A Balancing Act: A Systematic Review and Metasynthesis of Family-Focused Practice in Adult Mental Health Services.
Parental mental illness is a major international public health concern given its implications for whole families, including children. Family-focused practice (FFP), an approach that emphasises a "whole-family" approach to care, provides an opportunity to mitigate the significant risks associated with parental mental health difficulties. The positive benefits associated with FFP have led to a shift in policy and practice towards prioritising FFP within adult mental health services. However, evidence suggests that FFP remains scarce and is not routine. Research has identified the important role of practitioners in facilitating FFP. The current review identified, synthesised and appraised the international qualitative literature examining adult mental health practitioners' implementation experiences of FFP. It aimed to provide an evidence-informed account of practitioner experiences of FFP delivery and to identify key recommendations to enhance future FFP outcomes in AMHS. Ovid Medline, PsycInfo, CINAHL plus, EMBASE and Web of Science Core Collection were searched systematically, in line with PRISMA guidance, up to January 2022. The Critical Appraisal Skills Programme (CASP) was used to undertake the quality appraisal prior to a thematic synthesis being conducted. The review was registered on PROSPERO. Nineteen papers, spanning 17 years of research with 469 practitioners, were included. Three main themes and 14 subthemes were developed, representing different aspects of practitioner experiences of FFP delivery. Practitioners' approach to FFP was variable and influenced by their beliefs about FFP, perceived roles and responsibilities, competence, service setting, and personal parenting status. Practitioners engaged in a balancing act to maintain a dual focus on their service-users and their children, to navigate powerful emotions, and consider multiple perspectives in a biomedical organisational structure that advocates individualised treatment. Although working together unified teams, a greater need for external interagency collaboration was identified. The use of strength-based approaches with clients and dedicated staff resources, within clear guidelines and frameworks, was reported to be necessary to maximise FFP delivery. This review proposes a complex FFP dynamic whereby practitioners engage in a constant balancing act between FFP stakeholders to achieve meaningful FFP outcomes for service-users and their families. Service recommendations are provided.


Performance of limited sampling strategies for predicting mycophenolic acid area under the curve in thoracic transplant recipients.
Eight limited sampling strategies (LSSs) for estimating mycophenolic acid area under the concentration-time curve (4 developed from lung transplant recipients at our center, 4 developed for heart transplant recipients from other research groups) were evaluated in 27 heart or heart-kidney transplant patients. The LSSs from our lung transplant patients performed well when applied to the heart transplant population, with percent bias and percent precision within the acceptable limit of +/-15%. The LSSs developed at our center are robust enough to be applied to both lung and heart transplant populations. Application of LSSs from other research groups yielded less optimal results, reinforcing the need to re-establish or re-validate LSSs for each specific center.


How to ascertain the importance of autotrophic denitrification process in a bioelectrochemical system.
The ratio of autotrophic denitrification (Rauto) is proposed as a metric to better evaluate the nitrate removal efficiency of bioelectrochemical systems (BESs). Two methods for computing Rauto were compared, one based on electron charge transfer and the other on a controlled reaction. The experiment was conducted in a greenhouse with a temperature of 30±2 °C. A reaction with a constant voltage supply was used as a BES and open circuit control was used for the controlled reaction. The results indicated that calculating the Rauto based on electron charge transfer was more suitable for evaluating the performance of BESs. Further discussion about the factors influencing the result of this computing method is presented.


Method to estimate the rate and extent of intestinal absorption in conscious rats using an absorption probe and portal blood sampling.
A variety of methods exist which determine the rate and extent of intestinal absorption. The method described here employs an internal absorption reference probe and portal blood sampling in unanesthetized rat. Theophylline and tritiated water were selected as absorption reference probes since they are quantitatively absorbed in conscious rat. The fraction of an intestinal dose which reaches portal blood was determined from the resulting portal-systemic blood concentration gradients of the drug relative to the absorption probe. The absorption probes provide a means to calculate the drug mass reaching portal blood without the need of measuring the portal blood flow rate. The technique was evaluated with verapamil and a well-absorbed 5-lipoxygenase inhibitor, A-79035. The fraction of an intrajejunal dose of A-79035 reaching the portal vein (FG) was 0.86 using theophylline as the absorption probe. Verapamil, which is susceptible to extensive hepatic first-pass elimination, was completely absorbed (FG = 0.98) within 1 hour, but was only 21.4% bioavailable. Absorption rate constants, estimated from initial appearance rates in portal blood, were used to monitor factors that affect drug absorption. For example, with a dose solution containing 30% PEG-400, the absorption rate constants of theophylline and A-79035 were significantly reduced. Anesthesia reduced the absorption rate constant for theophylline in rats by 40% compared to conscious animals. The technique detailed here allows reliable, direct measurement of intestinal absorption which may assist in characterizing oral dosing for novel therapeutic agents.


Impact of Adapted Sports Activities on the Progression of Carotid Atherosclerosis in Subjects With Spinal Cord Injury.
To determine whether regular performance of adapted sports is associated with long-term changes in carotid atherosclerosis in subjects with spinal cord injury (SCI). Prospective observational study. Academic medical center. Men with chronic (>1y) SCI and no preserved motor function below the injury level were evaluated in 2007 and 2012 (N=17). Nine subjects did not perform physical activity between the studied time points (control group), whereas 8 subjects entered competitive upper-body sports programs (rugby: n=5, basketball: n=1, jiu-jitsu: n=1, and tennis: n=1) after baseline and were regularly training at the time of the second evaluation (sports group). Not applicable. Clinical, laboratory, hemodynamic, and carotid ultrasonography analysis. The studied groups showed no differences in all studied variables at baseline. After 5 years of follow-up, the control group showed increases in heart rate (87.0±3.1 vs 74.7±3.8 beats per minute; P=.004), but the participants had no significant changes in carotid intima-media thickness (IMT) (.65±.05 vs .67±.03mm; P=.73) or IMT/diameter (.118±.007 vs .136±.013; P=.24). In contrast, the sports group showed long-term decreases in carotid IMT (.56±.05 vs .74±.05mm; P=.001) and IMT/diameter (.097±.006 vs .141±.009; P<.001), but the participants did not show any variation in the other studied variables at follow-up. Regular upper-body sports activities are associated with long-term reductions in carotid atherosclerosis in subjects with SCI and might be a potential prevention strategy aiming to reduce cardiovascular risk in this population.


Patient-Specific Implants in Orthognathic Surgery.
Virtual surgical planning and three-dimensional (3D) printing have broadened the horizons of oral and maxillofacial surgery, including orthognathic surgery. 3D-printed personalized surgical guide and patient-specific implant (PSI) not only serve to guide accurate osteotomies and as a good fitting of osteosynthesis plate, but more importantly define a revolutionary waferless approach concept that is totally different from the conventional wafer-guided jaw fixation technique. This review discusses the limitations of the conventional orthognathic approach, and how PSI may overcome these limitations, improve accuracy, and bring additional benefits in the execution of orthognathic surgery.


Should we reframe how we think about physical activity and sedentary behaviour measurement? Validity and reliability reconsidered.
The measurement of physical activity (PA) and sedentary behaviour (SB) is fundamental to health related research, policy, and practice but there are well known challenges to these measurements. Within the academic literature, the terms "validity" and "reliability" are frequently used when discussing PA and SB measurement to reassure the reader that they can trust the evidence. In this paper we argue that a lack of consensus about the best way to define, assess, or utilize the concepts of validity and reliability has led to inconsistencies and confusion within the PA and SB evidence base. Where possible we propose theoretical examples and solutions. Moreover we present an overarching framework (The Edinburgh Framework) which we believe will provide a process or pathway to help researchers and practitioners consider validity and reliability in a standardized way. Further work is required to identify all necessary and available solutions and generate consensus in our field to develop the Edinburgh Framework into a useful practical resource. We envisage that ultimately the proposed framework will benefit research, practice, policy, and teaching. We welcome critique, rebuttal, comment, and discussion on all ideas presented.


Randomized clinical trial of laparoscopic versus open fundoplication: blind evaluation of recovery and discharge period.
There is a widespread belief that introduction of the laparoscopic technique in antireflux surgery has led to easier postoperative recovery. To test this hypothesis a prospective randomized clinical trial with blind evaluation was conducted between laparoscopic and open fundoplication. Sixty patients with gastro-oesophageal reflux disease were randomized to open or laparoscopic 360 degrees fundoplication. The type of operation was unknown to the patient and the evaluating nurses after operation. The operating time was longer in the laparoscopy group, median 148 versus 109 min (P < 0.0001). The need for analgesics was less in the laparoscopically operated patients, 33.9 versus 67.5 mg morphine per total hospital stay (P < 0.001). There was no significant difference in postoperative nausea and vomiting. On the first day after operation patients in the laparoscopy group had better respiratory function: forced vital capacity 3.2 versus 2. 2 litres (P = 0.004) and forced expiratory volume 2.6 versus 2.0 litres (P = 0.008). Postoperative hospital stay was shorter in the laparoscopic group, median (range) 3 (2-6) versus 3 (2-10) days (P = 0.021). No difference was found in the duration of sick leave. Laparoscopic fundoplication was associated with a longer operating time, better respiratory function, less need for analgesics and a shorter hospital stay, while no reduction in the duration of postoperative sick leave was found compared with open surgery.


Making the CEHRT Switch: EHR Upgrade Required for Incentive Payment Programs.
In medicine, a lot of things can be stressful. Done right, the switch to the latest certified electronic health record technology (CEHRT) doesn't have to be one of them. The change is inevitable in the coming year for physicians already using EHRs to participate in Medicare or Medicaid incentive payment programs. Most practices are using the 2014 version. Beginning in 2019, physicians must use 2015 CEHRT for the 2019 performance period, which ultimately determines their payment.


