[The morphogenetic reactions of the ectoderm in the early gastrula of the clawed toad to mechanical stretching].
The ventral ectoderm explants of the Xenopus laevis early gastrula were stretched on an elastic substrate 1.5- to twofold for 30 min, then fixed in the stretched state and incubated for up to 6 h. The stretching of explants generated their two-phase active reaction, which was estimated using the criterion of eccentricity of cells and whole explants developed in this study. At the first phase, during the external force application, the explant cells were elongated towards its stretching to a markedly greater extent than the whole explant: eccentricity of the whole cells exceeded that of the whole explants. Cell processes elongated in the same direction appeared, cell contacts and apical cytoskeleton structures developed, and mechanical tensions increased. At the second phase, within 5 h after the stretching, the shape of individual cells, rather than the whole explant, returned to the initial one (approximately isotropic), mechanical tensions decreased, and visible morphogenesis of the explant proceeded: it acquired a complex shape with longitudinal groove and polar thickenings. We conclude that intercalary movements of the cells are present at the second phase of the active explant reaction and morphogenesis is realized at the phase of relaxation of mechanical tensions.


Barriers to Cervical Cancer and Breast Cancer Screening Uptake in Low-Income and Middle-Income Countries: A Systematic Review
Background: Cervical cancer (CCa) and breast cancer (BCa) are the two leading cancers in women worldwide. Early detection and education to promote early diagnosis and screening of CCa and BCa greatly increases the chances for successful treatment and survival. Screening uptake for CCa and BCa in low and middle - income countries (LMICs) is low, and is consequently failing to prevent these diseases. We conducted a systematic review to identify the key barriers to CCa and BCa screening in women in LMICs. Methods: We performed a systematic literature search using Ovid MEDLINE, EMBASE, PsycINFO, SCOPUS, CINHAL Plus, and Google scholar to retrieve all English language studies from inception to 2015. This review was done in accordance with the PRISMA-P guidelines. Results: 53 eligible studies, 31 CCa screening studies and 22 BCa screening studies, provided information on 81,210 participants. We found fewer studies in low-income and lower - middle - income countries than in upper - middle - income countries. Lack of knowledge about CCa and BCa, and understanding of the role of screening were the key barriers to CCa and BCa screening in LMICs. Factors that are opportunities for knowledge acquisition, such as level of education, urban living, employment outside the home, facilitated CCa and BCa screening uptake in women in LMICs. Conclusions: Improvements to CCa and BCa screening uptake in LMICs must be accompanied by educational interventions which aim to improve knowledge and understanding of CCa and BCa and screening to asymptomatic women. It is imperative for governments and health policy makers in LMICs to implement screening programmes, including educational interventions, to ensure the prevention and early detection of women with CCa and BCa. These programmes and policies will be an integral part of a comprehensive population-based CCa and BCa control framework in LMICs.


Feature Counting Under Dichoptic Viewing in Anisometropic and Strabismic Amblyopia.
While using their amblyopic eye, individuals with strabismic amblyopia count inaccurately and underestimate the number of features. These deficits are attributed to limitations in high-level cortical functions and attention. In the current study, we examined whether feature counting is affected in strabismic and anisometropic amblyopia during dichoptic viewing, a setup that can better capture binocular function disruptions. Through a mirror stereoscope, Gabor patches were presented for 200 msec (Experiment 1) or 350 msec (Experiment 2) in both the left eye and the right eye of observers, who were required to combine the percepts and report the total number of patches. Counting performance and errors were compared across amblyopic groups and normal-sighted observers. The contribution and relation of each eye to performance was also evaluated. Anisometropic and strabismic amblyopia groups counted inaccurately and underestimated the number of features compared to the normal-sighted group. In both amblyopic groups, the amblyopic eye contributed less in comparison to the fellow eye. The strabismic group exhibited worse performance, and a more pronounced difference in eye contribution, in comparison to the anisometropic group. Overall, our results support the view of higher-level cortical and binocular function deficits in amblyopia. The current study bridges the gap between research on high-cortical function deficits and clinical binocular function disruptions in amblyopia, which can help us better understand the neural mechanism of amblyopia and inform clinical therapeutic tasks and strategies.


Knockdown of SOX12 expression inhibits the proliferation and metastasis of lung cancer cells.
Sex determining region Y-box protein 12 (SOX12) plays an important role in the tumorigenesis of hepatocellular carcinoma. The involvement of SOX12 in human lung cancer is not well-understood. The aim of the current study was to explore the expression pattern and function of SOX12 in lung cancer. SOX12 expression in lung cancer tissues was elevated as assessed by analyzing The Cancer Genome Atlas (TCGA) lung cancer cohort and real-time PCR data of our own cohort. We found that SOX12 mRNA expression was up-regulated in 83.3% (75/90) of the lung cancer tissues in comparison with paired normal tissues. Moreover, high SOX12 expression predicted reduced overall survival. We also found that knockdown of SOX12 in SPC-A-1 and A549 cells impaired lung cancer cell proliferation, migration and invasion in vitro, but promoted lung cancer cell apoptosis. In vivo tumorigenesis experiments showed that inhibition of SOX12 expression significantly suppressed the growth of xenograft tumors. Finally, the mRNA and protein levels of cell growth (PCNA and Cyclin E), apoptosis (Bcl-2 and Bax), invasion (matrix metalloproteinase-9) and epithelial-mesenchymal transition (EMT; Twist1 and E-cadherin) related moderators were affected by SOX12 knockdown. Chromatin immunoprecipitation assays showed that Cyclin E and Twist1 were direct transcriptional targets of SOX12. Taken together, our study suggests that SOX12 functions as an oncogenic molecule during the development of human lung cancer.


Managing occupational health information: an organizational approach.
The vital nature of health and safety information and the need for employers to collect, maintain, and use it wisely all provide excellent opportunities for occupational health nurses to demonstrate the value they bring to an organization. However, to capitalize on this opportunity, new and more efficient methods for managing expanded roles and responsibilities must be used. In some cases, this necessitates gaining new understanding and capabilities. Many resources are available to occupational health professionals who pursue the knowledge and skills to address the needs of clients and employers in the 21st century (Institute of Medicine, 2000). Occupational health nurses must assess their current abilities and seek the education and training required to develop the necessary competencies (Cox, 2001).


Twining Poly(polyoxometalate) Chains into Nanoropes.
Organic polymers and inorganic clusters belong to two different disciplines and have completely different properties and structures. When a cluster is attached to the backbone of a polymer as a pendant, the resultant hybrid polymers (polyclusters) exhibit unique behaviours totally different from those of conventional polymers owing to the nanoscale size of the cluster and its particular interactions. Herein, the aggregation of a poly(polyoxometalate)-a polynorbornene backbone with inorganic polyoxometalate cluster pendants-upon addition of a non-solvent to its dilute solution is reported. A three-dimensional network of tangled and snake-like nanothreads was observed. Direct visualisation of individual nanoscale clusters enabled identification of single chains within the nanothreads. These observations suggest that during the process of aggregation, the hybrid polymer forms curved or extended chains as a consequence of an armouring effect in which the collapsed cluster pendants wrap around the backbone. The collapse occurs because they become less soluble in the solvent/non-solvent mixture. The extended chains then become entwined and form nanoropes consisting of multiple chains wound around each other. This study provides a deeper understanding of the nature of polyclusters and should also prove useful for their future development and application.


Molecular diagnostic testing for congenital disorders of glycosylation (CDG): detection rate for single gene testing and next generation sequencing panel testing.
Congenital disorders of glycosylation (CDG) are comprised of over 60 disorders with the majority of defects residing within the N-glycosylation pathway. Approximately 20% of patients do not survive beyond five years of age due to widespread organ dysfunction. A diagnosis of CDG is based on abnormal glycosylation of transferrin but this method cannot identify the specific gene defect. For many individuals diagnosed with CDG the gene defect remains unknown. To improve the molecular diagnosis of CDG we developed molecular testing for 25 CDG genes including single gene testing and next generation sequencing (NGS) panel testing. From March 2010 through November 2012, a total of 94 samples were referred for single gene testing and 68 samples were referred for NGS panel testing. Disease causing mutations were identified in 24 patients resulting in a molecular diagnosis rate of 14.8%. Coverage of the 24 CDG genes using panel testing and whole exome sequencing (WES) was compared and it was determined that many exons of these genes were not adequately covered using a WES approach and a panel approach may be the preferred first option for CDG patients. A collaborative effort between physicians, researchers and diagnostic laboratories will be very important as NGS testing using panels and exome becomes more widespread. This technology will ultimately improve the molecular diagnosis of patients with CDG in hard to solve cases.


Evaluation of a Health Promoting Schools program to reduce smoking in Australian secondary schools.
This randomized controlled trial evaluated the effectiveness of a multicomponent Health Promoting Schools (HPS) intervention program in improving self-reported smoking outcomes among a cohort of adolescents in 22 public secondary schools in the Hunter Region of New South Wales, Australia. Pre-test surveys were completed by students in the first 2 years of secondary school, with a 2-year post-test survey. Multivariate analyses examined intervention effect for the main outcome, post-test smoking behavior, controlling for pre-test smoking status, school and other confounders. The sample comprised the cohort of 1852 students who completed both surveys. The results demonstrated that the HPS program failed to improve smoking behavior over the 2 years (equal increase of 10% in both groups). The program was successful in improving smoking knowledge, but not attitudes, in intervention versus control group (P < 0.001). Independent predictors of post-test smoking included: pre-test smoking [odds ratio (OR) = 5.44; 95% confidence interval (CI) = 3.20-9.28], being female (OR = 0.55; CI = 0.35-0.87), having more close friends who smoked (OR = 1.42; CI = 1.33-1.52), peer group having no clear opinion about smoking (OR = 3.23; CI = 1.27-8.27), having more positive and less negative attitudes towards smoking, and being less involved in school activities. We discuss methodological issues in multicomponent community-based interventions, and highlight the strengths and limitations of this study.


