Interaction between attention and bottom-up saliency mediates the representation of foreground and background in an auditory scene.
The mechanism by which a complex auditory scene is parsed into coherent objects depends on poorly understood interactions between task-driven and stimulus-driven attentional processes. We illuminate these interactions in a simultaneous behavioral-neurophysiological study in which we manipulate participants' attention to different features of an auditory scene (with a regular target embedded in an irregular background). Our experimental results reveal that attention to the target, rather than to the background, correlates with a sustained (steady-state) increase in the measured neural target representation over the entire stimulus sequence, beyond auditory attention's well-known transient effects on onset responses. This enhancement, in both power and phase coherence, occurs exclusively at the frequency of the target rhythm, and is only revealed when contrasting two attentional states that direct participants' focus to different features of the acoustic stimulus. The enhancement originates in auditory cortex and covaries with both behavioral task and the bottom-up saliency of the target. Furthermore, the target's perceptual detectability improves over time, correlating strongly, within participants, with the target representation's neural buildup. These results have substantial implications for models of foreground/background organization, supporting a role of neuronal temporal synchrony in mediating auditory object formation.


Using Biotechnology-Led Approaches to Uplift Cereal and Food Legume Yields in Dryland Environments.
Drought and heat in dryland agriculture challenge the enhancement of crop productivity and threaten global food security. This review is centered on harnessing genetic variation through biotechnology-led approaches to select for increased productivity and stress tolerance that will enhance crop adaptation in dryland environments. Peer-reviewed literature, mostly from the last decade and involving experiments with at least two seasons' data, form the basis of this review. It begins by highlighting the adverse impact of the increasing intensity and duration of drought and heat stress due to global warming on crop productivity and its impact on food and nutritional security in dryland environments. This is followed by (1) an overview of the physiological and molecular basis of plant adaptation to elevated CO2 (eCO2), drought, and heat stress; (2) the critical role of high-throughput phenotyping platforms to study phenomes and genomes to increase breeding efficiency; (3) opportunities to enhance stress tolerance and productivity in food crops (cereals and grain legumes) by deploying biotechnology-led approaches [pyramiding quantitative trait loci (QTL), genomic selection, marker-assisted recurrent selection, epigenetic variation, genome editing, and transgene) and inducing flowering independent of environmental clues to match the length of growing season; (4) opportunities to increase productivity in C3 crops by harnessing novel variations (genes and network) in crops' (C3, C4) germplasm pools associated with increased photosynthesis; and (5) the adoption, impact, risk assessment, and enabling policy environments to scale up the adoption of seed-technology to enhance food and nutritional security. This synthesis of technological innovations and insights in seed-based technology offers crop genetic enhancers further opportunities to increase crop productivity in dryland environments.


Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings.
The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and realism of agent-based simulations and limit the intrinsic biases of the homogeneous mixing.


[Functional dyspepsia, gastric emptying of solids, and Helicobacter pylori infection].
The origin of functional dyspepsia (FD) is unknown, however, abnormal gastric emptying and infection by H. pylori have been suggested as possible causes. The aim of this study was to test the hypothesis that infection by H. pylori could be related to alterations in gastric emptying of solids and play a role in the pathophysiology of dyspepsia. Studies were performed on 12 controls: 6 males, 6 females, age 40 +/- 13, and on 45 FD patients: 15 males and 30 females, age 43.5 +/- 12. Clinical criteria for FD diagnosis were post-prandial epigastric pain, nausea, vomiting or epigastric bloating, with normal blood test, upper endoscopy and abdominal ultrasound. Diagnosis of H. pylori infection was either by growth positive on culture of antral biopsy or by all of the following: on Gram stain, urease test positive and visualization of microorganisms in the antral biopsy. Gastric emptying of solids was studied with a radio-nuclide technique. Patients were prospectively classified in 4 groups according to the main symptom: reflux-like, ulcer-like, dysmotility, and non-specific. H. pylori infection was observed in 21/32 (66%) FD patients. No significant differences in the gastric emptying of solids between the control group and patients with FD (tl/2 80 +/- 17 minutes vs 75 +/- 16 min). The presence of H. pylori infection did not influence gastric emptying rates (78 +/- 16 minutes in infected patients vs 73 +/- 15 min in non infected patients). Gastric emptying times were similar among the four subgroups of FD patients. No significant differences in gastric emptying of solids were found in H. pylori infected persons as compared with the controls. These findings suggest that H. pylori infection and/or changes in gastric emptying of solids do not play a role in the pathophysiology of FD.


Recombinant Duffy binding-like-alpha domains of Plasmodium falciparum erythrocyte membrane protein 1 elicit antibodies in rats that recognise conserved epitopes.
Plasmodium falciparum parasites remodel the surface of human erythrocytes on invasion by the insertion of parasite-derived proteins in knob-like protrusions. P. falciparum erythrocyte membrane protein 1 (PfEMP-1), a variant surface antigen, has been shown to be anchored in these knobs and mediates adhesion to various host endothelial receptors. These proteins also undergo clonal antigenic variation as a means of immune evasion. Duffy binding-like-alpha(DBL-alpha) domain together with the cysteine-rich interdomain region form the head structure of the PfEMP1 molecule. In this report, we used ten different recombinant DBL-alpha fusion proteins expressed in Escherichia coli to generate antibodies in experimental animals. Five out of ten recombinant DBL-alpha fusion proteins were immunogenic and induced antibodies that reacted with conserved peptides derived from PfEMP1. Indirect immunofluorescence assay was used to localise PfEMP-1-DBL-alpha expressed in parasitised erythrocytes. Positive fluorescence reactivity was observed within the cytoplasm and with membrane structures but not on the surface of intact P. falciparum-infected erythrocytes.


Apical Longitudinal Strain Can Help Predict the Development of Left Ventricular Thrombus after Anterior Myocardial Infarction.
Left ventricular (LV) thrombus formation is a common complication of anterior myocardial infarction (ANT-MI). The aim of this study was to investigate the relationship between apical longitudinal strain (ALS) and LV apical thrombus after ANT-MI. The cross-sectional study included a total of 235 patients who were followed up after primary percutaneous coronary intervention performed for ANT-MI and had a reduced LV ejection fraction (LVEF) (< -40%). Of these patients, 24 were excluded from the study, and the remaining 211 patients were included in the analysis. Patients were divided into two groups based on the presence (n = 42) or absence (n = 169) of LV thrombus detected by echocardiography. ALS was measured using speckle-tracking echocardiography. Thrombus was detected in 42 of 211 patients. There was no significant difference between the groups regarding age or gender. Apical strain (AS), global longitudinal strain (GLS), apical wall thickness (AWT), and EF were significantly lower in patients with LV apical thrombus when compared to those without LV apical thrombus (AS, -5.00 +- 2.30% vs. -8.54 +- 2.48%, p < 0.001; GLS, -10.6 +- 3.54% vs. -12.1 +- 2.84%, p = 0.013; AWT, 4.71 +- 1.11 vs. 6.33 +- 1.78 mm, p < 0.001; EF, 31.40 +- 4.10% vs. 37.75 +- 3.17%, p < 0.001). On univariate and multivariate analyses, aneurysm (AA), AS, and AWT were found to be independent predictors of LV apical thrombus (AA, odds ratio [OR] 4.649, p = 0.010; AS, OR 1.749, p < 0.001; AWT, OR 0.729, p = 0.042). ALS is highly sensitive and specific for predicting LV thrombus after ANT-MI. An early and accurate evaluation of LV thrombus may prevent embolic complications, particularly cerebrovascular events.


Calcium channels controlling acetylcholine release from preganglionic nerve terminals in rat autonomic ganglia.
Little is known about the nature of the calcium channels controlling neurotransmitter release from preganglionic parasympathetic nerve fibres. In the present study, the effects of selective calcium channel antagonists and amiloride were investigated on ganglionic neurotransmission. Conventional intracellular recording and focal extracellular recording techniques were used in rat submandibular and pelvic ganglia, respectively. Excitatory postsynaptic potentials and excitatory postsynaptic currents preceded by nerve terminal impulses were recorded as a measure of acetylcholine release from parasympathetic and sympathetic preganglionic fibres following nerve stimulation. The calcium channel antagonists omega-conotoxin GVIA (N type), nifedipine and nimodipine (L type), omega-conotoxin MVIIC and omega-agatoxin IVA (P/Q type), and Ni2+ (R type) had no functional inhibitory effects on synaptic transmission in both submandibular and pelvic ganglia. The potassium-sparing diuretic, amiloride, and its analogue, dimethyl amiloride, produced a reversible and concentration-dependent inhibition of excitatory postsynaptic potential amplitude in the rat submandibular ganglion. The amplitude and frequency of spontaneous excitatory postsynaptic potentials and the sensitivity of the postsynaptic membrane to acetylcholine were unaffected by amiloride. In the rat pelvic ganglion, amiloride produced a concentration-dependent inhibition of excitatory postsynaptic currents without causing any detectable effects on the amplitude or configuration of the nerve terminal impulse. These results indicate that neurotransmitter release from preganglionic parasympathetic and sympathetic nerve terminals is resistant to inhibition by specific calcium channel antagonists of N-, L-, P/Q- and R-type calcium channels. Amiloride acts presynaptically to inhibit evoked transmitter release, but does not prevent action potential propagation in the nerve terminals, suggesting that amiloride may block the pharmacologically distinct calcium channel type(s) on rat preganglionic nerve terminals.


