Socioeconomic inequalities in children's health-related quality of life according to weight status.
This study explores the association between socioeconomic position (SEP) and health-related quality of life (HRQoL) among Portuguese children according to their weight status. A total of 1215 primary school-aged children (mean age 8.78 years) from three Portuguese districts (Lisbon, Porto, Coimbra) were assessed during 2016/2017. Father and mother's education (low, medium, high) and work status (employed, unemployed/retired) were used as SEP indicators. Self-reported HRQoL was assessed with the KIDSCREEN-27. Height and weight were objectively measured and body mass index categorized in normal, overweight or obese. Age, sex, and district-adjusted linear regression models were fitted to estimate associations between SEP indicators and HRQoL dimensions, according to weight status. We found that 24.9% of children were categorized as having overweight/obesity. The mean scores of the Physical Well-Being, and School Environment dimensions of HRQoL were lower among children classified with overweight/obesity compared to children with normal weight (57.21 vs 54.11, P < .001 and 57.85 vs 56.04, P = .010, respectively). Father's education was significantly associated with all HRQoL dimensions in children with a normal weight, but the same was not observed among children presenting overweight/obesity. An increase in the level of maternal education was also significantly associated with all HRQoL dimensions among children classified with a normal weight, and only for the School Environment dimension among children classified with overweight/obesity. These results suggest the presence of socioeconomic inequalities in self-reported HRQoL from early age, particularly among children with normal weight.


Neutral technetium(II)-99m complexes as potential brain perfusion imaging agents.
A series of eight neutral technetium(II)-99m complexes of general formula tr-[99mTcIID2X2]0, where D represents a chelating ditertary phosphine or arsine ligand and X represents a halide or pseudohalide ligand, has been prepared and characterized by HPLC comparisons to the known 99Tc analogs. Several members of this series exhibit significant brain uptake in rats, with maximum uptake (1.2% dose/brain at 1 min after injection) being exhibited by tr-[99mTcII (DIARS)2Cl2]0 where DIARS represents o-phenylenebis(dimethylarsine). Surprisingly, several cationic Tc(III) analogs, tr-[99mTcD2X2]+, also exhibit significant brain uptake, presumably via a mechanism which involves in vivo reduction to the neutral Tc(II) form. The complicated interrelationships among the chemical and biological properties of the tr-[99mTcIII/IID2X2]+/0 couples, and the dependencies of these properties on the nature of D and X, provide possible means by which this class of complexes might be manipulated to yield an effective 99mTc brain perfusion imaging agent.


Mechanical debulking versus balloon angioplasty for the treatment of true bifurcation lesions.
The purpose of this study was to compare the immediate angiographic and long-term results of debulking versus balloon angioplasty for treatment of true bifurcation lesions. Previous studies have shown true bifurcation lesions to be a high risk morphological subset for percutaneous transluminal coronary angioplasty (PTCA). Although atherectomy devices have been used to treat bifurcation lesions, no studies have compared the outcomes of these alternative treatment modalities. Between January 1992 and May 1997, we treated 70 consecutive patients with true bifurcation lesions (defined as a greater than 50% stenosis in both the parent vessel and contiguous side branch) with conventional PTCA (n = 30) or debulking (with rotational or directional atherectomy) plus adjunctive PTCA (n = 40). Paired angiograms were analyzed by quantitative angiography, and clinical follow-up was obtained in all patients. Acute procedural success was 73% in the PTCA group and 97% in the debulking group (p = 0.01). Major in-hospital complications occurred in two patients in the PTCA group and one in the debulking group. Treatment with atherectomy plus PTCA resulted in lower postprocedure residual stenoses than PTCA alone (16+/-15% vs. 33+/-17% in the parent vessel, and 6+/-15% vs. 39+/-22% in the side branch; p < 0.001 for both comparisons). At 1 year follow-up, the incidence of target vessel revascularization (TVR) was 53% in the PTCA group as compared with 28% in the debulking group (p = 0.05). Independent predictors of the need for repeat TVR were side branch diameter >2.3 mm, longer lesion lengths, and treatment with PTCA alone. For the treatment of true bifurcation lesions, atherectomy with adjunctive PTCA is safe, improves acute angiographic results, and decreases target vessel revascularization compared to PTCA alone. The benefits of debulking for bifurcation lesions were especially seen in lesions involving large side branches.


Coupled impacts of climate and land use changes on regional ecosystem services.
Ecosystem services (ES) are key to maintaining sustainable regional development. Climate change and land cover and land use change (LULC) are one of the main factors leading to changes in regional ecosystem services. Existing studies have simulated regional ES changes under different future scenarios, providing valuable guidance for regional sustainable management. However, most studies focus on the effects of individual factors (LULC or climate change) on ES, paying insufficient attention to the coupled effects of the two elements. Yunnan Province is a biodiversity hotspot facing challenges in ES in the context of future climate change and rapid socio-economic development. In order to achieve sustainable management, policies must be developed in advance to address possible future ecological risks. In this study, we simulated the coupled effects of climate change and LULC on six types of ES using the SD, FLUS, and InVEST models. The scenario framework of shared socioeconomic pathways SSP245 and SSP585 was combined with LULC scenario dynamics to assess the changes of ES in 2030 and 2050, identifying sensitive areas and providing a scientific basis for local ecosystem management. In 2020, the eastern part of Yunnan Province was the coldspot area for all ES. Under the future scenarios, Yunnan Province's ES show different loss rates and distinct spatial heterogeneity. Future climate change and LULC changes have a more significant negative impact on water conservation and water quality purification. About 66% of its counties will become sensitive areas for water production services, and 37% of counties will endure reduced water purification functions by more than 50%. According to the analytical results, we then proposed several suggestions to improve regional ES management.


Efficacy and tolerability of add-on Lacosamide treatment in adults with Lennox-Gastaut syndrome: An observational study.
To evaluate the efficacy, safety, and tolerability of lacosamide in adults with LGS in the clinical setting. The present report is a retrospective, open-label treatment study carried out from June 2013 to December 2014 at the National Institute of Colombia. Lacosamide was introduced as add-on therapy. All caregivers were instructed to initiate lacosamide at low doses (25-50 mg) and gradually increasing it every 2 weeks. The efficacy was evaluated based on the reduction in the rate of each countable type of seizure. We also evaluated the retention rate for lacosamide as the number of days with lacosamide during follow-up. The tolerability was evaluated base on account the adverse events. We found that lacosamide only improves the seizure rate in three out of 19 patients with LGS, in two of them by more than 50%. The highest seizure reduction rate was observed in the focal and tonic-clonic seizures. The most commonly reported adverse events were worsening of seizures, aggressiveness and irritability. Nine patients (47.4%) showed worsening of their behavior during the treatment with lacosamide. Lacosamide can exacerbate both, the tonic and astatic seizures, and the encephalopathy associated with this epileptic syndrome. However, it is interesting to consider the likelihood of suppression of generalized tonic-clonic and focal seizures. That is why; lacosamide could be an option after carefully balancing risks and benefits in each individual case.


Adverse Events Following the BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech) in Aotearoa New Zealand.
In February 2021, New Zealand began its largest ever immunisation programme with the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine. We aimed to understand the association between 12 adverse events of special interest (AESIs) and a primary dose of BNT162b2 in the New Zealand population aged ≥5 years from 19 February 2021 through 10 February 2022. Using national electronic health records, the observed rates of AESIs within a risk period (1-21 days) following vaccination were compared with the expected rates based on background data (2014-2019). Standardised incidence ratios (SIRs) were estimated for each AESI with 95% confidence intervals (CIs) using age group-specific background rates. The risk difference was calculated to estimate the excess or reduced number of events per 100,000 persons vaccinated in the risk period. As of 10 February 2022, 4,277,163 first doses and 4,114,364 second doses of BNT162b2 had been administered to the eligible New Zealand population aged ≥5 years. The SIRs for 11 of the 12 selected AESIs were not statistically significantly increased post vaccination. The SIR (95% CI) for myo/pericarditis following the first dose was 2.3 (1.8-2.7), with a risk difference (95% CI) of 1.3 (0.9-1.8), per 100,000 persons vaccinated, and 4.0 (3.4-4.6), with a risk difference of 3.1 (2.5-3.7), per 100,000 persons vaccinated following the second dose. The highest SIR was 25.6 (15.5-37.5) in the 5-19 years age group, following the second dose of the vaccine, with an estimated five additional myo/pericarditis cases per 100,000 persons vaccinated. A statistically significant increased SIR of single organ cutaneous vasculitis (SOCV) was also observed following the first dose of BNT162b2 in the 20-39 years age group only. A statistically significant association between BNT162b2 vaccination and myo/pericarditis was observed. This association has been confirmed internationally. BNT162b2 was not found to be associated with the other AESIs investigated, except for SOCV following the first dose of BNT162b2 in the 20-39 years age group only, providing reassurances around the safety of the vaccine.


Brilliant Cresyl Blue Negative Oocytes Show a Reduced Competence for Embryo Development after In Vitro Fertilisation with Sperm Exposed to Oxidative Stress.
The extent of oxidative damage transferred by the damaged sperm to the progeny is likely to be limited by the oocyte's repair and antioxidative capacity. We aimed to assess the association between Brilliant Cresyl Blue (BCB) staining in oocytes and their competence for embryo development after in vitro fertilisation (IVF) with damaged sperm. For this purpose, bovine sperm were incubated without (non-oxidised sperm, NOX S) or with 100 µM H2O2 (oxidised sperm, OX S) and were used to fertilise in-vitro-matured bovine oocytes (BCB-pos./BCB-neg.). Unstained oocytes served as controls (US). Development was assessed at 30, 46, 60 h and on Days (D) 7 and 8 after IVF. Total cell number and apoptotic index were analysed in D7 blastocysts. BCB-neg. oocytes showed lower cleavage rates and blastocyst rates than unstained oocytes after IVF with NOX S (p < 0.05). They showed the highest reduction in D7 blastocyst rate upon fertilisation with OX S and showed a delayed embryo development at 46 and 60 h after IVF compared to embryos produced with NOX S (p < 0.05). Total cell number in blastocysts produced with BCB-neg. oocytes was lower (p < 0.05) in the embryos produced with OX S than in embryos after IVF with NOX S. In conclusion, BCB-neg. oocytes have a lower competence to support embryo development after in vitro fertilisation with oxidised sperm.