Perspectives and Consensus among International Orthopaedic Surgeons during Initial and Mid-lockdown Phases of Coronavirus Disease.
With a lot of uncertainty, unclear, and frequently changing management protocols, COVID-19 has significantly impacted the orthopaedic surgical practice during this pandemic crisis. Surgeons around the world needed closed introspection, contemplation, and prospective consensual recommendations for safe surgical practice and prevention of viral contamination. One hundred orthopaedic surgeons from 50 countries were sent a Google online form with a questionnaire explicating protocols for admission, surgeries, discharge, follow-up, relevant information affecting their surgical practices, difficulties faced, and many more important issues that happened during and after the lockdown. Ten surgeons critically construed and interpreted the data to form rationale guidelines and recommendations. Of the total, hand and microsurgery surgeons (52%), trauma surgeons (32%), joint replacement surgeons (20%), and arthroscopy surgeons (14%) actively participated in the survey. Surgeons from national public health care/government college hospitals (44%) and private/semiprivate practitioners (54%) were involved in the study. Countries had lockdown started as early as January 3, 2020 with the implementation of partial or complete lifting of lockdown in few countries while writing this article. Surgeons (58%) did not stop their surgical practice or clinics but preferred only emergency cases during the lockdown. Most of the surgeons (49%) had three-fourths reduction in their total patients turn-up and the remaining cases were managed by conservative (54%) methods. There was a 50 to 75% reduction in the number of surgeries. Surgeons did perform emergency procedures without COVID-19 tests but preferred reverse transcription polymerase chain reaction (RT-PCR; 77%) and computed tomography (CT) scan chest (12%) tests for all elective surgical cases. Open fracture and emergency procedures (60%) and distal radius (55%) fractures were the most commonly performed surgeries. Surgeons preferred full personal protection equipment kits (69%) with a respirator (N95/FFP3), but in the case of unavailability, they used surgical masks and normal gowns. Regional/local anesthesia (70%) remained their choice for surgery to prevent the aerosolized risk of contaminations. Essential surgical follow-up with limited persons and visits was encouraged by 70% of the surgeons, whereas teleconsultation and telerehabilitation by 30% of the surgeons. Despite the protective equipment, one-third of the surgeons were afraid of getting infected and 56% feared of infecting their near and dear ones. Orthopaedic surgeons in private practice did face 50 to 75% financial loss and have to furlough 25% staff and 50% paramedical persons. Orthopaedics meetings were cancelled, and virtual meetings have become the preferred mode of sharing the knowledge and experiences avoiding human contacts. Staying at home, reading, and writing manuscripts became more interesting and an interesting lifestyle change is seen among the surgeons. Unanimously and without any doubt all accepted the fact that COVID-19 pandemic has reached an unprecedented level where personal hygiene, hand washing, social distancing, and safe surgical practices are the viable antidotes, and they have all slowly integrated these practices into their lives. Strict adherence to local authority recommendations and guidelines, uniform and standardized norms for admission, inpatient, and discharge, mandatory RT-PCR tests before surgery and in selective cases with CT scan chest, optimizing and regularizing the surgeries, avoiding and delaying nonemergency surgeries and follow-up protocols, use of teleconsultations cautiously, and working in close association with the World Health Organization and national health care systems will provide a conducive and safe working environment for orthopaedic surgeons and their fraternity and also will prevent the resurgence of COVID-19.


Campho-Phenique ingestion: an intentional overdose.
We report a suicide attempt with the camphorated phenol preparation Campho-Phenique. The total dose ingested was 68 mg/kg of camphor and 28.9 mg/kg of phenol. The patient had grand mal seizures minutes after ingestion. Supportive medical care and intubation resulted in full recovery within 12 hours. Although Campho-Phenique has been discussed extensively in the pediatric literature and its accidental ingestion by adults has occasionally been reported, intentional ingestion of the preparation has not been reported. We discuss our unusual case and review the literature.


Structural and functional studies of QdtC: an N-acetyltransferase required for the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-alpha-D-glucose.
3-Acetamido-3,6-dideoxy-alpha-D-glucose or Quip3NAc is an unusual dideoxy sugar found in the O-antigens of various Gram-negative bacteria and in the S-layer glycoprotein glycans of some Gram-positive bacteria. It is produced in these organisms as a dTDP-linked sugar, with five enzymes ultimately required for its biosynthesis. The focus of this investigation is on the enzyme QdtC, a CoA-dependent N-acetyltransferase that catalyzes the last step in the Quip3NAc biosynthetic pathway. For this analysis, three crystal structures were determined: the wild-type enzyme in the presence of acetyl-CoA and two ternary complexes of the enzyme with CoA and either dTDP-D-Quip3N or dTDP-3-amino-3,6-didexoy-alpha-D-galactose (dTDP-D-Fucp3N). Each subunit of the trimeric enzyme is dominated by a left-handed beta-helix motif with 11 turns. The three active sites are located at the subunit-subunit interfaces, and the two dTDP-sugar ligands employed in this study bind to the protein in nearly identical manners. Those residues responsible for anchoring the hexose moieties of the dTDP-sugars to the protein include Glu 141, Asn 159, and Asp 160 from one subunit and His 134 from another subunit. To probe the roles of various amino acid residues in the catalytic mechanism of the enzyme, 10 site-directed mutant proteins were constructed and their kinetic parameters measured. On the basis of these data, a catalytic mechanism is proposed for QdtC in which the acetylation of the sugar amino group does not require a catalytic base provided by the protein. Rather, the sulfur of CoA functions as the ultimate proton acceptor.


Glycosaminoglycans are required for translocation of amphipathic cell-penetrating peptides across membranes.
Cell-penetrating peptides (CPPs) are considered as one of the most promising tools to mediate the cellular delivery of various biologically active compounds that are otherwise cell impermeable. CPPs can internalize into cells via two different pathways - endocytosis and direct translocation across the plasma membrane. In both cases, the initial step of internalization requires interactions between CPPs and different plasma membrane components. Despite the extensive research, it is not yet fully understood, which of these cell surface molecules mediate the direct translocation of CPPs across the plasma- and endosomal membrane. In the present study we used giant plasma membrane vesicles (GPMVs) as a model membrane system to elucidate the specific molecular mechanisms behind the internalization and the role of cell surface glycosaminoglycans (GAGs) in the translocation of four well-known CPPs, classified as cationic (nona-arginine, Tat peptide) and amphipathic (transportan and TP10). We demonstrate here that GAGs facilitate the translocation of amphipathic CPPs, but not the internalization of cationic CPPs; and that the uptake is not mediated by a specific GAG class, but rather the overall amount of these polysaccharides is crucial for the internalization of amphipathic peptides.


The impact of neighborhood composition on work-family conflict and distress.
Theories of work-family conflict (WFC) and health remain limited because they emphasize individual-level antecedents to the exclusion of broader contexts, such as residential neighborhoods. We address this issue by focusing on the impact of neighborhood social composition on WFC. Among couples with children we assess whether socially similar neighbors relative to oneself reduce perceptions and mental health consequences of WFC, and whether these associations differ by gender. We argue that the convergence of similarities in residents' features relative to the respondent's own may affect WFC by influencing normative expectations about work and family, and assumptions of available support. We use data on intact families with at least one child between the ages of 9 and 16 from Toronto, Canada, linked to census data. Results highlight that greater similarity between respondents and residents reduces perceptions and consequences of WFC for women but not men. We discuss these findings in relation to neighborhood effects and mental health literature.


Physiologic and pathologic changes in patients with continuous-flow ventricular assist devices.
The clinical use of the newer continuous-flow pumps for mechanical circulatory support have resulted in superior outcomes including significantly reduced complication rates with improved durability over first generation pulsatile design pumps. However, as with all new technology, the newer LVADs have introduced a different set of management issues, as well as a unique risk profile into the mechanical circulatory support arena that were previously absent or unimportant with pulsatile LVADs. These include the effects of continuous flow on the systemic circulation and end-organ function, risk of thromboembolism, and pump thrombosis related to contact bearings in the blood path, the possible increased incidence of gastrointestinal bleeding, and ventricular arrhythmias, as well as alterations in the unloading characteristics of continuous-flow devices. This manuscript overviews the physiologic and pathologic effects that are associated with continuous-flow pumps and their unique management issues and complications.


A non local model for cell migration in response to mechanical stimuli.
Cell migration is one of the most studied phenomena in biology since it plays a fundamental role in many physiological and pathological processes such as morphogenesis, wound healing and tumorigenesis. In recent years, researchers have performed experiments showing that cells can migrate in response to mechanical stimuli of the substrate they adhere to. Motion toward regions of the substrate with higher stiffness is called durotaxis, while motion guided by the stress or the deformation of the substrate itself is called tensotaxis. Unlike chemotaxis (i.e. the motion in response to a chemical stimulus), these migratory processes are not yet fully understood from a biological point of view. In this respect, we present a mathematical model of single-cell migration in response to mechanical stimuli, in order to simulate these two processes. Specifically, the cell moves by changing its direction of polarization and its motility according to material properties of the substrate (e.g., stiffness) or in response to proper scalar measures of the substrate strain or stress. The equations of motion of the cell are non-local integro-differential equations, with the addition of a stochastic term to account for random Brownian motion. The mechanical stimulus to be integrated in the equations of motion is defined according to experimental measurements found in literature, in the case of durotaxis. Conversely, in the case of tensotaxis, substrate strain and stress are given by the solution of the mechanical problem, assuming that the extracellular matrix behaves as a hyperelastic Yeoh's solid. In both cases, the proposed model is validated through numerical simulations that qualitatively reproduce different experimental scenarios.