Secretion of collagen I and tenascin is modulated by laminin-111 in 3D culture of human adenoid cystic carcinoma cells.
Adenoid cystic carcinoma is a frequent malignant salivary gland neoplasm with high levels of recurrence and metastasis. This neoplasm expresses prominent extracellular matrix (ECM). We are studying regulatory mechanisms underlying secretion of ECM molecules in adenoid cystic carcinoma. We have previously demonstrated that laminin modulates the phenotype of a human adenoid cystic carcinoma (CAC2) cell line. Thus, this molecule would be a good candidate to regulate secretion of ECM molecules in these cells. Here we analysed the role played by laminin-111 [formerly laminin-1; Aumailley et al. (2005). Matrix Biol. 24, 326] stimulating secretory activity of CAC2 cells. Three-dimensional cultures of cells in laminin-111 (treated) or agarose (controls) were studied by light and electron microscopy. Ultrastructural analysis of CAC2 cells grown within laminin-111 showed pseudocysts filled with secretory-like material. Cells exhibited prominent and dilated endoplasmic reticulum and coated and uncoated vesicles. Ultrastructural findings suggested that laminin-111 induced secretory activity in CAC2 cells. We further investigated this point by light microscopy, immunofluorescence and confocal microscopy. Histochemistry showed periodic acid-Schiff (PAS)-positive diastase-resistant material in CAC2 cells treated by laminin-111. This material could represent laminin-induced secretion of ECM molecules. We searched for collagen I and tenascin in CAC2 cells treated by laminin-111. Confocal microscopy and immunoblot showed that laminin-111 enhanced secretion of collagen I and tenascin in CAC2 cells. We suggest that laminin-111 modulates secretion of collagen I and tenascin in cells derived from human adenoid cystic carcinoma.


Value chain management under COVID-19: responses and lessons from grape production in India.
The COVID-19 pandemic has affected several economic sectors in India, dragging many to the brink of survival. In particular, the already fragile horticulture industry is now facing a double burden of a weak value chain management system as well as perishability of produce (fresh fruits and vegetables), this pandemic season. Also, the strict enforcement of lockdown has altered both demand and supply factors, which in turn have shocked various linkages in the value chain of fresh fruits and vegetables. So, this paper dissects the value chain management of grapes and its processed products, namely juice, wine, and raisins in Maharashtra, the largest producer of grapes in India. For this, a value chain analysis (VCA) is carried out by computing the degree of value addition to uncover the rupture points caused by the pandemic as well as advocate policy measures to build a resilient system. The value chain analysis shows that post-COVID-19, the degree of value addition, has shot up for the intermediary agents, i.e., pre-harvest contractors, at the expense of the farmers. Using the insights from the VCA results plus the demand and supply shocks, various policy measures are elucidated to strengthen the grape value chain.


Gadolinium containing photochromic micelles as potential magnetic resonance imaging traceable drug carriers.
Novel photochromic amphipathic molecules, KMR-AZn (Gd-DTPA-AZCn), composed of hydrophilic Gd-DTPA and hydrophobic alkylated azobenzene were prepared. In aqueous environment, KMR-AZn indicated self-assembly. The resulting aggregates were demonstrated to be able to include a hydrophobic drug substitute (hydrophobic fluorescent dye) into the internal core, and to release the included compound upon photoirradiation within 10 min through the influence of azobenzene photoisomerization. This micellar MRI contrast agent exhibited three- to four-fold higher r(1) relaxivity (r(1) = 14.5-16.5 mM(-1) s(-1), 0.47 T at 40°C) than the widely applied small molecule contrast agent Gd-DTPA (Magnevist(®) r(1) = 4.1 mM(-1) s(-1), 0.47 T at 40°C). This dual functionality of encapsulated compound release and increased MR imaging contrast indicates that KMR-AZn is a potential candidate for application as a lipid-based MRI-traceable drug carrier.


Development of a Core outcome set for fetal Myelomeningocele (COSMiC): study protocol.
Open spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, but is associated with a significant risk of prematurity and maternal morbidity. Fetoscopic surgery comes with less maternal morbidity, yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies. The COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify outcomes previously reported for prenatally diagnosed OSB. We will assess maternal (primary and subsequent pregnancies), fetal, neonatal and childhood outcomes until adolescence. In a second phase, we will conduct semi-structured interviews with stakeholders, to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists/paediatricians and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential online rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a face-to-face consensus meeting with all stakeholder groups. Dissemination of the final COS will be ensured through different media and relevant societies. Development and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long-term childhood outcomes. International Prospective Register of Systematic Reviews (PROSPERO) CRD42018104880 . Registered on December 5, 2018. Core Outcome Measures in Effectiveness Trials (COMET): 1187.


Comparing restrictive versus liberal oxygen strategies for trauma patients - the TRAUMOX2 trial: protocol for a randomised clinical trial.
Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma. TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO2 of 94%. The liberal group receives 12-15 L O2/min or FiO2=0.6-1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group. TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal. EudraCT 2021-000556-19; NCT05146700.


A pilot study of evaluation of semi-rigid and flexible catheters for less invasive surfactant administration in preterm infants with respiratory distress syndrome-a randomized controlled trial.
In respiratory distress syndrome, many neonatology centers worldwide perform minimal invasive surfactant application in premature infants, using small-diameter catheters for endotracheal intubation and surfactant administration. In this single-center, open-label, randomized-controlled trial, preterm infants requiring surfactant administration after birth, using a standardized minimal invasive protocol, were randomized to two different modes of endotracheal catheterization: Flexible charrière-4 feeding tube inserted using Magill forceps (group 1) and semi-rigid catheter (group 2). Primary outcome was duration of laryngoscopy. Secondary outcomes were complication rate (intraventricular hemorrhage, soft-tissue damage in first week of life) and vital parameters during laryngoscopy. Between 2019 and 2020, 31 infants were included in the study. Prior to in-vivo testing, laryngoscopy durations were studied on a neonatal airway mannequin in students, nurses and doctors. Mean gestational age and birth weight were 27 + 6/7 weeks and 1009 g; and 28 + 0/7 weeks and 1127 g for group 1 and 2, respectively. Length of laryngoscopy was similar in both groups (61.1 s and 64.9 s) overall (p.77) and adjusted for weight (p.70) or gestational age (p.95). Laryngoscopy failed seven times in group 1 (43.8%) and four times (26.7%) in group 2 (p.46). Longer laryngoscopy was associated with lower oxygen saturation with lowest levels occurring after failed laryngoscopy attempts. Secondary outcomes were similar in both groups. In vitro data on 40 students, 40 nurses and 12 neonatologists showed significant faster laryngoscopy in students and nurses group 2 (p < .0001) unlike in neonatologists (p.13). This study showed no difference in laryngoscopy duration in endotracheal catheterization when comparing semi-rigid and flexible catheters for minimal invasive surfactant application in preterm infants. In accordance with preliminary data and in contrast to published in-vitro trials, experienced neonatologists were able to perform endotracheal catheterization using both semi-rigid and flexible catheters at similar rates and ease, in vitro and in vivo. ClinicalTrials.gov. NCT05024435 Registered 27 August 2021-Retrospectively registered.


Duration of the reproductive period decreases the frequency of preovulatory luteinizing hormone surges in heavy weight-sire line turkey hens.
The frequency of preovulatory luteinizing hormone (LH) surges is an important determinant of ovulation and oviposition rates in turkeys. Egg production rate is relatively poor in heavy weight-sire line type turkey hens and declines with advancing duration of the reproductive period. The purpose of this study was to measure frequency and characteristics of preovulatory LH surges in turkey hens of a heavy weight-sire line type early, at peak of egg production (Early), and late, after egg production rate had declined (Late), in a reproductive period. The Early hens were photostimulated with a continuous photoperiod [24 h light (L):0 h dark (D)] at 40 weeks of age and sampled during peak egg production at about 47 weeks of age. The Late hens were photostimulated at 40 weeks of age with a long day photoperiod (14L:10D). After a 27-week egg production period, the Late hens were switched to the 24L:0D photoperiod and sampled at 74 weeks of age. Continuous lighting was used during blood sampling to allow the rhythm of preovulatory LH surges to free run. All hens were cannulated 3-5 days before starting sampling and hourly blood samples were collected for 200 h. All hens were necropsied and ovarian and oviductal morphologies were measured after serial bleeding. The Late hens had a longer interval between intra-clutch preovulatory LH surges than the Early hens, and a higher incidence of atretic ovarian follicles. The Early hens had higher baseline and surge amplitude LH concentrations but lower progesterone (P4) surge amplitude concentrations than the Late hens. The duration of preovulatory LH surges, incidence of "blind" preovulatory LH surges, baseline P4 concentrations, and overall estradiol-17beta (E2) concentrations were not different between Early and Late hens. In conclusion, a longer interval between preovulatory LH surges, lower LH baseline and surge amplitude concentrations, a higher incidence of atretic follicles, and higher P4 surge amplitude concentration were associated with the decline in egg production late in the reproductive period in a heavy weight-sire line of turkey hens.


Analysis of assembly of secreted mucins.
Studies of assembly and secretion of gel-forming mucins are complex. The pulse-chase methods for mucins described here include metabolic radiolabeling and labeling in animals with azido-GalNAc. The labeled mucins are analyzed by composite agarose-polyacrylamide gel electrophoresis and autoradiography or by mucus-preserving tissue fixation and Click-iT(®) chemistry.


Two-dimensional transport analysis of transdermal drug absorption with a non-perfect sink boundary condition at the skin-capillary interface.
A transient percutaneous drug absorption model was solved in two dimensions. Clearance of the topically-applied pharmaceutical occured at the skin-capillary boundary. Timolol penetration profiles in the dermal tissue were produced revealing concentration gradients in the directions normal and parallel to the skin surface. Ninety-eight percent of the steady-state flux was reached after 85 h or four time constants. The analytical solution procedure agreed with published results. As the clearance rate increased relative to diffusion, the delivery rate and amount of drug absorbed into the bloodstream increased while the time to reach the equilibrium flux decreased. Researchers can apply the closed-form expressions to simulate the process, estimate key parameters and design devices that meet specific performance requirements.