Quasi-HKUST Prepared via Postsynthetic Defect Engineering for Highly Improved Catalytic Conversion of 4-Nitrophenol.
HKUST-1 [Cu3(BTC)2(H2O)3]n·nH2OMeOH was submitted to thermolysis under controlled conditions at temperatures between 100 and 300 °C. This treatment resulted in partial ligand decarboxylation, generating coordinatively unsaturated Cu2+ sites with extra porosity on the way to the transformation of the initial HKUST-1 framework to CuO. The obtained materials retaining in part the HKUST-1 original crystal structure (quasi-MOFs) were used to promote 4-nitrophenol conversion to 4-aminophenol. Because of the partial linker decomposition, the quasi-MOF treated at 240 °C contains coordinatively unsaturated Cu2+ ions distributed throughout the Q-HKUST lattice together with micro- and mesopores. These defects explain the excellent catalytic performance of QH-240 with an apparent rate constant of 1.02 × 10-2 s-1 in excess of NaBH4 and an activity factor and half-life time of 51 s-1g-1 and 68 s, respectively, which is much better than that of the HKUST parent. Also, the induction period decreases from the order of minutes to seconds in the presence of the HKUST and QH-240 catalysts, respectively. Kinetic studies fit with the Langmuir-Hinshelwood theory in which both 4-nitrophenol and BH4- should be adsorbed onto the catalyst surface. The values of the true rate constant (k), the adsorption constants of 4-nitrophenol and BH4- (K4-NP and KBH4-), as well as the activation energy are in agreement with a rate-determining step involving the reduction of 4-nitrophenol by the surface-bound hydrogen species.


Construction of super-rapid brain MRA using oblique transverse acquisition phase contrast angiography with tilted optimized non-saturated excitation pulse.
[Background] Magnetic resonance angiography (MRA) is one of the most important sequences to estimate a cerebrovascular disease. We often encounter poor image quality due to slow arterial flow related to aging and motion artifact caused by disturbance of consciousness. We focused on phase contrast angiography (PCA) to overcome these difficulties. PCA can reduce scan time drastically by combining transverse acquisition and partial slab setting covering entire brain arteries. However, transverse acquisition in PCA has a large difference in signal intensity between proximal and distal vessels. Therefore, we apply tilted optimized non-saturated excitation (TONE) to improve image quality. [Purpose] The purpose of this study to investigate the usefulness of TONE for PCA. [Method] We estimated the efficacy of TONE in transverse acquisition PCA using measurement of signal intensity in arteries. We compared image quality among 1 min PCA with/without TONE and time-of flight (TOF)-MRA, by visual. [Result] TONE improved the signal inhomogeneity in entire brain arteries. PCA with TONE (5°-9°) demonstrated the highest image quality. [Conclusion] Oblique transverse acquisition PCA with TONE provides superior image quality compared with TOF with similar scan time. TONE improved image quality by the homogenizing signal intensity of vessels from proximal to distal in oblique transvers acquisition PCA. Our MRA can be performed in about 1 min and provides sufficient quality to estimate brain vessels.


Absence of evidence for epidermal growth factor receptor and human homolog of the Kirsten rat sarcoma-2 virus oncogene mutations in breast cancer.
The epidermal growth factor receptor (EGFR) is an available target of effective anti-EGFR therapy for human breast cancer. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a main downstream signaling molecule in the EGFR pathway. The aim of this study was to assess the presence of EGFR and KRAS gene mutations in breast cancer. EGFR and KRAS gene mutations were investigated in formalin-fixed, paraffin-embedded tissues from 143 Chinese female patients with breast cancer by means of real-time quantitative polymerase chain reaction (RT-PCR). Based on RT-PCR, 2/143 (1.4%) samples and 1/143 (0.7%) had EGFR and KRAS gene mutations, respectively. Overall, none of the cases was identified with mutations of both of these two genes. In this study, both EGFR and KRAS mutations were present rarely in this cohort of samples with breast cancer. This suggested that mutation analyses for EGFR and KRAS are not useful as screening tests for sensitivity to anti-EGFR therapy for breast carcinomas.


Particle size distribution and morphological changes in activated carbon-metal oxide hybrid catalysts prepared under different heating conditions.
In catalysis processes, activated carbon (AC) and metal oxides (MOs) are widely used either as catalysts or as catalyst supports because of their unique properties. A combination of AC and a MO in a single hybrid material entails changes not only in the composition, microstructure and texture but also in the morphology, which may largely influence the catalytic behaviour of the resulting product. This work is aimed at investigating the modifications in the morphology and particle size distribution (PSD) for AC-MO hybrid catalysts as a result of their preparation under markedly different heating conditions. From a commercial AC and six MO (Al2O3, Fe2O3, ZnO, SnO2, TiO2 and WO3) precursors, two series of such catalysts are prepared by wet impregnation, oven-drying at 120 ºC, and subsequent heat treatment at 200 ºC or 850 ºC in inert atmosphere. The resulting samples are characterized in terms of their morphology and PSD by scanning electron microscopy and ImageJ processing program. Obtained results indicate that the morphology, PSD and degree of dispersion of the supported catalysts are strongly dependent both on the MO precursor and the heat treatment temperature. With the temperature rise, trends are towards the improvement of crystallinity, the broadening of the PSD and the increase in the average particle size, thus suggesting the involvement of sintering mechanisms. Such effects are more pronounced for the Fe, Sn and W catalysts due to the reduction of the corresponding MOs by AC during the heat treatment at 850 ºC.


Critical care nurse practitioners and clinical nurse specialists interface patterns with computer-based decision support systems.
The purposes of this review are to examine the types of clinical decision support systems in use and to identify patterns of how critical care advanced practice nurses (APNs) have integrated these systems into their nursing care patient management practices. The decision-making process itself is analyzed with a focus on how automated systems attempt to capture and reflect human decisional processes in critical care nursing, including how systems actually organize and process information to create outcome estimations based on patient clinical indicators and prognosis logarithms. Characteristics of APN clinicians and implications of these characteristics on decision system use, based on the body of decision system user research, are introduced. A review of the Medline, Ovid, CINAHL, and PubMed literature databases was conducted using "clinical decision support systems,""computerized clinical decision making," and "APNs"; an examination of components of several major clinical decision systems was also undertaken. Use patterns among APNs and other clinicians appear to vary; there is a need for original research to examine how APNs actually use these systems in their practices in critical care settings. Because APNs are increasingly responsible for admission to, and transfer from, critical care settings, more understanding is needed on how they interact with this technology and how they see automated decision systems impacting their practices. APNs who practice in critical care settings vary significantly in how they use the clinical decision systems that are in operation in their practice settings. These APNs must have an understanding of their use patterns with these systems and should critically assess whether their patient care decision making is affected by the technology.


Sustainable additives for the regulation of NH3 concentration and emissions during the production of biomethane and biohydrogen: A review.
This study reviews the recent advances and innovations in the application of additives to improve biomethane and biohydrogen production. Biochar, nanostructured materials, novel biopolymers, zeolites, and clays are described in terms of chemical composition, properties and impact on anaerobic digestion, dark fermentation, and photofermentation. These additives can have both a simple physical effect of microbial adhesion and growth, and a more complex biochemical impact on the regulation of key parameters for CH4 and H2 production: in this study, these effects in different experimental conditions are reviewed and described. The considered parameters include pH, volatile fatty acids (VFA), C:N ratio, and NH3; additionally, the global impact on the total production yield of biogas and bioH2 is reviewed. A special focus is given to NH3, due to its strong inhibition effect towards methanogens, and its contribution to digestate quality, leaching, and emissions into the atmosphere.


Home UV Phototherapy.
Phototherapy is an effective treatment for multiple dermatoses. However, patient inconvenience and poor access to office-based phototherapy may jeopardize adherence and treatment outcome. Home phototherapy offers a convenient, accessible, and effective therapy. We describe the history of home phototherapy, the devices available, and associated costs. A literature review used PubMed. Keywords included: "home phototherapy," "tanning beds," "narrowband ultraviolet B." In a randomized control trial, home phototherapy had similar efficacy to office-based phototherapy. Home phototherapy is associated with significant cost savings treatment and increased adherence. Home phototherapy should be considered for its economic value, good tolerability, adherence, and efficacy.


Trans-Sulcal Endoport-Assisted Evacuation of Supratentorial Intracerebral Hemorrhage: Initial Single-Institution Experience Compared to Matched Medically Managed Patients and Effect on 30-Day Mortality.
The surgical management of supratentorial intracerebral hemorrhages (ICH) remains controversial due to large trials failing to show clear benefits. Several minimally invasive techniques have emerged as an alternative to a conventional craniotomy with promising results. To report our experience with endoport-assisted surgery in the evacuation of supratentorial ICH and its effects on outcome compared to matched medical controls. Retrospective data were gathered of patients who underwent endoport-assisted evacuation between January 2014 and October 2016 by a single surgeon. Patients who were managed medically during the same period were matched to the surgical cohort. Previously published cohorts investigating the same technique were analyzed against the present cohort. Sixteen patients were identified and matched to 16 patients treated medically. Location, hemorrhage volume, and initial Glasgow Coma Scale (GCS) score did not differ significantly between the 2 cohorts. The mean volume reduction in the surgical cohort was 92.05% ± 7.05%. The improvement in GCS in the surgical cohort was statistically significant (7-13, P = .006). Compared to the medical cohort, endoport-assisted surgery resulted in a statistically significant difference in in-hospital mortality (6.25% vs 75.0%, P < .001) and 30-d mortality (6.25% vs 81.25%, P < .001). Compared to previously published cohorts, the present cohort had lower median preoperative GCS (7 vs 10, P = .02), but postoperative GCS did not differ significantly (13 vs 14, P = .28). Endoport-assisted surgery is associated with high clot evacuation and decreases 30-d mortality compared to a similar medical group.