Production of recombinant human acid α-glucosidase with high-mannose glycans in gnt1 rice for the treatment of Pompe disease.
Lysosomal storage diseases are a group of inherited metabolic disorders. Patients are treated with enzyme replacement therapy (ERT), in which the replacement enzymes are required to carry terminal mannose or mannose 6-phosphate residues to allow efficient uptake into target cells and tissues. N-acetylglucosaminyltransferase-I (GnTI) mediates N-glycosylation in the cis cisternae of the Golgi apparatus by adding N-acetylglucosamine to the exposed terminal mannose residue of core N-glycan structures for further processing. Mutant rice lacking GnTI produces only high mannosylated glycoproteins. In this study, we introduced a gene encoding recombinant human acid α-glucosidase (rhGAA), which is used in ERT for Pompe disease, into gnt1 rice callus by particle bombardment. Integration of the target gene into the genome of the gnt1 rice line and its mRNA expression were confirmed by PCR and Northern blot, respectively. Western blot analysis was performed to confirm secretion of the target proteins into the culture media. Using an indirect enzyme linked immunosorbent assay, we determined the maximum expression of rhGAA to be approximately 45mg/L, 13days after induction. To assay the enzymatic activity and determine the N-glycan profile of rhGAA, we purified the protein using a 6×histidine tag. The in vitro α-glucosidase activity of rhGAA from gnt1 rice callus (gnt1-GAA) was 3.092U/mg, similar to the activity of the Chinese hamster ovary cell-derived GAA (3.154U/mg). N-glycan analysis revealed the presence of high-mannose N-glycans on gnt1-GAA. In addition, the production of high-mannose GAA using gnt1 rice calli as an expression host was characterized, which may aid the future development of therapeutic enzymes for the treatment of Pompe disease.


Extract from Rhus verniciflua Stokes is capable of inhibiting the growth of human lymphoma cells.
Rhus verniciflua Stokes (RVS), used as a food additive and a traditional herbal medicine, has both antioxidant and antitumor activities which are known to be closely associated with the polyphenolic compounds that it contains. In the present study, we purified a fraction from a crude acetone extract of RVS, named RCMF (RVS chloroform-methanol fraction), and evaluated its ability to scavenge free radicals and inhibit cell growth. In addition, the active compounds responsible for the activities were identified. Results showed that RCMF contained an antioxidant potential and strongly suppressed the proliferative capability of B lymphoma cells. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increased DNA fragmentation and low fluorescence intensity in the nuclei after propidium iodide staining, and also on the appearance of DNA laddering. Finally, EI-MS, 1H-NMR, and 13C-NMR spectra confirmed that RCMF contained flavonoid derivatives, including protocatechuic acid, fustin, fisetin, sulfuretin, and butein, suggesting that these flavonoid derivatives are the main active compounds responsible for the antioxidant and antiproliferative activities of RCMF.


EFFECTS OF RENAL DYSFUNCTION ON HEALING OF COLONIC ANASTOMOSIS: EXPERIMENTAL STUDY IN WISTAR RATS.
Chronic kidney disease affects more than 500 million people worldwide. In this context, the uremic toxins present are related to worsening in tissue healing. Evaluate on healing of colonic anastomosis in uremic rats, serum and anatomopathological indicators, which may be related to the change tissue repair process. Twenty Wistar rats, were randomly separated into two groups. In the sham group they were submitted to 5/6 nephrectomy simulation in left kidney, simulation right nephrectomy, median laparotomy, colotomy and colorraphy. In the uremia group, they were submitted to 5/6 nephrectomy of the left kidney, total nephrectomy of the right kidney and median laparotomy, colotomy and colorraphy. Were collected for serum urea, creatinine and CRP dosages and the colonic segments were studied for evaluation of granulation tissue, collagen maturation, microvascular and myofibroblasts density, and cell viability. Through histochemical processing, microvascular density was evaluated by anti-CD34 monoclonal antibody marking, cell viability by cell proliferation nuclear antigen screening and myofibroblasts density with monoclonal anti-α-actin antibody. Computerized histometry was used for evaluations of collagens type I and III by the coloration of picrosirius. The group submitted to nephrectomy 5/6, compared to the sham group, show urea increase (p<0.0000) and higher C reactive protein (p=0.0142). Decrease of granulation tissue formation (border reepithelialization p=0,0196, angiofibroblast proliferation p=0.0379), mean collagen I (p=0,0009) and collagen III (p=0,016), microvascular density (p=0,0074), cell proliferation nuclear antigen (p<0,0000) and myofibroblasts (p<0,0001). The uremia induced by nephrectomy 5/6 model establishes negative impact in the colonic wound healing.


The PRECEDE-PROCEED model: application to planning a child pedestrian injury prevention program.
The objectives were first, to modify the PRECEDE-PROCEED model and to use it is as a basis for planning a three year intervention trial that aims to reduce injury to child pedestrians. A second objective was to assess the suitability of this process for planning such a relatively complex program. The project was carried out in 47 primary schools in three local government areas, in the Perth metropolitan area. The program was developed, based on extensive needs assessment incorporating formative evaluations. Epidemiological, psychosocial, environmental, educational, and demographic information was gathered, organised, and prioritised. The PRECEDE-PROCEED model was used to identify the relevant behavioural and environmental risk factors associated with child pedestrian injuries in the target areas. Modifiable causes of those behavioural and environmental factors were delineated. A description of how the model facilitated the development of program objectives and subobjectives which were linked to strategy objectives, and strategies is provided. The process used to plan the child pedestrian injury prevention program ensured that a critical assessment was undertaken of all the relevant epidemiological, behavioural, and environmental information. The gathering, organising, and prioritising of the information was facilitated by the process. The use of a model such as PRECEDE-PROCEED can enhance the development of a child injury prevention program. In particular, the process can facilitate the identification of appropriate objectives which in turn facilitates the development of suitable interventions and evaluation methods.


Application of a Neural Network Classifier to Radiofrequency-Based Osteopenia/Osteoporosis Screening.
There is an unmet need for quick, physically small, and cost-effective office-based techniques that can measure bone properties without the use of ionizing radiation. The present study reports the application of a neural network classifier to the processing of previously collected data on very-low-power radiofrequency propagation through the wrist to detect osteoporotic/osteopenic conditions. Our approach categorizes the data obtained for two dichotomic groups. Group 1 included 27 osteoporotic/osteopenic subjects with low Bone Mineral Density (BMD), characterized by a Dual X-Ray Absorptiometry (DXA) T-score below - 1, measured within one year. Group 2 included 40 healthy and mostly young subjects without major clinical risk factors such as a (family) history of bone fracture. We process the complex radiofrequency spectrum from 30 kHz to 2 GHz. Instead of averaging data for both wrists, we process them independently along with the wrist circumference and then combine the results, which greatly increases the sensitivity. Measurements along with data processing require less than 1 min. For the two dichotomic groups identified above, the neural network classifier of the radiofrequency spectrum reports a sensitivity of 83% and a specificity of 94%. These results are obtained without including any additional clinical risk factors. They justify that the radio transmission data are usable on their own as a predictor of bone density. This approach has the potential for screening patients at risk for fragility fractures in the office, given the ease of implementation, small device size, and low costs associated with both the technique and the equipment.


Telementorship in Underway Naval Operations: Leveraging Operational Virtual Health for Tactical Combat Casualty Care.
Virtual health (VH) may enhance mentorship to remote first responders. We evaluated the feasibility of synchronous bidirectional VH to mentor life-saving procedures performed by deployed novice providers. Video teleconferencing (VTC) was established between the USNS Mercy (T-AH 19) underway in the Pacific Ocean to Naval Medical Center San Diego using surgeon teleconsultation. The adult simulated clinical vignette included injuries following a shipboard explosion with subsequent fire. The pediatric simulated vignette included injuries that resulted from an improvised explosive device (IED) blast. Using VTC, augmented reality (AR) goggles, and airway simulation equipment, corpsmen (HMs) received visual cues to perform advanced life-saving procedures. In adult scenarios, 100% of novice hospital HMs performed tasks on first attempt (n = 12). Mean time for tourniquet placement was 46 seconds (standard deviation [SD], 19 seconds); needle thoracostomy, 70 seconds (SD, 67 seconds); tube thoracostomy, 313 seconds (SD, 152 seconds); and cricothyroidotomy, 274 seconds (SD, 82 seconds). In pediatric scenarios, 100% of novice HMs performed tasks on first attempt (n = 5). Mean time for tube thoracostomy completion was 532 seconds (SD, 109 seconds). VH can enhance the training and delivery of trauma care during prolonged field care in resource-limited settings.


Examination of the silver colloid binding behavior of disulfide-tethered bipyridine ligands and their fac-tricarbonylrheniumI complexes.
The syntheses of 2,2'-bipyridin-5-ylmethyl-5-(1,2-dithiolan-3-yl)pentanoate (L1) and N-(2,2'-bipyridin-5-ylmethyl)-5-(1,2-dithiolan-3-yl)pentanamide (L2) and their neutral fac carbonylrhenium(I) complexes [Re(L1)(CO)(3)Br] and [Re(L2)(CO)(3)Br] are reported. The electronic absorption and emission spectra of the complexes are similar to the spectrum of the reference compound [Re(bipy)(CO)(3)Br] and correlate well with the density functional theory calculations undertaken. The surface-enhanced Raman spectroscopy (SERS) spectra (excited at both 532 and 785 nm) of the ligands and complexes were examined and compared to the spectrum of ethyl 5-(1,2-dithiolan-3-yl)pentanoate (L3), revealing that there is very little contribution to the spectra of these species from the dithiolated alkyl chains. The spectra are dominated by the characteristic peaks of a metalated 2,2'-bipyridyl group, arising from the silver colloid/ion complexation, and the rhenium center. The rhenium complexes show weak SERS bands related to the CO stretches and a broad band at 510 cm(-1) assigned to Re-CO stretching. Concentration-dependent studies, measured by the relative intensity of several assigned peaks, indicate that, as the surface coverage increases, the bipyridine moiety lifts off the surface. In the case of L1 and L2, this gives rise to complexes with silver at low concentration, enhancing the signals observed, while for the tricarbonylbromorhenium complexes of these ligands, the presence of the disulfide tether allows an enhancement in the limits of detection of these surface-borne species of 20 times in the case of [ReL2(CO)(3)Br] over [Re(bipy)(CO)(3)Br].