A continuous molecular roadmap to iPSC reprogramming through progression analysis of single-cell mass cytometry.
To analyze cellular reprogramming at the single-cell level, mass cytometry was used to simultaneously measure markers of pluripotency, differentiation, cell-cycle status, and cellular signaling throughout the reprogramming process. Time-resolved progression analysis of the resulting data sets was used to construct a continuous molecular roadmap for three independent reprogramming systems. Although these systems varied substantially in Oct4, Sox2, Klf4, and c-Myc stoichiometry, they presented a common set of reprogramming landmarks. Early in the reprogramming process, Oct4(high)Klf4(high) cells transitioned to a CD73(high)CD104(high)CD54(low) partially reprogrammed state. Ki67(low) cells from this intermediate population reverted to a MEF-like phenotype, but Ki67(high) cells advanced through the M-E-T and then bifurcated into two distinct populations: an ESC-like Nanog(high)Sox2(high)CD54(high) population and a mesendoderm-like Nanog(low)Sox2(low)Lin28(high)CD24(high)PDGFR-α(high) population. The methods developed here for time-resolved, single-cell progression analysis may be used for the study of additional complex and dynamic systems, such as cancer progression and embryonic development.


Thermodynamics of ligand binding to a heterogeneous RNA population in the malachite green aptamer.
The malachite green aptamer binds two closely related ligands, malachite green (MG) and tetramethylrosamine (TMR), with nearly equal affinity. The MG ligand consists of three phenyl rings emanating from a central carbon, while TMR has two of the three rings connected by an ether linkage. The binding pockets for MG and TMR in the aptamer, known from high-resolution structures, differ only in the conformation of a few nucleotides. Herein, we applied isothermal titration calorimetry (ITC) to compare the thermodynamics of binding of MG and TMR to the aptamer. Binding heat capacities were obtained from ITC titrations over the temperature range of 15-60 °C. Two temperature regimes were found for MG binding: one from 15 to 45 °C where MG bound with a large negative heat capacity and an apparent stoichiometry (n) of ~0.4 and another from 50 to 60 °C where MG bound with a positive heat capacity and an n of ~1.1. The binding of TMR, on the other hand, revealed only one temperature regime for binding, with a more modest negative heat capacity and an n of ~1.2. The large difference in heat capacity between the two ligands suggests that significantly more conformational rearrangement occurs upon the binding of MG than that of TMR, which is consistent with differences in solvent accessible surface area calculated for available ligand-bound structures. Lastly, we note that the binding stoichiometry of MG was improved not only by an increase in the temperature but also by a decrease in the concentration of Mg(2+) or an increase in the time between ITC injections. These studies suggest that binding of a dynamical ligand to a functional RNA requires the RNA itself to have significant dynamics.


An objective estimate of energy intake during weight gain using the intake-balance method.
Estimates of energy intake (EI) in humans have limited validity. The objective was to test the accuracy and precision of the intake-balance method to estimate EI during weight gain induced by overfeeding. In 2 studies of controlled overfeeding (1 inpatient study and 1 outpatient study), baseline energy requirements were determined by a doubly labeled water study and caloric titration to weight maintenance. Overfeeding was prescribed as 140% of baseline energy requirements for 56 d. Changes in weight, fat mass (FM), and fat-free mass (FFM) were used to estimate change in energy stores (ΔES). Overfeeding EI was estimated as the sum of baseline energy requirements, thermic effect of food, and ΔES. The estimated overfeeding EI was then compared with the actual EI consumed in the metabolic chamber during the last week of overfeeding. In inpatient individuals, calculated EI during overfeeding determined from ΔES in FM and FFM was (mean ± SD) 3461 ± 848 kcal/d, which was not significantly (-29 ± 273 kcal/d or 0.8%; limits of agreement: -564, 505 kcal/d; P = 0.78) different from the actual EI provided (3490 ± 729 kcal/d). Estimated EI determined from ΔES in weight closely estimated actual intake (-7 ± 193 kcal/d or 0.2%; limits of agreement: -386, 370 kcal/d; P = 0.9). In free-living individuals, estimated EI during overfeeding determined from ΔES in FM and FFM was 4123 ± 500 kcal/d and underestimated actual EI (4286 ± 488 kcal/d; -162 ± 301 kcal or 3.8%; limits of agreement: -751, 427 kcal/d; P = 0.003). Estimated EI determined from ΔES in weight also underestimated actual intake (-159 ± 270 kcal/d or 3.7%; limits of agreement: -688, 370 kcal/d; P = 0.001). The intake-balance method can be used to estimate EI during a period of weight gain as a result of 40% overfeeding in individuals who are inpatients or free-living with only a slight underestimate of actual EI by 0.2-3.8%.


Brief antecedent ischemia enhances recombinant tissue plasminogen activator-induced coronary thrombolysis by adenosine-mediated mechanism.
Clinical studies have implicated preinfarct angina (brief antecedent ischemia/reperfusion [I/R]) as a predictor of more rapid thrombolysis and lower rates of reocclusion. However, the effects of antecedent ischemia on the efficacy of thrombolysis have not been rigorously assessed. Using a canine model of coronary thrombosis, we aimed to (1) reproduce these clinical findings and (2) determine whether release of adenosine (a potent inhibitor of platelet aggregation via stimulation of platelet A(2) receptors) during brief I/R contributes to this improved patency. To address our first objective, we compared the time required to achieve lysis with recombinant tissue plasminogen activator and patency during the first 2 hours after lysis in dogs in which 1-hour thrombotic occlusion was preceded by brief I/R (10-minute coronary occlusion/10-minute reperfusion) versus 20-minute uninterrupted perfusion (controls). Time to lysis was accelerated in the I/R group versus the control group (11+/-1 versus 35+/-6 minutes, P=0.004). In addition, the duration of subsequent reocclusion was reduced (17+/-12 versus 30+/-11 minutes), and the area of the flow-time profile (normalized to baseline flow x 120 minutes) was increased (64+/-12% versus 35+/-7%, P=0.04) in the I/R cohort. The protocol was then repeated, but all dogs were pretreated with the adenosine A(2)/A(1) antagonist CGS 15943 (CGS, 1.5 mg/kg). Time to lysis (38 versus 39 minutes) and subsequent patency were comparable in the CGS+control group versus the CGS+I/R group. Brief antecedent I/R enhances the efficacy of coronary thrombolysis in this canine model, which is due, at least in part, to an adenosine-mediated mechanism.


[Use of spiramycin in the treatment of inflammatory diseases ot the respiratory tract in children in ambulatory conditions].
Comparative efficacy of oral spiramycin and ampicillin was estimated in the treatment of 65 children at the age of 5 to 12 years with infectious inflammatory diseases of the respiratory tract, tonsils and middle ear. By the 7th day of the treatment with spiramycin the cure was stated in 97.7 per cent of the patients and 2.3 per cent of the patients showed the improvement. With the use of ampicillin the cure was recorded only by the 12th day. Marked advantages of spiramycin were observed as well with respect to the time course of the improvement of the disease main signs such as fever, pain in the throat on swallowing, intoxication and others.


Loss of dysbindin-1, a risk gene for schizophrenia, leads to impaired group 1 metabotropic glutamate receptor function in mice.
The expression of dysbindin-1, a protein coded by the risk gene dtnbp1, is reduced in the brains of schizophrenia patients. Evidence indicates a role of dysbindin-1 in dopaminergic and glutamatergic transmission. Glutamatergic transmission and plasticity at excitatory synapses is critically regulated by G-protein coupled metabotropic glutamate receptor (mGluR) family members, that have been implicated in schizophrenia. Here, we report a role of dysbindin-1 in hippocampal group 1 mGluR (mGluRI) function in mice. In hippocampal synaptoneurosomal preparations from sandy (sdy) mice, that have a loss of function mutation in dysbindin-1 gene, we observed a striking reduction in mGluRI agonist [(S)-3, 5-dihydroxyphenylglycine] (DHPG)-induced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2). This mGluR-ERK1/2 deficit occurred in the absence of significant changes in protein levels of the two members of the mGluRI family (i.e., mGluR1 and mGluR5) or in another mGluRI signaling pathway, i.e., protein kinase C (PKC). Aberrant mGluRI-ERK1/2 signaling affected hippocampal synaptic plasticity in the sdy mutants as DHPG-induced long-term depression (LTD) at CA1 excitatory synapses was significantly reduced. Behavioral data suggest that the mGluRI hypofunction may underlie some of the cognitive abnormalities described in sdy mice as the administration of CDPPB (3-cyano-N-(1, 3-diphenyl-1H-pyrazol-5-yl benzamide), a positive allosteric modulator of mGluR5, rescued short-term object recognition and spatial learning and memory deficits in these mice. Taken together, our data suggest a novel role of dysbindin-1 in regulating mGluRI functions.