Prevention of occlusion of cEnTral lInes for children with cancer: An implementation study.
Central venous access devices (CVADs) are vital medical devices to support the treatment of paediatric cancer; however, device occlusion is common, which disrupts treatment. This study aimed to improve the identification and management of CVAD occlusions in children with cancer, as well as to identify the demographic, clinical and device characteristics associated with increased risk for CVAD occlusion. A pre-post-implementation study was conducted at a metropolitan paediatric oncology facility in Australia, using the Theoretical Domains Framework. Patients with a CVAD for anti-cancer therapy were prospectively followed for occlusive events pre- and post- the implementation of clinical resources to support the identification and management of CVAD occlusive events. CVAD occlusion and management data were collected and compared pre- and post-implementation. Risk factors for CVAD occlusion were described by mixed-effects Poisson regression and incident rate ratios (IRR). A total of 133 CVADs were inserted into 131 patients for a total of 6784 catheter days. The incidence of CVAD-related occlusion pre-implementation was 59.7 (95% confidence interval (CI) 51.4-69.0, per 1000 catheter days); compared to 31.6 (95% CI 26.4-37.6); P < 0.01) post-implementation of clinical resources. In multivariate models, other than post-implementation phases (IRR 0.51 (95% CI 0.32-0.81)), only neutropaenia significantly increased the risk of CVAD occlusion (IRR 2.14 (95% CI 1.15-3.97)). CVAD occlusions in paediatric oncology are common. The development and implementation of CVAD occlusion resources to guide the identification and management of occlusive episodes led to a significant decrease in occlusive events.


PD-1 expression conditions T cell avidity within an antigen-specific repertoire.
Despite its negative regulatory role on tumor-specific T cells, Programmed cell death 1 (PD-1) is also a marker of activated tumor-infiltrating T cells. In cancer, PD-1 blockade partially reverses T cell dysfunction allowing the amplification of tumor reactive T cells. Here, we investigated the role of PD-1 signaling on effector/memory human T cells specific for shared melanoma antigens, derived from blood. We documented for the first time the existence of melanoma-specific T cell clones unable to express PD-1. This stable feature was due to the persistent methylation of the PDCD1 promoter. These PD-1neg clones were of lower avidity than their PD-1pos counterparts, suggesting that high-affinity-specific T cell clones unable to express PD-1 are not or rarely present in peripheral blood, as they are probably eliminated by negative selection, due to their high reactivity. We also documented the existence of such PD-1neg T cell clones in melanoma tumor-infiltrating lymphocytes (TIL), which also exhibited a lower functional avidity than PD-1pos TIL clones. This clearly shows that PD-1 expression identifies antigen-specific T cell clonotypes of high functional avidity. Finally, we demonstrated that PD-1 blockade during the in vitro selection process of Melan-A-specific T cells favored the amplification of higher avidity T cell clonotypes. This preferential amplification of high-avidity memory T cells upon PD-1 blockade resonates with the expansion of reactive T cells, including neo-antigen-specific T cells observed in anti-PD-1-treated patients. This feature should also be a useful biomarker of clinical efficiency, while providing new insights for adoptive transfer treatments.


Spine Fractures in Ankylosing Diseases: Recommendations of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU).
Review of literature and case series. Update and review of current treatment concepts for spine fractures in patients with ankylosing spinal disorders. Case presentation and description of a diagnostic and therapeutic algorithm for unstable spinal injuries with an underlying ankylosing spinal disorder (ASD) of the cervical and thoracolumbar spine. Nondisplaced fractures can be missed easily using conventional X-rays. Thus, computed tomography (CT) scans are recommended for all trauma patients with ASD. In doubt or presence of any neurologic involvement additional magnetic resonance imaging (MRI) scans should be obtained. Spine precautions should be maintained all times and until definitive treatment (<24 h). Nonoperative fracture treatment is not recommended given the mechanical instability of the most commonly seen fracture patterns (AOSpine B- and C-type, M2) in patients with ASD and inherent high risk of secondary neurologic deterioration. For patients with ankylosing spondylitis (AS) or diffuse idiopathic hyperostosis (DISH) sustaining cervical spine fractures, a combined anterior-posterior instrumentation for fracture fixation is recommended. Closed reduction and patient positioning can be challenging in presence of preexisting kyphotic deformities. In the thoracolumbar (TL) spine, a posterior instrumentation extending 2 to 3 levels above and below the fracture level is recommended to maintain adequate reduction and stability until fracture healing. Minimally invasive percutaneous pedicle screws and cement augmentation can help to minimize the surgical trauma and strengthen the construct stability in patients with diminished minor bone quality (osteopenia, osteoporosis). Current concepts, treatment options, and recommendations of the German Orthopedic Trauma Society-Spine Section for spinal fractures in the ankylosed spine have been outlined.


Kohn-Sham approach to quantum electrodynamical density-functional theory: Exact time-dependent effective potentials in real space.
The density-functional approach to quantum electrodynamics extends traditional density-functional theory and opens the possibility to describe electron-photon interactions in terms of effective Kohn-Sham potentials. In this work, we numerically construct the exact electron-photon Kohn-Sham potentials for a prototype system that consists of a trapped electron coupled to a quantized electromagnetic mode in an optical high-Q cavity. Although the effective current that acts on the photons is known explicitly, the exact effective potential that describes the forces exerted by the photons on the electrons is obtained from a fixed-point inversion scheme. This procedure allows us to uncover important beyond-mean-field features of the effective potential that mark the breakdown of classical light-matter interactions. We observe peak and step structures in the effective potentials, which can be attributed solely to the quantum nature of light; i.e., they are real-space signatures of the photons. Our findings show how the ubiquitous dipole interaction with a classical electromagnetic field has to be modified in real space to take the quantum nature of the electromagnetic field fully into account.


Orthopedic footwear has a positive influence on gait adaptability in individuals with hereditary motor and sensory neuropathy.
Individuals with Hereditary Motor and Sensory Neuropathy (HMSN) are commonly provided with orthopedic footwear to improve gait. Although orthopedic footwear has shown to improve walking speed and spatiotemporal parameters, its effect on gait adaptability has not been established. What is the effect of orthopedic footwear on gait adaptability in individuals with HMSN? Fifteen individuals with HMSN performed a precision stepping task on an instrumented treadmill projecting visual targets, while wearing either custom-made orthopedic or standardized footwear (i.e. minimally supportive, flexible sneakers). Primary measure of gait adaptability was the absolute Euclidean distance [mm] between the target center and the middle of the foot (absolute error). Secondary outcomes included the relative and variable error [mm] in both anterior-posterior (AP) and medial-lateral (ML) directions. Dynamic balance was assessed by the prediction of ML foot placement based on the ML center of mass position and velocity, using linear regression. Dynamic balance was primarily determined by foot placement deviation in terms of root mean square error. Another aspect of dynamic balance was foot placement adherence in terms of the coefficient of determination (R2). Differences between the footwear conditions were analyzed with a paired t-test or Wilcoxon signed-rank test (α = 0.05). The absolute error, relative error (AP) and variable error (AP and ML) decreased with orthopedic footwear, whereas the relative error in ML-direction slightly increased. As for dynamic balance, no effect on foot placement deviation or adherence was found. Gait adaptability improved with orthopedic compared to standardized footwear in people with HMSN, as indicated by improved precision stepping. Dynamic balance, as a possible underlying mechanism, was not affected by orthopedic footwear.


Epidemiological profile of rosacea in dermatology outpatient clinics in Brazil: an observational report from the Brazilian study group on rosacea.
Rosacea prevalence varies worldwide and there is a lack of information in Brazil. To describe the epidemiological profile of rosacea in subjects who consulted in dermatological outpatient clinics in Brazil. A cross-sectional study was conducted in 13 dermatological outpatient clinics across the country. Patients with rosacea diagnosis were eligible for the study according to the investigator's clinical assessment. Clinical, social and demographic data were collected. The overall and regional rosacea prevalence was calculated, and association with baseline characteristics was analysed. A total of 3,184 subjects were enrolled, and rosacea prevalence was 12.7%. The southern region of Brazil presented a higher prevalence, followed by the southeast. The subjects in the rosacea group were older than those without rosacea (52.5 ±14.9 vs. 47.5 ±17.5; p<0.001). Moreover, the rosacea group was associated with Fitzpatrick's phototypes I and II, Caucasian ethnicity, a family history of rosacea, and facial erythema, however, no association with gender was found. The most prevalent clinical sign and clinical subtype in rosacea patients were erythema and erythematotelangiectatic, respectively. Rosacea is highly prevalent in Brazil, mostly in the southern region, associated with phototypes I and II and a family history.


Role of baroreflex in the pressor response of rats with hypertension developed by renal artery stenosis.
We examined the interrelationships between the pressor response to the administration of norepinephrine and arginine vasopressin and baroreflex function in rats with hypertension of two days' duration induced by heminephrectomy and a clip placed on the right renal artery (2-day clipped rats). Mean arterial pressure was higher in the 2-day clipped rats than in heminephrectomized rats without clips (sham-operated rats). The pressor response in the 2-day clipped rats to both agents increased as compared to the sham-operated rats. This hyperresponsiveness was attenuated by administering an angiotensin II antagonist, [1-Sar, 8-Ile] angiotensin II. Baroreflex sensitivity was studied by measuring changes in arterial pressure and pulse interval in response to the injection of phenylephrine. Baroreflex sensitivity was not decreased but markedly increased in the 2-day clipped rats and unaffected by infusing the angiotensin II antagonist. These results provide evidence that 1) in the 2-day clipped rats there are exaggerated pressor responses to vasoconstrictors; 2) the hyperresponsiveness is not causally related to the change of baroreflex sensitivity; and 3) angiotensin II plays a significant role in the increased pressor responses; however, the baroreflex mechanism is not involved in attenuation of the hyperresponsiveness by the angiotensin II antagonist.


