Defining the role of medication adherence in poor glycemic control among a general adult population with diabetes.
This study assesses the attributable impact of adherence to oral glucose medications as a risk factor for poor glycemic control in population subgroups of a large general population, using an objective medication adherence measure. Using electronic health records data, adherence to diabetes medications over a two-year period was calculated by prescription-based Medication Possession Ratios for adults with diabetes diagnosed before January 1, 2010. Glycemic control was determined by the HbA1c test closest to the last drug prescription during 2010-2012. Poor control was defined as HbA1c>75 mmol/mol (9.0%). Medication adherence was categorized as "good" (>80%), "moderate" (50-80%), or "poor" (<50%). Logistic regression models assessed the role medication adherence plays in the association between disease duration, age, and poor glycemic control. We calculated the change in the attributable fraction of glucose control if the non-adherent diabetic medication population would become adherent by age-groups. Among 228,846 diabetes patients treated by oral antiglycemic medication, 46.4% had good, 28.8% had moderate, and 24.8% had poor adherence. Good adherence rates increased with increasing disease duration, while glycemic control became worse. There was a strong inverse association between adherence level and poor control (OR = 2.50; CI = 2.43-2.58), and adherence was a significant mediator between age and poor control. A large portion of the diabetes population is reported to have poor adherence to oral diabetes medications, which is strongly associated with poor glycemic control in all disease durations. While poor adherence does not mediate the poorer glycemic control seen in patients with longer-standing disease, it is a significant mediator of poor glycemic control among younger diabetes patients. A greater fraction of poorly controlled younger patients, compared to older patients, could be prevented if at least 80% adherence to their medications was achieved. Therefore, our results suggest that interventions to improve adherence should focus on this younger sub-group.


Quantitative analysis of ligand-EGFR interactions: a platform for screening targeting molecules.
Epidermal growth factor receptor (EGFR) is often constitutively stimulated in many cancers owing to the binding of ligands such as epidermal growth factor (EGF). Therefore, it is necessary to investigate the interaction between EGFR and its targeting biomolecules. The main aim of this study was to estimate the binding affinity and adhesion force of two targeting molecules, anti-EGFR monoclonal antibody (mAb LA1) and the peptide GE11 (YHWYGYTPQNVI), with respect to EGFR and to compare these values with those obtained for the ligand, EGF. Surface plasmon resonance (SPR) was used to determine the equilibrium dissociation constant (KD) for evaluating the binding affinity. Atomic force microscopy (AFM) was performed to estimate the adhesion force. In the case of EGFR, the KD of EGF, GE11, and mAb LA1 were 1.77 × 10-7, 4.59 × 10-4 and 2.07 × 10-9, respectively, indicating that the binding affinity of mAb LA1 to EGFR was higher than that of EGF, while the binding affinity of GE11 to EGFR was the lowest among the three molecules. The adhesion force between EGFR and mAb LA1 was 210.99 pN, which is higher than that observed for EGF (209.41 pN), while the adhesion force between GE11 and EGFR was the lowest (59.51 pN). These results suggest that mAb LA1 binds to EGFR with higher binding affinity than EGF and GE11. Moreover, the adhesion force between mAb LA1 and EGFR was greater than that observed for EGF and GE11. The SPR and AFM experiments confirmed the interaction between the receptor and targeting molecules. The results of this study might aid the screening of ligands for receptor targeting and drug delivery.


Association of number of live births with left ventricular structure and function. The Multi-Ethnic Study of Atherosclerosis (MESA).
Pregnancy is associated with marked maternal cardiovascular/hemodynamic changes. A greater number of pregnancies may be associated with long-term subclinical changes in left ventricular (LV) remodeling. Among 2,234 white, black, Hispanic, and Chinese women (mean age 62 years) in the MESA, we used linear regression to relate live births and cardiac magnetic resonance imaging LV measures. Covariates included age, ethnicity, height, income, education, birth country, smoking, menopause, and oral contraceptive duration. Models were additionally adjusted for potential mediators: systolic blood pressure, antihypertensive use, total/high-density lipoprotein cholesterol, triglycerides, diabetes, and body mass index. We performed sensitivity analyses excluding 763 women in the lowest socioeconomic group: annual income <$25,000 and lower high school level of education. With each live birth, LV mass increased 1.26 g; LV end-diastolic volume, 0.74 mL; and LV end-systolic volume, 0.45 mL; LV ejection fraction decreased 0.18% (P trend <0.05). Changes were most notable for the category of women with ≥5 pregnancies. Upon adjustment for potential biologic mediators, live births remained positively associated with LV mass and end-systolic volume. Live births remained significantly associated with LV end-systolic, end-diastolic volumes, and LV mass (P trend ≤0.02) after excluding women in the lowest socioeconomic group. Number of live births is associated with key LV structural and functional measures in middle to older ages, even after adjustment for sociodemographic factors and cardiovascular disease risk factors. Hemodynamic changes during pregnancy may be associated with cardiac structure/function beyond childbearing years.


Activity restriction in mild COPD: a challenging clinical problem.
Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD). However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression. Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance. As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry. Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status. Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill) using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation. In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea. This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance. Also discussed are the benefits of pulmonary rehabilitation and the potential role of pharmacologic treatment in symptomatic patients with mild COPD.


[Age, gender and individually-typological characteristics of reaction to acute hypoxic exposure].
Individual pequliarities of hypoxic resistance, assessed by the response of cardiorespiratory system to acute normobaric hypoxia (10% O2), were studied in healthy subjects. Age changes in dynamics of blood oxygen saturation after the acute hypoxia are shown at level of separate sites curve SpO2 (phases of a delay, decrease and lifting). It is established, that at children sensitivity to acute hypoxia above, than at teenagers, and at teenagers above, than at adults. Higher lability of mental processes, sympathetic activity, and personal anxiety are associated with choleric temperament. Cholerics are characterized by slower restoration of blood oxygen saturation after the acute hypoxia compared with sanguine persons that we consider an indication of less hypoxic tolerance of the first group. We have developed the complex algorithm, dynamics describing dependence oxygen saturation in various phases of the hypoxic test, which can be used as a universal method of an estimation hypoxic stability at different groups of the population.


[On the polypathias in males].
The structure and prevalence of polypatias (i.e. three and more diseases in single person), their qualitative and quantitative characteristics were investigated on the basis of comprehensive population study of 1050 males aged from 18 and older in unorganized rural population. It is established that in the structure of chronic infectious diseases the share of persons with multinozoology constituted 65.3%? with binozoology--18% and with mononozoology--16.7%. The prevalence level of multinozoology among males constituted 604.7 per thousand? binozoology--166.8 per thousand and mononozoology--154.4 per thousand. The leading positions among multinozoologies are taken by the circulatory system diseases (428.0 per thousand), respiratory system diseases (400.4 per thousand) and digestive system diseases (368.9 per thousand). This fact proves the leading role of the diseases of those classes in the development of polypatias.


Time interval between the last dose of propylthiouracil and I-131 therapy influences cure rates in hyperthyroidism caused by Graves' disease.
To examine the effects of propylthiouracil (PTU) pretreatment on the outcome of initial I-131 therapy for Graves' disease. A retrospective chart review was done. The authors studied 106 patients in an outpatient nuclear medicine setting who were given initial I-131 therapy for Graves' disease from September 1989 to March 1993 and followed for at least 6 months after therapy. These patients were divided into groups based on whether they had ever received PTU or, if they had received PTU, the length of time between the last dose of PTU and the I-131 therapy dose. Measured failure rates of initial I-131 therapy were based on recurrent or continued hyperthyroidism. Treatment failure rates increased markedly from 2.5% in non-PTU-treated patients (n = 80) to 23.1% (n = 26) in patients pretreated with PTU (P = 0.003). Although not significant, two PTU-pretreated subgroups showed a trend toward increased failure rates. The failure rate was 15.4% (n = 13) in patients whose last dose of PTU was 7-14 days before I-131 therapy, and it increased further to 30.8% (n = 13) in patients whose last dose of PTU was within 1 week of I-131 therapy. PTU pretreatment within 2 weeks of I-131 treatment is a strong independent risk factor in failure rates after initial I-131 therapy in patients with Graves' disease. Patients should be free of PTU for 2 weeks before I-131 therapy if they are able to tolerate it, otherwise the dose of I-131 may need to be adjusted upward to diminish the risk that the initial I-131 therapy will fail.


Isolation of a putative progenitor subpopulation of alveolar epithelial type 2 cells.
Alveolar epithelial type 2 cells (AEC2) isolated from hyperoxia-treated animals exhibit increases in both proliferation and DNA damage in response to culture. AEC2 express the zonula adherens proteins E-cadherin, -, - and -catenin, desmoglein, and pp120, as demonstrated by Western blotting. Immunohistochemical analysis of cultured AEC2 showed expression of E-cadherin on cytoplasmic membranes varying from strongly to weakly staining. When cultured AEC2 placed in suspension were labeled with fluorescent-tagged antibodies to E-cadherin, cells could be sorted into at least two subpopulations, either dim or brightly staining for this marker. With the use of antibody to E-cadherin bound to magnetic beads, cells were physically separated into E-cadherin-positive and -negative subpopulations, which were then analyzed for differences in proliferation and DNA damage. The E-cadherin-positive subpopulation contained the majority of damaged cells, was quiescent, and expressed low levels of telomerase activity, whereas the E-cadherin-negative subpopulation was undamaged, proliferative, and expressed high levels of telomerase activity.