Increased Postoperative Morbidity Associated With Prolonged Laparoscopic Colorectal Resections Is Not Increased by Resident Involvement.
Although longer operative times are associated with increased postoperative morbidity, the influence of surgical residents on this association is unclear. The purpose of this study was to evaluate whether morbidity associated with operative times in laparoscopic colorectal surgery is increased by resident training. This was a retrospective cohort study. The study was conducted using a national database. Laparoscopic ileocolectomies, partial colectomies, and low anterior resections were identified in the National Surgical Quality Improvement Project (2005-2012). This cohort was stratified by the presence of resident involvement (postgraduate clinical year ≤5) and then divided into tertiles of operative time (low, medium, and high), allowing comparisons of cases by duration with resident involvement with cases of similar length without resident involvement. Postoperative morbidity (infectious and noninfectious), length of hospital stay, and unplanned reoperations were the primary study outcomes. A total of 20,785 procedures were identified. In aggregate, prolonged operative time was associated with both infectious (OR = 1.49, p < 0.001 with residents; OR = 1.38, p < 0.001 without residents) and noninfectious complications (OR = 1.51, p < 0.001 with residents; OR = 1.48, p < 0.001 without residents) when compared with short cases without residents. Longer hospital stay was observed both within the highest (additional 1.2 days (p < 0.001) with residents; 1.1 days (p < 0.001) without residents) and middle (additional 0.4 days (p < 0.001) with residents; 0.4 days (p = 0.001) without residents) tertiles of operative time. Within the highest tertile of operative length, there was no statistically significant difference in complication rates between cases with and without resident participation. The study was limited by its retrospective design and inability to define the complexity of case and extent of resident involvement. Although longer operative times confer increased postoperative morbidity, there was no significant difference in complication rates within the highest tertile between cases with and without resident participation. Resident involvement does not appear to add to the risk of morbidity associated with longer and more complicated surgeries. See Video Abstract at http://links.lww.com/DCR/A440.


Whole brain radiotherapy versus stereotactic radiosurgery for 4-10 brain metastases: a phase III randomised multicentre trial.
Maintenance of quality of life is the primary goal during treatment of brain metastases (BM). This is a protocol of an ongoing phase III randomised multicentre study. This study aims to determine the exact additional palliative value of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with 4-10 BM. The study will include patients with 4-10 BM from solid primary tumours diagnosed on a high-resolution contrast-enhanced MRI scan with a maximum lesional diameter of 2.5 cm in any direction and a maximum cumulative lesional volume of 30 cm3. Patients will be randomised between WBRT in five fractions of 4 Gy to a total dose of 20 Gy (standard arm) and single dose SRS to the BMs (study arm) in the range of 15-24 Gy. The largest BM or a localisation in the brainstem will determine the prescribed SRS dose. The primary endpoint is difference in quality of life (EQ5D EUROQOL score) at 3 months after radiotherapy with regard to baseline. Secondary endpoints are difference in quality of life (EQ5D EUROQOL questionnaire) at 6, 9 and 12 months after radiotherapy with regard to baseline. Other secondary endpoints are at 3, 6, 9 and 12 months after radiotherapy survival, Karnofsky ≥ 70, WHO performance status, steroid use (mg), toxicity according to CTCAE V4.0 including hair loss, fatigue, brain salvage during follow-up, type of salvage, time to salvage after randomisation and Barthel index. Facultative secondary endpoints are neurocognition with the Hopkins verbal learning test revised, quality of life EORTC QLQ-C30, quality of life EORTC BN20 brain module and fatigue scale EORTC QLQ-FA13. Worldwide, most patients with more than 4 BM will be treated with WBRT. Considering the potential advantages of SRS over WBRT, i.e. limiting radiation doses to uninvolved brain and a high rate of local tumour control by just a single treatment with fewer side effects, such as hair loss and fatigue, compared to WBRT, SRS might be a suitable alternative for patients with 4-10 BM. Trial registration number: NCT02353000 , trial registration date 15th January 2015, open for accrual 1st July 2016, nine patients were enrolled in this trial on 14th April 2017.


JNK pathway and heat shock response mediate the survival of C26 colon carcinoma bearing mice fed with the mushroom Pleurotus eryngii var. eryngii without affecting tumor growth or cachexia.
In the last few years, there has been emerging interest in developing treatments against human diseases using natural bioactive content. Here, the powder of the edible mushroom Pleurotus eryngii var. eryngii was mixed with the normal diet of mice bearing C26 colon carcinoma. Interestingly, it was evidenced by a significant increase in the survival rate of C26 tumor-bearing mice accompanied by a significant increase in Hsp90 and Hsp27 protein levels in the tumors. These data were paralleled by a decrease in Hsp60 levels. The mushroom introduced in the diet induced the inhibition of the transcription of the pro-inflammatory cytokines IL-6 and IL-1 exerting an anti-inflammatory action. The effects of the mushroom were mediated by the activation of c-Jun NH2-terminal kinases as a result of metabolic stress induced by the micronutrients introduced in the diet. In the tumors of C26 bearing mice fed with Pleurotus eryngii there was also a decreased expression of the mitotic regulator survivin and the anti-apoptotic factor Bcl-xL as well as an increase in the expression levels of Atg7, a protein that drives autophagy. In our hypothesis the interplay of these molecules favored the survival of the mice fed with the mushroom. These data are promising for the introduction of Pleurotus eryngii as a dietary supplement or as an adjuvant in anti-cancer therapy.


Estimation of historical effective population size using linkage disequilibria with marker data.
Theory hypothesizes that the rate of decline in linkage disequilibrium (LD) as a function of distance between markers, measured by r(2), can be used to estimate effective population size (N(e)) and how it varies over time. The development of high-density genotyping makes feasible the application of this theory and has provided an impetus to improve predictions. This study considers the impact of several developments on the estimation of N(e) using both simulated and equine high-density single-nucleotide polymorphism data, when N(e) is assumed to be constant a priori and when it is not. In all models, estimates of N(e) were highly sensitive to thresholds imposed upon minor allele frequency (MAF) and to a priori assumptions on the expected r(2) for adjacent markers. Where constant N(e) was assumed a priori, then estimates with the lowest mean square error were obtained with MAF thresholds between 0.05 and 0.10, adjustment of r(2) for finite sample size, estimation of a [the limit for r(2) as recombination frequency (c) approaches 0] and relating N(e) to c (1 - c/2). The findings for predicting N(e) from models allowing variable N(e) were much less clear, apart from the desirability of correcting for finite sample size, and the lack of consistency in estimating recent N(e) (<7 generations) where estimates use data with large c. The theoretical conflicts over how estimation should proceed and uncertainty over where predictions might be expected to fit well suggest that the estimation of N(e) when it varies be carried out with extreme caution.


[Analysis of claims to conclusions of forensic medical examinations in legal proceedings relating to personal injury during dental treatment].
To analyze the quantitative and qualitative composition of main claims from proceeding parties, submitted to the conclusions of forensic medical examinations, based on appellate complaints from trial participants and associated with personal injury as a result of dental treatment. The judgment materials for the period from 2013 to 2022 yrs. were examined. The multiple increase in the claims frequency to the absence of normative references in experts' conclusions (from 5.7% in 2013-2017 yrs. to 32.2% in 2018-2022 yrs.) and answers on the presence of causal link (from 1.8% in 2013-2017 yrs. to 22.6% in 2018-2022 yrs.), as well as to ignoring the findings of other independent experts (from 7.9% in 2013-2017 yrs. to 19.1% in 2018-2022 yrs.), to the lack of documentation on used examination methods in research part (from 4.4% in 2013-2017 yrs. to 20.9% in 2018-2022 yrs.), to production of expert evidence without patient's observation (from 6.1% in 2013-2017 yrs. to 12.2% in 2018-2022 yrs.) and to a number of other issues, requiring a new approach to develop a system of internal quality and safety control for forensic medical examinations, have been revealed.


Two types of action potential configuration in single cardiac Purkinje cells of sheep.
Membrane potentials and currents of isolated sheep Purkinje and ventricular cells were compared using patch-clamp and microelectrode techniques. In approximately 50% of Purkinje cells, we observed action potentials that showed a prominent phase 1 repolarization and relatively negative plateau (LP cells). Action potential configuration of the remaining Purkinje cells was characterized by little phase 1 repolarization and relatively positive plateau (HP cells). Microelectrode impalement of Purkinje strands also revealed these two types of action potential configuration. In LP cells, the density of L-type Ca(2+) current (I(Ca,L)) was lower, whereas the density of transient outward K(+) current was higher, than in HP cells. Action potentials of HP cells strongly resembled those of ventricular cells. Densities of inward rectifier current and I(Ca,L) were significantly higher in ventricular cells compared with densities in both LP and HP Purkinje cells. Differences in current densities explain the striking differences in action potential configuration and the stimulus frequency dependency thereof that we observed in LP, HP, and ventricular cells. We conclude that LP Purkinje cells, HP Purkinje cells, and ventricular cells of sheep each have a unique action potential configuration.


Radiofrequency ablation of a fascicular tachycardia after orthotopic cardiac transplantation.
A 51 year old male received an orthotopic transplant because of end stage ischaemic heart disease. The donor was a healthy male teenager with no history of arrhythmias or other cardiac conditions. The patient presented with haemodynamically stable tachycardia and dyspnoea five weeks post-transplant. The ECG showed a regular tachycardia of 140 beats/min with a right bundle branch block morphology, left axis deviation, and a QRS duration of 135 ms. There were independent P waves, capture, and fusion beats confirming the diagnosis of ventricular tachycardia. Endomyocardial biopsy showed moderate focal rejection that was thought to be responsible for the arrhythmia. During the following six months the patient had recurrent tachyarrhythmias; on each occasion the ECG morphology was the same and there was no cellular rejection. The patient continued to have frequent hospital admissions with ventricular tachycardia requiring DC cardioversion despite the empirical use of amiodarone, sotalol, disopyramide, and procainamide. Eighteen months after transplantation the diagnosis of fascicular tachycardia was suspected by ECG morphology and supported by successful termination with intravenous verapamil. The arrhythmia was successfully managed by radiofrequency ablation. This patient shows that arrhythmias following transplantation are not always related to rejection, and that other potentially reversible causes should be considered, particularly when the ECG during arrhythmia conforms to a classic configuration.