Neural gliding versus neural tensioning: Effects on heat and cold thresholds, pain thresholds and hand grip strength in asymptomatic individuals.
Neural mobilization can be performed in a way that facilitates movement through a stretching technique (tensioning) or in a way that maximizes the gliding of peripheral nerves in relation to adjacent structures (gliding). Evidence on how these techniques compare in terms of effects are scarce. The aim of this study is to compare the effects of neural gliding and neural tensioning targeting the median nerve on heat and cold temperature threshold, heat pain threshold, pressure pain thresholds and hand grip strength in asymptomatic participants. Participants received 4 series of 10 repetitions of either neural gliding (n = 30) or neural tensioning (n = 30) and were assessed for heat and cold temperature threshold, heat pain threshold, pressure pain threshold, and hand grip strength at baseline, immediately after the intervention, and 30 min post-intervention. A significant main interaction between time and intervention was found for the PPT at the forearm (F(2,55) = 5.98; p = 0.004), favouring the tensioning neural mobilization. No significant differences were found for the other variables. Four series of 10 repetitions of neural tensioning targeting the median nerve in asymptomatic subjects seem to be enough to induce hypoalgesia and have no negative effects on A-delta and C mediated sensory function and on hand grip strength production.


Body composition assessment in athletes: Comparison of a novel ultrasound technique to traditional skinfold measures and criterion DXA measure.
This investigation compared ultrasound and skinfolds as measures of body fat for athletes, relative to dual-energy X-ray absorptiometry. Fifty-six well-trained athletes from various sports participated in a cross-sectional study. The participants attended one testing session, where total body fat mass was measured using dual-energy X-ray absorptiometry, and subcutaneous adipose tissue was measured using brightness-mode ultrasound and skinfolds with callipers. The ultrasound and skinfold measures were correlated independently against standardised fat mass from dual-energy X-ray absorptiometry. The correlation between standardised fat mass and sum-of-eight (Σ8) sites ultrasound (r=0.959, p<0.001), and with sum-of-seven (Σ7) sites skinfolds (r=0.911, p<0.001), were both high positive correlations. In the lowest quartile by fat proportion, the correlation between standardised fat mass and Σ8 ultrasound (r=0.811, p<0.001) was a high positive correlation, whilst the correlation with Σ7 skinfolds (r=0.652, p=0.011) was a moderate positive correlation. In the highest quartile by fat proportion, the correlation between standardised fat mass and Σ8 ultrasound (r=0.847, p<0.001) was a high positive correlation, whilst the correlation with Σ7 skinfolds (r=0.591, p=0.026) was a moderate positive correlation. Ultrasound and skinfolds are both very good methods to accurately assess body composition in athletes, relative to dual-energy X-ray absorptiometry. However, ultrasound delivered consistently more accurate results, throughout a broad athletic spectrum.


[Immediate risk of mitral valve prostheses after a previous closed mitral commissurotomy].
Two groups of patients (30 patients each) operated and reoperated upon for rheumatic mitral valve failure were compared by different parameters. The authors consider that risk of reoperations on the mitral valve is dependent upon the critical initial state of such patients and upon technical problems in maximum cardiolysis.


Effects of external trunk loads on lumbar spine stability.
Stability of the lumbar spine is an important factor in determining spinal response to sudden loading. Using two different methods, this study evaluated how various trunk load magnitudes and directions affect lumbar spine stability. The first method was a quick release procedure in which effective trunk stiffness and stability were calculated from trunk kinematic response to a resisted-force release. The second method combined trunk muscle EMG data with a biomechanical model to calculate lumbar spine stability. Twelve subjects were tested in trunk flexion, extension, and lateral bending under nine permutations of vertical and horizontal trunk loading. The vertical load values were set at 0, 20, and 40% of the subject's body weight (BW). The horizontal loads were 0, 10, and 20% of BW. Effective spine stability as obtained from quick release experimentation increased significantly (p<0.01) with increased vertical and horizontal loading. It ranged from 785 (S.D.=580) Nm/rad under no-load conditions to 2200 (S.D.=1015) Nm/rad when the maximum horizontal and vertical loads were applied to the trunk simultaneously. Stability of the lumbar spine achieved prior to force release and estimated from the biomechanical model explained approximately 50% of variance in the effective spine stability obtained from quick release trials in extension and lateral bending (0.53<R(2)<0.63). There was no such correlation in flexion trials. It was concluded that lumbar spine stability increased with increased trunk load magnitude to the extent that this load brought about an increase in trunk muscle activation. Indirectly, our data suggest that muscle reflex response to sudden loading can augment the lumbar spine stability level achieved immediately prior to the sudden loading event.


Web-based training for EMT continuing education.
New Internet technologies offer the opportunity to delivery quality instruction to emergency medical technicians (EMTs) in a cost-effective manner. The purpose of this study was to determine whether web-based continuing education (CE) could be developed at a low cost and provide a high level of satisfaction and acceptance among EMTs. EMTs completed web-based CE modules in place of traditional instructor-led instruction. The EMTs in the study completed a questionnaire that assessed acceptance and satisfaction. Expenses for producing and delivering web-based instruction and delivering instructor-led instruction were tracked for all aspects of the project. Seventy-four percent of the EMTs strongly preferred the web-based modules over instructor-led modules. Other survey items indicated a high level of acceptance of the format (87%). The web-based modules in this study were produced and delivered at a cost of dollar 3 per EMT/module, which is less than the costs of traditional instructor-led training, ranging from dollar 21 to dollar 82 per EMT/module. Although not a replacement for all instructor-led training, web-based training can be a cost-effective and acceptable alternative for achieving instructional objectives within the cognitive domain. It offers other benefits such as improved administration of training records and consistent delivery of content.


Isolation and characterization of a translation inhibitor from human term placenta.
An inhibitor of protein synthesis has been isolated from free cytoplasmic ribonucleoprotein particles of human term placenta. The inhibitor is resistant to phenol, DNase, proteinase K, and heating at 100 degrees C, but is sensitive to alkaline hydrolysis. These data suggest that the inhibitor is RNA. Experiments provide evidence that this preparation contains no RNase contaminant and does not induce an RNase in this assay system. Three lines of evidence suggest that the inhibitor acts at the initiation of protein synthesis in the wheat germ translation system. First, a lag occurs before cessation of translation when the inhibitor is added to translating polyribosomes. This lag is identical to that seen upon the addition of aurintricarboxylic acid, a known inhibitor of initiation. Second, sucrose gradient analyses demonstrate that, when the inhibitor is present at the start of translation, 40 S complexes form, but neither 80 S complexes nor polyribosomes are seen. Third, gradient analyses show that, when the inhibitor is added to translating polyribosomes, 40 S complexes accumulate with a progressive loss of polyribosomes. Finally, the extent of inhibition depends upon the amount of wheat germ extract added to the reaction mixture and not the amount of mRNA present. This suggests an interaction between the inhibitor and a component of the wheat germ extract.


[Chromatographic Fingerprinting Study of Zhenyuan Granules Dry Extract by HPLC-DAD and HPLC-MS/MS].
To establish a novel, accurate and valid fingerprint method of Zhenyuan granules dry extract by using HPLC-DAD method, to study herbs belonging of fingerprint peaks and to identify some of the chromatographic peaks by HPLC-MS/MS analysis, for providing the basis for scientific evaluation of the quality. The sample solutions were analyzed by an Agilent SB C18 (250 mm x 4.6 mm, 5 µm) column, and gradiently eluted with acetonitrile (containing 0.1% formic acid) and aqueous phase (containing 0.1% formic acid) as the mobile phase. The flow rates were 1.2 mL/min (0~70 min) and 0.8 mL/min (70~150 min); the column temperature was 30 °C; and the detection wavelength was 254 nm. 40 peaks were selected as fingerprint peaks under the optimal chromatographic condition, and the similarity coefficients of 10 batches of Zhenyuan granules dry extract were all greater than 0.98. 27 peaks were tentatively identified with reference to literature data based on their mass spectrometry. The chromatographic fingerprint of Zhenyuan granules is proved to be a reliable method for comprehensive quality control and assessment.


The Heyman-Herndon tarsometatarsal capsulotomy for metatarsus adductus: results in 48 feet.
Forty-eight Heyman-Herndon tarsometatarsal capsulotomies were performed over an 18-year period for idiopathic metatarsus adductus and residual adductus of clubfoot. There was a 41% overall failure rate and a 50% incidence of painful dorsal prominence at the surgical scar. Sixty-eight percent of the patients had difficulty with proper shoe fitting. Those with associated orthopedic anomalies were at high risk for a poor result. We believe that tarsometatarsal capsulotomy is of questionable benefit in treatment of forefoot adduction deformities of children.


Prion infections of the brain.
Prions are a rare cause of human disease but very important to recognize because of their potential for transmissibility and uniformly severe outcome. MR imaging plays an extremely important role in early diagnosis, especially with diffusion-weighted and fluid-attenuated inversion recovery images, which are the most sensitive for depicting prion-induced brain lesions. The lesions are characteristically shown as ribbons of cortical hyperintensity, or basal ganglia or thalamic hyperintensity. The cortical and deep lesions may appear alone or together, and although usually bilateral and symmetric, they may be asymmetric or purely unilateral. When these MRI findings are observed in an appropriate clinical context, the diagnosis of prion disease is very likely.