Studies on platelet membrane glycoproteins and platelet function during hemodialysis.
Hemodialysis only partially corrects the defects in platelet function associated with uremia. Platelet contact with the artificial surfaces of the dialysis filter during hemodialysis can itself cause platelet activation, degranulation, and loss of platelet membrane glycoproteins. Although the transient platelet dysfunction that occurs after platelet contact with foreign surfaces during cardiopulmonary bypass has been well characterized, there has been no such investigation of hemodialysis. In this study of hemodialysis patients, bleeding times (BT) and the response of their platelets to thrombin, ristocetin, and collagen were measured before, immediately after, and in some patients, the day after hemodialysis. In addition, membrane glycoproteins in platelets obtained at these time intervals were studied using fluorescein isothiocyanate (FITC) conjugated monoclonal antibodies (mAb) CD42b (anti-GPIb), CD41a (anti-GPIIb/IIIa), and CD62 (anti-P-selectin), with flow cytometry. BT was significantly prolonged, and response to thrombin and ristocetin was significantly decreased immediately after hemodialysis (P < 0.01). Binding of CD42b mAb to the platelet membrane was decreased in platelets obtained immediately after hemodialysis. Most patients had shortened BT and demonstrated increased response of their platelets to thrombin and increased CD42b binding to their platelets the day after hemodialysis. These findings suggest that in uremic patients, hemodialysis is associated with transient platelet dysfunction and decreased membrane expression of GPIb.


Apoptosis and Bbcl-2 expression in gastric carcinomas: correlation withclinicopathological variables, p53 expression, cell proliferation and prognosis.
We investigated apoptosis and Bcl-2 expression in 221 advanced gastric carcinomas in correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis, using the in situ DNA nick end labeling method and immunohistochemistry. Apoptosis was associated with high immunoreactivity of proliferating cell nuclear antigen. Bcl-2 expression correlated with a low apoptotic index and less malignant behavior of tumors. Prognostically, Bcl-2 expression was associated with a better prognosis, whereas p53 expression was the most important prognostic risk factor. Thus, apoptosis in gastric carcinomas is associated with cell proliferation, and Bcl-2 expression may have a prognostic importance as well as p53 expression.


Bringing Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) Closer to the Point of Injury.
The management of noncompressible torso hemorrhage remains a significant issue at the point of injury. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used in the hospital to control bleeding and bridge patients to definitive surgery. Smaller delivery systems and wirefree devices may be used more easily at the point of injury by nonphysician providers. We investigated whether independent duty military medical technicians (IDMTs) could learn and perform REBOA correctly and rapidly as assessed by simulation. US Air Force IDMTs without prior endovascular experience were included. All participants received didactic instruction and evaluation of technical skills. Procedural times and pretest/posttest examinations were administered after completion of all trials. The Likert scale was used to subjectively assess confidence before and after instruction. Eleven IDMTs were enrolled. There was a significant decrease in procedural times from trials 1 to 6. Overall procedural time (± standard deviation) decreased from 147.7 ± 27.4 seconds to 64 ± 8.9 seconds (ρ < .001). There was a mean improvement of 83.7 ± 24.6 seconds from the first to sixth trial (ρ < .001). All participants demonstrated correct placement of the sheath, measurement and placement of the catheter, and inflation of the balloon throughout all trials (100%). There was significant improvement in comprehension and knowledge between the pretest and posttest; average performance improved significantly from 36.4.6% ± 12.3% to 71.1% ± 8.5% (ρ < .001). Subjectively, all 11 participants noted significant improvement in confidence from 1.2 to 4.1 out of 5 on the Likert scale (ρ < .001). Technology for aortic occlusion has advanced to provide smaller, wirefree devices, making field deployment more feasible. IDMTs can learn the steps required for REBOA and perform the procedure accurately and rapidly, as assessed by simulation. Arterial access is a challenge in the ability to perform REBOA and should be a focus of further training to promote this procedure closer to the point of injury.


Acute Ingestion of Caffeinated Chewing Gum Improves Repeated Sprint Performance of Team Sport Athletes With Low Habitual Caffeine Consumption.
The effects of acute ingestion of caffeine on short-duration high-intensity performance are equivocal, while studies of novel modes of delivery and the efficacy of low doses of caffeine are warranted. The aims of the present study were to investigate the effect of acute ingestion of caffeinated chewing gum on repeated sprint performance (RSP) in team sport athletes, and whether habitual caffeine consumption alters the ergogenic effect, if any, on RSP. A total of 18 male team sport athletes undertook four RSP trials using a 40-m maximum shuttle run test, which incorporates 10 × 40-m sprints with 30 s between the start of each sprint. Each participant completed two familiarization sessions, followed by caffeine (CAF; caffeinated chewing gum; 200 mg caffeine) and placebo (PLA; noncaffeinated chewing gum) trials in a randomized, double-blind manner. RSP, assessed by sprint performance decrement (%), did not differ (p = .209; effect size = 0.16; N = 18) between CAF (5.00 ± 2.84%) and PLA (5.43 ± 2.68%). Secondary analysis revealed that low habitual caffeine consumers (<40 mg/day, n = 10) experienced an attenuation of sprint performance decrement during CAF relative to PLA (5.53 ± 3.12% vs. 6.53 ± 2.91%, respectively; p = .049; effect size =0.33); an effect not observed in moderate/high habitual caffeine consumers (>130 mg/day, n = 6; 3.98 ± 2.57% vs. 3.80 ± 1.79%, respectively; p = .684; effect size = 0.08). The data suggest that a low dose of caffeine in the form of caffeinated chewing gum attenuates the sprint performance decrement during RSP by team sport athletes with low, but not moderate-to-high, habitual consumption of caffeine.


Problems of problem-based learning: Towards transformative critical pedagogy in medical education.
Problem-based medical education is based in a biomedical worldview that works to entrench deterministic ways of thinking about socioculturally-influenced health disparities in the minds of medical trainees. This perspective paper considers the utility of Paolo Freire's critical pedagogy as a means of redressing this issue, as it may enable medical learners to perceive and address the social sources of illness that shape their patients' lives. With an eye to advancing health equity, and educating health professionals who are responsive to marginalized and vulnerable communities, this paper considers how a problem-posing medical education could redefine physicians' relationships to knowledge, identity, and to their patients.


Electrochemical Triggered Dissolution of Hydroxyapatite/Doxorubicin Nanocarriers.
The controlled release of drugs by an external stimulus is of pivotal interest and importance as a means of increasing administration efficacy. Accordingly, many responsive systems have been developed based on primarily pH, temperature, and light changes. Here, a novel electrochemical triggered release of a doxorubicin (Dox)-loaded hydroxyapatite (HAp) nanoparticle (NP) system is presented. Dox is loaded onto HAp NPs by producing a stable dispersion in DMSO. The Dox-HAp NPs are electrophoretically deposited on a stainless steel (S.S) surface. The adsorbed Dox-HAp NPs are released either by applying a moderate electrochemical potential pulse or upon scanning the potential. Two mechanisms were proposed. The first is that the positive potential induces the desorption of the Dox-HAp NPs. Alternatively, the positive potential could drive the oxidation of water and generation of protons, causing the dissolution of the Dox-HAp NPs. In situ characterization techniques, such as atomic force microscopy (AFM) and confocal microscopy, were used to gain insight on the release mechanism. All measurements allude to the electrochemically driven dissolution of the Dox-HAp NPs and release of the embedded drug. In vitro antitumor activity against both HT-29 and A2780 cancer cells revealed that the efficacy of the released Dox was not significantly affected by the electrochemical process. We believe that the electrochemically triggered release of NPs could be applied to many other responsive systems.


Coherence function-encoded optical palpation.
Optical palpation maps stress at the surface of biological tissue into 2D images. It relies on measuring surface deformation of a compliant layer, which to date has been performed with optical coherence tomography (OCT). OCT-based optical palpation holds promise for improved clinical diagnostics; however, the complexity and cost hinder broad adoption. In this Letter, we introduce coherence function-encoded optical palpation (CFE-OP) using a novel optical profilometry technique that exploits the envelope of the coherence function rather than its peak position, which is typically used to retrieve depth information. CFE-OP utilizes a Fabry-Perot laser diode (bandwidth, 2.2 nm) and a single photodiode in a Michelson interferometer to detect the position along the coherence envelope as a function of path length. This technique greatly reduces complexity and cost in comparison to the OCT-based approach. We perform CFE-OP on phantom and excised human breast tissue, demonstrating comparable mechanical contrast to OCT-based optical palpation and the capability to distinguish stiff tumor from soft benign tissue.


Cold urticaria associated with infectious mononucleosis.
We have evaluated two patients with cold urticaria associated with infectious mononucleosis and reviewed three case reports with this syndrome. The cold sensitivity ranged from urticaria to anaphylaxis and one patient had additional cold-related cutaneous manifestations. The duration of cold urticaria was transient and paralleled the clinical course of infectious mononucleosis. Analysis of these five cases revealed no correlation of cold urticaria with known cold-activated factors that often occur in this viral infection.