Fitness response variation within and among consumer species can be co-mediated by food quantity and biochemical quality.
In natural heterogeneous environments, the fitness of animals is strongly influenced by the availability and composition of food. Food quantity and biochemical quality constraints may affect individual traits of consumers differently, mediating fitness response variation within and among species. Using a multifactorial experimental approach, we assessed population growth rate, fecundity, and survival of six strains of the two closely related freshwater rotifer species Brachionus calyciflorus sensu stricto and Brachionus fernandoi. Therefore, rotifers fed low and high concentrations of three algal species differing in their biochemical food quality. Additionally, we explored the potential of a single limiting biochemical nutrient to mediate variations in population growth response. Therefore, rotifers fed a sterol-free alga, which we supplemented with cholesterol-containing liposomes. Co-limitation by food quantity and biochemical food quality resulted in differences in population growth rates among strains, but not between species, although effects on fecundity and survival differed between species. The effect of cholesterol supplementation on population growth was strain-specific but not species-specific. We show that fitness response variations within and among species can be mediated by biochemical food quality. Dietary constraints thus may act as evolutionary drivers on physiological traits of consumers, which may have strong implications for various ecological interactions.


Editorial Commentary: Please Simplify Hip Arthroscopy.
Hip arthroscopy is a challenging technical procedure for which basic science principles have not been thoroughly discerned with respect to the procedures we perform. In this commentary, a plea is made to continue to expand the science behind what we do, but in as simple a fashion as possible such that more surgeons are willing to learn perfect hip arthroscopy.


Molecular characterisation and diversity in Enterobacter cloacae from Edinburgh and Egypt carrying bla(CTX-M-14) and bla(VIM-4) β-lactamase genes.
The purpose of this study was to compare the carbapenemases and extended-spectrum β-lactamases (ESBLs) associated with resistance, the genetic environment of these genes, and their location on plasmids among Enterobacter cloacae isolates from Edinburgh (UK) and Egypt. Nine E. cloacae isolates were obtained from Egypt (n=3) and Edinburgh (n=6). Antimicrobial susceptibility testing was performed by agar dilution. Molecular detection of carbapenemase genes, blaCTX-M-14 and the presence of integron structures was done by PCR and sequencing. Genotyping of the strains was performed by pulsed-field gel electrophoresis (PFGE) with XbaI restriction. Plasmids were extracted to determine the location of the resistance genes. PCR sequencing revealed that all of the isolates carried the blaCTX-M-14 ESBL gene, whilst two isolates also carried the blaVIM-4 metallo-β-lactamase gene. The blaCTX-M-14 genes in two isolates were associated with the ISEcp1 transposase. Analysis of the integrons found an intI1 integron associated with the complex ISCR1. The blaVIM-4 gene was identified in the form of a gene cassette within the class 1 integron, followed downstream by the resistance genes aacA7, dfrA1 and aadA2. PFGE revealed genetic relatedness among six isolates, whereas the others were diverse although related. Plasmid analysis revealed a single plasmid carrying both blaVIM-4 and blaCTX-M-14. In conclusion, the presence of insertion sequence ISEcp1 upstream of blaCTX-M-14 suggests its involvement in the expression and mobilisation of this gene. Linked carriage of blaVIM-4 and blaCTX-M-14 on the same plasmid in E. cloacae results in resistance to all β-lactams and limits antibiotic treatment options.


Prognostic value of intratumoral vessel density in cutaneous mast cell tumors of the dog.
The biological behaviour of canine cutaneous mast cell tumours (MCTs) is highly variable. The aim of this study was to investigate whether intratumoral microvessel density (IMVD), as an indicator of angiogenesis, was predictive of biological behaviour in MCTs of canine skin, and to relate this parameter to histological grade and other histomorphological features. IMVD was evaluated by immunohistochemical labelling of the endothelial marker factor VIII (Von Willebrand's factor)-related antigen in 32 primary cutaneous MCTs. Computer image analysis was used to measure IMVD, expressed as the number of microvessels per square millimetre. Cases were assigned to low and high vessel density groups, the median value (14.1) being used as the "cut-off". Kaplan-Meier-estimated survival curves of the groups revealed that IMVD was significantly associated with survival time (P=0.046). One-way analysis of variance, performed to compare the IMVD values of tumours of different histological grades, showed a significant difference between grades I and III (P=0.0002). There was a significant difference in IMVD between moderately invasive and highly invasive tumours (P=0.002) and between tumours with different numbers of mitoses (P=0.0046). In multivariate analysis, performed to test the combined influence on survival of each parameter, only the mitotic index and IMVD were independent prognostic variables (P=0.00019). The relation of angiogenesis to biological behaviour and histological parameters of malignancy of cutaneous MCTs was consistent with previous findings in human and animal tumours.


Two different types of antimitochondrial antibodies (anti-M2 and anti-M4) may not differentiate primary biliary cirrhosis (PBC) with prominent piecemeal necrosis from classical PBC.
Clinical and morphological features in 13 patients with primary biliary cirrhosis (PBC) who had two different types of antimitochondrial antibodies (PBC-specific, anti-M2 and mixed-form, anti-M4) in serum tested, were studied. Patients were allocated to two groups purely on the basis of the presence or absence of prominent piecemeal necrosis (PN) to elucidate the clinical significance of PN for differentiating mixed forms of chronic active hepatitis and PBC from classical PBC. Histological staging showed 10 stage I and 3 stage II. All cases had histological features of chronic non-suppurative destructive cholangitis. Prominent PN was encountered in 8 and bridging hepatic necrosis in 6. Granulomas were present in all cases without PN, but only in 3 of 8 cases with PN. Antimitochondrial antibody (AMA) was positive in all cases and anti-M2 was also positive in all but one. On the contrary, anti-M4 was positive in 2. Both anti-M2 and anti-M4 were simultaneously positive in 2, of which PN was present in only one. Therefore, anti-M4 did not relate to the presence or morphological severity of PN in PBC. Simultaneous increases in IgG and IgM were prominent features in PBC with PN.


Performance assessment of microflow LC combined with high-resolution MS in bioanalysis.
There continues to be consistent pressure for bioanalytical scientists to achieve lower limits of quantitation. The reasons range from smaller sample volumes available for analysis, to more potent analytes and the growth of biologics in drug development. This has led scientists to investigate alternative LC techniques, including microflow and nanoflow. These techniques have been shown to increase sensitivity of electrospray methods and reduce ionization matrix effects. Because high-resolution MS has significant benefits for the analysis of biologics, this type of mass spectrometer is becoming increasingly important in bioanalysis. For microflow analysis, a new ion source and significant extra sample preparation or chromatographic separation are not required. However, increased sensitivity and reduced matrix effects were consistently demonstrated when compared with UHPLC flow rates. The extent of matrix effects observed were compound dependent. This paper presents the utility of combining high-resolution/accurate mass with microflow LC from a quantitative standpoint. This includes evaluating the typical quantitative parameters of sensitivity, linearity/dynamic range, precision and accuracy. It also includes the evaluation of changes in signal suppression using microflow LC and microspray ionization. The benefits and disadvantages of using the combination of these two technologies for quantitative bioanalysis are also discussed.


Compressive sampling with prior information in remotely detected MRI of microfluidic devices.
The design and operation of microfluidic analytical devices depends critically on tools to probe microscale chemistry and flow dynamics. Magnetic resonance imaging (MRI) seems ideally suited to this task, but its sensitivity is compromised because the fluid-containing channels in "lab on a chip" devices occupy only a small fraction of the enclosing detector's volume; as a result, the few microfluidic applications of NMR have required custom-designed chips harboring many detectors at specific points of interest. To overcome this limitation, we have developed remotely detected microfluidic MRI, in which an MR image is stored in the phase and intensity of each analyte's NMR signal and sensitively detected by a single, volume-matched detector at the device outflow, and combined it with compressed sensing for rapid image acquisition. Here, we build upon our previous work and introduce a method that incorporates our prior knowledge of the microfluidic device geometry to further decrease acquisition times. We demonstrate its use in multidimensional velocimetric imaging of a microfluidic mixer, acquiring microscopically detailed images 128 times faster than is possible with conventional sampling. This prior information also informs our choice of sampling schedule, resulting in a scheme that is optimized for a specific flow geometry. Finally, we test our approach in synthetic data and explore potential reconstruction errors as a function of optimization and reconstruction parameters.


[Fluorescent analogs of nucleoside-5'-phosphates for the study of nucleic acids by nonradioactive methods].
The synthesis of 2'-deoxyuridine 5'-triphosphate analogues with fluorescent residues of fluorescein and rhodamine nature at C5 of the uracil base was performed. Reverse transcriptase of avian myeloblastosis virus, DNA polymerase beta of rat liver, terminal deoxynucleotidyl transferase of calf thymus and E. coli DNA polymerase I, Klenow fragment, were shown to be capable to incorporate a nucleotide residue with fluorescent label into 3'-terminus of oligonucleotide. These fluorescent labeled oligonucleotides were used as primers for synthesis of (-)-chain of M13mp10 phage. Fluorescently labeling template-primer complexes were used for DNA sequencing.


Hypothyroidism, lipids, and lipidomics.
Hypothyroidism is a relatively common endocrine disorder and is well documented to be associated with lipid abnormalities. A narrative review was conducted of studies describing the alterations in the lipid profile accompanying both subclinical and overt hypothyroidism. Lipid abnormalities are seen with TSH values in the upper end of the accepted reference range, as well as with subclinical and overt hypothyroidism. The degree of lipid derangement is generally proportional to the degree of TSH elevation. Other factors such as age, sex, and body mass index can also influence the pattern of the lipid abnormalities seen. The most robust finding with TSH elevation is increases in the low density lipoprotein cholesterol. Thyroid hormone treatment is efficacious in reversing the lipid abnormalities in both subclinical and overt hypothyroidism. Given the association of lipid abnormalities with metabolic and cardiovascular disease, consideration of hypothyroidism as an important non-communicable disease may facilitate studies that test the hypothesis that thyroid hormone treatment to reverse hypothyroidism-associated lipid abnormalities may improve metabolic and cardiovascular outcomes.


Motor planning in Parkinson patients.
This study was designed to determine if Parkinsonian patients exhibited a deficit in motor planning. Thirty adult males, 15 with Parkinson's disease and 15 normal controls, were given a gestural test which had two components. The first component required the symbolic representation of implement usage on verbal command and on imitation (representational items) and the second component required the imitation of non-symbolic hand positions (non-representational items). The results indicated that Parkinsonian patients performed at a significantly lower gestural level on the representational tasks and made significantly more spatial errors on non-representational tasks than the normal controls.