Elevated levels of beta-catenin and fibronectin in three-dimensional collagen cultures of Dupuytren's disease cells are regulated by tension in vitro.
Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in the development of scar-like, collagen-rich disease cords within specific palmar fascia bands. Although the molecular pathology of DD is unknown, recent evidence suggests that beta-catenin may play a role. In this study, collagen matrix cultures of primary disease fibroblasts show enhanced contraction and isometric tension-dependent changes in beta-catenin and fibronectin levels. Western blots of beta-catenin and fibronectin levels were determined for control and disease primary cell cultures grown within stressed- and attached-collagen matrices. Collagen contraction was quantified, and immunocytochemistry analysis of filamentous actin performed. Disease cells exhibited enhanced collagen contraction activity compared to control cells. Alterations in isometric tension of collagen matrices triggered dramatic changes in beta-catenin and fibronectin levels, including a transient increase in beta-catenin levels within disease cells, while fibronectin levels steadily decreased to levels below those seen in normal cell cultures. In contrast, both fibronectin and beta-catenin levels increased in attached collagen-matrix cultures of disease cells, while control cultures showed only increases in fibronectin levels. Immunocytochemistry analysis also revealed extensive filamentous actin networks in disease cells, and enhanced attachment and spreading of disease cell in collagen matrices. Three-dimensional collagen matrix cultures of primary disease cell lines are more contractile and express a more extensive filamentous actin network than patient-matched control cultures. The elevated levels of beta-catenin and Fn seen in collagen matrix cultures of disease fibroblasts can be regulated by changes in isometric tension.


Activities of sodium and potassium ions in epithelial cells of small intestine.
Intracellular molar Na(+) activity (a(Na)), measured with cation-selective glass microelectrodes, in epithelial cells of isolated bullfrog small intestine immersed at 26 degrees C in a sodium sulfate Ringer solution containing mannitol was 0.0144 +/- 0.0031 (average value plus or minus standard deviation). The corresponding K(+) activity (a(K)) was 0.0854 +/- 0.0060. Combination of these values with previous estimates of intracellular Na(+) and K(+) concentrations under identical conditions indicated that a substantial fraction of the cellular Na(+) is in an osmotically inactive state. When the cells were exposed to a Ringer solution in which 26 millimoles of mannitol per liter were replaced by 3-O-methyl glucose, highly significant decreases in a(K) and a(Na) were observed. The decrease in a(K) was proportionately larger than the corresponding decrease in a(Na).


Association of Checkpoint Inhibitor-Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non-Small Cell Lung Cancer.
Immunotherapy with checkpoint inhibitors targeting the PD-1 (programmed cell death 1) axis has brought notable progress in patients with non-small cell lung cancer (NSCLC) and other cancers. However, autoimmune toxic effects are frequent and poorly understood, making it important to understand the pathophysiologic processes of autoimmune adverse effects induced by checkpoint inhibitor therapy. To gain mechanistic insight into autoimmune skin toxic effects induced by anti-PD-1 treatment in patients with non-small cell lung cancer. This prospective cohort study was conducted from July 1, 2016, to December 31, 2018. Patients (n = 73) with non-small cell lung cancer who received anti-PD-1 therapy (nivolumab or pembrolizumab) were recruited from 4 different centers in Switzerland (Kantonsspital St Gallen, Spital Grabs, Spital Wil, and Spital Flawil). Peripheral blood mononuclear cells, tumor biopsy specimens and biopsies from sites of autoimmune skin toxic effects were collected over a 2-year period, with patient follow-up after 1 year. Response to treatment, overall survival, progression-free survival, and development of autoimmune toxic effects (based on standard laboratory values and clinical examinations). Of the cohort of 73 patients with NSCLC (mean [SD] age, 68.1 [8.9] years; 44 [60%] men), 25 (34.2% [95% CI, 24.4%-45.7%]) developed autoimmune skin toxic effects, which were more frequent in patients with complete remission or partial remission (68.2% [95% CI, 47.3%-83.6%]) than those with progressive or stable disease (19.6% [95% CI, 11.0%-32.5%]) (χ2 = 14.02, P < .001). Nine T-cell antigens shared between tumor tissue and skin were identified. These antigens were able to stimulate CD8+ and CD4+ T cells in vitro. Several of the antigen-specific T cells found in blood samples were also present in autoimmune skin lesions and lung tumors of patients who responded to anti-PD-1 therapy. These findings highlight a potential mechanism of checkpoint inhibitor-mediated autoimmune toxic effects and describe the association between toxic effects and response to therapy; such an understanding will help in controlling adverse effects, deciphering new cancer antigens, and further improving immunotherapy.


Reciprocal Hosts' Responses to Powdery Mildew Isolates Originating from Domesticated Wheats and Their Wild Progenitor.
The biotroph wheat powdery mildew, Blumeria graminis (DC.) E.O. Speer, f. sp. tritici Em. Marchal (Bgt), has undergone long and dynamic co-evolution with its hosts. In the last 10,000 years, processes involved in plant evolution under domestication, altered host-population structure. Recently both virulence and genomic profiling separated Bgt into two groups based on their origin from domestic host and from wild emmer wheat. While most studies focused on the Bgt pathogen, there is significant knowledge gaps in the role of wheat host diversity in this specification. This study aimed to fill this gap by exploring qualitatively and also quantitatively the disease response of diverse host panel to powdery mildew [105 domesticated wheat genotypes (Triticum turgidum ssp. dicoccum, T. turgidum ssp. durum, and T. aestivum) and 241 accessions of its direct progenitor, wild emmer wheat (T. turgidum ssp. dicoccoides)]. A set of eight Bgt isolates, originally collected from domesticated and wild wheat was used for screening this wheat collection. The isolates from domesticated wheat elicited susceptible to moderate plant responses on domesticated wheat lines and high resistance on wild genotypes (51.7% of the tested lines were resistant). Isolates from wild emmer elicited reciprocal disease responses: high resistance of domesticated germplasm and high susceptibility of the wild material (their original host). Analysis of variance of the quantitative phenotypic responses showed a significant Isolates × Host species interaction [P(F) < 0.0001] and further supported these findings. Furthermore, analysis of the range of disease severity values showed that when the group of host genotypes was inoculated with Bgt isolate from the reciprocal host, coefficient of variation was significantly higher than when inoculated with its own isolates. This trend was attributed to the role of major resistance genes in the latter scenario (high proportion of complete resistance). By testing the association between disease severity and geographical distance from the source of inoculum, we have found higher susceptibility in wild emmer close to the source. Both qualitative and quantitative assays showed a reciprocal resistance pattern in the wheat host and are well aligned with the recent findings of significant differentiation into wild-emmer and domesticated-wheat populations in the pathogen.


Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: possible role in Down syndrome.
Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system.


A conserved dendritic-cell regulatory program limits antitumour immunity.
Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8+ T cells1-3. Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name 'mature DCs enriched in immunoregulatory molecules' (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-γ and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.


CLH-3, a ClC-2 anion channel ortholog activated during meiotic maturation in C. elegans oocytes.
ClC anion channels are ubiquitous and have been identified in organisms as diverse as bacteria and humans. Despite their widespread expression and likely physiological importance, the function and regulation of most ClCs are obscure. The nematode Caenorhabditis elegans offers significant experimental advantages for defining ClC biology. These advantages include a fully sequenced genome, cellular and molecular manipulability, and genetic tractability. We show by patch clamp electrophysiology that C. elegans oocytes express a hyperpolarization- and swelling-activated Cl(-) current with biophysical characteristics strongly resembling those of mammalian ClC-2. Double-stranded RNA-mediated gene interference (RNAi) and single-oocyte RT-PCR demonstrated that the channel is encoded by clh-3, one of six C. elegans ClC genes. CLH-3 is inactive in immature oocytes but can be triggered by cell swelling. However, CLH-3 plays no apparent role in oocyte volume homeostasis. The physiological signal for channel activation is the induction of oocyte meiotic maturation. During meiotic maturation, the contractile activity of gonadal sheath cells, which surround oocytes and are coupled to them via gap junctions, increases dramatically. These ovulatory sheath cell contractions are initiated prematurely in animals in which CLH-3 expression is disrupted by RNAi. The inwardly rectifying Cl(-) current in C. elegans oocytes is due to the activity of a ClC channel encoded by clh-3. Functional and structural similarities suggest that CLH-3 and mammalian ClC-2 are orthologs. CLH-3 is activated during oocyte meiotic maturation and functions in part to modulate ovulatory contractions of gap junction-coupled gonadal sheath cells.


Prevalence of metabolic syndrome in older Indonesians.
There is an increasing prevalence of chronic disease, including metabolic syndrome in Indonesian older persons. A cross sectional study was undertaken in Jakarta, Indonesia. The objective of the study was to assess the prevalence of risk factors of metabolic syndrome in the elderly. The respondents were 395 elderly women and 161 elderly women, selected using multistage random sampling. Data collected included anthropometric measurements, blood analyses, nutrient intake assessment, activity index and stress score. Discriminant analysis techniques were used to determine factors related to metabolic syndrome in the elderly. In general elderly women had higher prevalence of metabolic syndrome than elderly men, 18.2% in women and 6.6% in men respectively. Discriminant analysis results showed that body mass index and serum total cholesterol were significant factors of metabolic syndrome. The final discriminant model was Y = -8.231 + 0.200 BMI + 0.014 Total cholesterol (P = .000). The results show the importance of routine plasma lipid tests and anthropometric measurements in promoting continuing health of elderly patients.