Dynamics of Cations around DNA and Protein as Revealed by 23Na Diffusion NMR Spectroscopy.
Counterions are vital for the structure and function of biomolecules. However, the behavior of counterions remains elusive due to the difficulty in characterizing mobile ions. Here, we demonstrate that the dynamics of cations around biological macromolecules can be revealed by 23Na diffusion nuclear magnetic resonance (NMR) spectroscopy. NMR probe hardware capable of generating strong magnetic field gradients enables 23Na NMR-based diffusion measurements for Na+ ions in solutions of biological macromolecules and their complexes. The dynamic properties of Na+ ions interacting with the macromolecules can be investigated using apparent 23Na diffusion coefficients measured under various conditions. Our diffusion data clearly show that Na+ ions retain high mobility within the ion atmosphere around DNA. The 23Na diffusion NMR method also permits direct observation of the release of Na+ ions from nucleic acids upon protein-nucleic acid association. The entropy change due to the ion release can be estimated from the diffusion data.


News Stories of Intimate Partner Violence: An Experimental Examination of Media Framing and Perpetrator Sex in LGBTQ Versus Heterosexual Relationships.
This study experimentally examines the effects of perpetrator sex (male or female), relationship context (heterosexual or homosexual), and the type of media framing (episodic or thematic) on endorsement for public health perspectives about intimate partner violence (IPV) and punishment preferences for IPV perpetrators. Participants (N = 750) were randomly assigned to a condition, exposed to a composite news story, and then completed a survey. Manipulation check responses demonstrated a pattern suggesting that participants had difficulty attending to details of IPV in stories where the perpetrator was a woman, or where the violence occurred in a homosexual relationship. Results revealed significant interaction effects for the endorsement of public health perspectives and for perpetrator punishment preferences. Results for the endorsement of public health perspectives showed that thematic framing caused stronger support only when the perpetrator was a heterosexual man. Results for perpetrator punishment preferences revealed a pattern where participants preferred stronger punishments for heterosexual male perpetrators over any other group. Participants did not distinguish in their punishment preferences for male or female homosexual perpetrators, but these were still stronger than their punishment preferences for heterosexual female perpetrators. Theoretical implications are presented with attention to extending research about media portrayals of IPV, and discussion is offered concerning practical considerations for public health support services that address IPV.


Impact of COVID-19 outbreak on esophageal cancer surgery in Northern Italy: lessons learned from a multicentric snapshot.
Coronavirus Disease-19 (COVID-19) outbreak has significantly burdened healthcare systems worldwide, leading to reorganization of healthcare services and reallocation of resources. The Italian Society for Study of Esophageal Diseases (SISME) conducted a national survey to evaluate changes in esophageal cancer management in a region severely struck by COVID-19 pandemic. A web-based questionnaire (26 items) was sent to 12 SISME units. Short-term outcomes of esophageal resections performed during the lockdown were compared with those achieved in the same period of 2019. Six (50%) centers had significant restrictions in their activity. However, overall number of resections did not decrease compared to 2019, while a higher rate of open esophageal resections was observed (40 vs. 21.7%; P = 0.034). Surgery was delayed in 24 (36.9%) patients in 6 (50%) centers, mostly due to shortage of anesthesiologists, and occupation of intensive care unit beds from intubated COVID-19 patients. Indications for neoadjuvant chemo (radio) therapy were extended in 14% of patients. Separate COVID-19 hospital pathways were active in 11 (91.7%) units. COVID-19 screening protocols included nasopharyngeal swab in 91.7%, chest computed tomography scan in 8.3% and selective use of lung ultrasound in 75% of units. Postoperative interstitial pneumonia occurred in 1 (1.5%) patient. Recovery from COVID-19 pandemic was characterized by screening of patients in all units, and follow-up outpatient visits in only 33% of units. This survey shows that clinical strategies differed considerably among the 12 SISME centers. Evidence-based guidelines are needed to support the surgical esophageal community and to standardize clinical practice in case of further pandemics.


Modulation of viewpoint effects in object recognition by shape and motion cues.
In three experiments, we examined the role of structural similarity and different types of motion on the efficiency of performing same--different shape judgments across changes in viewpoints. In all experiments, participants judged whether two novel, multi-part objects were structurally identical, and they were to ignore any viewpoint or motion differences between the objects. In experiment 1, participants were affected by viewpoint differences more for structurally similar than structurally distinct objects, but this interaction was mitigated by rigid motion. In experiments 2 and 3, we used only structurally similar objects that moved only some of their parts, either in a similar way between objects within a pair or in distinctive ways. Participants' recognition performance was facilitated by this articulated motion relative to both static and scrambled controls. We conclude that coherent motion facilitates generalisation across different views of dynamic objects under some conditions.


Spectroscopic Doppler analysis for visible-light optical coherence tomography.
Retinal oxygen metabolic rate can be effectively measured by visible-light optical coherence tomography (vis-OCT), which simultaneously quantifies oxygen saturation and blood flow rate in retinal vessels through spectroscopic analysis and Doppler measurement, respectively. Doppler OCT relates phase variation between sequential A-lines to the axial flow velocity of the scattering medium. The detectable phase shift is between -π and π due to its periodicity, which limits the maximum measurable unambiguous velocity without phase unwrapping. Using shorter wavelengths, vis-OCT is more vulnerable to phase ambiguity since flow induced phase variation is linearly related to the center wavenumber of the probing light. We eliminated the need for phase unwrapping using spectroscopic Doppler analysis. We split the whole vis-OCT spectrum into a series of narrow subbands and reconstructed vis-OCT images to extract corresponding Doppler phase shifts in all the subbands. Then, we quantified flow velocity by analyzing subband-dependent phase shift using linear regression. In the phantom experiment, we showed that spectroscopic Doppler analysis extended the measurable absolute phase shift range without conducting phase unwrapping. We also tested this method to quantify retinal blood flow in rodents in vivo.


The idiosyncrasy of spatial structure in bacterial competition.
The spatial structure of a habitat can have a strong impact on community dynamics. Different experimental approaches exist to explore the effect of spatial structure on bacterial communities. To investigate the effect of 'space', a single implementation of spatial structure is often contrasted to bacterial community dynamics in well-mixed cultures. While such comparisons are useful, it is likely that the observed dynamics will be particular to the specific experimental implementation of spatial structure. In order to address this question, we track the community dynamics of a two-strain Escherichia coli community in various spatial habitats and relate the observed dynamics to the structure of a habitat. By tracking the community dynamics of rpoS wild-type and mutant E. coli in radially expanding colonies on solid and semi-solid agar plates, we find that the mutant strain outcompetes the wild-type on semi-solid agar plates, whereas the two strains coexist on solid agar. We compare these results to previous studies in which the same two strains were shown to coexist in habitats spatially structured by microfabrication, while the mutant outcompeted the wild-type in well-mixed batch cultures. Together, these observations show that different implementations of space may result in qualitatively different community dynamics. Furthermore, we argue that the same competitive outcome (e.g. coexistence) may arise from distinct underlying dynamics in different experimental implementations of spatial structure. Our observations demonstrate that different experimental implementations of spatial structure may not only lead to quantitatively different communities (changes in the relative abundance of types) but can also lead to qualitatively different outcomes of long-term community dynamics (coexistence versus extinction and loss of biodiversity).


Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies; translational issues.
Binary blend polymers offer the opportunity to combine different desirable properties into a single scaffold, to enhance function within the field of tissue engineering. Previous in vitro and murine in vivo analysis identified a polymer blend of poly(l-lactic acid)-poly(ε-caprolactone) (PLLA:PCL 20:80) to have characteristics desirable for bone regeneration. Polymer scaffolds in combination with marrow-derived skeletal stem cells (SSCs) were implanted into mid-shaft ovine 3.5 cm tibial defects, and indices of bone regeneration were compared to groups implanted with scaffolds alone and with empty defects after 12 weeks, including micro-CT, mechanical testing and histological analysis. The critical nature of the defect was confirmed via all modalities. Both the scaffold and scaffold/SSC groups showed enhanced quantitative bone regeneration; however, this was only found to be significant in the scaffold/SSCs group (p = 0.04) and complete defect bridging was not achieved in any group. The mechanical strength was significantly less than that of contralateral control tibiae (p < 0.01) and would not be appropriate for full functional loading in a clinical setting. This study explored the hypothesis that cell therapy would enhance bone formation in a critical-sized defect compared to scaffold alone, using an external fixation construct, to bridge the scale-up gap between small animal studies and potential clinical translation. The model has proved a successful critical defect and analytical techniques have been found to be both valid and reproducible. Further work is required with both scaffold production techniques and cellular protocols in order to successfully scale-up this stem cell/binary blend polymer scaffold. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.


Solar retinopathy and foveomacular retinitis.
The visual disturbances caused by looking into the sun or a solar eclipse have been known for many years. Recently, there have been discussions about whether or not solar retinopathy is a distinct clinical entity or identical to the disease termed foveomacular retinitis. A series of 36 patients has been evaluated at Letterman Army Medical Center with the ophthalmoscopic appearance compatible with both conditions in various stages of the disease. By use of clinical history, funduscopy, visual fields, Amsler Grid, color acuity testing, color fundus photography, and fluorescein dye studies, it is our distinct impression that these two conditions are identical.


