibers via solution blow spinning, a rapid fiber forming technology. The morphology, chemical composition and thermal properties of the spun fibers were characterized by field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC), respectively. Produced fibers were combined with a self-adhesive resin cement (RelyX U200, 3M ESPE) in four formulations: (1) U200 resin cement (control); (2) U200+1wt.% PDLLA fibers; (3) U200+1wt.% Nb2O5-filled PDLLA composite fibers and (4) U200+1wt.% Nb2O5/SiO2-filled PDLLA inorganic-organic hybrid fibers. Physical properties were assessed in flexure by 3-point bending (n=10), Knoop microhardness (n=5) and degree of conversion (n=3). Data were analyzed with One-way ANOVA and Tukey's HSD (α=5%). Composite fibers formed of PDLLA-Nb2O5 exhibited an average diameter of ∼250nm, and hybrid PDLLA+Nb2O5/SiO2 fibers were slightly larger, ∼300nm in diameter. There were significant differences among formulations for hardness and flexural strength (p<0.05). Degree of conversion of resin cement was not affected for all groups, except for Group 4 (p<0.05). Hybrid reinforcement nanofibers are promising as fillers for dental materials. The self-adhesive resin cement with PDLLA+Nb2O5 and PDLLA+Nb2O5/SiO2 presented superior mechanical performance than the control group.


Adverse childhood experiences, chronic diseases, and risky health behaviors in Saudi Arabian adults: a pilot study.
Adverse childhood experiences (ACEs) have been linked with risky health behaviors and the development of chronic diseases in adulthood. This study examined associations between ACEs, chronic diseases, and risky behaviors in adults living in Riyadh, Saudi Arabia in 2012 using the ACE International Questionnaire (ACE-IQ). A cross-sectional design was used, and adults who were at least 18 years of age were eligible to participate. ACEs event scores were measured for neglect, household dysfunction, abuse (physical, sexual, and emotional), and peer and community violence. The ACE-IQ was supplemented with questions on risky health behaviors, chronic diseases, and mood. A total of 931 subjects completed the questionnaire (a completion rate of 88%); 57% of the sample was female, 90% was younger than 45 years, 86% had at least a college education, 80% were Saudi nationals, and 58% were married. One-third of the participants (32%) had been exposed to 4 or more ACEs, and 10%, 17%, and 23% had been exposed to 3, 2, or 1 ACEs respectively. Only 18% did not have an ACE. The prevalence of risky health behaviors ranged between 4% and 22%. The prevalence of self-reported chronic diseases ranged between 6% and 17%. Being exposed to 4 or more ACEs increased the risk of having chronic diseases by 2-11 fold, and increased risky health behaviors by 8-21 fold. The findings of this study will contribute to the planning and development of programs to prevent child maltreatment and to alleviate the burden of chronic diseases in adults.


Effect of probiotic, prebiotic, and synbiotic on the gut microbiota of autistic children using an in vitro gut microbiome model.
Imbalances in gut microbiota composition occur in individuals with autism spectrum disorder (ASD). The administration of probiotics, prebiotics, and synbiotics is emerging as a potential and promising strategy for regulating the gut microbiota and improving ASD-related symptoms. We first investigated the survival of the probiotics Limosilactobacillus (L.) reuteri and Bifidobacterium (B.) longum alone, mixed and combined with a galacto-oligosaccharide (GOS) under simulated gastrointestinal conditions. Next, we evaluated the impact of probiotics (L. reuteri + B. longum), prebiotic (GOS), and synbiotic (L. reuteri + B. longum + GOS) on gut microbiota composition and metabolism of children with ASD using an in vitro fermentation model (SHIME®). The combination of L. reuteri, B. longum, and GOS showed elevated gastrointestinal resistance. The probiotic, prebiotic, and synbiotic treatments resulted in a positive modulation of the gut microbiota and metabolic activity of children with ASD. More specifically, the probiotic treatment increased the relative abundance of Lactobacillus, while the prebiotic treatment increased the relative abundance of Bifidobacterium and decreased the relative abundance of Lachnoclostridium. Changes in microbial metabolism were associated with increased short-chain fatty acid concentrations and reduced ammonium levels, particularly in the prebiotic and synbiotic treatments.


Radioactive impact of Fukushima accident on the Iberian Peninsula: evolution and plume previous pathway.
High activity concentrations of several man-made radionuclides (such as (131)I, (132)I, (132)Te, (134)Cs and (137)Cs) have been detected along the Iberian Peninsula from March 28th to April 7th 2011. The analysis of back-trajectories of air masses allowed us to demonstrate that the levels of manmade radionuclide activity concentrations in the southwest of the Iberian Peninsula come from the accident produced in the nuclear power plant of Fukushima. The pathway followed by the radioactive plume from Fukushima into Huelva (southwest of the Iberian Peninsula) was deduced through back-trajectories analysis, and this fact was also verified by the activity concentrations measured of those radionuclides reported in places crossed by this radioactive cloud. In fact, activity concentrations reported by E.P.A., and by IAEA, in several places of Japan, Pacific Ocean and United States of America are according to the expected ones from the air mass trajectory arriving at Huelva province.