Long-term exposure to fine particulate matter relates with incident myocardial infarction (MI) risks and post-MI mortality: A meta-analysis.
Air pollution has become a global challenge, and a growing number of studies have suggested possible relationships between long-term exposure to fine particulate matter (PM2.5) and risks of cardiovascular events, specifically, myocardial infarction (MI). However, the recently reported results were inconsistent. We thus performed a meta-analysis and sought to assess whether long-term exposure to PM2.5 relates with incident MI risks and post-MI mortality. EMBASE, Web of Science and PubMed were searched for all potentially eligible studies published before August 2, 2020 using a combination of keywords related to PM2.5 exposure, its long-term effects and myocardial infarction. Key information was extracted, and calculated hazard ratio (HR) values were combined by selecting corresponding models according to heterogeneity test. A sensitivity analysis and a publication bias assessment were also performed to determine the reliability of the results. Of the initially identified 2100 citations, 12 studies met our inclusion criteria and observed a total population of approximately 7.2 million. Pooled estimates (per 10 μg/m3 increase) indicated a statistically significant association between long-term PM2.5 exposure and MI incidence (HR = 1.10, 95% CI: 1.02-1.18) or post-MI mortality (HR = 1.07, 95% CI: 1.04-1.09). Results for MI incidence from Egger's linear regression method (P = 0.515) and Begg's test (P = 0.711) showed no obvious publication bias. Our quantitative analysis reveals a significant link between long-term PM2.5 exposure and greater MI incidence risks or higher post-MI mortality. Our findings may therefore have implications for individual protection and policy support to improve public health.


A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety.
Melittin is the main effective component of bee venom and has extensive biological functions; however, serious side effects have restricted its clinical application. Preclinical and clinical studies showed that the main adverse events were allergic reaction and pain at the administration site. To decrease the toxicity, we prepared melittin nano-liposomes by encapsulating melittin with poloxamer 188 and explored the inhibitory activities on liver cancer together with biological safety. Here, we showed that melittin nano-liposomes significantly inhibited the survival of hepatocellular carcinoma (HCC) cells in vitro and prominently suppressed the growth of subcutaneous and orthotopic HCC transplantation tumors in vivo. It was important that it induced less inflammation and allergy in mice compared with melittin. Overall, melittin nano-liposomes would have a better application in HCC therapy due to its significant anti-tumor activity and better biological safety.


Ca2+ channels as targets of neurological disease: Lambert-Eaton Syndrome and other Ca2+ channelopathies.
In the nervous system, voltage-gated Ca2+ channels regulate numerous processes critical to neuronal function including secretion of neurotransmitters, initiation of action potentials in dendritic regions of some neurons, growth cone elongation, and gene expression. Because of the critical role which Ca2+ channels play in signaling processes within the nervous system, disruption of their function will lead to profound disturbances in neuronal function. Voltage-gated Ca2+ channels are the targets of several relatively rare neurological or neuromuscular diseases resulting from spontaneously-occurring mutations in genes encoding for parts of the channel proteins, or from autoimmune attack on the channel protein responses. Mutations in CACNAIA, which encodes for the alpha1A subunit of P/Q-type Ca2+ channels, lead to symptoms seen in familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6. Conversely, autoimmune attack on Ca2+ channels at motor axon terminals causes peripheral cholinergic nerve dysfunction observed in Lambert-Eaton Myasthenic Syndrome (LEMS), the best studied of the disorders targeting voltage-gated Ca2+ channels. LEMS is characterized by decreased evoked quantal release of acetylcholine (ACh) and disruption of the presynaptic active zones, the sites at which ACh is thought to be released. LEMS is generally believed to be due to circulating antibodies directed specifically at the Ca2+ channels located at or near the active zone of motor nerve terminals (P/Q-type) and hence involved in the release of ACh. However, other presynaptic proteins have also been postulated to be targets of the autoantibodies. LEMS has a high degree of coincidence (approximately 60%) with small cell lung cancer; the remaining 40% of patients with LEMS have no detectable tumor. Diagnosis of LEMS relies on characteristic patterns of electromyographic changes; these changes are observable at neuromuscular junctions of muscle biopsies from patients with LEMS. In the majority of LEMS patients, those having detectable tumor, the disease is thought to occur as a result of immune response directed initially against voltage-gated Ca2+ channels found on the lung tumor cells. In these patients, effective treatment of the underlying tumor generally causes marked improvement of the symptoms of LEMS as well. Animal models of LEMS can be generated by chronic administration of plasma, serum or immunoglobulin G to mice. These models have helped dramatically in our understanding of the pathogenesis of LEMS. This "passive transfer" model mimics the electrophysiological and ultrastructural findings seen in muscle biopsies of patients with LEMS. In this model, we have shown that the reduction in amplitude of Ca2+ currents through P/Q-type channels is followed by "unmasking" of an L-type Ca2+ current not normally found at the motor nerve terminal which participates in release of ACh from terminals of mice treated with plasma from patients with LEMS. It is unclear what mechanisms underlie the development of this novel L-type Ca2+ current involved in release of ACh at motor nerve terminals during passive transfer of LEMS.


Metabolic alkalosis in hemodialysis patients.
Hemodialysis solutions typically contain a high alkali concentration designed to counter interdialytic acidosis, but this could result in persistent alkalosis in some patients. The prevalence and significance of persistent alkalosis were therefore examined at four outpatient centers over a 10-year period. Alkalosis was defined as a pre-dialysis serum [HCO3 ] ≥ 26 meq/L in >6 months of a 12-month period and was persistent if present in a majority of months thereafter. Control patients had a serum [HCO3 ] of 19-23 meq/L > 6 of every 12 months. Standard, citrate-containing dialysate was used in all patients without adjustment of bicarbonate concentration. 444 of 1271 patients had alkalosis that persisted in 73. Compared to control patients, persistently alkalotic patients were older, but gender, race, starting weight, comorbidities, and mortality did not differ. Dialysis dose was 7% greater, protein catabolic rate was 11% lower, and interdialytic weight gain was 29% lower, all p < 0.001. Persistently alkalotic patients had double the incidence of cardiac arrhythmias (p = 0.07) and a 20% greater intradialytic blood pressure decrease (p < 0.001). Alkalosis is common in hemodialysis patients and can be persistent, likely due to decreased protein catabolic rate and increased dialysis dose, and may have detrimental cardiovascular effects.


Detection of SARS-CoV-2 IgG Targeting Nucleocapsid or Spike Protein by Four High-Throughput Immunoassays Authorized for Emergency Use.
A total of 1,200 serum samples that were tested for SARS-CoV-2 IgG antibody using the Abbott Architect immunoassay targeting the nucleocapsid protein were run in 3 SARS-CoV-2 IgG immunoassays targeting spike proteins (DiaSorin Liaison, Ortho Vitros, and Euroimmun). Consensus-positive and consensus-negative interpretations were defined as qualitative agreement in at least 3 of the 4 assays. Agreement of the 4 individual assays with a consensus-negative interpretation (n = 610) ranged from 96.7% to 100%, and agreement with a consensus-positive interpretation (n = 584) ranged from 94.3% to 100%. Laboratory-developed inhibition assays were utilized to evaluate 49 consensus-negative samples that were positive in only one assay; true-positive reactivity was confirmed in only 2 of these 49 (4%) samples. These findings demonstrate very high levels of agreement among 4 SARS-CoV-2 IgG assays authorized for emergency use, regardless of antigen target or assay format. Although false-positive reactivity was identified, its occurrence was rare (no more than 1.7% of samples for a given assay).


Generation and potential biomedical applications of embryonic stem cell-derived glial precursors.
Recent progress in embryonic and adult stem cell research has opened new perspectives for generating large numbers of different neural cell types in vitro and using them for nervous system repair. Several lines of arguments suggest that myelin diseases represent particularly attractive targets for cell-based therapies. First, in contrast to neuronal cell replacement, a single and uniform cell type, the oligodendrocyte progenitor, suffices for therapeutic remyelination in all areas of the CNS, with no need for complex circuit integration. Second, there is an increasing understanding of the mechanisms regulating the recruitment of stem and progenitor cells into CNS lesions. Third, stem cells represent excellent vehicles for cell-mediated gene transfer, enabling novel approaches, which combine classic cell replacement with the delivery of therapeutic factors. Among the various donor sources, embryonic stem (ES) cells stand out as a population featuring pluripotency, unlimited self-renewal and amenability to gene targeting. Here we discuss the advantages, challenges and perspectives of bringing this unique cell type closer to a clinical application for treating myelin diseases and other neurological disorders.


A meta-review of qualitative research on adult cancer survivors: current strengths and evidence gaps.
The number of qualitative studies exploring cancer survivor experiences has significantly increased in recent years, with a large number of systematic reviews now published. This meta-review (systematic review of systematic reviews) aimed to assess the evidence base-summarising existing qualitative findings and identifying gaps for further research. Systematic reviews published from 1950 to 2018 were identified via database searches (MEDLINE, Embase, CINAHL, PsycINFO). Two authors assessed eligibility and extracted data. Review quality was assessed using the JBI Critical Appraisal Checklist for Systematic Reviews. A total of 1465 titles were retrieved, and 60 reviews were included in the final review. All included reviews were conducted between 1998 and 2018. Whilst many reviews included mixed cancer types (21), the majority included only one cancer type (breast (19), gynaecological (10), prostate (5), haematological (2), colorectal (1), bladder (1) and melanoma (1)). Reviews focused on several survivorship topic areas including quality of life, experiences of survivors from ethnic minorities, returning to work and experiences of survivorship healthcare services. Less frequently reviewed topics included fertility, body image, coping strategies and spirituality. This meta-review provides insight into the areas of research density and paucity. Breast and gynaecological cancer survivors are strongly represented. Gaps in synthesis include reviews for other common cancers (e.g. lung, colorectal, melanoma, haematological) as well as survivorship topic areas such as side/late effects, psychological issues, financial toxicity and health behaviours. Qualitative research into cancer survivor experiences can guide intervention development, as well as provide survivors with insight into the experiences and challenges faced by others with cancer.