Effect of a new liner/base on human dentin permeability.
Resin-modified glass ionomers (RMGI) have demonstrated clinical success in their ability to minimize post-operative sensitivity of restorations. RMGIs have been recently introduced as paste-liquid systems for convenience of clinical usage. The objective of this study was to measure the ability of a new paste-liquid RMGI liner/base to reduce fluid flow through human dentin. Dentin permeability was measured on human crown sections on etched dentin, using etched dentin as a model for the exposed tubules typical of root sensitivity, and permitting measurement of the maximum permeability. In the one group, the etched dentin was coated with the RMGI, and pre- and post-treatment permeability was measured on the coated dentin. In the second group, a smear layer was created on the dentin with sandpaper, then the samples were coated with the RMGI; permeability was measured on the smeared and coated dentin. Samples from each group were sectioned and examined via scanning electron microscopy (SEM). The new paste-liquid RMGI liner/base significantly reduced fluid flow through dentin, and exhibited excellent seal on dentin with either a smear layer or open tubules. SEM images show evidence that the RMGI infiltrated the smear layer with resin during placement, penetrated dentin tubules, and formed resin tags in acid-etched dentin. Based on these results, combined with previous research on adhesion and microleakage, it is concluded that the new RMGI liner/base should minimize post-operative sensitivity in restorations.


Substitution of general practitioners by nurse practitioners in out-of-hours primary care home visits: A quasi-experimental study.
General practitioners experience a high workload during out-of-hours care. A possible solution is the shifting of care to nurse practitioners. To provide insight into patient- and care characteristics, safety, efficiency, and patient satisfaction of substituting general practitioners with nurse practitioners for home visits by out-of-hours primary care services. Quasi-experimental non-randomised study comparing home visits by nurse practitioners (intervention group; one out-of-hours care service) with home visits by general practitioners (control group; two out-of-hours care services) for 24 protocolised health problems. Three out-of-hours primary care services in the East of the Netherlands. 1601 patients who received a home visit by a nurse practitioner (N = 386) or a general practitioner (N = 1215). Of these patients, 639 gave informed consent to be included in the protocol adherence assessment and follow-up record review (nurse practitioner: N = 358; general practitioner: N = 281). Five nurse practitioners with experience in ambulance care were recruited and trained. From September 2016 to March 2017 the nurse practitioners took over home visits under supervision of a general practitioners. This was evaluated using: (1) data-extraction from the patient registration system, (2) follow-up record review in the patients' general practices, and (3) patient satisfaction survey. Two general practitioners independently assessed protocol adherence based on the extracted registration data. Nurse practitioners prescribed medication significantly less often than general practitioners (19.9% versus 30.6%), and referred patients significantly more often to the hospital (24.1% versus 15.9%). The mean length of the home visit was significantly longer for nurse practitioners (34.1 versus 21.1 min). Nurse practitioners adhered to the protocol significantly more often than general practitioners (84.9% versus 76.2%) and their medication prescribing was significantly more often appropriate (93.7% versus 79.5%). There were no differences in the number of missed diagnoses and complications. The number of follow-up contacts was also similar in both groups. Patient satisfaction was generally high and significantly higher for nurse practitioners on several items. Nurse practitioners with experience in ambulance care can safely, efficiently, and satisfactorily perform low complex out-of-hours primary care home visits. It is recommended to study the safety and efficiency of nurse practitioners' home visits in other regions and with nurse practitioners with different educational levels and different specialisations. In addition, we recommend to evaluate the cost-effectiveness and if it leads increased quality of care.


Effects of prebiotics on sepsis, necrotizing enterocolitis, mortality, feeding intolerance, time to full enteral feeding, length of hospital stay, and stool frequency in preterm infants: a meta-analysis.
Prebiotics are increasingly recognized as an effective measure to promote health and prevent adverse health outcomes in preterm infants. We aimed to systematically review the randomized controlled trials (RCTs) in this area. Relevant studies from January 2000 to June 2018 were searched and selected from PubMed, Medline, Scopus, and the Cochrane Library. RCTs were included if they involved preterm infant participants, included a prebiotic intervention group, measured incidence of sepsis, feeding intolerance, mortality, time to full enteral feeding, necrotizing enterocolitis (NEC), length of hospital stay, and stool frequency as outcomes. Eighteen RCTs (n = 1322) were included in the final meta-analysis. Participants who took prebiotics showed significant decreases in the incidence of sepsis (with a risk ratio (RR) of 0.64, 95% CI: 0.51, 0.78), mortality (RR = 0.58. 95% CI: 0.36, 0.94), length of hospital stay (mean difference (MD): -5.18, 95% CI: -8.94, -1.11), and time to full enteral feeding (MD: -0.99, 95% CI: -1.15, 0.83). The pooled effects showed no significant differences between intervention and control groups in relation to the morbidity rate of NEC (RR = 0.79, 95% CI: 0.44, 1.44) or feeding intolerance (RR = 0.87, 95% CI: 0.52, 1.45). The results showed that the use of prebiotics with preterm infants is safe and can decrease the incidence of sepsis, mortality, length of hospital stay, and time to full enteral feeding but not NEC.


Are we in this together? Changes in anti-immigrant sentiments during the COVID-19 pandemic.
The COVID-19 pandemic is posing a threat to people all across the globe. According to traditional literature, threat perceptions induce anti-immigrant sentiments, as ingroup identity and self-interest are strengthened at the expense of the outgroup. In this study, we investigate whether the COVID-19 pandemic indeed increases anti-immigrant sentiments, or that this type of threat elicits other or no group related responses. We also look at whether such responses are expressed more strongly among specific subgroups in Dutch society. To do so, we use unique longitudinal panel data based on the European Values Study 2017, with a repeated measure in May 2020, during the national 'intelligent lockdown' in the Netherlands. Based on structural equation modeling, we demonstrate that anti-immigrant sentiments have not increased due to (perceived threat of) the COVID-19 pandemic. In fact, negative opinions towards immigrants decreased between 2017 and 2020 in the Netherlands, for which we provide alternative explanations. Although some subgroups do experience more threat than others due to the coronavirus, such as women, first generation immigrants, and the elderly, this does not lead to more negative feelings towards outgroups. Whether this is due to the fact that individuals feel threatened by everyone, regardless of group membership, should be explored in future research.


A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor-Associated Macrophages for Potentiating Immunotherapy.
The progress of antitumor immunotherapy is usually limited by tumor-associated macrophages (TAMs) that account for the highest proportion of immunosuppressive cells in the tumor microenvironment, and the TAMs can also be reversed by modulating the M2-like phenotype. Herein, a biomimetic polymer magnetic nanocarrier is developed with selectively targeting and polarizing TAMs for potentiating immunotherapy of breast cancer. This nanocarrier PLGA-ION-R837 @ M (PIR @ M) is achieved, first, by the fabrication of magnetic polymer nanoparticles (NPs) encapsulating Fe3 O4 NPs and Toll-like receptor 7 (TLR7) agonist imiquimod (R837) and, second, by the coating of the lipopolysaccharide (LPS)- treated macrophage membranes on the surface of the NPs for targeting TAMs. The intracellular uptake of the PIR @ M can greatly polarize TAMs from M2 to antitumor M1 phenotype with the synergy of Fe3 O4 NPs and R837. The relevant mechanism of the polarization is deeply studied through analyzing the mRNA expression of the signaling pathways. Different from previous reports, the polarization is ascribed to the fact that Fe3 O4 NPs mainly activate the IRF5 signaling pathway via iron ions instead of the reactive oxygen species-induced NF-κB signaling pathway. The anticancer effect can be effectively enhanced through potentiating immunotherapy by the polarization of the TAMs in the combination of Fe3 O4 NPs and R837.


Lumen-apposing covered self-expandable metal stents for short benign gastrointestinal strictures: a multicenter study.
Background and study aim Use of the fully covered self-expandable metal stent (SEMS) for benign luminal gastrointestinal (GI) stricture (BLGS) has been limited by the migration rate. The role of the lumen-apposing metal stent (LAMS) for BLGS is not well defined. We assessed the safety, feasibility, and efficacy of LAMS for the treatment of BLGS. Patients and methods This was an observational, open-label, retrospective, single-arm, multicenter consecutive case series of patients undergoing LAMS placement for BLGS. Technical success was defined as successful placement of the LAMS. Short- and long-term clinical success rates were defined as symptom improvement/resolution with indwelling stent and after stent removal, respectively. All adverse events and additional interventions were recorded. Results A total of 30 patients (mean age 51.6 years; 63.3 % women) underwent LAMS placement for GI strictures (83.9 % anastomotic). Median stricture diameter and length were 4.5 mm (range 2 - 10 mm) and 8 mm (range 5 - 10 mm), respectively. Technical success was achieved in 29 patients (96.7 %), with an adverse event rate of 13.3 %. The stent migration rate was 8.0 % (2/25) on follow-up endoscopy. Short-term clinical success was achieved in 90.0 % (27/30) at a median of 60 days (interquartile range [IQR] 40 - 90 days). Most patients (19/23; 82.6 %) experienced sustained symptom improvement/resolution without the need for additional interventions at a median follow-up of 100 days (IQR 60 - 139 days) after LAMS removal. Conclusion This multicenter study demonstrated that LAMS placement represents a safe, feasible, and effective therapeutic option for patients with BLGS and is associated with a low stent migration rate. Our initial findings suggest that future prospective comparative studies are needed on the use of LAMS, endoscopic dilation, and conventional SEMS. .