Comparative analysis of condom lubricants on pre & post-coital vaginal swabs using AccuTOF-DART.
In this study we demonstrate the use of Direct Analysis in Real Time Mass Spectrometry (DART) as a powerful tool for detection of nonoxynol in vaginal fluid post contact with a condom, enabling rapid tracing and added evidences in sexual assault crimes. Vaginal fluid was sampled using cotton swabs and glass rods and measured directly with DART. Sample preparation using water, hexane, methanol, and dichloromethane extraction, was explored for comparison and optimization of signals. Nonoxynol was detected up to eight hours after sampling. Optimal sampling conditions and mass spectrometry parameters are reported and discussed.


Clinical utility of remote monitoring for patients with cardiac implantable electrical devices.
Remote monitoring of cardiac implantable electronic devices (CIEDs) offers practical and clinical benefits juxtaposed against burdens associated with high transmission volume. We identified patients receiving de novo pacemakers (PPMs) and implantable cardiac defibrillators (ICDs) at a single academic medical center (January 2016-December 2019) with at least 1 year of follow-up device care. We collected patient- and device-specific data at time of implant and assessed all remote and in-person interrogation reports for clinically actionable findings based on pre-specified criteria. Among 963 patients (mean age of 71 (± 14) years, 37% female), 655 (68%) underwent PPM, and 308 (32%) underwent ICD implant. Median follow-up was 874 (627-1221) days, during which time patients underwent a mean of 13 (10-16) total interrogations; remote interrogations comprised 53% of all device evaluations; and of these, 96% were scheduled transmissions. Overall, 22% of all CIED interrogations yielded significant findings with a slightly higher rate in the PPM than in the ICD group (23% vs. 20%, p < 0.01). Only 8% of remote interrogations produced clinically meaningful results, compared with 38% of in-person ones. In adjusted models, routine, remote transmissions were least likely to be useful for both PPM and ICD patients (p < 0.001), whereas time from initial device implant was inversely associated with probability of obtaining a useful interrogation (p < 0.001). Routine remote interrogations constitute the majority of device evaluations performed, but uncommonly identify clinically actionable findings.


Studies of the effects and mechanisms of ginsenoside Re and Rk3 on myelosuppression induced by cyclophosphamide.
Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk3 (Rk3) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk3 on cyclophosphamide-induced myelosuppression. The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. Both Re and Rk3 could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G0/G1 phase cells, and increase the proliferation index. Finally, Re and Rk3 could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Re and Rk3 could improve the hematopoietic function of myelosuppressed mice. The effect of Rk3 was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rk3 on myelosuppression.


Signal transducer and activator of transcription 3 (STAT3) gene polymorphisms are associated with treatment outcomes in acute myeloid leukemia.
In the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, STAT3 is one of the most prominent prognosis factors for cancer and leukemia. STAT3 activation might promote cellular transformation and therefore have an important role in human tumors. This study aimed to investigate the relationship between STAT3 polymorphisms and treatment response of acute myeloid leukemia (AML) in the Chinese population. Three single-nucleotide polymorphisms (SNPs) were tested in 130 patients with AML. Genomic DNA was isolated from peripheral blood and assayed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The results of response to chemotherapy showed that there were strong relationships between unfavorable cytogenetics, partial remission (and even no remission), and GG genotype frequency in rs9909659 (P = 0.01 and 0.03). Patients younger than 45 years were associated significantly with GA/AA genotype (P = 0.01). The results of this study suggest that the GG genotype in rs9909659 might confer increased resistance to standard chemotherapy.


Influence of 4-aminopyrazolopyrimidine on morphology, synthesis of triglyceride and protein and their secretion in rat hepatocytes.
The influence of 4-aminopyrazolopyrimidine (4-APP) on morphology and on synthesis and secretion ability of isolated rat hepatocytes was investigated: 4-APP was found to inhibit both the synthesis and secretion of proteins. The synthesis of triglycerides was unaffected by 4-APP, while the secretion of triglycerides was markedly reduced. Transmission electron microscopy revealed that 4-APP induced morphological changes in the smooth membrane systems, the smooth endoplasmic reticulum and the Golgi apparatus. The possibility that 4-APP inhibits lipoprotein formation by inhibition of the apoprotein synthesis is discussed.


Autogenous attachment technique with esthetics in mind: trauma management case report.
The majority of dental trauma involves anterior teeth, especially the maxillary central incisors. A crown fracture with pulp tissue involvement, severe sensitivity, and pain is certainly unpleasant for the patient. This case report will discuss the endodontic therapy and restoration with an autogenous tooth fragment attachment technique. When treating an emergency situation that involves trauma, it is challenging to provide the patient with both pain relief and esthetic restoration.


High rate of virological failure in maintenance antiretroviral therapy with didanosine and tenofovir.
We evaluated the virological outcome of tenofovir plus didanosine-based regimens in 67 HIV-suppressed patients. After a median follow-up of 26 months (IQR 10.5-40.5), 12 (18%) discontinued the therapy because of virological failure. At virological failure 'de novo' selected mutations were identified in 11 of the 12 failing patients, including the K65R mutation in seven patients. These results argue against the use of tenofovir-didanosine not only in naive patients, but also in previously suppressed patients.


Gastrointestinal complications of renal failure.
ESRD has well-documented effects on the esophagus, stomach, duodenum, and pancreas. Unless the supply of donor kidneys increases dramatically, these complications of ESRD will continue to be an important clinical issue for gastroenterologists given the large percentage of patients with symptoms. Further study of uremic retention products and abnormal gastrointestinal hormone profiles on the gastrointestinal tract should help provide additional insights into this complex group of patients.


Development of a simple selective SFE method for the determination of desorption behaviour of PCBs in two Swedish sediments.
A simple selective supercritical fluid extraction (SFE) method was developed for the determination of desorption behaviour of PCBs in sediments. This method was applied to determine the distribution of individual PCB congeners among sites of differing bonding strengths in two Swedish sediments (Lake Järnsjön and Baltic bay Orserumsviken). Four different PCB fractions were distinguished in each sediment by applying consecutively harsher supercritical fluid extraction conditions on the same sample. Even though the two sediments had completely different textures, they showed very similar extraction behaviour. It was shown that, in both sediments, a major part of the PCBs (58% and 65%, respectively) were located at "fast sites", from which they were extractable already with the mildest extraction conditions (60 min, 40 degrees C and 120 bar). Only a small fraction of the PCBs were so tightly bound to the sediments (located at "slow sites"), that they could be extracted only under the harshest conditions (60 min, 150 degrees C and 400 bar). Information of this kind should be of great value for the determination of bioavailability of pollutants in sediments and soils, and it is the author's belief that this technique has the potential to develop into a powerful tool in environmental risk assessment.


Machine learning approaches for the prediction of postoperative complication risk in liver resection patients.
For liver cancer patients, the occurrence of postoperative complications increases the difficulty of perioperative nursing, prolongs the hospitalization time of patients, and leads to large increases in hospitalization costs. The ability to identify influencing factors and to predict the risk of complications in patients with liver cancer after surgery could assist doctors to make better clinical decisions. The aim of the study was to develop a postoperative complication risk prediction model based on machine learning algorithms, which utilizes variables obtained before or during the liver cancer surgery, to predict when complications present with clinical symptoms and the ways of reducing the risk of complications. The study subjects were liver cancer patients who had undergone liver resection. There were 175 individuals, and 13 variables were recorded. 70% of the data were used for the training set, and 30% for the test set. The performance of five machine learning models, logistic regression, decision trees-C5.0, decision trees-CART, support vector machines, and random forests, for predicting postoperative complication risk in liver resection patients were compared. The significant influencing factors were selected by combining results of multiple methods, based on which the prediction model of postoperative complications risk was created. The results were analyzed to give suggestions of how to reduce the risk of complications. Random Forest gave the best performance from the decision curves analysis. The decision tree-C5.0 algorithm had the best performance of the five machine learning algorithms if ACC and AUC were used as evaluation indicators, producing an area under the receiver operating characteristic curve value of 0.91 (95% CI 0.77-1), with an accuracy of 92.45% (95% CI 85-100%), the sensitivity of 87.5%, and specificity of 94.59%. The duration of operation, patient's BMI, and length of incision were significant influencing factors of postoperative complication risk in liver resection patients. To reduce the risk of complications, it appears to be important that the patient's BMI should be above 22.96 before the operation, and the duration of the operation should be minimized.


Early circulating erythroid progenitors (BFU-E) in sickle cell anemia.
Sickle cell anemia (SS) patients can be divided into two sub-populations according to peripheral HbF levels. Patients with low (< 9%) HbF levels (LFSS) are characterized by an increased number of circulating BFU-E in active DNA synthesis, and release of burst promoting activity (BPA) by unstimulated low density (LD) adherent cells. In contrast, circulating BFU-E from SS patients with high (> 9%) HbF levels (HFSS) are normal in number, largely in resting phase, and their LD cells do not release BPA-like activity. More recently further heterogeneity has been found among these two groups. In LFSS patients GM-CSF is constitutively produced by unstimulated monocytes. In contrast, HFSS patients' adherent cell depletion increases cycling of BFU-E in culture. CM from HFSS patients inhibits BFU-E expression in culture. Hence, LD adherent cells from HFSS patients may release an inhibitory factor(s). The nature of this factor has to be determined. In addition, there are distinct subpopulations of BFU-E responsiveness to growth factor (GM-CSF, IL-3): a) LFSS patients have a homogeneous BFU-E population, equally responsive to GM-CSF and IL-3; b) HFSS patients, in addition to this subpopulation, have a subset of BFU-E dependent exclusively on IL-3 which is 20 to 40% of the total number of circulating BFU-E. This is similar to BFU-E from normal individuals. Hence, LFSS BFU-E represent an actively proliferating population, equally responsive to GM-CSF and IL-3, controlled by at least constitutively produced GM-CSF and possibly other factors. These observations suggest a significant modification in BFU-E behavior in the subset of SS patients with low HbF levels and high hemopoietic stress. The heterogenous regulation of BFU-E in SS disease seems to be an epiphenomenon of HbF levels, and not vice-versa.