High-Throughput Identification and Screening of Single Microbial Cells by Nanobowl Array.
High-throughput screening and fast identification of single bacterial cells are crucial for clinical diagnosis, bioengineering, and fermentation engineering. Although single-cell technologies have been developed extensively in recent years, the single-cell technologies for bacteria still need further exploration. In this study, we demonstrate an identification and screening technology for single bacterial cells based on a large-scale nanobowl array, which is well-ordered and size-adjustable for use with different kinds of bacteria. When the culture medium with monodispersed bacteria was placed on the nanobowl array, it successfully enabled loading of single bacterium into a single nanobowl. Because of the limitative size and depth of the nanobowls, mixture of different bacteria species could be screened according to their sizes. In addition, with the help of a low electrical current, the bacteria can be further screened according to their intrinsic surface charges. If combined with micromanipulation technology, high-throughput single bacterial selection can be achieved in future.


A subcortical correlate of P300 in man.
Event-related potentials in visual and auditory target detection tasks were recorded simultaneously from the scalp, somatosensory thalamus and periaqueductal gray in a chronic pain patient with electrodes implanted subcortically for therapeutic purposes. Short latency tactile responses confirmed the location of the thalamic electrodes. Rare auditory stimuli which were detected by the subject were accompanied by a prominent P300 component at the scalp, and by negative activity at the subcortical sites with the same latency as the scalp positivity. This activity was not seen in responses to frequent non-target stimuli and was not dependent on an overt motor response. Similarly, rare visual stimuli generated a scalp P300 and negative activity subcortically; both scalp and subcortical waves had a longer latency than in the auditory experiment. The reaction time was similarly longer to visual targets. These data are inconsistent with a hippocampal generator for P300, but are consistent with a generator in the thalamus or more dorsally located structures.


Transcatheter embolisation of a suprarenal aortic aneurysm persisting after bypass graft surgery.
We present a case of a large suprarenal aneurysm which recurred following aorto-biliac bypass grafting and ligation of the aneurysm. Successful thrombosis was achieved with selective embolisation.


Global realignment after posterior vertebral column resection in severe thoracolumbar post-tubercular kyphosis: correlation with patient-reported outcomes.
To investigate spinal realignment in patients with severe post-tubercular kyphosis (PTK) who underwent posterior vertebral column resection (PVCR) and its correlation with patient-reported outcomes (PROs). Eighty-two patients were included in this study. Spinopelvic parameters (focal scoliosis (FS), coronal balance (CB), sagittal vertical axis (SVA), focal kyphosis (FK), C2-7 lordosis (CL), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and pelvic incidence minus lumbar lordosis (PI-LL)) and PROs (Visual Analog Scale (VAS) and Oswestry Disability Index (ODI)) were analyzed. The correlation between spinopelvic parameters and PROs was evaluated. FK, FS, CL, TK, LL, and PI-LL significantly changed after surgery. FK decreased from pre-operative 108.5 ± 16.4° to 31.8 ± 4.5° at three months after surgery and increased to 38.7 ± 6.6° at final follow-up (P < 0.001). FS decreased from pre-operative 20.9 ± 2.2° to 5.1 ± 2.2° at final follow-up (P < 0.001). CL decreased from pre-operative 7.2 ± 7.3° to 3.3 ± 8.3° at final follow-up (P = 0.002). TK improved from pre-operative - 5.6 ± 7.1° to 12.9 ± 8.2° at final follow-up (P < 0.001). LL decreased from pre-operative 75.5 ± 12.6° to 45.5 ± 7.9° at final follow-up (P < 0.001). PI-LL improved from pre-operative - 24.8 ± 13.4° to 4.8 ± 9.9° at final follow-up (P < 0.001). The improvement of PROs was found to be significantly correlated with the variations of FK, CL, TK, LL, and PI-LL. The multiple regression analysis revealed that FK was an independent predictor for the improvement of VAS and ODI. PVCR is effective in treating severe PTK, which can significantly improve patients' clinical and radiographic outcomes. Spine surgeons should pay more attention to reducing the residual kyphosis.


The PLE(2)NO self-management and exercise program for knee osteoarthritis: Study Protocol for a Randomized Controlled Trial.
International recommendations suggest exercise and self-management programs, including non-pharmacological treatments, for knee osteoarthritis (KOA) because they can benefit pain relief and improve function and exercise adherence. The implementation of a combined self-management and exercise program termed PLE(2)NO may be a good method for controlling KOA symptoms because it encourages the development of self-efficacy to manage the pathology. This study will assess the effects of a self-management and exercise program in comparison to an educational intervention (control program) on symptoms, physical fitness, health-related quality of life, self-management behaviors, self-efficacy, physical activity level and coping strategies. This PLE(2)NO study is a single-blinded, randomized controlled trial of elderly (aged above 60 yrs old) patients with clinical and radiographic KOA. The patients will be allocated into either an educational group (control) or a self-management and exercise group (experimental). All participants will receive a supplement of chondroitin and glucosamine sulfates. This paper describes the protocol that will be used in the PLE(2)NO program. This program has several strengths. First, it involves a combination of self-management and exercise approaches, is available in close proximity to the patients and occurs over a short period of time. The latter two characteristics are crucial for maintaining participant adherence. Exercise components will be implemented using low-cost resources that permit their widespread application. Moreover, the program will provide guidance regarding the effectiveness of using a self-management and exercise program to control KOA symptoms and improve self-efficacy and health-related quality of life. NCT02562833 (09/23/2015).


Phenotypic and functional analysis of EBV-specific memory CD8 cells in SLE.
T cell dysfunction has been described in systemic lupus erythematosus (SLE). However, the specific phenotype and function of antigen-specific CD8 cells is less clear. Here we determined phenotype and function of Epstein-Barr virus (EBV)-specific CD8 cells at the single-cell level in SLE. HLA-A2-restricted EBV-BMLF-1-specific CD8 cells were enumerated by flow cytometry using tetramers in SLE and healthy control subjects. Antigen-specific CD8 cells were analyzed for expression of differentiation, activation, proliferation, and anti-apoptotic markers. EBV-specific, other virus-specific (specific against a viral peptide pool consisting of cytomegalovirus, EBV and influenza virus peptides), and mitogen-induced CD8 cell function was assessed by INF-gamma ELISPOT assay. Frequencies of EBV-specific CD8 cells tended to be greater in SLE subjects than in healthy control subjects (p=0.07). While over 10% of EBV-specific CD8 cells were capable of producing IFN-gamma in four out of five healthy control subjects, such proportions of EBV-specific CD8 cells capable of IFN-gamma production were observed in only one out of six SLE subjects (p=0.04). In contrast, viral peptide pool-specific and mitogen-induced IFN-gamma-producing T cell function was intact in SLE subjects. Phenotypic analysis revealed EBV-specific CD8 cells to be in an early to intermediate differentiation and resting memory state in both groups. While EBV-specific CD8 cells are similar in phenotype, their frequency tends to be increased, and function appears to be decreased in SLE. Therefore, an impaired EBV-specific CD8 immune response may exist in SLE, potentially contributing to disease pathogenesis.


Determining relative thickness of inner retinal layers on single-line foveal optical coherence tomography (OCT) in healthy pediatric eyes-normative data for handheld OCT.
Handheld optical coherence tomography (HH-OCT) lacks integrated segmentation/analysis software. Optic neuropathies cause ganglion cell layer (GCL) thinning, with normal to thickened inner nuclear layer (INL), suggesting the potential value of estimating the GCL/INL ratio on single-line foveal HH-OCT scans. This study determines this ratio in macular scans from healthy eyes of young children using HH-OCT and overhead-mounted OCT. Macular OCT scans were obtained using either HH-OCT or overhead-mounted Spectralis FLEX-OCT in children ages 0-5 years undergoing clinically indicated anesthesia/sedation. Exclusion criteria included gestational age <37 weeks, neurologic disease, amblyopia, ocular disease, or large refractive error (spherical equivalent beyond -3.00 D to +8.00 D). For HH-OCT, the GCL and INL were manually measured in pixels from single-line macular scans at the thickest point nasal and temporal to the fovea. For FLEX-OCT images, measurements were aided by automated software. HH-OCT was obtained on 38 eyes (38 children, mean age 2.4 ± 1.8 years) and FLEX-OCT on 56 eyes (56 children, mean age 2.3 ± 1.5 years). Mean nasal GCL/INL was 1.24 ± 0.18 (min/max = 0.92/1.75) for HH-OCT and 1.29 ± 0.18 (min/max = 0.96/1.66) for FLEX-OCT (P = 0.11). Mean temporal GCL/INL was 1.22 ± 0.24 (min/max = 0.66/1.70) for HH-OCT and 1.19 ± 0.16 (min/max = 0.86/1.47) for FLEX-OCT (P = 0.47). Mean normative GCL/INL ratios were approximately 1.2 at the thickest macular areas both nasal and temporal to the fovea, with either HH-OCT or FLEX-OCT in young children's eyes. These values may prove useful when HH-OCT is used to assess optic neuropathies, in which the GCL/INL ratio is expected to be decreased.


The impact of common metal allergens in daily devices.
We are widely exposed to metal allergens in our daily doings. As exposures constantly changes because of fashion trends and technological developments, there is a need for a continuous update of patch testers. An overview of consumer metal exposure studies that have been published in 2012 and 2013 is provided as well as lists of common metal exposures. Nickel release in concentrations that cause nickel allergy and contact dermatitis is seen from laptop computers. Cobalt is found in leather as a dye and may cause chronic dermatitis. Chromium is used as a dye and for tanning in leather items and is found in nearly all shoes and released from a high proportion. New consumer items should continuously be considered and investigated for metal release when patients with positive patch test results to metal allergens are evaluated.