Karyotype analysis of Panax ginseng C.A.Meyer, 1843 (Araliaceae) based on rDNA loci and DAPI band distribution.
Ginseng has long been considered a valuable plant owing to its medicinal properties; however, genomic information based on chromosome characterization and physical mapping of cytogenetic markers has been very limited. Dual-color FISH karyotype and DAPI banding analyses of Panax ginseng C. A. Meyer, 1843 were conducted using 5S and 45S rDNA probes. The somatic chromosome complement was 2n=48 with lengths from 3.3 μm to 6.3 μm. The karyotype was composed of 12 metacentric, 9 submetacentric, and 3 subtelocentric pairs. The 5S rDNA probe localized to the intercalary region of the short arm of pair 11, while the 45S rDNA was located at the secondary constriction of the subtelocentric satellited chromosome 14. DAPI bands were clearly observed for most chromosomes, with various signal intensities and chromosomal distributions that consequently improved chromosome identification. As a result, all 24 chromosomes could be distinguished and numbers were assigned to each chromosome for the first time. The results presented here will be useful for the on-going ginseng genome sequencing and further molecular-cytogenetic studies and breeding programs of ginseng.


Repurposing Drugs in Oncology (ReDO)-mebendazole as an anti-cancer agent.
Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer therapeutic is warranted. A number of possible combinations with other drugs are discussed in the Appendix.


A Practical Method to Estimate the Resolving Power of a Chemical Sensor Array: Application to Feature Selection.
A methodology to calculate analytical figures of merit is not well established for detection systems that are based on sensor arrays with low sensor selectivity. In this work, we present a practical approach to estimate the Resolving Power of a sensory system, considering non-linear sensors and heteroscedastic sensor noise. We use the definition introduced by Shannon in the field of communication theory to quantify the number of symbols in a noisy environment, and its version adapted by Gardner and Barlett for chemical sensor systems. Our method combines dimensionality reduction and the use of algorithms to compute the convex hull of the empirical data to estimate the data volume in the sensor response space. We validate our methodology with synthetic data and with actual data captured with temperature-modulated MOX gas sensors. Unlike other methodologies, our method does not require the intrinsic dimensionality of the sensor response to be smaller than the dimensionality of the input space. Moreover, our method circumvents the problem to obtain the sensitivity matrix, which usually is not known. Hence, our method is able to successfully compute the Resolving Power of actual chemical sensor arrays. We provide a relevant figure of merit, and a methodology to calculate it, that was missing in the literature to benchmark broad-response gas sensor arrays.


[Expression of CDK6 and FOXM1 in peripheral T-cell lymphoma and their significance].
Objective: To investigate the expression of CDK6 and FOXM1 in peripheral T-cell lymphoma (PTCL), and its correlation with clinicopathologic features and patient prognosis. Methods: The Oncomine was used for data mining and analyzing the expression levels of CDK6 and FOXM1 in PTCL. Immunohistochemistry (IHC) of EnVision method was used to detect the expression of CDK6 and FOXM1 proteins in 166 cases of PTCL diagnosed at Shanxi Provincial Cancer Hospital from January 2016 to December 2018, and 30 cases of lymph node with reactive hyperplasia as control. Results: Among the PTCL patients, 104 were male and 62 were female, aged from 3 to 85 years, with an average age of 53 years. Analyses of the Oncomine 4.5 database showed that mRNA expression of CDK6 and FOXM1 in PTCL tissues was significantly higher than that in normal tissue (P<0.05). IHC staining showed the positive rates of CDK6 and FOXM1 proteins in PTCL tissues were 27.7% (46/166) and 80.7% (134/166), respectively. The expression was mainly present in the nuclei of tumor cells, showing a diffuse, strongly positive pattern. The positive rates of CDK6 and FOXM1 proteins among the 30 cases of lymph-node reactive hyperplasia were 0 (0/30) and 30% (9/30), respectively. The expression of FOXM1 was mainly found in the lymphoid follicle germinal center, and not present in the T-zone cells. CDK6 protein, FOXM1 protein and the co-expression of CDK6 and FOXM1 proteins in PTCL were associated with higher Ann Arbor staging and international prognostication index score (P<0.05), and inversely associated with overall survival (P<0.05). Meanwhile, CDK6 protein expression was positively correlated with FOXM1 protein expression (P<0.05). Conclusions: CDK6 and FOXM1 may be new targets for the diagnosis and treatment of PTCL. The overexpression of CDK6 may lead to enhanced function of the transcription factor FOXM1, while the overexpression of CDK6 and FOXM1 also promotes the development and progression of PTCL.


[Total calvarial reconstruction for sagittal synostosis].
To study the technique of total calvaria reconstruction for sagittal synostosis. 11 children with sagittal synostosis were treated. The David II procedure was used to reconstruct the calvarial gap in 6 cases; Osteotomies with reversal change was performed on 2 cases; Plum-plasty of the calvaria was performed on 3 cases. The 11 cases were cured with satisfactory head shape. The David II procedure is applicable for patient of 1 approximately 3 months. The technique of floating skull flap plasty and plum-plasty of the calvaria can be performed on patients older than 3 months.


Ultrasonographic determination of resistive index and graft size for evaluating clinical feline renal allografts.
Ultrasonographic examination is a commonly employed technique for postoperative renal allograft evaluation after transplantation. Allograft size and resistive index (RI) are two objective ultrasonographic measures that may help establish a diagnosis and direct postoperative management for grafts with suboptimal function but their diagnostic efficacy has not been evaluated in clinical veterinary patients. Results of 69 feline renal transplant ultrasonographic examinations and RI determinations were studied. Based on clinical parameters at the time of the ultrasonographic examination, patients were grouped into six clinical/functional categories including evaluations of clinically normal grafts, delayed graft function, ureteral obstruction, uroabdomen, graft thrombosis, and rejection. RI, graft size (length, cross-sectional area, and volume), cyclosporine A whole blood trough concentration, Doppler blood pressure, creatinine concentration, and days from transplantation were compared between these categories and associations with each other were examined. RI was of little value in differentiating among the clinical categories with the exception of graft thrombosis. Graft volume and time from transplantation were significantly greater in grafts with signs of rejection and ureteral obstruction compared to clinically normal ultrasound examinations. Graft volume, cross-sectional area and length were generally associated. Cyclosporine A blood concentrations was associated with RI in both the pooled data and in the delayed graft function category. These results indicate RI should be used only as part of a larger clinical picture and in light of other factors including cyclosporine A concentration and the timing of the study relative to the implantation surgery for the diagnosis of postoperative transplantation complications. Graft volume may provide a more sensitive, albeit, nonspecific, indicator of allograft dysfunction.


Haematologic parameters in metastatic colorectal cancer patients treated with capecitabine combination therapy.
The standard treatment in the metastatic colorectal cancer consists of 5-FU based infusional regimens. However, with oral fluoropyrimidines, equal tumor responses may be obtained. Capecitabine causes macrocytosis of the cells by inhibition of DNA synthesis. In this context, a relationship was found between mean corpuscular volume (MCV) and response to therapy in breast cancer patients treated with Capecitabine, but whether this relationship also pertains in colorectal cancer has not been established. A total of 102 metastatic colorectal cancer patients treated with a oxaliplatin (XELOX) ±Bevacizumab combination were retrospectively evaluated. Patients were randomized into three groups. Hematological parameters (MCV, MPV, PCT, PLT, NLR) were recorded retrospectively, before treatment and after 3 cycles of chemotherapy. After three cycles of therapy, 20 (19.6%) patients had progressive disease (PD), 41 (40.1%) had stable disease (SD), and 41 (40.1%) demonstrated a partial response (PR). In 62 (60.7%) treatment was with capesitabin plus XELOX therapy, and in 40 (39.2%) it was XELOX-Bevacizumab combination therapy. There was no difference among three groups before the treatment in terms of MCV, MPV, PCT, PLT, and NLR. MCV showed significant increase in chemotherapy response groups (PR and SD). In addition, a significant decrease was observed for platelet count in chemotherapy response groups. While NLR decrease was seen in only a PR group, PCT decrease was observed in all three groups. PCT and PLT values were higher in patients receiving Bevacizumab. PLT, PCT, MPV, and NLR values were decreased due to Capecitabine- based chemotherapy, however MCV was increased. PCT and PLT values were higher in patients who received Bevacizumab than those who did not. MCV, PLT, and NLR can be considered as important factors in predicting response to colorectal carcinoma treatment.


Transgenic tobacco plants expressing the geminivirus BL1 protein exhibit symptoms of viral disease.
Bipartite geminiviruses, such as squash leaf curl virus (SqLCV), encode two movement proteins (MPs), BR1 and BL1, that are essential for viral movement in and subsequent infection of the host plant. To elucidate the biochemical functions of these MPs and define their respective contributions to viral infection, we have generated transgenic Nicotiana benthamiana plants expressing SqLCV BR1 and BL1. Transgenic plants expressing BR1 or a truncated BL1 were phenotypically indistinguishable from wild-type N. benthamiana. In contrast, transgenic plants expressing full-length BL1, alone or in combination with BR1, were strikingly abnormal both in their growth properties and phenotypic appearance, with leaves that were mosaic and curled under, thus mimicking typical SqLCV disease symptoms in this host. BL1 was localized to the cell wall and plasma membrane fractions, whereas BR1 was predominantly in the microsomal membrane fraction. These findings demonstrate that expression of BL1 in transgenic plants is sufficient to produce viral disease symptoms, and they further suggest that BL1 and BR1 carry out distinct and independent functions in viral movement.