Management of Type 1 Late Sleeve Leak with Gastrobronchial Fistula by Laparoscopic Suturing and Conversion to Roux-en-Y Gastric Bypass: Video Report.
Gastrobronchial fistula (GBF) is a rare but serious complication after laparoscopic sleeve gastrectomy (LSG). It commonly appears sometime after the primary LSG. (Alharbi Ann Thorac Med. 8(3):179-80, 2013; Albanopoulos et al. Surg Obes Relat Dis. 9(6):e97-9, 2013). Surgical approach is an effective treatment. (Rebibo et al. Surg Obes Relat Dis. 10(3):460-67, 2014). The aim of this video was to demonstrate the operative management of a gastrobronchial fistula after LSG by laparoscopic suturing and conversion to a Roux-en-Y gastric bypass (RYGB). We present the case of a 53-year-old woman, with a BMI of 50.2 who presented with a left lower lobe consolidation 7 months after LSG. Imaging revealed a gastrobronchial fistula with left lower lobe consolidation and small sub-diaphragmatic collections. Endoscopy done revealed a fistulous opening beyond the oesophago-gastric junction and a trial of endoscopic stenting failed. In this multimedia high definition video, we present step-by-step the operative management of a late sleeve leak with gastrobronchial fistula by laparoscopic suturing and conversion to a RYGB. The procedure included mobilization of the gastric sleeve, identification and suturing of the fistulous opening, creation of a gastric pouch, creation of an ante-colic Roux limb, gastro-jejunal anastomosis and jejuno-jejunal anastomosis. Drainage of the fistula decreased with absence of a leak on imaging and pneumonia resolved in 15 days. This patient was diagnosed 7 months postoperatively with a gastric sleeve leak and the time to fistula closure from diagnosis was 2 months. GBF is a severe complication of bariatric surgery that usually presents late in the postoperative period. GBF after LSG can be treated by surgical fistula repair and conversion of the sleeve into a RYGB.


Comments to the article "Artefacts with ascorbate and other redox-active compounds in cell culture: epigenetic modifications, and cell killing due to hydrogen peroxide generation in cell culture media".
Previously, we reported that high-dose ascorbic acid induced carcinostatic effects through hydrogen peroxide and superoxide anion radical generation-induced cell death and growth arrest in human tongue carcinoma cells. Recently, the comments and concerns related to this article were pointed out regarding especially the hydrogen peroxide generation in the experimental condition. In this article, I would like to reply to these comments and concerns and state our thoughts related to the study.


Involvement of the spleen by renal angiomyolipoma: metastasis or multicentricity?
Angiomyolipoma has been regarded as a benign renal neoplasm composed of adult fat cells, atypical blood vessels and smooth muscle. We report a case in which a renal angiomyolipoma showed clear evidence of involvement of the spleen and regional lymph nodes. The consensus in the literature suggests that this phenomenon is a manifestation of the multicentric nature of angiomyolipoma, rather than metastasis.


Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.
Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery. Men with localized PC treated with radical prostatectomy at the Durham VA Medical Center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1 and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics an risk of PSA recurrence over time. Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; three died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N-cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence or Gleason sum were noted for SNAIL, ZEB1, vimentin or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (P=0.043), National Comprehensive Cancer Network risk (P=0.013) and PSA recurrence (hazard ratio 1.07, P=0.016). The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery.


Changes in [Ca2+]0, [K+]0 and neuronal activity during oenanthotoxin-induced epilepsy in cat sensorimotor cortex.
Effects of the convulsant drug oenanthotoxin on field potentials, neuronal discharges and extracellular free Ca2+ and K+ concentrations were studied in the sensorimotor cortex of cats. Fifteen to 20 min after topical OETX application spike activity developed (surface negative, deeper layers positive) with a frequency of 0.5-1/sec. With the maturation of the focus spikes became multipeaked and the reversal point of field potential polarity shifted deeper into the cortex. Spontaneous seizures developed when the spike activity had become negative in polarity in recording depths of 1300 micron below the cortical surface. Spontaneous seizures were associated with large rises in [K+]0 and reductions in [Ca2+]0 (delta [K+]0, delta [Ca]0). The latter were often larger than maximum changes in normal cortex. The decay in [Ca2+]0 associated with spontaneous seizures tended to precede the onset of ictal activity. The findings suggest that OETX, like other epileptogenic drugs, uses Ca2+-dependent mechanisms for the initiation of epileptiform activity.


LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p.
Long non-coding RNA (lncRNA) MEG3 has proven to be an important regulator involved in the pathogenesis and development of various human diseases. However, the functional involvement of MEG3 in postmenopausal osteoporosis (PMOP) and its mechanism is still unclear. Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured from mouse pathologic models and patients with PMOP, respectively. The expression of MEG3 and miR-133a-3p in BMSCs was detected using qRT-PCR. The recombinant expression vector was constructed and transfected into BMSCs to regulate the endogenous expression of MEG3 and miR-133a-3p. The mineralized nodules formation, alkaline phosphatase (ALP) activity and Runx2, OCN, OPN expressions were used as specific markers for the differentiation of osteoblasts. The expressions of MEG3 and miR-133a-3p in BMSCs from PMOP were increased, and there was a positive correlation between MEG3 and miR-133a-3p expression in BMSCs. In the differentiation process from BMSCs to osteoblasts, the expressions of MEG3 and miR-133a-3p were markedly decreased, and MEG3 overexpression reversed the osteogenic induction-mediated downregulation of miR-133a-3p, which was accompanied by significant decline in SLC39A1 expression. Furthermore, miR-133a-3p silencing or upregulation eliminated the effects of MEG3 on the osteogenic differentiation of BMSCs through direct binding. The research indicated that MEG3 regulated the expression of miR-133a-3p, and inhibited the osteogenic differentiation of BMSCs induced PMOP.


Synthesis and characterization of trans-4-(4-chlorophenyl)pyrrolidine-3-carboxamides of piperazinecyclohexanes as ligands for the melanocortin-4 receptor.
A series of trans-N-alkyl-4-(4-chlorophenyl)pyrrolidine-3-carboxamides of piperazinecyclohexanemethylamines was synthesized and characterized for binding and function at the melanocortin-4 receptor (MC4R), and several potent benzylamine derivatives were identified. Compound 18 v was found to bind MC4R with potent affinity (K(i)=0.5 nM) and high selectivity over the other melanocortin subtypes and behaved as a functional antagonist (IC(50)=48 nM).


Structure of the major glycolipid from Rothia dentocariosa.
Structural studies of the major glycolipid isolated from Rothia dentocariosa were carried out by specific chemical degradation and nuclear magnetic resonance spectroscopy. The glycolipid was found to be a dimannosylacylmonoglyceride in which the carbohydrate part was the glycerol-linked dimannoside alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-sn-Gro, and the internal mannose was esterified at C-6 by fatty acid residue. The other fatty acyl chain substituted the primary methylene position of glycerol. The occurrence of this glycolipid is limited to the related microorganisms. The structural characteristics can facilitate the differentiation of some genera.


Effects of L- and T-type Ca²(+) channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis.
To assess the involvement of L-type and T-type Ca²(+) channel blockers in inducing male infertility. Prepubertal male mice were fed Ca²(+) channel blockers nifedipine and ethosuximide for 20 days at dosages below maximum tolerated dose (MTD) and assayed for gross morphological changes in the testis such as body weight, testis size and weight. Sperm and Leydig cell counting were conducted concomitantly with serum testosterone level measurement by radioimmunoassay (RIA) and StAR protein mRNA measurement by reverse transcription and polymerase chain reaction (RT-PCR). A chronic exposure to nifedipine or ethosuximide caused a significant reduction in body weight, testis size/weight and sperm production in a dose-dependent fashion associated with a spermatogenic arrest largely at the elongating spermatid stage. The number of Leydig cells, the serum testosterone level but not the luteinizing hormone level, and the content of StAR protein mRNA were also drastically reduced relative to the controls. Both T- and L-type Ca²(+) channel blockers play an adverse role in normal spermatogenesis and steroidogenesis partly by blocking postmeiotic germ cell maturation and/or by abrogating StAR protein expression, contributing to male sterility. Therefore, any therapeutic application of Ca²(+) channel blockers must be used with caution due to its potential adverse side effects on male infertility.


Usefulness of transesophageal echocardiography in unexplained cerebral ischemia.
Two-hundred seventy consecutive patients with "unexplained cerebral ischemia" were studied with transesophageal echocardiography to determine the value of this test in identifying potential cardiac sources of cerebral embolism. The findings of this group were compared with those of 772 consecutive patients undergoing transesophageal echocardiographic evaluation for indications other than cerebral ischemia. This study also examined this group of patients with unexplained cerebral ischemia to determine differences in relation to underlying cardiac rhythm and patient age. Intracardiac thrombus, atrial septal aneurysm, patent foramen ovale, spontaneous left atrial contrast and protruding debris in the thoracic aorta were found more often in patients with unexplained cerebral ischemia. Wall motion abnormalities of the left ventricle, as well as mild to moderate valvular lesions including mitral valve prolapse, were found to be similar in both groups. Spontaneous left atrial contrast, as well as mild to moderate valvular abnormalities, were found more often in patients with atrial fibrillation (22% of the group with unexplained cerebral ischemia). However, the presence of intracardiac thrombus was no more frequent in patients with atrial fibrillation than in those with normal sinus rhythm. Patients aged > 50 years were found to have atrial fibrillation and larger left atrial size more often than their younger cohorts, as well as a greater incidence of valvular abnormalities and left ventricular wall motion abnormalities. Mitral valve prolapse was seen more frequently in the younger cohort of patients.


Proposed tertiary structure of the sodium channel.
On the basis of our recent results of the complete amino acid sequence of the squid Loligo bleekeri sodium channel deduced by cloning and sequence analysis of the complementary DNA (Sato, C. and Matsumoto, G. Biochem. Biophys. Res. Comm. 186, 1), we have proposed a tertiary structure model of the sodium channel where the transmembrane segments are octagonally aligned and the four linkers of S5-6 between segments S5 and S6 play a crucial role in the activation gate, voltage sensor and ion selective pore, which can slide, depending on membrane potentials, along inner walls consisting of segments S2 and S4 alternately. The proposed model is contrasted with that of Noda et al. (Nature 320; 188-192, 1986).