A scoping review of sexual transmission related HIV research among key populations in Malaysia: Implications for interventions across the HIV care cascade.
The Malaysian government has committed to 'Fast Tracking the HIV Response' to achieve UNAIDS 2030 targets to end AIDS. The epidemic is concentrated among key populations and has shifted from people who inject drugs to HIV infection through sexual transmission among men who have sex with men, sex workers and transgender people. The aim of this scoping review was to examine social and behavioural research published since 2005 that can inform understanding of each stage of the 90:90:90 treatment cascade (as proposed by UNAIDS), including HIV risk behaviours and testing practices that precede entry. We found a concentration of studies related to predictors or correlates of HIV infections (mostly among men who have sex with men) and a shortfall in literature pertaining to sex workers or transgender people. While several studies examined factors associated with HIV testing, only one examined uptake of antiretroviral therapy and two explored issues of treatment adherence. No study examined broader care and support of people living with HIV. To scale-up effective programmes and apprise investment to achieve the ambitious targets set-out in the Malaysian National HIV/AIDS Strategic Plan, a combination of comprehensive strategic information and evidence generated through primary research is critical.


Ocular and periocular hemangiosarcoma in six horses.
To determine the characteristics of and prognosis for ocular and periocular hemangiosarcoma in horses. Six horses treated for ocular or periocular hemangiosarcoma. A retrospective review of medical records from 2007 to 2015 was performed to identify horses with a histologic diagnosis of ocular or periocular hemangiosarcoma. Signalment (age, sex, breed), duration of clinical signs, prior treatment, tumor size and location, medical and surgical treatment including postoperative chemotherapy, follow-up time, and outcome were obtained from medical records. Histopathology was reviewed by a board-certified pathologist. In six horses diagnosed with ocular or periocular hemangiosarcoma, no breed, age, or sex was overrepresented. Sites included the temporal limbus (3), third eyelid (2), and uvea (1). With the exception of one horse with uveal hemangiosarcoma, 5/6 horses had lightly pigmented periocular haircoat. Histologic features of ocular hemangiosarcoma in 6/6 cases included high cellularity, nuclear pleomorphism, and inflammation with a mitotic index ranging from 0 to 8 mitoses per 10 consecutive 400× fields. Five of six tumors displayed solar elastosis, indicating ultraviolet light-induced damage to sub-epithelial collagen. Treatment included surgical excision in all cases and was not associated with recurrence in 4/6. Three cases that received ancillary treatment with topical mitomycin C had no postoperative recurrence. Two cases with postexcisional recurrence had histologic evidence of incomplete excision. Complete surgical excision may be associated with resolution of periocular and ocular hemangiosarcoma in horses. Etiopathogenesis may include exposure to ultraviolet light.


Decellularization for whole organ bioengineering.
Organ transplantation in an orthotopic location is the current treatment for end-stage organ failure. However, the need for transplantable organs far exceeds the number of available donor organs. As a result, new options, such as tissue engineering and regenerative medicine, have been explored to achieve functional organ replacement. Although there have been many advances in the laboratory leading to the reconstruction of tissue and organ structures in vitro, these efforts have fallen short of producing organs that contain intact vascular networks capable of nutrient and gas exchange and are suitable for transplantation. Recently, advances in whole organ decellularization techniques have enabled the fabrication of scaffolds for engineering new organs. These scaffolds, consisting of naturally-derived extracellular matrix (ECM), provide biological signals and maintain tissue microarchitecture, including intact vascular systems that could integrate into the recipient's circulatory system. The decellularization techniques have led to the development of scaffolds for multiple organs, including the heart, liver, lung and kidney. While the experimental studies involving the use of decellularized organ scaffolds are encouraging, the translation of whole organ engineering into the clinic is still distant. This paper reviews recently described techniques used to decellularize whole organs such as the heart, lung, liver and kidney and describes possible methods for using these matrices for whole organ engineering.


Early resection of congenital pseudarthrosis of the tibia and successful reconstruction using the Masquelet technique.
Congenital pseudarthrosis of the tibia remains one of the most difficult orthopaedic problems. We describe early excision and the use of the Masquelet technique to reconstruct the bone defect in a child aged 14 months. Consolidation sufficient for complete weight-bearing was achieved by seven weeks. After two and a half years, the child was asymptomatic with a fully reconstructed tibia and no leg-length discrepancy.


Novel one-step immunoassays to quantify α-synuclein: applications for biomarker development and high-throughput screening.
Familial Parkinson disease (PD) can result from α-synuclein gene multiplication, implicating the reduction of neuronal α-synuclein as a therapeutic target. Moreover, α-synuclein content in human cerebrospinal fluid (CSF) represents a PD biomarker candidate. However, capture-based assays for α-synuclein quantification in CSF (such as by ELISA) have shown discrepancies and have limited suitability for high-throughput screening. Here, we describe two sensitive, in-solution, time-resolved Förster's resonance energy transfer (TR-FRET)-based immunoassays for total and oligomeric α-synuclein quantification. CSF analysis showed strong concordance for total α-synuclein content between two TR-FRET assays and, in agreement with a previously characterized 36 h protocol-based ELISA, demonstrated lower α-synuclein levels in PD donors. Critically, the assay suitability for high-throughput screening of siRNA constructs and small molecules aimed at reducing endogenous α-synuclein levels was established and validated. In a small-scale proof of concept compound screen using 384 well plates, signals ranged from <30 to >120% of the mean of vehicle-treated cells for molecules known to lower and increase cellular α-synuclein, respectively. Furthermore, a reverse genetic screen of a kinase-directed siRNA library identified seven genes that modulated α-synuclein protein levels (five whose knockdown increased and two that decreased cellular α-synuclein protein). This provides critical new biological insight into cellular pathways regulating α-synuclein steady-state expression that may help guide further drug discovery efforts. Moreover, we describe an inherent limitation in current α-synuclein oligomer detection methodology, a finding that will direct improvement of future assay design. Our one-step TR-FRET-based platform for α-synuclein quantification provides a novel platform with superior performance parameters for the rapid screening of large biomarker cohorts and of compound and genetic libraries, both of which are essential to the development of PD therapies.


COVID-19 Response Unites Perioperative Teams at a Recently Merged Health Care System.
Advocate Aurora Health, located in the north-central United States, is the result of a merger between two large health care organizations in April 2018. The health care system comprises 26 hospitals, offers more than 500 sites of care, and employs 75,000 team members. This article discusses the effects that coronavirus disease 2019 had on the perioperative services departments while directors and site leaders were still managing the complexities of the merger. Included are strategies used to address the challenges created by the pandemic, special considerations based on level-of-care capacity, the effect that the hold on elective surgeries had on staffing assignments, the reactivation process when elective surgery resumed, and the importance of keeping the perioperative team members informed and safe. It also illustrates how facing the challenges caused by the pandemic helped to solidify the merger of the two health care organizations.


An Active Model of Research Translation for the General Public: Content Analysis of a YouTube-Based Health Podcast.
Online health information seeking is changing the way people engage with health care and the health system. Recent changes in practices related to seeking, accessing, and disseminating scientific research, and in particular health information, have enabled a high level of user engagement. This study aims to examine an innovative model of research translation, The Huberman Lab Podcast (HLP), developed by Andrew Huberman, Professor of Neurobiology and Ophthalmology at the Stanford School of Medicine. The HLP leverages social media to deliver health information translated into specific, actionable practices and health strategies directly to the general public. This research characterizes the HLP as an Active Model of Research Translation and assesses its potential as a framework for replicability and wider adoption. We applied conventional content analysis of the YouTube transcript data and directed content analysis of viewers' YouTube comments to 23 HLP episodes released from January to October 2021, reflecting the time of data analysis. We selected 7 episodes and a welcome video, to describe and identify key characteristics of the HLP model. We analyzed viewer comments for 18 episodes to determine whether viewers found the HLP content valuable, accessible, and easy to implement. The key HLP features are direct-to-the-consumer, zero-cost, bilingual, and actionable content. We identified 3 main organizing categories and 10 subcategories as the key elements of the HLP: (1) Why: Educate and Empower and Bring Zero Cost to Consumer Information to the General Public; (2) What: Tools and Protocols; Underlying Mechanisms; and Grounded in Science; (3) How: Linear and Iterative Knowledge Building Process; Lecture-Style Sessions; Interactive and Consumer Informed; Easily Accessible; and Building the Community. Analysis of viewers' comments found strong consumer support for the key HLP model elements. This Active Model of Research Translation offers a way to synthesize scientific evidence and deliver it directly to end users in the form of actionable tools and education. Timely evidence translation using effective consumer engagement and education techniques appears to improve access and confidence related to health information use and reduces challenges to understanding and applying health information received from health providers. Framing complex content in an approachable manner, engaging the target audience, encouraging participation, and ensuring open access to the content meet current recommendations on innovative practices for leveraging social media or other digital platforms for disseminating science and research findings to the general public, and are likely key contributors to HLP impact and potential for success. The model offers a replicable framework for translating and disseminating scientific evidence. Similar active models of research translation can have implications for accessing health information and implementing health strategies for improved outcomes. Areas for further investigation are specific and measurable impacts on health, usability, and relevance of the model for reaching marginalized and high-risk populations.


Improving research quality: the view from the UK Reproducibility Network institutional leads for research improvement.
The adoption and incentivisation of open and transparent research practices is critical in addressing issues around research reproducibility and research integrity. These practices will require training and funding. Individuals need to be incentivised to adopt open and transparent research practices (e.g., added as desirable criteria in hiring, probation, and promotion decisions, recognition that funded research should be conducted openly and transparently, the importance of publishers mandating the publication of research workflows and appropriately curated data associated with each research output). Similarly, institutions need to be incentivised to encourage the adoption of open and transparent practices by researchers. Research quality should be prioritised over research quantity. As research transparency will look different for different disciplines, there can be no one-size-fits-all approach. An outward looking and joined up UK research strategy is needed that places openness and transparency at the heart of research activity. This should involve key stakeholders (institutions, research organisations, funders, publishers, and Government) and crucially should be focused on action. Failure to do this will have negative consequences not just for UK research, but also for our ability to innovate and subsequently commercialise UK-led discovery.