A posttraumatic, joint-connected sural intraneural ganglion cyst-with a new mechanism of intraneural recurrence: a case report.
Intraneural ganglion cysts are rare in occurrence and most commonly involve the peroneal nerve at the fibular neck. We present a case of a traumatically induced intraneural ganglion cyst of the sural nerve that developed after a nondisplaced posterior malleolus ankle fracture. The intraneural ganglion cyst was connected to the subtalar joint by its articular branch and ascended several centimeters into the distal fourth of the leg. It was resected from the sural nerve proper and the posterior branch of the lateral calcaneal nerve, and the articular trunk was ligated. The patient developed subclinical intraneural recurrence, which was detected on a postoperative magnetic resonance imaging (MRI). Retrospective reinterpretation of the preoperative and postoperative MRIs revealed that ligation of the articular trunk proximal to a major branch (ie, the anterior branch of the lateral calcaneal nerve) led to increased intraneural cyst propagation distally: within the blind stump of the articular trunk and within several anterior branches of the lateral calcaneal nerve but not within the parent sural nerve or its continuation, the lateral dorsal cutaneous nerve. This mode of intraneural, but extraparental nerve recurrence can be easily understood by considering the altered fluid dynamics, particularly the increased resistance. This case report provides further evidence not only supporting the articular theory of intraneural ganglion formation but also highlighting the importance of searching for, identifying, and treating the pathologic articular branch connection near its joint connection in all cases. 4.


[Absorption profile and absolute bioavailability of a theophylline--retard preparation].
Absorption Profile and Absolute Bioavailability of a Theophylline Retard Preparation. In a single-dose cross-over study with 16 healthy male nonsmoking volunteers the absorption profile and absolute bioavailability of the retard pellets contained in all dosage strengths of Bronchoretard (100, 200, 350, 500 mg anhydrous theophylline) were investigated. One capsule (500 mg theophylline) was given after an evening meal. The reference treatment consisted of an i.v. infusion over 8 h in a total dosage of 350 mg theophylline. Plasma concentration-time profiles were evaluated for 72 h after dosing, respectively start of infusion. Theophylline was measured by high-performance liquid chromatography (HPLC). Absorption profiles (Wagner-Nelson) were derived and the absolute bioavailability was calculated. For the retard pellets a liberation/absorption of zero order for 12 h could be noted; the dose-corrected mean absolute bioavailability was 88%. The assumptions of an investigation on absolute bioavailability are discussed and the limitations on generalizability resulting therefrom.


[The importance of works of the G.Ye. Rhein commission for public health in Russia].
The article analyses the history of development, functioning and historical importance of works of imperially established interdepartmental commission for revision of medical sanitary legislation (the G.Ye. Rhein commissions 1912-1916). The commission developed several progressive legislation projects which were not accepted by medical community of Russia. On the contrary, these proposals were implemented by Narkomzdrav of the Russian Soviet Federative Socialist Republic.


[Intraoperative histological sections in obstetric brachial plexus lesions--comparison of macroscopic appearance, HE staining and toluidine blue staining].
In brachial plexus lesions and their revision, evaluation of nerve stumps is very important for the reconstructive strategy. We intraoperatively perform cryostat sections, Haematoxilin-Eosin (HE) stained, and compare the clinical appearance of the nerves to the microscopic results. Toluidine blue staining is later used to validate the structural details. Intraneural fibrosis can be traced safely with both staining methods, in root avulsions a histology is helpful, too. For more proximal, intraforaminal lesions semithin section stained with toluidine-blue are less informative than are HE-stained cryostat sections. In these lesions the clinical control by electrical stimulation and evoked potentials is superior.


In vitro cytotoxic and genotoxic effect of the crude and ethanolic extract from the rhizome of Curcuma longa L.
To determine the in vitro cytotoxic and genotoxic effect of the crude and ethanolic extract from the Curcuma longa L. rhizome. The cytotoxic effect was evaluated using DU-145, HT-29, 3T3 BALB/c cell lines. The growth percentages in 48 hours; and the half maximal inhibitory concentration (IC50) were determined. The genotoxic effect on human genomic DNA was determined using the Tomasevich method. Crude extract produced an IC50 of 12.98 ± 0.21 μg/mL for the HT-29 tumor cell line, which is lower than the value obtained for DU-145, with an IC50 of 36.77 ± 9.12 μg/mL. The ethanolic extract presented an IC50 of 13.24 ± 0.77 and 20.54 ± 2.58 μg/mL for both cell lines, respectively; the curcumin standard compound presented an IC50 of 3.96 ± 0.60 and 13.94 ± 2.79 μg/mL, respectively. Crude extract concentrations of 50 and 100 mg/mL fragmented between 40% to 95% of human genomic DNA; while at 200 mg/mL, fragmentation was greater than 95%. The ethanolic extract at all concentrations did not fragment the DNA. Curcumin at 200 mg/mL fragmented less than 5% of human genomic DNA. The crude and ethanolic extracts of Curcuma longa L. demonstrate different in vitro cytotoxic effects for the human tumor cell lines DU-145 and HT-29; similar to the standard curcumin compound. The crude extract of Curcuma longa L. shows a potent genotoxic in vitro activity against human genomic DNA; this type of effect is not produced by the ethanolic extract.


Activation and allosteric modulation of a muscarinic acetylcholine receptor.
Despite recent advances in crystallography and the availability of G-protein-coupled receptor (GPCR) structures, little is known about the mechanism of their activation process, as only the β2 adrenergic receptor (β2AR) and rhodopsin have been crystallized in fully active conformations. Here we report the structure of an agonist-bound, active state of the human M2 muscarinic acetylcholine receptor stabilized by a G-protein mimetic camelid antibody fragment isolated by conformational selection using yeast surface display. In addition to the expected changes in the intracellular surface, the structure reveals larger conformational changes in the extracellular region and orthosteric binding site than observed in the active states of the β2AR and rhodopsin. We also report the structure of the M2 receptor simultaneously bound to the orthosteric agonist iperoxo and the positive allosteric modulator LY2119620. This structure reveals that LY2119620 recognizes a largely pre-formed binding site in the extracellular vestibule of the iperoxo-bound receptor, inducing a slight contraction of this outer binding pocket. These structures offer important insights into the activation mechanism and allosteric modulation of muscarinic receptors.


ANG II activates effectors of mTOR via PI3-K signaling in human coronary smooth muscle cells.
We have previously shown that the vasoconstrictive peptide angiotensin II (ANG II) is a hypertrophic agent for human coronary artery smooth muscle cells (cSMCs), which suggests that it plays a role in vascular wall thickening. The present study investigated the intracellular signal transduction pathways involved in the growth response of cSMCs to ANG II. The stimulation of protein synthesis by ANG II in cSMCs was blocked by the immunosuppressant rapamycin, which is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway that includes the 70-kDa S6 kinase (p70(S6k)) and plays a key role in cell growth. The inhibitory effect of rapamycin was reversed by a molar excess of FK506; this indicates that both agents act through the common 12-kDa immunophilin FK506-binding protein. ANG II caused a rapid and sustained activation of p70(S6k) activity that paralleled its phosphorylation, and both processes were blocked by rapamycin. In addition, both of the phosphatidylinositol 3-kinase inhibitors wortmannin and LY-294002 abolished the ANG II-induced increase in protein synthesis, and wortmannin also blocked p70(S6k) phosphorylation. Furthermore, ANG II triggered dissociation of the translation initiation factor, eukaryotic initiation factor-4E, from its regulatory binding protein 4E-BP1, which was also inhibited by rapamycin and wortmannin. In conclusion, we have shown that ANG II activates components of the rapamycin-sensitive mTOR signaling pathway in human cSMCs and involves activation of phosphatidylinositol 3-kinase, p70(S6k), and eukaryotic initiation factor-4E, which leads to activation of protein synthesis. These signaling mechanisms may mediate the growth-promoting effect of ANG II in human cSMCs.


Wavelength dependence of the Raman cross section for liquid water.
We report measurements of the wavelength dependence of the 3400-cm(-1) Raman scattering cross section of liquid water for excitation wavelengths between 215 and 550 nm. Using previous measurements of the absolute Raman scattering cross section, we have determined an expression for the wavelength dependence of the absolute Raman cross section for water.