Stage D1 prostate cancer. A nonrandomized comparison of conservative treatment options versus radical prostatectomy.
Untreated Stage D1 prostate cancer is associated with a high progression rate. Various treatment modalities involving monotherapy alone have been associated with dismal results. In this retrospective study, the impact of combination therapy, local (surgery or radiation) and systemic (hormonal), compared with that of monotherapy on disease outcome was evaluated. The authors reviewed 631 patients who underwent pelvic lymphadenectomy for Stage D1 prostate cancer: 251 had radical prostatectomies and orchiectomies, 78 had radical prostatectomies alone, 97 received local irradiation and underwent orchiectomies, and 60 had orchiectomies alone. Cause-specific survival rates for prostatectomy-orchiectomy-treated (PO) patients at 5 and 10 years were 91% and 78%, respectively; they were 84% and 54% for irradiation-orchiectomy-treated (IO) patients and 66% and 39% for orchiectomy alone-treated (O) patients, respectively. Controlling for the number of nodes, the difference between PO-treated and IO-treated patients was not significant; the former group had a significantly longer survival than the O-treated patients (P = 0.037). The 5-year and 10-year cause-specific survival rates for prostatectomy alone-treated patients were 91% and 75%, respectively, and 84% and 45% for irradiation alone-treated patients. Thus, cause-specific survival rates in prostatectomy alone-treated patients were significantly better (P = 0.0085). For patients with Stage D1 prostate adenocarcinoma, radical prostatectomy and local irradiation as local treatments when combined with orchiectomy produce similar outcomes. These results should be verified in a prospective study.


Chromophobe-like carcinoma of the thymus: A clinicopathological and immunohistochemical correlation of 5 cases.
Five cases of primary thymic carcinoma with distinct histopathological features resembling chromophobe carcinomas are presented. The patients were four men and one woman ranging in age between 43 and 72 years. Clinically, the patients presented with non-specific symptoms of dyspnea and chest pain. Diagnostic imaging revealed the presence of anterior mediastinal masses. All patients underwent complete surgical resection of their tumors via thoracotomy. Grossly, the tumors measured between 4.0 and 5.5 cm in greatest diameter and were ill-defined neoplasms with infiltrative borders; they were light brown in color and had a lobulated surface. Areas of hemorrhage and necrosis were not identified. Histologically, all tumors shared similar histopathological features, mainly the presence of infiltrative tumor islands separated by a fibrocollagenous stroma. At higher magnification, the neoplastic cellular proliferation was composed of medium-sized, round to polygonal cells with eosinophilic or granular cytoplasm and a clear perinuclear cytoplasmic halo, which imparted a chromophobe-like appearance. Nuclear atypia and mitotic activity were identified. Histochemical stains for colloidal iron were negative while immunohistochemical stains for pancytokeratin, cytokeratin 5/6, and p40 were positive in all cases, supporting squamous differentiation in these tumors. Clinical follow-up information was obtained in three patients all of whom died between 3 and 5 years after initial diagnosis, while two patients were lost to follow-up. The cellular characteristics of these tumors represent an unusual variant of thymic carcinoma that may pose a diagnostic challenge in small biopsies and that could be easily confused with other primary or metastatic tumors.


Rapid methods for identification of poliovirus isolates and determination of polio neutralizing antibody titers in human sera.
A new rapid method for identification and determination of the titer of polioviruses and other enteroviruses in cell monolayers grown in microtiter plates is described. The method is based on immunoperoxidase staining of infected cells with commercial monoclonal antibodies (MAb) and biotin-labeled secondary antibody. The presence of poliovirus or other enteroviruses was established as the appearance of at least one focus of cells with stained cytoplasm 6 h post-infection. Viral titers determined by this method were expressed as focus forming unit (FFU) per ml which was found to correspond approximately to 10 TCID(50)/ml. The suitability of this technique to determine poliovirus antibody titers in human sera was also tested comparing the immunocytochemical neutralization assay with a conventional neutralization in microtiter plates. The test was standardized using reference human sera in order to produce antibody titers expressed in international units (IU). In addition to high reproducibility, the new neutralization test appears to be sensitive, specific and rapid, and might thus represent a useful tool for the diagnosis of polio and other enterovirus infections.


New horizons in hCG detection.
The advent of high technology in the field of hCG measurement has created a greater requirement for high expertise in the analysis and evaluation of hCG levels, particularly low-positive levels, and for the concomitant clinical management of the patient. This implies an imperative to treat trophoblastic disease patients in trophoblast disease referral centers.


[Visual evoked potentials and the time of motor reaction to visual stimuli in chronic metallic mercury poisoning].
In a group of 10 patients with diagnosed occupational chronic poisoning with metallic mercury a correlation was sought between the parameters of the visual evoked potentials and the results of the psychological test evaluating the rapidity of motor response to the visual stimuli. The analysis suggest a cerebral dysfunction of the visual neurons and reduced rate of visual information transformation to the motor effector at the level of the cortical association centre.


Predictors of breastfeeding duration in a predominantly Māori population in New Zealand.
Although breastfeeding duration in New Zealand's indigenous Māori is shorter than in non-Māori, we know little about barriers or motivators of breastfeeding in this community. The aim of this analysis was to identify predictors for extended duration of breastfeeding amongst participants drawn from predominantly Māori communities in regional Hawke's Bay. Mother/baby dyads were recruited from two midwifery practices serving predominantly Māori women in mostly deprived areas, for a randomised controlled trial comparing the risks and benefits of an indigenous sleeping device (wahakura) and a bassinet. Questionnaires were administered at baseline (pregnancy) and at one, three and six months postnatal. Several questions relating to breastfeeding and factors associated with breastfeeding were included. The data from both groups were pooled to examine predictors of breastfeeding duration. Māori comprised 70.5% of the 197 participants recruited. The median time infants were fully breastfed was eight weeks and Māori women were more likely to breastfeed for a shorter duration than New Zealand European women with an odds-ratio (OR) of 0.45 (95% CI 0.24, 0.85). The key predictors for extended duration of breastfeeding were the strong support of the mother's partner (OR = 3.64, 95% CI 1.76, 7.55) or her mother for breastfeeding (OR = 2.47, 95% CI 1.27, 4.82), longer intended duration of maternal breastfeeding (OR = 1.02, 95% CI 1.00, 1.03) and being an older mother (OR = 1.07, 95% CI 1.02, 1.12). The key predictors for shorter duration of breastfeeding were pacifier use (OR = 0.28, 95% CI 0.17, 0.46), daily cigarette smoking (OR = 0.51, 95% CI 0.37, 0.69), alcohol use (OR = 0.54, 95% CI 0.31, 0.93) and living in a more deprived area (OR 0.40, 95% CI 0.22, 0.72). Breastfeeding duration in this group of mainly Māori women was shorter than the national average. Increasing the duration of breastfeeding by these mothers could be further facilitated by ante and postnatal education involving their own mothers and their partners in the support of breastfeeding and by addressing pacifier use, smoking and alcohol use.


The Trigeminal Nerve Injury.
Trigeminal nerve branches are never far from the operating field of the oral and maxillofacial surgeon. Increasingly the surgeon is required to provide accurate diagnosis and grading of trigeminal nerve injury, and surgical management by oral and maxillofacial surgeons will become common. Although trauma and ablative procedures for head and neck pathology can cause injuries, dentoalveolar surgical procedures remain an important cause of injury to the fifth cranial nerve, with the third division being the main branch affected. Oral and maxillofacial surgeons should be aware of strategies of avoiding iatrogenic injury, and know when referral and surgical management are appropriate.


A multilevel analysis of the influence of Apolipoprotein E genotypes on depressive symptoms in late-life moderated by the environment.
This study aimed to clarify the relationship between the APOE alleles and depressive symptoms of older adults, considering individual characteristics and the effect of neighborhood environment. Using a multilevel, stratified sampling strategy, 500 elders were recruited from official household records. Depressive symptoms were assessed using the Taiwanese Depression Questionnaire [TDQ]. Cognitive function was assessed by the Short Portable Mental Status Questionnaire [SPMSQ]. Blood samples were collected for the determination of the Apolipoprotein E [APOE] polymorphism. Perceived neighborhood experience was brought together using the Neighborhood Quality Index [NQI]. Three hundred and three subjects (58.8% male, with a mean age of 69.2 [SD=2.7] years) completed all questionnaires and the collection of blood samples. Risk factors for depressive symptoms of elders included lower educational level, cognitive impairment, having 2 or more chronic diseases, and having the APOE epsilon4 allele. In the 2-level model with individual characteristics and neighborhood environmental factors, the effect of the APOE epsilon4 allele on depressive symptoms was significantly attenuated. The APOE epsilon4 allele is correlated with depressive symptoms among older adults, but moderated by neighborhood environmental factors.


Prey features affecting ingestion rates by Acanthocyclops robustus (Copepoda: Cyclopoida) on zooplankton.
(1) Ingestion rates by adult female and juvenile Acanthocyclops robustus on a number of prey types were measured at a prey concentration of 100/l in experimental volumes of 300-400 ml. (2) For the adult predator, Synchaeta pectinata was most vulnerable (22.3, standard error 1.4, prey ingested per predator per day) as compared to Brachiomus calyciflorus, Brachionus diversicornis, Keratella cochlearis (two morphs), Asplanchna priodonta, Polyarthra major, Synchaeta kitina, Pompholyx sulcata, Daphnia spec., and Bosmina longirostris. For these latter prey, the lowest ingestion rate was on one morph of K. cochlearis and the highest on A. priodonta, being, respectively, 1.0, SE 0.5, and 11.3, SE 1.0, prey per predator per day. (3) With regard to the juvenile predator (mostly copepodite stages I, II and III), ingestion rates on K. cochlearis and P. sulcata were low (respectively 1.2, SE 0.7, and 0.3, SE 0.1, prey per predator per day) but quite high on S. kitina (5.7, SE 0.6). (4) In addition, the effect of increasing prey concentration on the ingestion rate (functional response) by the adult female predator was examined for B. calyciflorus, K. cochlearis, S. pectinata, S. kitina and Daphnia spec.. Increases in ingestion rate with prey density were minimal for B. calyciflorus and K. cochlearis, greater for Daphnia spec., still greater for S. pectinata and of greatest magnitude for S. kitina. (5) The reasons for these results are discussed with particular reference to prey features.