Octopaminergic modulation of the visual flight speed regulator of Drosophila.
Recent evidence suggests that flies' sensitivity to large-field optic flow is increased by the release of octopamine during flight. This increase in gain presumably enhances visually mediated behaviors such as the active regulation of forward speed, a process that involves the comparison of a vision-based estimate of velocity with an internal set point. To determine where in the neural circuit this comparison is made, we selectively silenced the octopamine neurons in the fruit fly Drosophila, and examined the effect on vision-based velocity regulation in free-flying flies. We found that flies with inactivated octopamine neurons accelerated more slowly in response to visual motion than control flies, but maintained nearly the same baseline flight speed. Our results are parsimonious with a circuit architecture in which the internal control signal is injected into the visual motion pathway upstream of the interneuron network that estimates groundspeed.


A Role for Mediator Core in Limiting Coactivator Recruitment in Saccharomyces cerevisiae.
Mediator is an essential, multisubunit complex that functions as a transcriptional coactivator in yeast and other eukaryotic organisms. Mediator has four conserved modules, Head, Middle, Tail, and Kinase, and has been implicated in nearly all aspects of gene regulation. The Tail module has been shown to recruit the Mediator complex to the enhancer or upstream activating sequence (UAS) regions of genes via interactions with transcription factors, and the Kinase module facilitates the transition of Mediator from the UAS/enhancer to the preinitiation complex via protein phosphorylation. Here, we analyze expression of the Saccharomyces cerevisiaeHO gene using a sin4 Mediator Tail mutation that separates the Tail module from the rest of the complex; the sin4 mutation permits independent recruitment of the Tail module to promoters without the rest of Mediator. Significant increases in recruitment of the SWI/SNF and SAGA coactivators to the HO promoter UAS were observed in a sin4 mutant, along with increased gene activation. These results are consistent with recent studies that have suggested that the Kinase module functions negatively to inhibit activation by the Tail. However, we found that Kinase module mutations did not mimic the effect of a sin4 mutation on HO expression. This suggests that at HO the core Mediator complex (Middle and Head modules) must play a role in limiting Tail binding to the promoter UAS and gene activation. We propose that the core Mediator complex helps modulate Mediator binding to the UAS regions of genes to limit coactivator recruitment and ensure proper regulation of gene transcription.


Alzheimer disease genetic risk factor APOE e4 and cognitive abilities in 111,739 UK Biobank participants.
the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment.


Prognosis of occult breast carcinoma presenting as isolated axillary nodal metastasis.
Axillary metastasis from an occult breast carcinoma is an uncommon presentation and presents a therapeutic dilemma. The objective of this study is to describe the presenting clinical features, management approach and treatment outcomes for occult breast carcinoma. We conducted a retrospective review of patients who presented with axillary nodal metastases from an occult breast carcinoma between 1997 and 2004 at the Roswell Park Cancer Institute; 2,150 patients were diagnosed and treated for breast cancer during this period. After excluding stage I and IV patients, we identified 642 who had disease metastatic to lymph nodes, 10 of these had no primary tumor in the breast despite a thorough evaluation including bilateral mammography and breast ultrasound. Of these, 7 had undergone breast magnetic resonance imaging as well. All patients underwent axillary nodal dissection. The breast was managed with radiotherapy alone in 8 patients, wide local excision with radiation therapy in 1 patient and 1 patient underwent mastectomy. No patient had a recurrence with a median 57 months of follow-up. Breast conservation with radiation therapy alone can be considered as a management option for women with occult breast cancer presenting with axillary nodal metastasis.


Perceptions of Health-Related Community Reentry Challenges among Incarcerated Drug Users in Azerbaijan, Kyrgyzstan, and Ukraine.
Facing competing demands with limited resources following release from prison, people who inject drugs (PWID) may neglect health needs, with grave implications including relapse, overdose, and non-continuous care. We examined the relative importance of health-related tasks after release compared to tasks of everyday life among a total sample of 577 drug users incarcerated in Ukraine, Azerbaijan, and Kyrgyzstan. A proxy measure of whether participants identified a task as applicable (easy or hard) versus not applicable was used to determine the importance of each task. Correlates of the importance of health-related reentry tasks were analyzed using logistic regression, with a parsimonious model being derived using Bayesian lasso method. Despite all participants having substance use disorders and high prevalence of comorbidities, participants in all three countries prioritized finding a source of income, reconnecting with family, and staying out of prison over receiving treatment for substance use disorders, general health conditions, and initiating methadone treatment. Participants with poorer general health were more likely to prioritize treatment for substance use disorders. While prior drug injection and opioid agonist treatment (OAT) correlated with any interest in methadone in all countries, only in Ukraine did a small number of participants prioritize getting methadone as the most important post-release task. While community-based OAT is available in all three countries and prison-based OAT only in Kyrgyzstan, Kyrgyz prisoners were less likely to choose help staying off drugs and getting methadone. Overall, prisoners consider methadone treatment inapplicable to their pre-release planning. Future studies that involve patient decision-making and scale-up of OAT within prison settings are needed to better improve individual and public health.


Collapsing Focal Segmental Glomerulosclerosis with Acute Interstitial Nephritis Associated with Plasmodium Falciparum: A Case Report and Review of the Literature.
BACKGROUND Malaria adversely affects the kidney in a variety of ways. The most common kidney injury is acute tubular necrosis, although various glomerular lesions are also described. Of these, collapsing focal segmental glomerulosclerosis (cFSGS) is the most rarely seen. Thus, the natural history of this lesion and response to treatment are not clear. Herein, we present a case of cFSGS complicated by acute interstitial nephritis caused by Plasmodium falciparum (P. falciparum) unresponsive to prednisone. CASE REPORT A 64-year-old Nigerian man with chronic kidney disease due to hypertensive nephropathy was admitted to the hospital, diagnosed with active P. falciparum malaria infection after returning from Nigeria. He developed acute kidney injury and nephrotic range proteinuria. Renal biopsy showed acute interstitial nephritis and cFSGS. Despite corticosteroid therapy, his kidney function worsened, requiring initiation of renal replacement therapy. This is the fifth case report of cFSGS due to malaria P. falciparum but the first to report the presence of acute interstitial nephritis in association with cFSGS due to malaria. CONCLUSIONS cFSGS is rarely seen as a manifestation of P. falciparum infection. When associated with acute interstitial nephritis, the prognosis seems to be worse. It appears that age and co-morbidities are the risk factors for unresponsiveness to corticosteroids, and treatment of the renal disease should focus on rapidly eradicating the parasitemia and providing supportive care. Our case report is the first to describe a combination of cFSGS and interstitial nephritis caused by P. falciparum unresponsive to corticosteroids.


Learning new tricks from old dogs: beta-adrenergic receptors teach new lessons on firing up adipose tissue metabolism.
The three beta AR (beta-adrenergic receptor) subtypes (beta(1)AR, beta(2)AR, and beta(3)AR) are members of the large family of G protein-coupled receptors, each of which is coupled to G alpha s and increases in intracellular cAMP levels. In white adipose tissues, catecholamine activation of the beta ARs leads to the mobilization of stored fatty acids and regulates release of several adipokines, whereas in brown adipose tissue they stimulate the specialized process of adaptive nonshivering thermogenesis. Noteworthy, in most models of obesity the beta AR system is dysfunctional, and its ability to stimulate lipolysis and thermogenesis are both impaired. Nevertheless, selective agonists for the beta(3)AR, a subtype that is found predominantly in adipocytes, have been able to prevent or reverse obesity and accompanying insulin resistance in animal models. Whether this is a viable therapeutic option for human obesity is much debated with regard to the existence of brown adipocytes in humans or their ability to be recruited. Nevertheless, probing the physiological changes in adrenoceptor function in rodent obesity, as well as the process by which beta(3)AR agonists promote a thermogenic shift in fuel use, have yielded unexpected new insights into beta AR signaling and adipocyte physiology. These include the recent discovery of an essential role of p38 MAPK in mediating adaptive thermogenesis, as well as the accessory role of the ERK MAPK pathway for the control of lipolysis. Because these metabolic events were traditionally ascribed solely to the cAMP/protein kinase A system, the integration of these signaling mechanisms may pose new therapeutic directions in the quest to counter the obesity epidemic in our midst.