The Oral Microbiome of Children: Development, Disease, and Implications Beyond Oral Health.
In the era of applied meta-omics and personalized medicine, the oral microbiome is a valuable asset. From biomarker discovery to being a powerful source of therapeutic targets and to presenting an opportunity for developing non-invasive approaches to health care, it has become clear that oral microbes may hold the answer for understanding disease, even beyond the oral cavity. Although our understanding of oral microbiome diversity has come a long way in the past 50 years, there are still many areas that need to be fine-tuned for better risk assessment and diagnosis, especially in early developmental stages of human life. Here, we discuss the factors that impact development of the oral microbiome and explore oral markers of disease, with a focus on the early oral cavity. Our ultimate goal is to put different experimental and methodological views into perspective for better assessment of early oral and systemic disease at an early age and discuss how oral microbiomes-at the community level-could provide improved assessment in individuals and populations at risk.


Impact of comorbidity on management and mortality in women diagnosed with breast cancer.
To investigate associations between comorbidity burden, management, and mortality in women with breast cancer. A total of 42,646 women diagnosed with breast cancer between 1992 and 2008 were identified in two Clinical Quality Registers in Central Sweden. Breast cancer-specific, conditional breast cancer, competing-cause and all-cause mortality were estimated in relation to comorbidity burden assessed by the Charlson comorbidity index. All analyses were stratified by stage at diagnosis using competing risk analyses, and all-cause mortality was estimated as a function of follow-up time. Following adjustment for age and calendar period, breast conserving surgery was significantly less likely to be offered to women with severe comorbidity (OR 0.63; 95 % CI 0.58-0.69). Similarly, the proportion treated with radiotherapy, tamoxifen, or chemotherapy was lower in women with severe compared to those with no comorbidity. In women with early stage disease, breast cancer-specific mortality was higher among patients with severe comorbidity (sHR 1.47; 95 % CI 1.11-1.94). In all stages of breast cancer, conditional breast cancer and competing-cause mortality were elevated in women with severe comorbidity. For all stages, the relative risk of all-cause mortality between women with severe versus no comorbidity varied by time since diagnosis, and was most pronounced at early follow-up. Comorbidity affects treatment decisions and mortality. In women with early stage breast cancer, severe comorbidity was associated not only with conditional breast cancer, competing-cause and all-cause mortality, but also breast cancer-specific mortality. The observed differences in breast cancer-specific mortality may be due to less extensive treatment, impaired tumor defense and differences in general health status and lifestyle factors.


Fluorescence study of inclusion complexes between star-shaped cholic acid derivatives and polycyclic aromatic fluorescent probes and the size effects of host and guest molecules.
Star-shaped host molecules containing two, three, and four cholic acid moieties have been used to form inclusion complexes with polycyclic aromatic hydrocarbon probes (guests) varying in size from four (pyrene) to five (benzo(e)pyrene) and seven aromatic rings (coronene) and investigated by steady-state fluorescence measurements and fluorescence lifetime techniques. The results indicated that these hydrophobic guest probes prefer to locate in the hydrophobic cavities formed by the host molecules in an aqueous solution. Further studies showed that the stoichiometric ratios of the complexes depended on the relative size of both the host and the guest. The complexes of 1:1 ratio (guest:host) were formed between pyrene and the host molecules of different sizes, while the complexes of 1:2 ratio (guest:host) were found for coronene in all cases. For benzo(e)pyrene with an intermediate size, the complexes with 1:1 and 1:2 ratios (guest:host) were formed depending on the relative sizes of the host molecules. The stability of the inclusion complexes was observed to change with the solvent polarity, indicative of an adaptation of the hydrophobicity of the host pockets to the polarity of the solvent. The formation of the complexes was driven by the solvophobic interactions.


Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives.
In all cells, proteins are continuously synthesized and degraded to maintain protein homeostasis and modify gene expression levels in response to stimuli. Collectively, the processes of protein synthesis and degradation are referred to as protein turnover. At a steady state, protein turnover is constant to maintain protein homeostasis, but in dynamic responses, proteins change their rates of synthesis and degradation to adjust their proteomes to internal or external stimuli. Thus, probing the kinetics and dynamics of protein turnover lends insight into how cells regulate essential processes such as growth, differentiation, and stress response. Here, we outline historical and current approaches to measuring the kinetics of protein turnover on a proteome-wide scale in both steady-state and dynamic systems, with an emphasis on metabolic tracing using stable isotope-labeled amino acids. We highlight important considerations for designing proteome turnover experiments, key biological findings regarding the conserved principles of proteome turnover regulation, and future perspectives for both technological and biological investigation.


Bilateral wrist drop complicating axillary crutches mobilization in a young adult.
Axillary crutches are simple rehabilitative devices that are globally used temporarily or permanently to assist in ambulation of patients and rarely present with complication. This report is about bilateral wrist drop incidentally noticed in a young adult patient mobilized on axillary crutches after internal fixation of a simple right tibia fracture. The fracture was fixed by intramedullary nailing and the patient was mobilized on axillary crutches. At six weeks, patient fearfully refused to be commenced on partial weight bearing and at 12 weeks after surgery he was noticed to be totally weightbearing on the bars of the appropriately long axillary crutches and had developed bilateral wrist drop. There was radiological evidence of healing at the fracture sites. Treatment included mobilization on one elbow crutch on the left, physical therapy and nerve stimulation. At six weeks of physiotherapy, the power of the dorsiflexors of the wrists had recovered completely. Bilateral posterior cord palsy of brachial plexus could occur even in young healthy patients but total recovery could occur if the diagnosis and treatment are prompt. Patients should be told in unequivocal terms not to weight bear directly on axillary bars.


Statistical significance of partial base-pairing potential: implications for recombination of SV40 DNA in eukaryotic cells.
The frequent detection of "patchy homology" between recombining DNAs in eukaryotic systems suggests that partial sequence homology might facilitate formation of partially base-paired hybrid structures and thus define a specific target for recombination. Indeed, the extent of such "patchy homology" initially appears impressive. The question of whether such homology is statistically significant, however, has not been addressed. In this paper we compare the extent of "patchy homology" within the sequence of SV40 recombination sites and within randomly-generated sequences with the same average GC content. We have found no statistically significant differences favoring the existence of "patchy homology" within the recombining regions of SV40. On the average 50% of the bases in randomly-generated sequences with the same GC content can be paired in a pattern of "patchy homology". We have also assessed the ability of sequences near recombination junctions in SV40 to form partially base-paired intra-strand secondary structures. Again, the ability of these sequences to form such configurations was unremarkable when compared with random sequences. Thus, the notion that partial base-pairing provides specificity for sites of recombination must be considered with caution.


Mechanisms of testicular torsion and potential protective agents.
Testicular torsion is a urological emergency most commonly seen in adolescence, involving a decrease in blood flow in the testis resulting from torsion of the spermatic cord that can result in gonad injury or even loss if not treated in time. Testicular ischaemia-reperfusion injury represents the principle pathophysiology of testicular torsion, with ischaemia caused by twisting of the spermatic cord, and reperfusion on its subsequent release. Many cellular and molecular mechanisms are involved in ischaemia-reperfusion injury following testicular torsion. Studies have investigated the use of pharmacological agents as supportive therapy to surgical repair in order to prevent the adverse effects of testicular torsion. Numerous substances have been proposed as important in the prevention of post-ischaemia-reperfusion testicular injury. A range of chemicals and drugs has been successfully tested in animal models for the purpose of mitigating the dangerous effects of ischaemia-reperfusion in testis torsion.


Clinical utility of reflex testing using focused next-generation sequencing for management of patients with advanced lung adenocarcinoma.
The growing number of genomically targeted therapies has made genomic testing an important part of the care for patients with non-small cell lung cancer. However, limited tissue availability, cost and long turnaround times can create barriers to efficient genomic testing and subsequent treatment. Effective approaches to reduce these barriers are needed. 302 advanced lung adenocarcinomas from consecutive patients seen at University Hospitals Cleveland Medical Center (UHCMC) were tested inhouse using a hybrid DNA/RNA next-generation sequencing (NGS) panel. Sample testing was reflexed from pathology for all stage III or IV tumours. Genomic alterations were tiered according to their clinical relevance and reported with guideline-recommended therapies. Clinical implications of genomic testing results were assessed by manual chart review. With a sample cohort consisting of 64% biopsies, 16% excisions/resections and 20% fine needle aspirations, the assay was reliable with a 95% success rate. The average turnaround time from receipt of unstained formalin-fixed paraffin embedded slides to reporting was 4.8±2.1 days, half of the recommended 10 days and similar to single-gene testing. Alterations with Food and Drug Administration-approved or the National Cancer Center Network guideline-recommended targeted therapies were found in 18% of cases. Within this group, 60% of patients went on genomically driven therapies. We found our reflexed inhouse NGS assay to be reliable, cost-effective and efficient. Incorporation of reflex testing with our NGS assay led to an expansion of successful genomic profiling for all guideline-recommended alterations, and by including an expanded number of alterations within our panel we obtained clinically useful information outside the guidelines without changing cost or efficiency. This approach has enabled UHCMC clinicians to efficiently initiate genomically driven therapies for patients with lung adenocarcinoma.