Contribution of unfolding and intermolecular architecture to fibronectin fiber extensibility.
The extracellular matrix contains components with remarkable mechanical properties, including fibronectin (Fn) fibers with extensibilities of >700% strain. We utilized what we consider a novel technique to quantify the extent of molecular unfolding that contributes to Fn fiber extension, and we compared this behavior with stochastic models of Fn fibers with different molecular arrangements. In vitro unfolding as a function of strain was measured by fluorescently labeling cysteines in modules FnIII7 and III15 in artificial Fn fibers. A calibration technique we also consider novel made it possible to demonstrate that 44% of cysteines in these modules were exposed in Fn fibers strained to 421% extension, up from 8% exposure without strain. In silico unfolding was measured by applying a constant strain rate to a fiber represented by a network of wormlike chain springs, each representing an individual Fn molecule. Unfolding rates were calculated with a tension-dependent stochastic model applied to FnIII modules in each molecule. A comparison of these approaches revealed that only a molecular arrangement permitting unequal mechanical loading of Fn molecules recapitulates in vitro unfolding. These data have implications for Fn-dependent mechanotransduction and give insight into how the molecular architecture of natural materials permits such remarkable extensibility.


A highly polymorphic CA repeat marker at the human tumor necrosis factor alpha (TNFA alpha) locus.
Tumor necrosis factor alpha (TNF alpha) in activated monocytes exerts cytotoxic activity and has a variety of other biological effects. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the gene located at 6p21.3. High heterozygosity (0.80) makes this polymorphism a useful marker in the genetic study of disorders affecting immunological response and cell differentiation.


MRI demonstration of intra-articular median nerve entrapment after elbow dislocation.
We report a case of median nerve entrapment in the elbow joint diagnosed with MRI 14 months after closed reduction of a dislocated elbow joint.


Groundwater chemistry, distribution and potential health risk appraisal of nitrate enriched groundwater: A case study from the semi-urban region of South India.
In recent years, an elevated concentration of nitrate in groundwater has been a growing problem on a global scale. It directly shows the adverse effects on human health via various intake pathways. Herein, the aim of the present study was to evaluate the nitrate concentration in groundwater and its associated human health risk in various age groups (females, males and children) in the investigated region. For this purposes, thirty groundwater samples were collected and analyzed physico-chemical parameters including nitrate concentration. The results showed that, the concentration of nitrate ranges from 14 to 82 mg/L and about 43.3% of these groundwater samples beyond the safe level of 45 mg/L according to Indian guidelines. The higher nitrate contamination is observed in the vicinity of Sarvepalli and Timmapur villages where groundwater chemistry is majorly influenced by anthropogenic sources. Health risks were assessed through oral/ingestion and dermal contact exposure routes for females, males and children population in the study region. Oral exposure was much higher than dermal contacts. For the non-carcinogenic risk, the HITotal values of groundwater in the investigated region varied from 0.313 to 1.976 (mean of 0.941) for males, 0.370 to 2.336 (mean of 1.112) for females and 0.443 to 2.694 (mean of 1.314) for children. The health risk assessment for nitrate divulged that 60%, 57% and 50% of groundwater samples pose a non-carcinogenic health risk for children, females and males, respectively.


Freeze-cast hydroxyapatite scaffolds for bone tissue engineering applications.
Freeze casting of aqueous suspensions was investigated as a method for preparing porous hydroxyapatite (HA) scaffolds for eventual application to bone tissue engineering. Suspensions of HA particles (10-20 volume percent) were frozen unidirectionally in a cylindrical mold placed on a cold steel substrate (-20 degrees C). After sublimation of the ice, sintering for 3 h at 1350 degrees C produced constructs with dense HA lamellae, with porosity of approximately 50%, and inter-lamellar pore widths of 5-30 microm. These constructs had compressive strengths of 12 +/- 1 MPa and 5 +/- 1 MPa in the directions parallel and perpendicular to the freezing direction, respectively. Manipulation of the microstructure was achieved by modifying the solvent composition of the suspension used for freeze casting. The use of water-glycerol mixtures (20 wt% glycerol) resulted in the production of constructs with finer pores (1-10 microm) and a larger number of dendritic growth connecting the HA lamellae, and higher strength. On the other hand, the use of water-dioxane mixtures (60 wt% dioxane) resulted in a cellular-type microstructure with larger pores (90-110 microm). The mechanical response showed high strain tolerance (5-10% at the maximum stress), high strain for failure (>20%) and sensitivity to the loading rate. The favorable mechanical behavior of the porous constructs, coupled with the ability to modify their microstructure, indicates the potential of the present freeze casting route for the production of porous scaffolds for bone tissue engineering.


Coronavirus disease 2019 pandemic and pregnancy and neonatal outcomes in general population: A living systematic review and meta-analysis (updated Aug 14, 2021).
Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods. We searched PubMed and Embase databases, reference lists of articles published up until August 14, 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and the pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method. Forty-five studies with low-to-moderate risk of bias, reporting on 1 843 665 pregnancies during the pandemic period and 23 564 552 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (35 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.92-0.98), but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). This reduction was noted in studies from single centers/health areas (25 studies, uaOR 0.90, 95% CI 0.86-0.96) but not in regional/national studies (10 studies, uaOR 0.99, 95% CI 0.95-1.02). There was reduction in spontaneous PTB (six studies, uaOR 0.89, 95% CI 0.81-0.96) and induced PTB (five studies, uaOR 0.89, 95% CI 0.81-0.97). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (24 studies, uaOR 1.11, 95% CI 0.97-1.26 and four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (six studies, mean difference 17 g, 95% CI 7-28 g). The odds of maternal mortality were increased (four studies, uaOR 1.15, 95% CI 1.05-1.26); however, only unadjusted estimates were available and the result was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB. The COVID-19 pandemic may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no statistically significant difference in stillbirth between pandemic and pre-pandemic periods.


Asialoorosomucoid hepatobiliary transport is unaltered by the loss of liver asialoglycoprotein receptors in aged rats.
The hepatobiliary transport of asialoorosomucoid (ASOR) was examined in aging male Fischer 344 rats. The time course of transport of 125I-ASOR from blood to bile was identical in both senescent and young adult rats. Peak secretion occurred at approximately 35 minutes after injection via the femoral vein. Total secretion of radiolabeled ASOR (3.6% of injected dose), bile secretion and rate of secretion of radiolabeled ligand (approximately 2% of administered dose/hr/gm bile/liver) were not significantly different for the two age groups. Determination of the binding capacity for 125I-ASOR with liver plasma membrane-enriched preparations showed the membranes from old animals capable of binding approximately 50% less radiolabeled ligand as the young adult animals. Analysis of the distribution of 125I-ASOR autoradiographic grains along the liver lobule indicated extensive uptake of ligand in Zone 2 and 3 cells in senescent animals, whereas uptake in young rats was essentially limited to Zone 1 parenchymal cells. These results indicate that, contrary to the age-related loss of hepatic receptors for dimeric IgA and the concomitant reduction in hepatobiliary secretion of IgA, loss of ASOR binding capacity on liver plasma membranes from old animals is not reflected in diminished hepatobiliary secretion of ASOR. The loss of ASOR binding capacity is offset by the recruitment of Zone 2 and 3 hepatocytes along the liver lobule. This result suggests that hepatic metabolism and hepatobiliary secretion of macromolecules which exhibit a lobular gradient of uptake (e.g. ASOR) will be relatively less affected by loss of receptors compared to ligands which do not display such a gradient (e.g. IgA).


Insights into the invasive diagnostic challenges of coronary artery vasospasm - A systematic review.
Coronary provocation testing is an essential diagnostic procedure when evaluating vasospastic angina. Invasive methods using acetylcholine or ergonovine are considered the current gold standard. Despite efforts from global cardiovascular institutions, current protocols vary in dosage, administration time, and procedural approach. In addition, concerns over the specificity of findings and potential complications have limited routine uptake of this procedure in clinical practice. This systematic review evaluates current diagnostic protocols, focusing on invasive provocation testing. We included studies using intracoronary provocation testing with acetylcholine or ergonovine for the assessment of coronary artery vasospasm that detailed specific elements of the procedure (dosage, administration time, etc.) and included ≥50 patients. A total of 28 articles met strict inclusion criteria. Our review highlights the heterogeneity between current diagnostic protocols for invasive provocation testing. We believe standardization of a diagnostic protocol will encourage both current and future cardiologists to incorporate such procedures in the evaluation of variant angina.


Vitalism and cognition in a conscious universe.
According to the current scientific paradigm, what we call 'life', 'mind', and 'consciousness' are considered epiphenomenal occurrences, or emergent properties or functions of matter and energy. Science does not associate these with an inherent and distinct existence beyond a materialistic/energetic conception. 'Life' is a word pointing at cellular and multicellular processes forming organisms capable of specific functions and skills. 'Mind' is a cognitive ability emerging from a matrix of complex interactions of neuronal processes, while 'consciousness' is an even more elusive concept, deemed a subjective epiphenomenon of brain activity. Historically, however, this has not always been the case, even in the scientific and academic context. Several prominent figures took vitalism seriously, while some schools of Western philosophical idealism and Eastern traditions promoted conceptions in which reality is reducible to mind or consciousness rather than matter. We will argue that current biological sciences did not falsify these alternative paradigms and that some forms of vitalism could be linked to some forms of idealism if we posit life and cognition as two distinct aspects of consciousness preeminent over matter. However, we will not argue in favor of vitalistic and idealistic conceptions. Rather, contrary to a physicalist doctrine, these were and remain coherent worldviews and cannot be ruled out by modern science.


TRPM8-Rap1A Interaction Sites as Critical Determinants for Adhesion and Migration of Prostate and Other Epithelial Cancer Cells.
Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing the motility of these cancer cells. Here, we reveal a novel facet of PCa motility control via direct protein-protein interaction (PPI) of the channel with the small GTPase Rap1A. The functional interaction of the two proteins was assessed by active Rap1 pull-down assays and live-cell imaging experiments. Molecular modeling analysis allowed the identification of four putative residues involved in TRPM8-Rap1A interaction. Point mutations of these sites impaired PPI as shown by GST-pull-down, co-immunoprecipitation, and PLA experiments and revealed their key functional role in the adhesion and migration of PC3 prostate cancer cells. More precisely, TRPM8 inhibits cell migration and adhesion by trapping Rap1A in its GDP-bound inactive form, thus preventing its activation at the plasma membrane. In particular, residues E207 and Y240 in the sequence of TRPM8 and Y32 in that of Rap1A are critical for the interaction between the two proteins not only in PC3 cells but also in cervical (HeLa) and breast (MCF-7) cancer cells. This study deepens our knowledge of the mechanism through which TRPM8 would exert a protective role in cancer progression and provides new insights into the possible use of TRPM8 as a new therapeutic target in cancer treatment.