Inhibitory effect of ouabain and acetazolamide on secretin-stimulated pancreatic exocrine secretion in anaesthetized dog.
1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were added together, the inhibitory effects were significantly higher than for each drug alone. 3. The bicarbonate concentration in the pancreatic juice was decreased and the chloride concentration was increased by ouabain and acetazolamide, but sodium and protein concentrations were not modified. 4. The results suggest that the Na+,K+-ATPase and carbonic anhydrase activities play important roles in water and electrolyte secretion, and that ouabain and acetazolamide inhibit secretin-stimulated pancreatic secretion by acting on different systems in the exocrine cells in dogs.


Use of academic electronic medical records in nurse education: A scoping review.
Use of academic electronic medical records is internationally recognised as a means for preparing health professional students for the digital healthcare environment. Reported practice benefits include skills for electronic documentation, health informatics, point-of-care clinical decision support systems, as well as preparation for information technology-enabled clinical settings, while challenges include lack of access to simulation software, faculty-related barriers, limited finances and educational software costs. However, little is known about best practices related to its use within pre-licensure or entry-to-practice nursing curricula and impact on clinical practice outcomes. This review sought to explore how academic electronic medical records are used in entry-to-practice nursing curricula. A scoping review guided by the Joanna Briggs Institute three-step search strategy, exploring existing publications and grey literature. Quantitative and qualitative studies related to use of academic electronic medical records in pre-licensure nurse education. A range of databases were searched including CINAHL, Medline, Proquest Central, ERIC, ScienceDirect, PubMed, IOS Press, as well as grey literature, reference lists and handsearching. The search yielded 580 articles, from which inductive thematic analysis of 34 included studies was conducted. Included articles were nine qualitative, 21 quantitative and five mixed methods studies. Most originated from the USA. Academic electronic medical records are mainly used to teach documentation, safe use of health technology, and for clinical preparation. Most are used for fundamental or junior levels courses, with problem-based learning and simulation embedded. Institution's technology resources and faculty capability are essential to implementation. There is a need for more research that examines optimal timing and duration of use of academic electronic medical records in curricula, and their impact on critical thinking and clinical performance. Finally, there is a need to explore greater academic-clinical partnerships in the education process.


In vivo transcription of rRNA operons in Escherichia coli initiates with purine nucleoside triphosphates at the first promoter and with CTP at the second promoter.
32P-labeled RNA was isolated from growing Escherichia coli and the 5' end nucleoside triphosphates of rRNA were analyzed after hybridization to various DNA fragments derived from one of the rRNA operons, rrnE. The results show that there are two transcription start sites for each rRNA operon in vivo, one initiating with ATP (or GTP), and the second initiating with CTP. Transcription from the first site was observed to be stronger than that from the second site. These two sites correspond to the two promoters identified in the previous in vitro studies, indicating that the two promoters are used in vivo. These results also demonstrate previously unrecognized transcription initiation with CTP in growing E. coli cells.


Expression of a whey acidic protein transgene during mammary development. Evidence for different mechanisms of regulation during pregnancy and lactation.
Expression of the mouse whey acidic protein (WAP) gene is specific to the mammary gland, is induced several thousand-fold during pregnancy, and is under the control of steroid and peptide hormones. To study developmental regulation of the mouse WAP gene, a 7.2-kilobase (kb) WAP transgene, including 2.6 kb of 5'- and 1.6 kb of 3'-flanking sequences, was introduced into mice. Of the 13 lines of mice examined, 6 expressed the transgenes during lactation at levels between 3 and 54% of the endogenous gene. Although expression was dependent on the site of integration, the transgenes within a given locus were expressed in a copy number-dependent manner and were coordinately regulated. The WAP transgenes were expressed specifically in the mammary gland, but showed a deregulated pattern of expression during mammary development. In all six lines of mice, induction of the WAP transgenes during pregnancy preceded that of the endogenous gene. During lactation, expression in two lines increased coordinately with the endogenous gene, and in three other lines of mice, transgene expression decreased to a basal level. These data indicate that the 7.2-kb gene contains some but not all of the elements necessary for correct developmental regulation. At a functional level it appears as if a repressor element, which inactivates the endogenous gene until late pregnancy, and an element necessary for induction during lactation are absent from the transgene. Complementary results from developmental and hormone induction studies suggest that WAP gene expression during pregnancy and lactation is mediated by different mechanisms.