International Scope of Emergency Ultrasound: Barriers in Applying Ultrasound to Guide Central Line Placement by Providers in Nairobi, Kenya.
While ultrasound (US) use for internal jugular central venous catheter (CVC) placement is standard of care in North America, most developing countries have not adopted this practice. Previous surveys of North American physicians have identified lack of training and equipment availability as the most important barriers to the use of US. We sought to identify perceived barriers to the use of US to guide CVC insertion in a resource-constrained environment. Prior to an US-guided CVC placement training course conducted at the Aga Khan University Hospital in Nairobi, Kenya, physicians were asked to complete a survey to determine previous experience and perceived barriers. Survey responses were analyzed using summary statistics and the Rank-Sum test based on different specialty, gender, and previous US experience. There were 23 physicians who completed the course and the survey. 52% (95% CI: 0.30-0.73) had put in >20 CVCs. 21.7% (95% CI: 0.08-0.44) of participants had previous US training, but none in the use of US for CVC insertion. The respondents expressed agreement with statements describing the ease of the use and improved success rate with US guidance. There was less agreement to statements describing the relative convenience and cost effectiveness of US CVC placement compared to the landmark technique. The main perceived barriers to utilization of US guidance included lack of training and limited availability of US equipment and sterile sheaths. Perceived barriers to US-guided CVC placement in our population closely mirrored those found among North American physicians, including lack of training and limited availability of US machines and equipment. These barriers have the potential to be addressed by targeted educational and administrative interventions.


Accessing and engaging women from socio-economically disadvantaged areas: a participatory approach to the design of a public health intervention for delivery in a Bingo club.
Our aim was to use participatory methods to investigate the feasibility and acceptability of using Bingo clubs for the design and delivery of an evidence-based physical activity and/or healthy eating intervention to socio-economically disadvantaged women. This paper describes the participatory process that has resulted in a physical activity intervention for women aged >55 years, ready for pilot-testing in a Bingo club setting. Studies using different quantitative and qualitative approaches were conducted among customers and staff of a Bingo club in a city of 85,000 inhabitants in central Scotland. These were designed to take the views of different stakeholders into account, with a view to enhancing uptake, engagement and effectiveness with any proposed intervention. Sixteen relevant studies were identified in a literature review that generated ideas for intervention components. A questionnaire completed by 151 women in the Bingo club showed that almost half (47 %) aged >55 years were not meeting physical activity guidelines; evidence backed up by accelerometer data from 29 women. Discussions in six focus groups attended by 27 club members revealed different but overlapping motivations for attending the Bingo club (social benefits) and playing Bingo (cognitive benefits). There was some scepticism as to whether the Bingo club was an appropriate setting for an intervention, and a dietary intervention was not favoured. It was clear that any planned intervention needed to utilise the social motivation and habitual nature of attendance at the Bingo club, without taking women away from Bingo games. These results were taken forward to a 5-h long participative workshop with 27 stakeholders (including 19 Bingo players). Intervention design (form and content) was then finalised during two round table research team meetings. It was possible to access and engage with women living in areas of socio-economic disadvantage through a Bingo club setting. A physical activity intervention for women >55 years is realistic for recruitment, will address the needs of potential recipients in the Bingo club, appears to be feasible and acceptable to club members and staff, and has been designed with their input. A pilot study is underway, investigating recruitment, retention and feasibility of delivery.


Development of an in situ injectable hydrogel containing hyaluronic acid for neural regeneration.
In this work, a novel enzymatically crosslinked injectable hydrogel comprising hyaluronic acid (HyA), dopamine (DA), and 3-(4-hydroxyphenyl) propionic acid (HPA) conjugates was successfully developed. To the best of our knowledge, it is the first time that HPA is conjugated to a HyA-based backbone. In situ hydrogelation of HyA-DA-HPA occurred in the presence of hydrogen peroxide (H2O2) as an oxidant and horseradish peroxidase (HRP) as a catalyst. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to characterize the chemical reactions between HyA, DA, and HPA. Gel formation completed between 3 s to 5 min depending on the concentrations of polymer, HRP, and H2O2. Crosslinked HyA-DA-HPA gels acquired storage moduli ranging from ∼100 Pa to ∼20 000 Pa (at f = 2000 rad s-1). Biocompatibility of the hydrogels was examined with human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cell-derived neural stem cells. The hydrogels made of 2.0 w/v% HyA-DA-HPA hydrogels, 0.24 U ml-1 HRP and ≤ 0.5 µmol ml-1 H2O2 were found biocompatible with hMSCs cultured on and encapsulated within the hydrogels. Since HyA serves as a backbone of the extracellular matrix in the central nervous system (CNS) and DA acquires the ability to restore dopaminergic neurons, use of this injectable HyA-DA-HPA hydrogel for stem cell transplantation is a potential treatment strategy for CNS repair and regeneration.


Socio-economic importance of forest resources and their conservation measures in Ethiopia: the case of area closure in South Gonder of Ethiopia.
Area closures that set aside to degraded lands for rehabilitation purposes are a popular forest conservation measure in various parts of the world. However, their use can be controversial because, if poorly designed, they can accelerate the degradation of neighboring unprotected lands and deny local residents' access to important ecosystem services. This paper reports the results of a study on the area closure approach used in south Gonder within the Lake Tana watershed of Ethiopia to stem the rapid decline of vegetation cover that has occurred there over the last four decades. We used a mixed-methods approach that combined data from a household survey, focus group discussions, key informant interviews, and official documents. We found that support for the area closures was high. We also found that area closures have had a mixed effect on access to key ecosystem services while a number of important concerns about the negative impacts to surrounding unprotected forests were also expressed. We conclude that area closures have garnered broad public support within our study region but this support appears to be mostly contingent on management successes within protected forests and does not necessarily capture the unintended negative consequences to surrounding unprotected forests.


Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status.
Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (>0.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.


Service suspension for mental disorders in armed forces draftees in the Penghu area.
It is important to monitor draftees for mental disorders before or at an early stage of military service. The aim of this study was to characterize the draftees who were suspended from service for mental disorders among draftees in a high readiness military zone in the Taiwan Strait. A total of 152 draftees consulted the outpatient service of the Department of Psychiatry at Penghu branch, Tri-Service General Hospital in Taiwan during the period between August 2004 and July 2008, and whose severity of mental disorder fit the criteria for service suspension were recruited as the study group (SG). Draftees who had adjusted normally were the control group (CG). The major causes for suspension were major depressive disorders and personality disorders. In the study group, the number of draftees seeking psychiatric outpatient treatment increased from 49.3% before service to 100% during service. In addition, higher rates of suicidal ideation, suicide plans, attempted suicide, and homicidal ideation were found in the study group than in the control group. The percentages of draftees who were unwilling to serve and absent without official leave (AWOL) during military service in Penghu were also significantly higher in the study group than in the control group. Based on the characteristics of the draftees who were suspended from service for mental disorders, psychological factors such as suicidal ideation, suicide attempts and adjustment disorders should be surveyed and monitored before the draft and at an early stage of military service.


Probing the molecular mechanisms of AZT drug resistance mediated by HIV-1 reverse transcriptase using a transient kinetic analysis.
Several hypotheses have been proposed to explain the development of resistance to the anti-HIV drug AZT. Clinical findings show that AZT resistance mutations in HIV-1 reverse transcriptase (RT) not only reduce susceptibility to thymidine analogues but may also confer multi-dideoxynucleoside resistance. In this report, we describe transient kinetic studies establishing the biochemical effects of AZT resistance mutations in HIV-1 RT on the incorporation and removal of natural and unnatural deoxynucleotides. While the physiological role remains to be elucidated, the largest biochemical difference between wild-type and AZT resistant HIV-1 RT manifested itself during ATP-mediated deoxynucleotide removal. Enhanced removal resulted from an increase in the maximum rate of chain terminator excision, suggesting that mutated residues play a role in the optimal alignment of substrates for ATP-mediated removal. The efficiency of pyrophosphorolysis was not increased by the presence of AZT resistance mutations. However, a 2-fold decrease in the extent of inhibition caused by the next correct nucleotide during pyrophosphorolytic cleavage of a D4TMP chain-terminated primer may illustrate how this mutant can utilize pyrophosphate to enhance resistance. The inability of RT to catalyze removal of a chain terminator from an RNA-RNA primer-template may show how slight changes in selectivity against AZTMP incorporation during the initiation of DNA synthesis can contribute to high-level resistance. Taken together, these results suggest that multiple modes of resistance may be conferred by these mutations. Structure-activity studies of chain terminator removal suggest that analogues that form tight interactions with residues in the RT active site may be more prone to resistance mechanisms mediated by removal.


Platelet-derived or soluble CD154 induces vascularized allograft rejection independent of cell-bound CD154.
CD154 is a cell surface molecule expressed on activated T cells that binds to CD40, an activating molecule on APCs. Its blockade has been shown to prevent allograft rejection, presumably by interrupting interactions between T cells and APCs. It is known that activated human platelets express and shed CD154 and can induce APC activation and other immune processes in vitro. Here we show that platelet-derived CD154 is sufficient to initiate cardiac allograft rejection independent of any cellular source of this molecule. CD154-KO mice reject cardiac allografts after receiving CD154-expressing human platelets or recombinant CD154 (rCD154) trimers. Treatment with the human CD154-specific mAb 5c8 specifically prevents this induced rejection. Soluble trimers, but not platelets, induce rejection when infused temporally remote from the surgical procedure, suggesting that surgically induced platelet activation is required for CD154 release. Allograft rejection can thus be instigated by activated platelets through CD154. These data implicate platelets as a proximal component of acquired alloimmunity, providing insight into the mechanisms of allograft rejection and the physiological response to trauma in general.