Assessments of tumor mutational burden estimation by targeted panel sequencing: A comprehensive simulation analysis.
Tumor mutational burden (TMB), when at a high level, is an emerging indicative factor of sensitivity to immune checkpoint inhibitors. Previous studies have shown that the more affordable and accurate targeted panels can be used to measure TMB as a substitute for whole exome sequencing (WES). However, additional processes, such as hotspot mutations exclusion and TMB adjustment, are usually required to deal with the effect of the limited panel sizes. A comprehensive investigation of the effective factors is needed for accurate TMB estimation by targeted panels. In this study, we quantitatively evaluated the variances of TMB values calculated by WES and targeted panels using 10,000 simulated targeted panels with panel sizes ranging from 0.2 to 3.1 million bases. With The Cancer Genome Atlas (TCGA) cancer samples and mutation profiles, we fixed regressions on WES-TMBs and panel-TMBs to assess the performance of a given targeted panel. Panel size was found as one of the major effective factors of TMB estimation. Meanwhile, by investigating the well-performing small panels that reported TMB values similar to those of WES, we demonstrated the evidence of the cancer type-specific impacts of genes on TMB estimation and identified high-impact gene sets for different cancer types based on the TCGA data. This study revealed the quantitative correlations between TMB variance and panel size, and the potential impacts of individual genes on TMB estimation. Our results suggested that for cancer patients diagnosed using targeted panels, it would be highly beneficial to have the capability to directly measure TMB from the targeted sequencing data. This would greatly assist in making decisions regarding the use of immunotherapies.


An activator binding module of yeast RNA polymerase II holoenzyme.
The Mediator complex of Saccharomyces cerevisiae is required for both general and regulated transcription of RNA polymerase II (PolII) and is composed of two stable subcomplexes (Srb4 and Rgr1 subcomplexes). To decipher the function of each Mediator subcomplex and to delineate the functional relationship between the subcomplexes, we characterized the compositions and biochemical activities of PolII-Mediator complexes (holoenzymes) prepared from several Mediator mutant strains of S. cerevisiae. We found that holoenzymes devoid of a functional Gal11 module were defective for activated but not basal transcription in a reconstituted in vitro system. This activation-specific defect was correlated with a crippled physical interaction to transcriptional activator proteins, which could be bypassed by artificial recruitment of a mutant holoenzyme to a promoter. Consistent with this observation, a direct interaction between Gal11 and gene-specific transcriptional activator proteins was detected by far-Western analyses and column binding assays. In contrast, the srb5 deletion mutant holoenzyme was defective for both basal and activated transcription, despite its capacity for activator binding that is comparable to that of the wild-type holoenzyme. These results demonstrate that the Gal11 module of the Rgr1 subcomplex is required for the efficient recruitment of PolII holoenzyme to a promoter via activator-specific interactions, while the Srb4 subcomplex functions in the modulation of general polymerase activity.


Exploiting Purine as an Internal Standard for SERS Quantification of Purine Derivative Molecules Released by Bacteria.
Surface-enhanced Raman scattering (SERS) is a highly sensitive technique used in diverse biomedical applications including rapid antibiotic susceptibility testing (AST). However, signal fluctuation in SERS, particularly the widespread of signals measured from different batches of SERS substrates, compromises its reliability and introduces potential errors in SERS-AST. In this study, we investigate the use of purine as an internal standard (IS) to recalibrate SERS signals and quantify the concentrations of two important purine derivatives, adenine and hypoxanthine, which are the most important biomarkers used in SERS-AST. Our findings demonstrate that purine IS effectively mitigates SERS signal fluctuations and enables accurate prediction of adenine and hypoxanthine concentrations across a wide range (5 orders of magnitude). Calibrations with purine as an IS outperform those without, exhibiting a 10-fold increase in predictive accuracy. Additionally, the calibration curve obtained from the first batch of SERS substrates remains effective for 64 additional substrates fabricated over a half-year period. Measurements of adenine and hypoxanthine concentrations in bacterial supernatants using SERS with purine IS closely align with the liquid chromatography-mass spectrometry results. The use of purine as an IS offers a simple and robust platform to enhance the speed and accuracy of SERS-AST, while also paving the way for in situ SERS quantification of purine derivatives released by bacteria under various stress conditions.


Effect of the hexane extract of Piper auritum on insulin release from β-cell and oxidative stress in streptozotocin-induced diabetic rat.
The large-leafed perennial plant Piper auritum known as Hoja Santa, is used for its leaves that because of their spicy aromatic scent and flavor have an important presence in Mexican cuisine, and in many regions, this plant is known for its therapeutic properties. In the present study, we investigated the effect of hexane, chloroform and methanol extracts from Piper auritum on cell culture system and the effect in streptozotocin-induced type 1 diabetic rats treated by 28 days on the physiological, metabolic parameters and oxidative stress. The hexane extract of P. auritum (HS) treatment significantly reduced the intake of both food, water and body weight loss as well as levels of blood glucose, serum cholesterol, triglycerides and increase HDL-cholesterol. After 4-week administration of HS antioxidant enzyme as SOD, CAT, GSH, GPx in pancreas were determined. These enzyme increased significantly compared with those of the diabetic rats control and normal animals. For all estimated, the results of HS treated groups leading to a restoration of the defense mechanism. The treatment also improves pancreatic TBARS-reactive substance level and serum NO and iNOS. To determine the insulin releasing activity, after extract treatment the serum and pancreatic sections were processed for examination of insulin-releasing activity using an immunocytochemistry kit. The results showed that administration of the hexane extract (200 and 400 mg/kg) exhibited a significant increase in serum and pancreas tissue insulin. Administration of streptozotocin decreased the insulin secretory activity in comparison with intact rats, but treatment with the HS extract increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin-induced diabetic rats and increased insulin release from the beta cells of the pancreas. In cultured RIN-5F cells, we examined whether hexane extract of P. auritum would protect the pancreas-derived β-cells from oxidative stress. Moreover, HS could protect pancreatic β-cells from advanced glycation end products-induced oxidative stress. From these results, HS is suggested to show anti-diabetic effect by stimulating insulin-dependent and by protecting pancreatic β-cells from advanced glycation end products-induced oxidative stress.


Prevalence of periodontal disease, its association with systemic diseases and prevention.
Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care.


Exciton-phonon dynamics on complex networks: Comparison between a perturbative approach and exact calculations.
A method combining perturbation theory with a simplifying ansatz is used to describe the exciton-phonon dynamics in complex networks. This method, called PT^{*}, is compared to exact calculations based on the numerical diagonalization of the exciton-phonon Hamiltonian for eight small-sized networks. It is shown that the accuracy of PT^{*} depends on the nature of the network, and three different situations were identified. For most graphs, PT^{*} yields a very accurate description of the dynamics. By contrast, for the Wheel graph and the Apollonian network, PT^{*} reproduces the dynamics only when the exciton occupies a specific initial state. Finally, for the complete graph, PT^{*} breaks down. These different behaviors originate in the interplay between the degenerate nature of the excitonic energy spectrum and the strength of the exciton-phonon interaction so that a criterion is established to determine whether or not PT^{*} is relevant. When it succeeds, our study shows the undeniable advantage of PT^{*} in that it allows us to perform very fast simulations when compared to exact calculations that are restricted to small-sized networks.


Optimal sampling of recruitment curves for functional electrical stimulation control.
A major challenge in controlling multiple-input multiple output functional electrical stimulation systems is the large amount of time required to identify a workable system model due to the high dimensionality of the space of inputs. To address this challenge we are exploring optimal methods to sample the input space. In this paper we present two methods for optimally sampling isometric muscle force recruitment curves. One method maximizes the information about the recruitment curve parameters, and the second method minimizes the average variance of the predicted output force. We compared these methods to two previously-used methods in simulation. The simulation model was identified from recruitment data collected during experiments with a human subject with a high spinal cord injury. The optimal sampling methods on average produced estimates of the output force with less error than the two previously-used methods. The optimal sampling methods require fewer system identification experiments to identify models with similar output prediction accuracy.


1550 nm modulating retroreflector based on coated nanoparticles for free-space optical communication.
Nowadays, there is a renaissance in the field of space exploration. Current and future missions depend on astronauts and a swarm of robots for reconnaissance. In order to reduce the power consumption, weight, and size of the robots, an asymmetric communication system may be used. This is achieved by installing modulating retroreflectors (MRRs) on one side of the link and an interrogating laser on the other side. In this paper, we theoretically study an innovative device that can serve as an MRR in the infrared range of the spectrum. The device is based on a ferroelectric PZT thin film containing TiO2 coated Ag nanoparticles, which exhibit strong plasmonic resonance in the infrared range. After intensive analyses, which included calculations and simulations, we were able to design the device to operate at the 1550 nm wavelength. This is of great importance since the design of devices operating at 1550 nm as this wavelength is a mature technology widely used in free-space optics. Hence, this MRR can serve in asymmetric communication links relying on 1550 nm transmissions, which are also eye-safe. To the best of our knowledge, this is the first time coated metal nanoparticles have been proposed to modulate light in the infrared region. The performance of this device is unique, reaching a 17.5 dB modulation contrast with only a ±2 V operating voltage. This modulator may also be used for terrestrial communication such as fiber optics and optical interconnects in future data centers.


Partial nephrectomy and enbloc liver resection using a bipolar radiofrequency device for renal cell carcinoma invading the liver.
A 66-year-old man presented with right- sided abdominal pain. Ultrasound, CT and MRI scans showed a right renal mass arising from the upper pole with direct involvement of the right lobe of the liver. Biopsy confirmed renal cell carcinoma. After Multi Disciplinary Team (MDT) discussion, right partial nephrectomy with enbloc resection of segments VI and VII of the liver was performed with the help of intraoperative ultrasound scan and the Habib 4X bipolar radiofrequency device. Apart from symptomatic collection, which was drained radiologically, the patient made a good recovery. The patient developed recurrence at the resection margin but is in remission following chemotherapy at 12 months.