Dental practitioner's knowledge, opinions and methods of management of oral premalignancy and malignancy.
The present study outlines the results of a pilot study to determine the knowledge and awareness of a cohort of dentists in United Arab Emirates (UAE) regarding aetiology, clinical features and appropriate early management of oral premalignant and malignant lesions. A self-administered questionnaire was constructed and posted to 300 UAE Dental Practitoners (DPs), selected randomly from the register of Emirates Dental Association. The present report details the responses of this cohort. 182 questionnaires were completed and returned (response rate 60.6%). One hundred and twenty-seven (69.8%) of the responding dentists were male and the median age of the DPs was 40 years (range 24-75 years). The majority (84%) practised or had practised in or around Dubai and Sharjah, 75% had graduated from a dental school after 1980. Eighty-two respondents (45.0%) had attended specific courses on premalignant or malignant oral lesions. During their undergraduate training 70% of DPs had witnessed more than 10 patients with oral SCC. Only 60.4% of respondents indicated that the tobacco and alcohol use were the principle causes of oral SCC while 19.7% suggested that HIV disease was a risk factor for oral SCC. 29% of DPs routinely recorded the tobacco or alcohol use of their patients and only 3.8% offered advice to patients regarding modification of these habits. Eight-three percent of the respondents suggested that clinical screening was an effective means of reducing the frequency of premalignant and malignant oral lesions. In view of the gradual rise in oral malignancy worldwide there is an increased need for DPs to be able to recognize the signs and symptoms of oral malignancy and premalignancy, provide appropriate preventive advice and be aware of the appropriate early management of patients with such oral lesions.


[To analyse diagnosis, management and prognosis of florid cystitis glandularis (pseudoneoplastic entity)].
To analyse diagnosis, management and prognosis of florid cystitis glandularis (pseudoneplastic entity). A retrospective study of 6 consecutive patients with florid cystitis glandularis seen at the department of Urology of Monastir (Tunisia) from January 1996 to July 2006. All patients underwent ultrasonography, and cystoscopy. Computed tomography (CT) was performed in four patients and magnetic resonance imaging (MRI) in one patient. The six patients, all of whom were male, ranged from 22 to 68 (average 42) years of age. The most common complaints was haematuria. Radiological examination and cystoscopy suggested a bladder tumor in all patients. Histopathology revealed features of cystitis glandularis of intestinal type. Features of the pelvic CT and MRI were consistent with the diagnosis of pelvic lipomatosis in one patient. The endoscopic resection was performed in 5 patients. Recurrence occurred in one of these 5 patients within one and 7 years of follow-up. The other patient had developed a low compliance small-capacity bladder and bilateral ureteral obstruction. A total cystoprostatectomy and ileal neobladder construction was considered, but it was declined by the patient. The patient was treated with anti-inflammatory drug (Indometacine 100 mg/day). Cystitis glandularis may be mistaken for bladder tumor The diagnosis is histological. Treatment is based on eradication of the irritative factors and endoscopic resection of the tumoral masses. The clinical course is unclear, requiring long-term fellow-up.


The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities.
Leucine-rich repeat kinase 2 (LRRK2) is the gene responsible for autosomal-dominant Parkinson's disease (PD), PARK8, but the mechanism by which LRRK2 mutations cause neuronal dysfunction remains unknown. In the present study, we investigated for the first time a transgenic (TG) mouse strain expressing human LRRK2 with an I2020T mutation in the kinase domain, which had been detected in the patients of the original PARK8 family. The TG mouse expressed I2020T LRRK2 in dopaminergic (DA) neurons of the substantia nigra, ventral tegmental area, and olfactory bulb. In both the beam test and rotarod test, the TG mice exhibited impaired locomotive ability in comparison with their non-transgenic (NTG) littermates. Although there was no obvious loss of DA neurons in either the substantia nigra or striatum, the TG brain showed several neurological abnormalities such as a reduced striatal dopamine content, fragmentation of the Golgi apparatus in DA neurons, and an increased degree of microtubule polymerization. Furthermore, the tyrosine hydroxylase-positive primary neurons derived from the TG mouse showed an increased frequency of apoptosis and had neurites with fewer branches and decreased outgrowth in comparison with those derived from the NTG controls. The I2020T LRRK2 TG mouse exhibited impaired locomotive ability accompanied by several dopaminergic neuron abnormalities. The TG mouse should provide valuable clues to the etiology of PD caused by the LRRK2 mutation.


Cholecystokinin facilitates ejaculation in male rats: blockade with proglumide and apomorphine.
Systemic administration of the active, sulfated form of cholecystokinin-octapeptide (CCK-8S), at a dose known to inhibit dopamine (DA) release, significantly reduced the latency to ejaculate and number of intromissions preceding ejaculation in sexually active male rats. This effect was identical to that reported for low doses of the DA receptor agonist apomorphine, which bind preferentially to presynaptic DA autoreceptors. The facilitatory effect of CCK-8S on ejaculation was blocked by the putative CCK receptor antagonist proglumide and by a presynaptic dose of apomorphine. Blockade of the effect of CCK-8S with a presynaptic dose of apomorphine is consistent with CCK induction of depolarization block in DA neurons. These data suggest that CCK-8S and apomorphine may reduce the ejaculation threshold in sexually active male rats by inhibition of DA release via two different mechanisms of action.


The utility of the emergency department observation unit for children with abdominal pain.
This study aimed to determine the outcome of children with unclear etiology for acute abdominal pain admitted to the emergency department observation unit (EDOU). This is a retrospective cohort study of children 18 years or younger who presented with acute abdominal pain to a tertiary pediatric ED and were observed in the EDOU. Children with alternative explanations for abdominal pain were excluded. Patients were classified based on disposition, and data were analyzed using χ tests. There were 237 patients included in the study (median age, 9 years; 46% male). Mean length of stay in EDOU was 14.4 hours. Fifty-four percent were evaluated by surgery. Two hundred (84%) were discharged; 37 (16%) were admitted, of whom 22 (9%) underwent surgical intervention (13 appendectomies, 6 ovarian cystectomies, 2 small-bowel obstructions, 1 cholecystectomy). Eight had acute appendicitis on pathology reports. The duration of symptoms, the presence of fever, nausea/vomiting, right-lower-quadrant pain, rebound tenderness, or leukocytosis greater than 10,000 cells/μL did not predict admission. Patients with diarrhea were more likely to be discharged home (P = 0.02). Intravenous hydration (86%) and pain control (63%) were the most common interventions in the EDOU. Abdominal pain not otherwise specified and acute gastroenteritis were the 2 most common discharge diagnoses. Eight (4%) of the 200 discharged patients returned to the ED within 48 hours, and all were discharged home from the ED. The majority of children admitted to the EDOU with abdominal pain have nonsurgical causes of abdominal pain. The EDOU provides a reasonable alternative for monitoring these patients pending disposition.


Heart failure with recovered ejection fraction.
Substantial or complete myocardial recovery occurs in many patients with heart failure (HF). HF patients with myocardial recovery or recovered left ventricular (LV) ejection fraction (EF; HFrecEF) are a distinct population of HF patients with different underlying etiologies, comorbidities, response to therapies, and outcomes compared with HF patients with persistent reduced or preserved EF. Improvement in LVEF has been systematically linked to improved quality of life, and lower rehospitalization rates and mortality. However, the mortality and morbidity in HFrecEF patients remain higher than those in the normal population. Currently, data to guide the management of HFrecEF patients are lacking. This review discusses specific characteristics, pathophysiology, and clinical implications for HFrecEF.


Modulation of the sympathetic nervous system by renal denervation prevents reduction of aortic distensibility in atherosclerosis prone ApoE-deficient rats.
Apolipoprotein E-deficient (ApoE(-/-)) rodents spontaneously develop severe hypercholesterolemia and increased aortic stiffness, both accepted risk factors for cardiovascular morbidity and mortality in humans. In patients with resistant hypertension renal denervation (RDN) may improve arterial stiffness, however the underlying mechanisms are incompletely understood. This study investigates the impact of RDN on aortic compliance in a novel atherosclerosis prone ApoE(-/-)-rat model. Normotensive, 8 weeks old ApoE(-/-) and Sprague-Dawley (SD) rats were subjected to bilateral surgical RDN (n = 6 per group) or sham operation (n = 5 per group) and fed with normal chow for 8 weeks. Compliance of the ascending aorta was assessed by magnetic resonance imaging. Vasomotor function was measured by aortic ring tension recordings. Aortic collagen content was quantified histologically and plasma aldosterone levels were measured by enzyme-linked immunosorbent assay (ELISA). After 8 weeks, ApoE(-/-)-sham demonstrated a 58 % decrease in aortic distensibility when compared with SD-sham (0.0051 ± 0.0011 vs. 0.0126 ± 0.0023 1/mmHg; p = 0.02). This was accompanied by an impaired endothelium-dependent relaxation of aortic rings and an increase in aortic medial fibrosis (17.87 ± 1.4 vs. 12.27 ± 1.1 %; p = 0.006). In ApoE(-/-)-rats, RDN prevented the reduction of aortic distensibility (0.0128 ± 0.002 vs. 0.0051 ± 0.0011 1/mmHg; p = 0.01), attenuated endothelial dysfunction, and decreased aortic medial collagen content (12.71 ± 1.3 vs. 17.87 ± 1.4 %; p = 0.01) as well as plasma aldosterone levels (136.33 ± 6.6 vs. 75.52 ± 8.4 pg/ml; p = 0.0003). Cardiac function and metabolic parameters such as hypercholesterolemia were not influenced by RDN. ApoE(-/-)-rats spontaneously develop impaired vascular compliance. RDN improves aortic distensibility and attenuated endothelial dysfunction in ApoE(-/-)-rats. This was associated with a reduction in aortic fibrosis formation, and plasma aldosterone levels.