Cellular Immune Response Involving Multinucleated Giant Hemocytes with Two-Step Genome Amplification in the Drosophilid Zaprionus indianus.
Previously, a novel cell type, the multinucleated giant hemocyte (MGH) was identified in the ananassae subgroup of Drosophilidae. These cells share several features with mammalian multinucleated giant cells, a syncytium of macrophages formed during granulomatous inflammation. We were able to show that MGHs also differentiate in Zaprionus indianus, an invasive species belonging to the vittiger subgroup of the family, highly resistant to a large number of parasitoid wasp species. We have classified the MGHs of Z. indianusas giant hemocytes belonging to a class of cells which also include elongated blood cells carrying a single nucleus and anuclear structures. They are involved in encapsulating parasites, originate from the lymph gland, can develop by cell fusion, and generally carry many nuclei, while possessing an elaborated system of canals and sinuses, resulting in a spongiform appearance. Their nuclei are all transcriptionally active and show accretion of genetic material. Multinucleation and accumulation of the genetic material in the giant hemocytes represents a two-stage amplification of the genome, while their spongy ultrastructure substantially increases the contact surface with the extracellular space. These features may furnish the giant hemocytes with a considerable metabolic advantage, hence contributing to the mechanism of the effective immune response.


BJS commission on surgery and perioperative care post-COVID-19.
Coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO on 11 March 2020 and global surgical practice was compromised. This Commission aimed to document and reflect on the changes seen in the surgical environment during the pandemic, by reviewing colleagues' experiences and published evidence. In late 2020, BJS contacted colleagues across the global surgical community and asked them to describe how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had affected their practice. In addition to this, the Commission undertook a literature review on the impact of COVID-19 on surgery and perioperative care. A thematic analysis was performed to identify the issues most frequently encountered by the correspondents, as well as the solutions and ideas suggested to address them. BJS received communications for this Commission from leading clinicians and academics across a variety of surgical specialties in every inhabited continent. The responses from all over the world provided insights into multiple facets of surgical practice from a governmental level to individual clinical practice and training. The COVID-19 pandemic has uncovered a variety of problems in healthcare systems, including negative impacts on surgical practice. Global surgical multidisciplinary teams are working collaboratively to address research questions about the future of surgery in the post-COVID-19 era. The COVID-19 pandemic is severely damaging surgical training. The establishment of a multidisciplinary ethics committee should be encouraged at all surgical oncology centres. Innovative leadership and collaboration is vital in the post-COVID-19 era.


Total, Added, and Free Sugar Consumption and Adherence to Guidelines in Switzerland: Results from the First National Nutrition Survey menuCH.
The World Health Organization (WHO) recommends reducing free sugars to less than 10% of total energy intake (TEI) due to their potential implications in weight gain and dental caries. Our objectives were to (1) estimate the intake of total, added, and free sugars, (2) define the main sugar sources, and (3) evaluate the adherence to sugar guidelines. The first national nutrition survey 2014-2015 included non-institutional adults aged 18-75 years. Diet was assessed with two non-consecutive 24-hour dietary recalls in 2057 participants. Added and free sugar content was systematically estimated by two dietitians using available information from the manufacturer and/or standard recipe/composition. Usual daily intake distributions were modeled and weighted for sampling design, non-response, weekdays, and seasons. Total, added, and free sugar intake was respectively 107 g (±44), 53 g (±36), and 65 g (±40), representing 19%, 9%, and 11% of TEI. Sugar consumption was higher among younger adults and lower among people living in the Italian-speaking region. The three main food sources of free sugars were: (1) sweet products (47% of total free sugars), in particular sweet spreads (15%) and cakes/cookies (11%); (2) beverages (29%), mainly fruit and vegetable juices (13%), and sugar-sweetened beverages (12%, but 20% in younger adults); and (3) dairy products (9%), with yogurt accounting for 6%. Respectively, 44% of women and 45% of men had free sugar intake below 10% of TEI. Of people aged between 18-29, 30-64, and 65-75 years, 36%, 45%, and 53% had free sugar intake below 10% of TEI, respectively. The prevalence of Swiss people with free sugar intake that was <5% of the TEI was 8%. Adherence to the WHO recommendations guidelines was generally low in Switzerland, particularly among young adults, and in line with other high-income countries.


Zika virus: Global health challenge, threat and current situation.
ZIKV has emerged as grave global health issue in the past few years. ZIKV was firstly isolated in 1947 from a rhesus sentinel monkey in the Zika forest in Uganda. It is usually transmitted by the bite of infected mosquitoes and infects skin fibroblasts, skin keratinocytes, etc. ZIKV until now was under reported because of its clinical similarity with the dengue and chikungunya. It is usually spread through the course of the sylvatic cycle. In this cycle, the virus or pathogen lifespan is spent between the wild animal and vectors. The intrinsic incubation period is not yet fully known but it is observed that the very first symptoms of ZIKV infection can appear or develop within 3-12 days of time period and usually subside within 7 days of time. There is a strong relationship between prenatal Zika virus infection and microcephaly; other serious brain anomalies to the infant or newborn are Guillain-Barré syndrome. To date no vaccines are available for ZIKV prevention hence only symptomatic treatment is recommended in infected patients. Usually ZIKV is detected by serologic (IgM ELISA), plaque reduction neutralization test (PRNT) along with in-house" molecular techniques (RT-PCR). ZIKV infection being imminent global health issue warrants strong protective measures to prevent it from becoming an epidemic. Early detection and prevention is the key to tackle this grave potential health hazard. J. Med. Virol. 89:943-951, 2017. © 2017 Wiley Periodicals, Inc.


Targeted inhibition of SRC kinase signaling attenuates pancreatic tumorigenesis.
Elevated Src expression correlates with malignant potential and metastatic disease in many tumors including pancreatic cancer. We sought to characterize the molecular effects of Src kinase inhibition with dasatinib (BMS-354825), a novel, multitargeted kinase inhibitor that targets Src family kinases in pancreatic ductal adenocarcinoma (PDA). We identified sensitive and resistant PDA cell lines to dasatinib treatment and tested the molecular effects of Src inhibition in vitro and in vivo. We show for the first time that cellular localization of Src expression affects survival in patients with PDA. Pancreatic tumors with increased membranous expression of Src resulted in decreased survival compared with tumors that had increased cytoplasmic Src expression. Src kinase inhibition with dasatinib markedly inhibits cell proliferation, migration, invasion, cell cycle progression and anchorage-independent growth, and stimulates apoptosis. This was accompanied by decreased phosphorylation of Src, focal adhesion kinase, paxillin, AKT, signal transducers and activators of transcription 3 (STAT3), extracellular signal-regulated kinase, and mitogen-activated protein kinase (MAPK), as well as decreased cyclin D1 expression in a time- and concentration-dependent manner. Furthermore, small interfering RNA to Src results in a significant decrease in cell proliferation, invasion, and migration of pancreatic cancer cells. Dasatinib treatment also inhibits in vivo pancreatic tumor growth. Mechanisms of resistance to Src inhibition seem to be related to a lack of inhibition of STAT3 and MAPK signaling. These results establish a mechanistic rationale for Src inhibition with dasatinib as a therapeutic target in the treatment of pancreatic cancer and identify potential biomarkers of resistance to Src inhibition.


The Northwick Park Therapy Dependency Assessment scale: a psychometric analysis from a large multicentre neurorehabilitation dataset.
To assess the internal reliability, construct and concurrent validity and responsiveness of the Northwick Park Therapy Dependency Assessment (NPTDA) scale. A cohort of 2505 neurorehabilitation patients submitted to the UK Rehabilitation Outcomes Collaborative database. Cronbach's coefficient-α was used to assess internal reliability and factor analysis (FA) to assess construct validity. We compared NPTDA scores at admission and discharge to determine responsiveness. Coefficient-α for the whole scale was 0.74. The exploratory FA resulted in a four-factor model (Physical, Psychosocial, Discharge planning and Activities) that accounted for 43% of variance. This model was further supported by the confirmatory FA. The final model had a good fit: root-mean-square error of approximation of 0.069, comparative fit index/Tucker-Lewis index of 0.739/0.701 and the goodness of fit index of 0.909. The NPTDA scores at admission and discharge were significantly different for each of the factors. Expected correlations were seen between the admission scores for the NPTDA, the Rehabilitation Complexity Scale (r = 0.30, p < 0.01) and the Functional Independence Measure (r = -0.25, p < 0.01). The scale demonstrated acceptable internal reliability and good construct and concurrent validity. NPTDA may be used to describe and quantify changes in therapy inputs in the course of a rehabilitation programme. Implications for Rehabilitation The Northwick Park Therapy Dependency Assessment (NPTDA) is designed as a measure therapy intervention, which reflects both quantitative and qualitative aspects of the inputs provided (including staff time and the different types of intervention) during inpatient rehabilitation. The scale demonstrated acceptable internal reliability and good construct and concurrent validity. NPTDA is responsive to change in the therapy inputs provided during neurorehabilitation between admission and discharge.


Management of cervical cancer patients during the COVID-19 pandemic: a challenge for developing countries.
During the COVID-19 pandemic, health services worldwide are going through important adaptations to assist patients infected with COVID-19, at the same time as continuing to provide assistance to other potentially life-threatening diseases. Although patients with cancer may be at increased risk for severe events related to COVID-19 infection, their oncologic treatments frequently cannot be delayed for long periods without jeopardising oncologic outcomes. Considering this, a careful consideration for treatment management of different malignancies is required. Cervical cancer is concentrated mainly in low-middle income countries (LMICs), which face particular challenges during the COVID-19 pandemic due to the scarcity of health resources in many places. Although cervical cancer is the fourth cause of cancer death among women, it receives little attention from international Oncology societies and scientific research studies. In this review paper, we discuss the cervical cancer landscape and provide specialists recommendations for its management during the COVID-19 pandemic, particularly focused on LMICs' reality.