Antileukemic properties of the kinase inhibitor OTSSP167 in T-cell acute lymphoblastic leukemia.
Novel drugs are needed to increase treatment response in children with high-risk T-cell acute lymphoblastic leukemia (T-ALL). Following up on our previous report on the activation of the MAP2K7-JNK pathway in pediatric T-ALL, here we demonstrate that OTSSP167, recently shown to inhibit MAP2K7, has antileukemic capacity in T-ALL. OTSSP167 exhibited dose-dependent cytotoxicity against a panel of T-ALL cell lines with IC50 in the nanomolar range (10-50 nM). OTSSP167 induces apoptosis and cell cycle arrest in T-ALL cell lines, associated at least partially with the inhibition of MAP2K7 kinase activity and lower activation of its downstream substrate, JNK. Other leukemic T-cell survival pathways, such as mTOR and NOTCH1 were also inhibited. Daily intraperitoneal administration of 10 mg/kg OTSSP167 was well tolerated, with mice showing no hematological toxicity, and effective at reducing the expansion of human T-ALL cells in a cell-based xenograft model. The same dosage of OTSSP167 efficiently controlled the leukemia burden in the blood, bone marrow, and spleen of 3 patient-derived xenografts, which resulted in prolonged survival. OTSSP167 exhibited synergistic interactions when combined with dexamethasone, L-asparaginase, vincristine, and etoposide. Our findings reveal novel antileukemic properties of OTSSP167 in T-ALL and support the use of OTSSP167 as an adjuvant drug to increase treatment response and reduce relapses in pediatric T-ALL.


Building Bridges Between Evidence and Policy in Mental Health Services Research: Introducing the Policy Review Article Type.
Although it is widely accepted that patients do better when evidence-based health care practices are used, there is less acknowledgment of the positive outcomes associated with evidence-based policy making. To address the need for high-quality evidence to inform mental health policies, Psychiatric Services has recently launched a new article format: the Policy Review. This review type defines a specific policy-relevant issue affecting behavioral health systems, describes current knowledge and limitations, and discusses policy implications. Reviews can focus on mental health policies or examine how other health or social policies affect people with mental illness or substance use disorders. This brief overview of the need for a policy review article type describes differences between evidence-based policy making and practices and looks at research approaches focused on evidence-based policy making, as well as legislative and other efforts to support it. Broad guidelines for potential submissions are also provided.


Genetic algorithm usage in water quality monitoring networks optimization in Gediz (Turkey) river basin.
Selection procedure of the optimum station combination for decreasing the station number from 33 to 14 in water quality monitoring network of Gediz river basin was applied using an optimization method. Gediz basin is one of the important basins and it covers 2.3% of the total surface area of Turkey. The technique includes two stages as the data preparation and the optimization. In the data preparation stage, firstly, alternative station combinations decreased and then station combination scores obtained from assigned selection criteria for point and nonpoint pollution management objectives. Finally, genetic algorithm applied to select the best combination. The results were compared with a prior solution that used dynamic programming as the optimization technique.


(4'-Chloro-2,2':6',2''-terpyridine-κ3 N,N',N'')bis(nitrato-κO)zinc(II).
In the title complex, [Zn(C15H10ClN3)(NO3)2], the central zinc(II) atom is penta-coordinated by two O-bonded nitrate ions and three N atoms of the 4'-chloro-2,2':6',2''-terpyridine ligand in a slightly distorted trigonal-bipyramidal shape. The main feature of the title complex packing is the presence of offset π-π inter-actions between the terpyridine rings in different layers. This structure constitutes the first known example of a zinc(II) 4-chloro-terpyridine complex with coordinating nitrate ions.


Ambulatory surgery in urogynaecology.
Ambulatory surgery offers advantages to both patients and providers. It is imperative to ensure appropriate case selection, pre-operative counseling, a suitable environment, trained staff, adequate analgesia and post-operative care both in the hospital and the community. Many well-established urogynaecological procedures such as cystoscopy and vaginal repair may be performed in an ambulatory setting. Newer procedures such as injection of botulinum toxin or peri-urethral bulking agents and tension-free tapes for stress incontinence may also be performed in this way. To date, the literature is deficient in robust studies comparing outcomes and patient satisfaction between conventional and ambulatory surgical procedures, and randomized controlled trials are required.


Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes.
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related deaths in the world with an estimated number of 1.8 million new cases and about 881,000 deaths worldwide in 2018. The epidemiology of CRC varies significantly between different regions in the world as well as between different age, gender and racial groups. Multiple factors are involved in this variation, including risk factor exposure, demographic variations in addition to genetic susceptibility and genetic mutations and their effect on the prognosis and treatment response. In this mini-review, we discuss the recent epidemiological trend including the incidence and mortality of colorectal cancer worldwide and the factors affecting these trends.


Solitary rectal ulcer syndrome.
Solitary rectal ulcer syndrome is a rare disorder characterized by erythema or ulceration of the rectal wall, associated with typical histological features, and disturbed defaecatory behaviour with the passage of blood and mucus. This is a review based on a literature search using a computer database (Medline) and manual cross-referencing. The pathogenesis is likely to vary in different patients; it includes trauma from straining, direct digital trauma and possibly primary neuromuscular pathology. The histological findings of extension of the muscularis mucosa between crypts and muscularis propria disorganization on full-thickness specimens are characteristic. Biofeedback defaecation retraining, including habit training, can lead to symptom improvement and return to work in a majority of patients. Abdominal rectopexy offers long-term symptom improvement in approximately 50 per cent of patients. Rectal ulceration may persist after any treatment, even if symptoms improve. Behavioural therapy and carefully considered operations offer the best treatment results. Further work on psychological factors and neuromuscular and vascular pathology is required.


The ROCKs on which tumour cells thrive.
A new study reveals that the ROCK proteins play key roles in the formation of tumours in mice.


Evidence-Based Precision Oncology with the Cancer Targetome.
A core tenet of precision oncology is the rational choice of drugs to interact with patient-specific biological targets of interest, but it is currently difficult for researchers to obtain consistent and well-supported target information for pharmaceutical drugs. We review current drug-target interaction resources and critically assess how supporting evidence is handled. We introduce the concept of a unified Cancer Targetome to aggregate drug-target interactions in an evidence-based framework. We discuss current unmet needs and the implications for evidence-based clinical omics. The focus of this review is precision oncology but the discussion is highly relevant to targeted therapies in any area.


Functional connectivity gradients of the cingulate cortex.
Heterogeneity of the cingulate cortex is evident in multiple dimensions including anatomy, function, connectivity, and involvement in networks and diseases. Using the recently developed functional connectivity gradient approach and resting-state functional MRI data, we found three functional connectivity gradients that captured distinct dimensions of cingulate hierarchical organization. The principal gradient exhibited a radiating organization with transitions from the middle toward both anterior and posterior parts of the cingulate cortex and was related to canonical functional networks and corresponding behavioral domains. The second gradient showed an anterior-posterior axis across the cingulate cortex and had prominent geometric distance dependence. The third gradient displayed a marked differentiation of subgenual and caudal middle with other parts of the cingulate cortex and was associated with cortical morphology. Aside from providing an updated framework for understanding the multifaceted nature of cingulate heterogeneity, the observed hierarchical organization of the cingulate cortex may constitute a novel research agenda with potential applications in basic and clinical neuroscience.


Continuing challenges for computer-based neuropsychological tests.
A number of issues critical to the development of computer-based neuropsychological testing systems that remain continuing challenges to their widespread use in occupational and environmental health are reviewed. Several computer-based neuropsychological testing systems have been developed over the last 20 years, and they have contributed substantially to the study of neurologic effects of a number of environmental exposures. However, many are no longer supported and do not run on contemporary personal computer operating systems. Issues that are continuing challenges for development of computer-based neuropsychological tests in environmental and occupational health are discussed: (1) some current technological trends that generally make test development more difficult; (2) lack of availability of usable speech recognition of the type required for computer-based testing systems; (3) implementing computer-based procedures and tasks that are improvements over, not just adaptations of, their manually-administered predecessors; (4) implementing tests of a wider range of memory functions than the limited range now available; (5) paying more attention to motivational influences that affect the reliability and validity of computer-based measurements; and (6) increasing the usability of and audience for computer-based systems. Partial solutions to some of these challenges are offered. The challenges posed by current technological trends are substantial and generally beyond the control of testing system developers. Widespread acceptance of the "tablet PC" and implementation of accurate small vocabulary, discrete, speaker-independent speech recognition would enable revolutionary improvements to computer-based testing systems, particularly for testing memory functions not covered in existing systems. Dynamic, adaptive procedures, particularly ones based on item-response theory (IRT) and computerized-adaptive testing (CAT) methods, will be implemented in new tests that will be more efficient, reliable, and valid than existing test procedures. These additional developments, along with implementation of innovative reporting formats, are necessary for more widespread acceptance of the testing systems.


Neuro-Behçet syndrome presenting as acute meningeal syndrome.
Behçet's disease is a systemic vasculitic disease characterized mainly by recurrent oral and genital aphthous ulcers, uveitis and skin findings. Central nervous system involvement is a serious manifestation. A case of acute meningeal syndrome secondary to Behçet's disease is presented. Behçet's disease should always be considered in differential diagnosis of acute meningeal syndrome without signs of viral infection, particularly in the context of multisystem manifestations.