Analysis of Microstructure of the Cardiac Conduction System Based on Three-Dimensional Confocal Microscopy.
The specialised conducting tissues present in the ventricles are responsible for the fast distribution of the electrical impulse from the atrio-ventricular node to regions in the subendocardial myocardium. Characterisation of anatomical features of the specialised conducting tissues in the ventricles is highly challenging, in particular its most distal section, which is connected to the working myocardium via Purkinje-myocardial junctions. The goal of this work is to characterise the architecture of the distal section of the Purkinje network by differentiating Purkinje cells from surrounding tissue, performing a segmentation of Purkinje fibres at cellular scale, and mathematically describing its morphology and interconnections. Purkinje cells from rabbit hearts were visualised by confocal microscopy using wheat germ agglutinin labelling. A total of 16 3D stacks including labeled Purkinje cells were collected, and semi-automatically segmented. State-of-the-art graph metrics were applied to estimate regional and global features of the Purkinje network complexity. Two types of cell types, tubular and star-like, were characterised from 3D segmentations. The analysis of 3D imaging data confirms the previously suggested presence of two types of Purkinje-myocardium connections, a 2D interconnection sheet and a funnel one, in which the narrow side of a Purkinje fibre connect progressively to muscle fibres. The complex network analysis of interconnected Purkinje cells showed no small-world connectivity or assortativity properties. These results might help building more realistic computational PK systems at high resolution levels including different cell configurations and shapes. Better knowledge on the organisation of the network might help in understanding the effects that several treatments such as radio-frequency ablation might have when the PK system is disrupted locally.


AtALMT12 represents an R-type anion channel required for stomatal movement in Arabidopsis guard cells.
Stomatal pores formed by a pair of guard cells in the leaf epidermis control gas exchange and transpirational water loss. Stomatal closure is mediated by the release of potassium and anions from guard cells. Anion efflux from guard cells involves slow (S-type) and rapid (R-type) anion channels. Recently the SLAC1 gene has been shown to encode the slow, voltage-independent anion channel component in guard cells. In contrast, the R-type channel still awaits identification. Here, we show that AtALMT12, a member of the aluminum activated malate transporter family in Arabidopsis, represents a guard cell R-type anion channel. AtALMT12 is highly expressed in guard cells and is targeted to the plasma membrane. Plants lacking AtALMT12 are impaired in dark- and CO₂ -induced stomatal closure, as well as in response to the drought-stress hormone abscisic acid. Patch-clamp studies on guard cell protoplasts isolated from atalmt12 mutants revealed reduced R-type currents compared with wild-type plants when malate is present in the bath media. Following expression of AtALMT12 in Xenopus oocytes, voltage-dependent anion currents reminiscent to R-type channels could be activated. In line with the features of the R-type channel, the activity of heterologously expressed AtALMT12 depends on extracellular malate. Thereby this key metabolite and osmolite of guard cells shifts the threshold for voltage activation of AtALMT12 towards more hyperpolarized potentials. R-Type channels, like voltage-dependent cation channels in nerve cells, are capable of transiently depolarizing guard cells, and thus could trigger membrane potential oscillations, action potentials and initiate long-term anion and K(+) efflux via SLAC1 and GORK, respectively.


Mesoscale modulation of supramolecular ureidopyrimidinone-based poly(ethylene glycol) transient networks in water.
In natural systems, highly synergistic non-covalent interactions among biomolecular components exert mesoscopic control over hierarchical assemblies. We herein present a multicomponent self-assembly strategy to tune hierarchical supramolecular polymer architectures in water using highly affine and directional ureidopyrimidinone-poly(ethylene glycol)s (UPy-PEG). Using scattering methods and oscillatory rheology, we observe the structural and mechanical regulation of entangled monofunctional UPy-PEG fibrils by cross-linking bifunctional UPy-PEG fibrils. This supramolecular mixing approach opens the door to a range of subtly distinct materials for chemical and biological applications.


Total Elbow Arthroplasty for Distal Humeral Fractures: A Ten-Year-Minimum Follow-up Study.
Total elbow arthroplasty is commonly considered for elderly patients with comminuted distal humeral fractures. Satisfactory short-term outcomes have been reported, but long-term outcomes are unknown. Our purpose was to assess the long-term outcomes of total elbow arthroplasty after distal humeral fracture and to determine differences between elbows with or without inflammatory arthritis at the time of fracture. Forty-four total elbow arthroplasties were performed after distal humeral fracture; those patients were followed for a minimum of 10 years and were evaluated with regard to pain, motion, Mayo Elbow Performance Scores, complications, and reoperations. The outcomes in elbows with and without inflammatory arthritis were compared. Kaplan-Meier survivorship analysis was performed. Total elbow arthroplasty provided good pain relief and motion; the mean visual analog scale for pain was 0.6, the mean flexion was 123°, and the mean loss of extension was 24°. The mean Mayo Elbow Performance Score was 90.5 points, with 3 patients scoring <75 points. Five elbows (11%) developed deep infection, treated surgically with component retention (3 acute) or resection (2 chronic). Implant revision or resection was performed in 8 elbows (18%): 3 for infections (1 reimplantation and 2 resections), 3 for ulnar loosening (associated with periprosthetic fracture in 1), and 2 for ulnar component fractures. Additional periprosthetic fractures were observed in 5 elbows. The survival rates for elbows with rheumatoid arthritis were 85% at 5 years and 76% at 10 years, and the survival rates for elbows without rheumatoid arthritis were 92% at both 5 and 10 years. The most relevant risk factor for revision was male sex (hazard ratio, 12.6 [95% confidence interval, 1.7 to 93.6]). Selective use of total elbow arthroplasty to treat fractures of the distal part of the humerus for infirm, less active older patients and patients with inflammatory arthritis has acceptable longevity in surviving patients, but at the cost of a number of major complications. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Sphenopalatine arteriovenous fistula complicating transsphenoidal pituitary surgery: A rare cause of delayed epistaxis treatable by endovascular embolization.
Vascular injuries in transsphenoidal surgery for pituitary adenomas are uncommon but can result in serious disability or death. A 46-year-old man, who underwent resection of a pituitary adenoma with suprasellar extension via a transsphenoidal approach, presented with massive epistaxis five days postoperatively. Angiography revealed an arteriovenous fistula (AVF) between the right sphenopalatine artery and a deep vein draining to the right internal jugular vein, as well as contrast agent extravasation at the fistula point. The AVF was catheterized and successfully occluded with N-butyl-2-cyanoacrylate. Transsphenoidal pituitary surgery can be complicated by massive epistaxis from a lesion of a small branch of the external carotid artery. Airway protection through intubation and investigation with conventional digital subtraction angiography is recommended. The treatment of choice is endovascular embolization because it can be done immediately at the angiography suite.


Open Versus Robotic Cystectomy: A Propensity Score Matched Analysis Comparing Survival Outcomes.
To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available.


Inpatient psychiatric care experience and its relationship to posthospitalization treatment participation.
This study used factor analysis of a Veterans Health Administration (VHA) survey to identify factors that measure satisfaction with inpatient treatment and to examine the factors' utility in evaluating treatment participation following discharge. The Survey of Healthcare Experiences of Patients (inpatient version) (I-SHEP) was mailed to 34,237 veterans who were discharged from inpatient to outpatient care in the VHA during fiscal year 2009 and was completed by 7,408 patients. A factor analysis of survey responses identified underlying I-SHEP factors and evaluated relationships between the factors, patient characteristics, and attendance at VHA mental health appointments within seven and 30 days of discharge. The factor analysis identified three domains of satisfaction: respect and caring by nurses-overall hospital impression; involvement and information about care; and respect and caring by doctors. These factors demonstrated good internal consistency (Cronbach's α=.93, .90, and .94, respectively) and accounted for a moderate amount of variance in patient responses (r2=.167). Only the care involvement and information factor was associated with participation in follow-up care: increased satisfaction (one standard deviation change in scale score) was associated with improved odds of a mental health visit within seven and 30 days of discharge (odds ratio=1.14 and 1.17, respectively, p<.01). After discharge, persons may not generalize satisfaction about the respect and caring shown by inpatient treatment teams toward their decision to attend outpatient care. Providing patients with information about treatment and involving them in care decisions during inpatient care may help facilitate the transition to outpatient settings.


A plant-microbe interaction framework explaining nutrient effects on primary production.
In most terrestrial ecosystems, plant growth is limited by nitrogen and phosphorus. Adding either nutrient to soil usually affects primary production, but their effects can be positive or negative. Here we provide a general stoichiometric framework for interpreting these contrasting effects. First, we identify nitrogen and phosphorus limitations on plants and soil microorganisms using their respective nitrogen to phosphorus critical ratios. Second, we use these ratios to show how soil microorganisms mediate the response of primary production to limiting and non-limiting nutrient addition along a wide gradient of soil nutrient availability. Using a meta-analysis of 51 factorial nitrogen-phosphorus fertilization experiments conducted across multiple ecosystems, we demonstrate that the response of primary production to nitrogen and phosphorus additions is accurately predicted by our stoichiometric framework. The only pattern that could not be predicted by our original framework suggests that nitrogen has not only a structural function in growing organisms, but also a key role in promoting plant and microbial nutrient acquisition. We conclude that this stoichiometric framework offers the most parsimonious way to interpret contrasting and, until now, unresolved responses of primary production to nutrient addition in terrestrial ecosystems.


Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.
Autophagic dysregulation has been suggested in a broad range of neurodegenerative diseases including age-related macular degeneration (AMD). To test whether the autophagy pathway plays a critical role to protect retinal pigmented epithelial (RPE) cells against oxidative stress, we exposed ARPE-19 and primary cultured human RPE cells to both acute (3 and 24 h) and chronic (14 d) oxidative stress and monitored autophagy by western blot, PCR, and autophagosome counts in the presence or absence of autophagy modulators. Acute oxidative stress led to a marked increase in autophagy in the RPE, whereas autophagy was reduced under chronic oxidative stress. Upregulation of autophagy by rapamycin decreased oxidative stress-induced generation of reactive oxygen species (ROS), whereas inhibition of autophagy by 3-methyladenine (3-MA) or by knockdown of ATG7 or BECN1 increased ROS generation, exacerbated oxidative stress-induced reduction of mitochondrial activity, reduced cell viability, and increased lipofuscin. Examination of control human donor specimens and mice demonstrated an age-related increase in autophagosome numbers and expression of autophagy proteins. However, autophagy proteins, autophagosomes, and autophagy flux were significantly reduced in tissue from human donor AMD eyes and 2 animal models of AMD. In conclusion, our data confirm that autophagy plays an important role in protection of the RPE against oxidative stress and lipofuscin accumulation and that impairment of autophagy is likely to exacerbate oxidative stress and contribute to the pathogenesis of AMD.


Coverage of rare disease names in standard terminologies and implications for patients, providers, and research.
Small numbers of patients are a special challenge for rare diseases research. Electronic health record (EHR) data can facilitate research if patients with rare diseases can be reliably identified. We estimate the coverage of the names of a set of 6,519 rare diseases. Using the UMLS, 697 (11%) diseases were matched to ICD-9-CM, 1,386 (21%) to ICD-10-CM and 2,848 (44%) to SNOMED CT. Using published mappings from SNOMED CT to ICD, we further estimate additional broader matches of 2,569 (39%) rare diseases to ICD-9-CM and 1,635 (25%) to ICD-10-CM. The number of codes that match one and only one disease are 1,081 (62%) for ICD-9-CM, 1,403 (73%) for ICD-10-CM, and 3,311 (85%) for SNOMED CT. Our findings confirm that SNOMED CT has the greatest coverage and specificity needed to identify patients with a rare disease from EHR-data, and can facilitate research and evidence-based care.


Reasons for Repeat Rapid Response Team Calls, and Associations with In-Hospital Mortality.
Previous publications noted increased mortality risk in patients subject to repeat rapid response team (RRT) calls. These patients were examined as a homogenous group, but there may be many reasons for repeat calls. Those potentially preventable by the rapid response system have not been investigated. In a retrospective cohort study, patients with potentially preventable repeat calls were classified into two categories: type 1 (patients who had a repeat call following an initial call that ended despite the patient still triggering RRT calling criteria [T1-PRC]) and type 2 (patients with a repeat call within 24 hours of an initial call and for the same reason [T2-PRC]). In-hospital mortality for these patients and for those with repeat calls for all other reasons (ORC) were compared to patients with only a single call during their admission (SC). Mortality occurred in 31 (43.7%) T1-PRC, 13 (15.1%) T2-PRC, 56 (28.9%) ORC, and 289 (13.9%) SC patients. Univariate odds ratios (ORs), in comparison to SC patients, were 4.81 (95% confidence interval [CI]: 2.96-7.81; p < 0.001), 1.10 (95% CI: 0.60-2.02; p = 0.75), and 2.52 (95% CI: 1.80-3.52; p < 0.001), respectively. Mortality effects persisted for the T1-PRC and ORC groups after adjustment for patient, admission, and initial call characteristics with ORs of 4.07 (95% CI: 2.36-7.01; p < 0.001) and 2.29 (95% CI: 1.57-3.34; p < 0.001), respectively. This study found that repeat calls following an initial call that ended with ongoing breach of predefined calling criteria were strongly associated with increased mortality. This highlights the risk to patients when the RRT leaves reversible clinical deterioration unresolved at the end of a call.


Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways.
Combination of cis-platinum with ionizing radiation is one of the most promising anticancer treatments that appears to be more efficient than radiotherapy alone. Unlike conventional X-ray emitters, accelerators of high energy particles like synchrotrons display powerful and monochromatizable radiation that makes the induction of an Auger electron cascade in cis-platinum molecules [also called photoactivation of cis-platinum (PAT-Plat)] theoretically possible. Here, we examined the molecular consequences of one of the first attempts of synchrotron PAT-Plat, performed at the European Synchrotron Research Facility (Grenoble-France). PAT-Plat was found to result in an extra number of slowly repairable DNA double-strand breaks, inhibition of DNA-protein kinase activity, dramatic nuclear relocalization of RAD51, hyperphosphorylation of the BRCA1 protein, and activation of proto-oncogenic c-Abl tyrosine kinase.


Bilateral central vein occlusion in a case of diaphragmatic eventration.
Central Retinal Vein Occlusion (CRVO) is a severe retinal pathology, which causes visual impairment usually after the age of 40. Mostly unilateral, less than 10% of cases are bilateral. Affected young adults (under the age of 40), usually exhibit a hidden, underlying systemic disease. Thorough testing has to be done in order to spot the pathogenic agent. We present the case of a 25 years old woman with bilateral CRVO caused by Diaphragmatic Eventration and Chronic Respiratory Failure.


Allometry of alarm calls: black-capped chickadees encode information about predator size.
Many animals produce alarm signals when they detect a potential predator, but we still know little about the information contained in these signals. Using presentations of 15 species of live predators, we show that acoustic features of the mobbing calls of black-capped chickadees (Poecile atricapilla) vary with the size of the predator. Companion playback experiments revealed that chickadees detect this information and that the intensity of mobbing behavior is related to the size and threat of the potential predator. This study demonstrates an unsuspected level of complexity and sophistication in avian alarm calls.


Access to personalized medicine: factors influencing the use and value of gene expression profiling in breast cancer treatment.
Genomic information is increasingly being used to personalize health care. One example is gene expression profiling (gep) tests, which estimate recurrence risk to inform chemotherapy decisions in breast cancer. Recently, gep tests were publicly funded in Ontario. We explored the perceived utility of gep tests, focusing on the factors influencing their use and value in treatment decision-making by patients and oncologists. We conducted interviews with oncologists (n = 14) and interviews and a focus group with early-stage breast cancer patients (n = 28) who underwent gep testing. Both groups were recruited through oncology clinics in Ontario. Data were analyzed using the content analysis and constant comparison techniques. Narratives from patients and oncologists provided insights into various factors facilitating and restricting access to gep. First, oncologists are positioned as gatekeepers of gep, providing access in medically appropriate cases. However, varying perceptions of appropriateness led to perceived inequities in access and negative impacts on the doctor-patient relationship. Second, media attention facilitated patient awareness of gep, but also complicated gatekeeping. Third, the dedicated administration attached to gep was burdensome and led to long waits for results and also to increased patient anxiety and delayed treatment. Collectively, because of barriers to access, those factors inadvertently heightened the perceived value of gep for patients relative to other prognostic indicators. Our study delineates the factors facilitating and restricting access to gep, and highlights the roles of media and organization of services in the perceived value and utilization of gep. The results identify a need for administrative changes and practice guidelines to support streamlined and standardized use of gep tests.


Adverse outcome pathway-based screening strategies for an animal-free safety assessment of chemicals.
Currently, the assessment of risk to human health from exposure to manufactured chemicals is mainly based on experiments performed on living animals (in vivo). Substantial efforts are being undertaken to develop alternative solutions to in vivo toxicity testing. This new paradigm, based on the Mode-of-Action (MoA) framework, postulates that any adverse human health effect caused by exposure to an exogenous substance can be described by a series of causally-linked biochemical or biological key events with measurable parameters. The elaboration of mechanistic knowledge through literature research is necessary for a MoA-driven design of integrated testing strategies using in vitro methods for in vivo predictions. The objective of our ongoing research is to demonstrate the feasibility of an integrated approach to predict human toxicity following the Adverse Outcome Pathway (AOP) framework. In our previous work on MoA with the HepaRG cell model, we developed a strategy to identify chemicals that were hepatotoxic. This pioneered an innovative way of using data from in vitro experiments to group chemicals based on their MoA, which is likely to be an important step in a toxicity testing strategy.


Limited associations of dopamine system genes with alcohol dependence and related traits in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD).
Over 50 years of evidence from research has established that the central dopaminergic reward pathway is likely involved in alcohol dependence (AD). Additional evidence supports a role for dopamine (DA) in other disinhibitory psychopathology, which is often comorbid with AD. Family and twin studies demonstrate that a common genetic component accounts for most of the genetic variance in these traits. Thus, DA-related genes represent putative candidates for the genetic risk that underlies not only AD but also behavioral disinhibition. Many linkage and association studies have examined these relationships with inconsistent results, possibly because of low power, poor marker coverage, and/or an inappropriate correction for multiple testing. We conducted an association study on the products encoded by 10 DA-related genes (DRD1-D5, SLC18A2, SLC6A3, DDC, TH, COMT) using a large, ethnically homogeneous sample with severe AD (n = 545) and screened controls (n = 509). We collected genotypes from linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (SNPs) and employed a gene-based method of correction. We tested for association with AD diagnosis in cases and controls and with a variety of alcohol-related traits (including age-at-onset, initial sensitivity, tolerance, maximum daily drinks, and a withdrawal factor score), disinhibitory symptoms, and a disinhibitory factor score in cases only. A total of 135 SNPs were genotyped using the Illumina GoldenGate and Taqman Assays-on-Demand protocols. Of the 101 SNPs entered into standard analysis, 6 independent SNPs from 5 DA genes were associated with AD or a quantitative alcohol-related trait. Two SNPs across 2 genes were associated with a disinhibitory symptom count, while 1 SNP in DRD5 was positive for association with the general disinhibitory factor score. Our study provides evidence of modest associations between a small number of DA-related genes and AD as well as a range of alcohol-related traits and measures of behavioral disinhibition. While we did conduct gene-based correction for multiple testing, we did not correct for multiple traits because the traits are correlated. However, false-positive findings remain possible, so our results must be interpreted with caution.