The role of intradermal skin testing in inhalant allergy.
To provide an overview of the role of intradermal skin testing (IDST) in inhalant allergy. A literature search was conducted in MEDLINE to identify peer-reviewed articles related to IDST using the following keywords: skin testing, intradermal, intracutaneous, aeroallergen, and inhalant allergen. In addition, references cited within these articles were also reviewed. Articles were selected based on their relevance to the topic. The use of IDST for inhalant allergy varies widely among allergists. When performed, it is necessary to use a 100- to 1,000-fold dilution from the stock allergen extract. IDST is used routinely in the standardization of extracts in the United States. With a negative skin prick test result, a positive IDST result has low agreement with in vitro and challenge results and generally adds little to the diagnostic evaluation. In contrast, a negative IDST result generally has a high negative predictive value. Only a few inhalant allergens have been evaluated with challenge models for IDST. A summary of the data is also presented in tabular form. Most of the literature suggests that with a negative skin prick test result, a positive IDST result adds little to the diagnostic evaluation of inhalant allergy. However, additional studies are necessary using challenge models for less potent and nonstandardized inhalant allergens (molds, trees, dog, weeds).


Prepregnancy exposure to dietary arsenic and congenital heart defects.
Arsenic crosses the placenta and accumulates in fetal tissues. In the United States, diet is the predominant route of arsenic exposure, but epidemiologic data are sparse regarding this exposure and development of birth defects. Using data from a large case-control study, we explored associations between maternal dietary arsenic exposure and congenital heart defects (CHDs), the most prevalent birth defects. We used maternal self-reported dietary assessments and arsenic concentration estimates in food items to estimate average daily exposure to dietary arsenic during the year before pregnancy for mothers of 10,446 unaffected control children and 6,483 case children diagnosed with CHDs. Using tertiles of dietary exposure to total arsenic (all species) and inorganic arsenic, we applied logistic regression analysis to estimate associations for middle and high tertiles, compared with the low tertile. Positive associations (odds ratio [OR] ≥ 1.2) for total arsenic were observed in both tertiles for perimembranous ventricular septal defect (VSD) and high tertile only for double outlet right ventricle-transposition of the great arteries (DORV-TGA), partial anomalous pulmonary venous return (PAPVR), and tricuspid atresia. Positive associations were also observed in both tertiles (tricuspid atresia) and high tertile only (DORV-TGA, conoventricular VSD, PAPVR, and pulmonary atresia) for inorganic arsenic. Most remaining associations were near or below unity. Exploration of maternal dietary exposure to total and inorganic arsenic and CHDs produced few positive associations but was limited by available food item concentrations. Future research requires expanded collection of dietary data, improved estimates of concentrations, and consideration of nondietary sources of arsenic exposure.


On the Effectiveness of Deep Representation Learning: the Atrial Fibrillation Case.
The automatic and unsupervised analysis of biomedical time series is of primary importance for diagnostic and preventive medicine, enabling fast and reliable data processing to reveal clinical insights without the need for human intervention. Representation learning (RL) methods perform an automatic extraction of meaningful features that can be used, e.g., for a subsequent classification of the measured data. The goal of this study is to explore and quantify the benefits of RL techniques of varying degrees of complexity, focusing on modern deep learning (DL) architectures. We focus on the automatic classification of atrial fibrillation (AF) events from noisy single-lead electrocardiographic signals (ECG) obtained from wireless sensors. This is an important task as it allows the detection of sub-clinical AF which is hard to diagnose with a short in-clinic 12-lead ECG. The effectiveness of the considered architectures is quantified and discussed in terms of classification performance, memory/data efficiency and computational complexity.


Efficient management of new patient referrals to a breast service: the safe introduction of an advanced nurse practitioner-led telephone breast pain service.
There has been an almost 100% increase in referrals to breast cancer diagnostic clinics in the past decade. Breaching of the two-week cancer referral target is now commonplace, potentially delaying diagnoses of breast malignancy in many women. Almost one in five of these referrals are women with mastalgia, not a symptom linked to breast cancer. The objective of the study was the safe introduction of an advanced nurse practitioner-led telephone service for women with mastalgia to improve the service for women and create capacity for those with "red flag" breast symptoms. Referrals to clinic were triaged, women with mastalgia only were directed to a telephone-based assessment clinic and symptoms evaluated using a multidisciplinary created proforma. Within 23 months, 1,427 women were assessed in the breast pain telephone assessment clinic: 863 (61%) were aged over 40 and 564 (39%) aged under 40. A total of 1,238 underwent telephone assessment. Reassurance and discharge only was needed for 365 (26%). The aetiology of pain was identified as musculoskeletal in 1,104/1,238 (89%) of patients, with only 39/1,238 (3.2%) identified as having true breast pain. Additional symptoms were mentioned by 264 women (18%) during the consultation; all immediately redirected back to a diagnostic clinic. Mammography was undertaken in 609 women (43%). Seven women (0.6%) were diagnosed with a breast malignancy. Patient survey indicated that 93% of patients were satisfied with the care received and 97% said they would recommend the service to a family member or friend. Although face-to-face assessments for breast pain remain the standard practice in many breast units, data indicating the safety of a telephone assessment clinic, along with high levels of patient satisfaction, question whether services can be delivered differently.


The trapezium-thumb metacarpal joint: the relationship of joint shape and degenerative joint disease.
An investigation of sixty-seven embalmed cadaver hands was performed to determine if the topography of articular surfaces was related to thumb basal joint arthritis. The trapezial articular surface tended to be flatter in women and joints with early degenerative changes. The trapezial surface was transformed from a saddle type to a semi-cylindrical type with advancing arthritis.


Equilibrium sampling through membrane based on a single hollow fibre for determination of drug-protein binding and free drug concentration in plasma.
The determination of drug-protein binding and free drug concentration in plasma applying the equilibrium sampling through membrane (ESTM) technique has been studied using supported liquid membrane extraction in a single hollow fibre without any membrane carrier. In the extraction setup, the donor phase (plasma or buffer) was placed in the vial, into which was immersed the hollow fibre with the acceptor phase situated in the lumen. This proposed technique was applied to study the drug-protein binding of five local anaesthetics and two antidepressants as model substances, and the influence of the total drug concentration on the drug-protein binding was investigated. The brief theoretical background for determination of the drug-protein binding under equilibrium conditions is described. The developed method shows a new, improved and simple procedure for determination of free drug concentration in plasma and extent of drug-protein binding.


"Volunteering by chance" to promote civic responsibility and civic engagement: does it work?
This study investigated the effectiveness of a program to promote civic responsibility and prevent antisocial behavior in a sample of Italian adolescents. Participants were 83 Italian male adolescents, attending the second year of high school (Mean age = 15.79; SD = 0.87). In order to test the efficacy of different strategies (in-classroom training and service activity in a voluntary organization) we divided students into two experimental groups--one classroom of students participated in both strategies (training + volunteering group) and another classroom only participated in the training (training only group)--and one control group. Process and efficacy evaluations were completed. Data were collected before and following the intervention. The process evaluation revealed that the program was highly accepted and appreciated by students. The efficacy evaluation revealed no intervention effects on civic responsibility. However, the training + volunteering group reported a significant decrease in antisocial behavior after the program. Thus, the program was effective in preventing antisocial behavior but not in promoting civic responsibility in our sample.


DNA induced sequestration of a bioactive cationic fluorophore from the lipid environment: A spectroscopic investigation.
The effect of calf-thymus DNA (ctDNA) on the lipid bound probe, formed by the cationic phenazinium dye phenosafranin (PSF) and the anionic lipid dimyristoyl-L-α-phosphatidylglycerol (DMPG), has been unearthed exploiting various spectroscopic techniques. Steady state and time-resolved fluorometric studies and measurements of circular dichroism and DNA helix melting temperature reveal that in the presence of DNA the probe is dislodged from the lipid environment and gets intercalated within the DNA helix. The work qualitatively illustrates that the anionic lipid can be used as a potential nanocarrier for delivering the cationic drugs to the most relevant biomacromolecular target, DNA.


Characterizing the spatial signal of environmental DNA in river systems using a community ecology approach.
Environmental DNA (eDNA) is gaining a growing popularity among scientists but its applicability to biodiversity research and management remains limited in river systems by the lack of knowledge about the spatial extent of the downstream transport of eDNA. Here, we assessed the ability of eDNA inventories to retrieve spatial patterns of fish assemblages along two large and species-rich Neotropical rivers. We first examined overall community variation with distance through the distance decay of similarity and compared this pattern to capture-based samples. We then considered previous knowledge on individual species distributions, and compared it to the eDNA inventories for a set of 53 species. eDNA collected from 28 sites in the Maroni and 25 sites in the Oyapock rivers permitted to retrieve a decline of species similarity with increasing distance between sites. The distance decay of similarity derived from eDNA was similar and even more pronounced than that obtained with capture-based methods (gill-nets). In addition, the species upstream-downstream distribution range derived from eDNA matched to the known distribution of most species. Our results demonstrate that environmental DNA does not represent an integrative measure of biodiversity across the whole upstream river basin but provides a relevant picture of local fish assemblages. Importantly, the spatial signal gathered from eDNA was therefore comparable to that gathered with local capture-based methods, which describes fish fauna over a few hundred metres.


β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593.
Actinomycetes bacteria produce diverse bioactive molecules that are useful as drug seeds. To improve their yield, researchers often optimize the fermentation medium. However, exactly how the extracellular chemicals present in the medium activate secondary metabolite gene clusters remains unresolved. BR-1, a β-carboline compound, was recently identified as a chemical signal that enhanced reveromycin A production in Streptomyces sp. SN-593. Here we show that BR-1 specifically bound to the transcriptional regulator protein RevU in the reveromycin A biosynthetic gene cluster, and enhanced RevU binding to its promoter. RevU belongs to the LuxR family regulator that is widely found in bacteria. Interestingly, BR-1 and its derivatives also enhanced the production of secondary metabolites in other Streptomyces species. Although LuxR-N-acyl homoserine lactone systems have been characterized in Gram-negative bacteria, we revealed LuxR-β-carboline system in Streptomyces sp. SN-593 for the production of secondary metabolites. This study might aid in understanding hidden chemical communication by β-carbolines.