Tendon needling for treatment of tendinopathy: A systematic review.
To summarize the best available evidence to determine if tendon needling is an effective treatment for tendinopathy. Data source. Medline and Cochrane Databases through November 2013. Utilizing the search terms tendinopathy, needle, needling, tenotomy, dry needling, needling tendon, needle fenestration, and tendon fenestration, 17 articles were identified through our systematic literature search. Of these, 4 studies met the inclusion criteria. Four independent reviewers reviewed the articles. The study results and generated conclusions were agreed upon. The studies that were included in this review suggest that tendon needling improves patient reported outcomes in patients with tendinopathy. In 2 studies evaluating tendon needling in lateral epicondylosis, one showed an improvement in a subjective visual analogue scale score of 34% (significant change > 25%) from baseline at 6 months. The other showed an improvement of 56.1% in a visual analogue scale score from baseline. In 1 study evaluating tendon needling in addition to eccentric therapy for Achilles tendinosis, the subjective Victorian Institute of Sport Assessment-Achilles (VISA-A) score improved by 19.9 (significant change > 10) (95% CI, 13.6-26.2) from baseline. In 1 study evaluating tendon needling in rotator cuff tendinosis, the subjective shoulder pain and disability index showed statistical significant improvement from baseline at 6 months (P < 0.05). The evidence suggests that tendon needling improves patient-reported outcome measures in patients with tendinopathy. There is a trend that shows that the addition of autologous blood products may further improve theses outcomes.


Single- versus dual-attending strategy for spinal deformity surgery: 2-year experience and systematic review of the literature.
Adult spinal deformity (ASD) surgery is complex and associated with high morbidity and complication rates. There is growing evidence in the literature for the beneficial effects of an approach to surgery in which two attending physicians rather than a single attending physician perform surgery for and oversee the surgical care of a single patient in a dual-attending care model. The authors developed a dual-attending care collaboration in August 2017 in which a neurosurgeon and an orthopedic surgeon mutually operated on patients with ASD. The authors recorded data for 2 years of experience with ASD patients operated on by dual attending surgeons. Analyses included estimated blood loss (EBL), transfusions, length of stay (LOS), discharge disposition, complication rates, emergency room visits and readmissions, subjective health status improvement, and disability (Oswestry Disability Index [ODI] score) and pain (visual analog scale [VAS] score) at last follow-up. In addition, the pertinent literature for dual-attending spinal deformity correction was systematically reviewed. The study group comprised 19 of 254 (7.5%) consecutively operated patients who underwent thoracolumbar fusion during the period from January 2017 to June 2019 (68.4% female; mean patient age 65.1 years, ODI score 44.5, VAS pain score 6.8). The study patients were matched by age, sex, anesthesia risk, BMI, smoking status, ODI score, VAS pain score, prior spine surgeries, and basic operative characteristics (type of interbody implants, instrumented segments, pelvic fixation) to 19 control patients (all p > 0.05). There was a trend toward less EBL (mean 763 vs 1524 ml, p = 0.059), fewer intraoperative red blood cell transfusions (mean 0.5 vs 2.3, p = 0.079), and fewer 90-day readmissions (0% vs 15.8%, p = 0.071) in the dual-attending group. LOS and discharge disposition were similar, as were the rates of any < 30-day postsurgery complications, < 90-day postsurgery emergency room visits, and reoperations, and ODI and VAS pain scores at last follow-up (all p > 0.05). At last follow-up, 94.7% vs 68.4% of patients in the dual- versus single-attending group stated their health status had improved (p = 0.036). In the authors' literature search of prior articles on spinal deformity correction, 5 of 8 (62.5%) articles reported lower EBL and 6 of 8 (75%) articles reported significantly lower operation duration in dual-attending cases. The literature contained differing results with regard to complication- or reoperation-sparing effects associated with dual-attending cases. Similar clinical outcomes of dual- versus single-attending cases were reported. Establishing a dual-attending care management platform for ASD correction was feasible at the authors' institution. Results of the use of a dual-attending strategy at the authors' institution were favorable. Positive safety and outcome profiles were found in articles on this topic identified by a systematic literature review.


Network geometry inference using common neighbors.
We introduce and explore a method for inferring hidden geometric coordinates of nodes in complex networks based on the number of common neighbors between the nodes. We compare this approach to the HyperMap method, which is based only on the connections (and disconnections) between the nodes, i.e., on the links that the nodes have (or do not have). We find that for high degree nodes, the common-neighbors approach yields a more accurate inference than the link-based method, unless heuristic periodic adjustments (or "correction steps") are used in the latter. The common-neighbors approach is computationally intensive, requiring O(t4) running time to map a network of t nodes, versus O(t3) in the link-based method. But we also develop a hybrid method with O(t3) running time, which combines the common-neighbors and link-based approaches, and we explore a heuristic that reduces its running time further to O(t2), without significant reduction in the mapping accuracy. We apply this method to the autonomous systems (ASs) Internet, and we reveal how soft communities of ASs evolve over time in the similarity space. We further demonstrate the method's predictive power by forecasting future links between ASs. Taken altogether, our results advance our understanding of how to efficiently and accurately map real networks to their latent geometric spaces, which is an important necessary step toward understanding the laws that govern the dynamics of nodes in these spaces, and the fine-grained dynamics of network connections.


Treatment of intestinal Behçet's syndrome with chimeric tumour necrosis factor alpha antibody.
Few patients with Behçet's syndrome have gastrointestinal ulceration. Such patients are difficult to treat and have a higher mortality. Faced with refractory symptoms in two patients with intestinal Behçet's, we used the tumour necrosis factor alpha (TNF-alpha) monoclonal antibody infliximab to induce remission. Both women (one aged 27 years, the other 30 years) presented with orogenital ulceration, pustular rash, abdominal pain, bloody diarrhoea due to colonic ulceration, weight loss, and synovitis. One had thrombophlebitis, digital vasculitis, perianal fistula, and paracolic abscess; the other had conjunctivitis and an ulcer in the natal cleft. Treatment with prednisolone, methyl prednisolone, and thalidomide in one and prednisolone, colchicine, and cyclosporin in the other was ineffective. After full discussion, infliximab (3 mg/kg, dose reduced because of recent sepsis in one, and 5 mg/kg in the other) was administered. Within 10 days the ulcers healed, with resolution of bloody diarrhoea and all extraintestinal manifestations. A second infusion of infliximab was necessary eight weeks later in one case, followed by sustained (>15 months) remission on low dose thalidomide. Remission was initially sustained for 12 months in the other but thalidomide had to be stopped due to intolerance, and a good response to retreatment lasted only 12 weeks without immunosuppression, before a third infusion. The cause of Behçet's syndrome is unknown but peripheral blood CD45 gammadelta T cells in Behçet's produce >50-fold more TNF-alpha than controls when stimulated with phorbol myristate acetate and anti-CD3. Infliximab could have a role for inducing remission in Behçet's syndrome.


Characterization of patients with angioedema without wheals: the importance of F12 gene screening.
Sporadic and familiar forms of non-histaminergic angioedema and normal C1 inhibitor encompass a group of disorders possibly caused by bradikinin. We aimed to study the subgroups of hereditary angioedema with FXII mutation (FXII-HAE), unknown genetic defect (U-HAE) and idiopathic non-histaminergic acquired angioedema (InH-AAE). We screened the F12 locus in our cohort and delineated the clinical, laboratory and genetic features. Four families carried the p.Thr309Lys mutation in F12 gene. Haplotyping confirmed the hypothesis of a common founder. Six families were affected by U-HAE and 13 patients by sporadic InH-AAE. C4 levels were significantly lower in FXII-HAE than in InH-AAE. In the FXII-HAE group, none had attacks exclusively in high estrogenic states; acute attacks were treated with icatibant. Prophylaxis with tranexamic acid reduced the attack frequency in most patients. Our study provides new data on the diagnosis, clinical features and treatment of non-histaminergic angioedema, underlying the role of the screening for F12 mutations.


Update of the risk assessment of hexabromocyclododecanes (HBCDDs) in food.
The European Commission asked EFSA to update its 2011 risk assessment on hexabromocyclododecanes (HBCDDs) in food. HBCDDs, predominantly mixtures of the stereoisomers α-, β- and γ-HBCDD, were widely used additive flame retardants. Concern has been raised because of the occurrence of HBCDDs in the environment, food and in humans. Main targets for toxicity are neurodevelopment, the liver, thyroid hormone homeostasis and the reproductive and immune systems. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour in mice can be considered the critical effects. Based on effects on spontaneous behaviour in mice, the Panel identified a lowest observed adverse effect level (LOAEL) of 0.9 mg/kg body weight (bw) as the Reference Point, corresponding to a body burden of 0.75 mg/kg bw. The chronic intake that would lead to the same body burden in humans was calculated to be 2.35 μg/kg bw per day. The derivation of a health-based guidance value (HBGV) was not considered appropriate. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Over 6,000 analytical results for HBCDDs in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary LB exposure to HBCDDs were fish meat, eggs, livestock meat and poultry. The CONTAM Panel concluded that the resulting MOE values support the conclusion that current dietary exposure to HBCDDs across European countries does not raise a health concern. An exception is breastfed infants with high milk consumption, for which the lowest MOE values may raise a health concern.