Impact of rivaroxaban on point-of-care assays.
Point-of-care testing (POCT) is regularly used to assess haemostasis in various clinical settings. The impact of rivaroxaban on those POCT is still elusive. We aimed to study the effects of rivaroxaban on most commonly used POCT assays. Blood samples were taken before, 3h, and 24h after administration of 20mg rivaroxaban to 20 healthy volunteers as part of a prospective, multicenter validation study (clinicaltrials.govNCT01710267). Blood samples were analysed with thromboelastometry (ROTEM®), two platelet function assays (INNOVANCE® PFA-200 and Multiplate®), and the CoaguChek® XS. Rivaroxaban plasma levels were determined using liquid chromatography-mass spectrometry. Rivaroxaban significantly modified some thromboelastometry parameters (CT INTEM: mean difference 56.1s, 95% CI: 41.8, 70.3; CT EXTEM: 47.5s, 95% CI: 37.8, 57.1; CT HEPTEM: 50.1s, 95% CI: 34.7, 65.6), and CoaguChek® XS parameters (prothrombin time: mean difference 3.8s, 95% CI: 3.3, 4.2; INR: 0.32, 95% CI: 0.27, 0.38; prothrombin ratio: -36.1%, 95% CI: -32.3, -39.9). CT EXTEM and INR showed a moderate correlation with rivaroxaban plasma levels (r=0.83; 95% CI 0.69, 0.9 and r=0.83; 95% CI 0.70, 0.91, respectively) and a high sensitivity to detect rivaroxaban treatment at peak levels (0.95; 95% CI: 0.76, 1.0 and 0.90, 95% CI 0.70, 0.99, respectively). Rivaroxaban 20mg treatment significantly alters ROTEM® and CoaguChek® XS parameters. Even though POCT do not allow precise quantification of rivaroxaban plasma concentration, CT EXTEM and CoaguChek XS detect the presence of rivaroxaban at peak level with a high sensitivity.


Increased reaction time predicts visual learning deficits in Parkinson's disease.
To determine whether the process involved in movement preparation of patients in the early stages of Parkinson's disease (PD) shares attentional resources with visual learning, we tested 23 patients with PD and 13 healthy controls with two different tasks. The first was a motor task where subjects were required to move as soon as possible to randomly presented targets by minimizing reaction time. The second was a visual learning task where targets were presented in a preset order and subjects were asked to learn the sequence order by attending to the display without moving. Patients with PD showed higher reaction and movement times, while visual learning was reduced compared with controls. For patients with PD, reaction times, but not movement times, displayed an inverse significant correlation with the scores of visual learning. We conclude that visual declarative learning and movement preparation might share similar attentional and working memory resources. (c) 2010 Movement Disorder Society.


Added value of high-resolution ultrasound and MRI in the evaluation of rheumatologic diseases.
Rheumatologic diseases are a widespread group of disorders affecting the joints, bones, and connective tissue, and leading to significant disability. Imaging is an indispensable component in diagnosing, assessing, monitoring, and managing these disorders, providing information about the structural and functional alterations occurring within the affected joints and tissues. This review article aims to compare the utility, specific clinical applications, advantages, and limitations of high-resolution ultrasound and magnetic resonance imaging in the context of rheumatologic diseases. It also provides insights into the imaging features of various types of inflammatory arthritis with clinical relevance and a focus on high-resolution ultrasound and magnetic resonance imaging. By understanding the comparative aspects of high-resolution ultrasound and magnetic resonance imaging, it is easier for the treating physicians to make informed decisions when selecting the optimal imaging modality for specific diagnostic purposes, effective treatment planning, and improve patient outcomes. The patterns of soft tissue and joint involvement; bony erosion and synovitis help in differentiating between various type of arthritis. Involvement of various small joints of the hands also gives an insight into the type of arthritis. We also briefly discuss the potential applications of emerging techniques, such as ultrasound elastography, contrast-enhanced ultrasound, and dual-energy CT, in the field of rheumatology.


[Restriction analysis of autonomously replicating molecules containing exogenous DNA in a transgenic silkworm line].
Early embryos of the silkworm, Bombyx mori, were injected with plasmid p1,5LTR, harboring DNA copies of the Rous sarcoma long terminal repeats (LTR). Three generations of insects were obtained whose total DNA carried DNA sequences of the injected plasmid. Plasmid rescue method revealed that exogenous DNA was present in extrachromosomal molecules that harbored also cellular DNA sequences. A restriction map of the plasmid rescued from the F2 generator was constructed.


R6K plasmid replication: influence of chromosomal genotype in minicell-producing strains of Escherichia coli K-12.
Alkaline sucrose velocity sedimentation and cesium chloride-ethidium bromide equilibrium centrifugation have been used to determine the number of copies per chromosomal equivalent of the relaxedly replicating R6K plasmid (a conjugative plasmid conferring ampicillin and streptomycin resistance) in two minicell-producing strains of Escherichia coli K-12. In one strain, the average number of covalently closed circular R6K molecules per chromosomal equivalent is 13 in log-phase and 35 in stationary-phase cells. In the other strain, there is an average of six covalently closed circular R6K molecules per chromosomal equivalent in both log- and stationary-phase cells. Selection from this strain of spontaneously occurring mutants resistant to high concentrations of ampicillin has been accomplished and such mutants show a two- to threefold increase in the number of R6K copies per chromosomal equivalent. Relative to the parental strain, mutants display the following properties: (i) elevated streptomycin resistance, (ii) a 10-fold increase in R6K conjugal transfer, (iii) a 10-fold increase in the amount of R6K plasmid deoxyribonucleic acid segregated into minicells, and (iv) a two- to threefold increase in R6K-specified beta-lactamase. The mutation(s) responsible for the increase in the number of R6K molecules per chromosomal equivalent is located on the bacterial chromosome. No R6K-linked mutations conferring the above phenotypes have been obtained. The mutations are presumed to be in chromosomal genes which play a role in the regulation of R6K replication in this strain.


Modeling and forecasting of COVID-19 using a hybrid dynamic model based on SEIRD with ARIMA corrections.
The outbreak of novel coronavirus (COVID-19) attracted worldwide attention. It has posed a significant challenge for the global economies, especially the healthcare sector. Even with a robust healthcare system, countries were not prepared for the ramifications of COVID-19. Several statistical, dynamic, and mathematical models of the COVID-19 outbreak including the SEIR model have been developed to analyze the infection its transmission dynamics. The objective of this research is to use public data to study the properties associated with the COVID-19 pandemic to develop a dynamic hybrid model based on SEIRD and ascertainment rate with automatically selected parameters. The proposed model consists of two parts: the modified SEIRD dynamic model and ARIMA models. We fit SEIRD model parameters against historical values of infected, recovered and deceased population divided by ascertainment rate, which, in turn, is also a parameter of the model. Residuals of the first model for infected, recovered, and deceased populations are then corrected using ARIMA models. The model can analyze the input data in real-time and provide long- and short-term forecasts with confidence intervals. The model was tested and validated on the US COVID statistics dataset from the COVID Tracking Project. For validation, we use unseen recent statistical data. We use five common measures to estimate model prediction ability: MAE, MSE, MLSE, Normalized MAE, and Normalized MSE. We proved a great model ability to make accurate predictions of infected, recovered, and deceased patients. The output of the model can be used by the government, private sectors, and policymakers to reduce health and economic risks significantly improved consumer credit scoring.


FISH on sperm heads allows the analysis of chromosome segregation and interchromosomal effects in carriers of structural rearrangements: results in a translocation carrier, t(5;8)(q33;q13).
Using three-color fluorescence in situ hybridization (FISH) with specific DNA probes, we have determined the chromosome segregation pattern of the translocated chromosomes in a human male carrier of a reciprocal translocation, t(5;8)(q33;q13). At the same time, we have assessed the possible interchromosomal effect on pair 21 using dual-color FISH. The segregation results showed that a 45.12% of the spermatozoa analyzed resulted from alternate segregation, 38.31% resulted from adjacent I, 6.97% from adjacent II, and 6.56% from 3:1 segregation. Finally, 1.23% could be either diploid sperm or 4:0 segregation. In both types of adjacent segregations, an excess of products containing short translocated segments (adjacent I) and interstitial regions (adjacent II) were found. Products resulting from the presence of an interstitial chiasma in pair 5 (1.26%), were found much more frequently (P < 0.0001) than those resulting from an interstitial chiasma in pair 8 (0.13%) (evaluated after adjacent II segregation). In 3:1 segregation, the products containing one chromosome were observed more frequently than those containing three chromosomes (P < 0.0001). No evidence of an interchromosomal effect on chromosome 21 was detected, the percentage of disomy 21 being similar to that in the controls (0.23% vs. 0.37%). However, the percentage of diploid sperm (1.18%) was significantly higher (P < 0. 0001) than that in the controls (0.27%). FISH therefore appears to be a useful technique for assessing the percentage of abnormal sperm in translocation carriers. Their application in assisted reproduction centers could offer patients more accurate genetic counseling.


Chapter 7: Allergic fungal rhinosinusitis.
Allergic fungal rhinosinusitis (AFRS) is a type of chronic rhinosinusitis in which patients classically exhibit nasal polyps, type I IgE-mediated hypersensitivity, characteristic findings on computed tomography scans, eosinophilic mucin, and positive fungal stain. New research has sought to further understand the pathophysiology of AFRS. However, this has also led to debate about the classification and predominance of this interesting disease process. Historically, patients with AFRS are immunocompetent. The disease is most prevalent in the southeast and south central United States and typically presents with sinus pressure, hyposmia, and congestion. Radiographically, cases of AFRS have a distinct appearance, often exhibiting unilateral heterogeneously dense material, which may erode and expand the paranasal sinus bony walls. Treatment typically consists of surgery, sinonasal irrigations, and topical and systemic steroids, all with the effort to decrease the fungal load and antigenic response. Immunotherapy is also often included in the treatment regimen for AFRS.


Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM).
Expectations towards surgeons in modern surgical practice are extremely high with minimal complication rates and maximal patient safety as paramount objectives. Both of these aims are highly dependent on individual technical skills that require sustained, focused, and efficient training outside the clinical environment. At the same time, there is an increasing moral and ethical pressure to reduce the use of animals in research and training, which has fundamentally changed the practice of microsurgical training and research. Various animal models were introduced and widely used during the mid-20th century, the pioneering era of experimental microsurgery. Since then, high numbers of ex vivo training concepts and quality control measures have been proposed, all aiming to reduce the number of animals without compromising quality and outcome of training. Numerous microsurgical training courses are available worldwide, but there is no general agreement concerning the standardization of microsurgical training. The major aim of this literature review and recommendation is to give an overview of various aspects of microsurgical training. We introduce here the findings of a previous survey-based analysis of microsurgical courses within our network. Basic principles behind microsurgical training (3Rs, good laboratory practice, 3Cs), considerations around various microsurgical training models, as well as several skill assessment tools are discussed. Recommendations are formulated following intense discussions within the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM), based on scientific literature as well as on several decades of experience in the field of experimental (micro)surgery and preclinical research, represented by the contributing authors. Key Messages: Although ex vivo models are crucial for the replacement and reduction of live animal use, living animals are still indispensable at every level of training which aims at more than just a basic introduction to microsurgical techniques. Modern, competency-based microsurgical training is multi-level, implementing different objective assessment tools as outcome measures. A clear consensus on fundamental principles of microsurgical training and more active international collaboration for the sake of standardization are urgently needed.


Ways of knowing: Howard Stein's border-crossing use of poetry to interrogate clinical medicine, medical education, and health care organizations.
This article explores how medical anthropologist Howard Stein's poetry and his unique practice of sharing this poetry with the patients, physicians, and administrators who inspired it create ways of knowing that are at once revelatory and emancipatory. Stein's writing shows readers that poetry can be considered as a form of data and as a method of investigation into the processes of the human soul. Furthermore, it represents a kind of intervention that invites health professional readers toward connection, bridge building, and solidarity with their patients and with one another. (PsycINFO Database Record


Pre-ictal heart rate variability assessment of epileptic seizures by means of linear and non-linear analyses.
The purpose of the present study was to analyze the effects of epilepsy on the autonomic control of the heart in pre-ictal phase in order to find an algorithm of early detection of seizure onset. Overall 133 epileptic seizures were analyzed from 12 patients with epilepsy (seven males and five females; mean age 43.91 years, SD: 10.16) participated in this study. Single lead electrocardiogram recordings of epileptic patients were compiled. 240, 90-30, 30-10 and 5 minutes heart rate variability (HRV) signals of preseizure were chosen for analysis of heart rate. As HRV signals are non-stationary, a set of time and frequency domain features (Mean HR, Triangular Index, LF, HF, LF/HF) and nonlinear parameters (SD1, SD2 and SD2/SD1 indices derived from Poincare plots) extracted from HRV is analyzed. Statistical analysis was performed using paired sample t-test for comparisons of the segments and differences between pre-ictal segments were evaluated by Tukey tests. There was slight tachycardia in segments near the seizure (30 minutes before: 85.3517 bpm, 5 minutes before: 119.3630.82 bpm, p=0.0207) which significantly differ from baseline in segments far from seizure (240 minutes before: 66.5211.7 bpm). Also there was significant increase in LF/HF ratio (30 minutes before: 1.10.22, 5 minutes before: 2.120.5, p=0.0332) and SD2/SD1 ratio (30 minutes before: 1.20.15, 5 minutes before: 2.030.55, p=0.0431) when compared to segments far from the seizure (240 minutes before: 0.780.24 and 0.780.14) respectively. Although there was about decrease of triangular index in segments near the seizure the percentage of decrease was not comparable to segments far from the seizure. Significant changes of HRV parameters in pre-ictal (5 minutes before the seizure) are obviously higher in comparison to interictal baseline. Pre-ictal significant changes of HRV suggesting that this time can be considered as prediction time for designing an algorithm of early detection of seizure onset based on HRV.


[Peritoneal dialysis in treatment of diffuse purulent peritonitis].
Peritoneal dialysis (PD) as a method of sanitation of the abdominal cavity was used in treatment of 221 patients (140 males and 81 females aged 17-89 years) with extended purulent peritonitis. In all patients toxic (138) of terminal (83) stage of purulent peritonitis was diagnosed. PD was carried dut in flow-fractional regimen with the use of 10-15 l of isotonic physiologic solution with the addition of antibiotics and heparin 4 times per day during 4-6 days. Carrying out PD in patients with purulent diffuse peritonitis resulted in improvement of general condition of the patients, normalization of hemodynamics, diuresis, and in lessening the paresis of gastro-intestinal tract as well as decrease of intoxication. Thus, in the group of patients in whom PD was not used the mortality rate was high--36%, and including PD in the complex of treatment contributed to the decrease of lethality to 23%.


Association of early-stage incidence and mortality in malignant melanoma - a population-based ecological study.
Germany-wide skin cancer screening was introduced in 2008 to reduce skin cancer mortality and morbidity. However, the effectiveness of the program is still unclear. We explore the relationship between early-stage melanoma incidence and melanoma mortality in subsequent years, using early-stage melanoma incidence as surrogate for screening participation and early detection. Data on melanoma incidence for 2005-2016 and melanoma mortality for 2005-2018 were obtained for 244 German counties. We investigated the correlation between several measures of incidence and mortality with correlation analyses and linear regressions. Melanoma incidence of early stages (in situ and T1) rose by 69% between pre-screening (2005-2007) and screening period (2008-2010). In contrast, there was no temporal trend in mortality over time. Correlation coefficients between incidence and mortality variables ranged between -0.14 and 0.10 (not significant). Linear regression indicated that mortality 6 years after screening introduction decreases with increasing change in early-stage incidence (b = -0.0029, 95% confidence interval [-0.0066, 0.0007]). The estimated population-based effects of skin cancer screening on melanoma mortality were minimal and not significant. A potential effectiveness cannot be demonstrated.


Beyond Mentalizing: Epistemic Trust and the Transmission of Culture.
We explore the interpersonal origins of human culture, arguing that culture emerges as a necessary consequence of our helplessness in infancy, which in turn requires a greater degree of collaboration and social organization than is necessary for other mammals. We propose a model of cultural transmission that depends on a dyadic interpersonal process whose vicissitudes can have a lifelong impact. We explore the role played by imagining subjectively experienced psychological states and processes in others, which we have defined as mentalizing, in the process of cultural transmission, and propose that mentalizing is key to the establishment of epistemic trust-that is to say, an experience of trust that enables the individual to absorb and use the knowledge they are being offered. We suggest that psychoanalysis can be viewed as a paradigmatic example of a process of transferring knowledge from one human being (the teacher, the caregiver, the analyst) to another (the learner, the young person, the patient) and argue that the mechanisms of psychic change in analysis cannot be fully understood without appreciating this aspect of the biological/evolutionary origins of our essential humanity. Finally, we discuss the clinical implications of the model we are proposing for the psychoanalytic process.


En bloc minimal laser resection for T3-chest wall lung cancer in patients with poor pulmonary function.
To analyze the value of en bloc minimal laser resection in patients with marginal function with non-small cell lung cancer invading the chest wall. Retrospective study from March 1987 to December 1993. University teaching hospital. Study group consists of 10 patients with impaired pulmonary function (FEV1 < or = 1.3 L and forced expiratory flow between 25% and 75% < or = 0.8 L/s) operated on for lung cancer invading the chest wall. There were 7 men and 3 women; ages ranged between 51 and 77 years (mean, 66.2 years). None of the patients had tumors greater than 3 cm or involving the first 2 ribs as well as clinical N2 or T4 disease. All patients underwent en bloc chest wall combined with minimal resection. Parenchyma dissection was accomplished by Nd:YAG laser encompassing the lesion at distance of 2.0 cm. The median number of ribs resected was 1.6 and no patients required chest wall reconstruction. Local postoperative radiation therapy beginning within 1 month after resection was always performed. Tumor resection was considered complete in every case. Four patients had adenocarcinoma, three had squamous cell carcinoma, and three had large cell carcinoma. Currently, 7 patients had NO, 2 had N1, and 1 had N2 disease. There was no perioperative mortality. Postoperative complications were prolonged air leak (n = 2) and atelectasis (n = 1). At the present moment, 6 patients are alive, 5 of whom are free from tumor, 2 with a follow-up longer than 5 years. Three patients died: 2 from disseminated disease, after 47 months and 32 months, respectively, and the third at 27 months from another cause. One patient was unavailable for follow-up. Only 1 patient had a local recurrence, 15 months later, and he underwent a new, successful, limited resection. These findings suggest that en bloc minimal laser resection can offer an acceptable risk/benefit ratio in the case of patients who cannot tolerate a lobectomy.


Assessment of completeness of thyroid ablation by estimation of neck uptake of 131I on whole-body scans: comparison of quantification and visual assessment of thyroid bed uptake.
Thyroid cancer is treated by thyroidectomy followed by radioiodine ablation of the residual active tissue in the thyroid bed. Completeness of ablation can be assessed from neck images of whole-body 131I scans by visual estimation or quantitative analysis By visual assessment, ablation can be considered complete if there is no uptake in the neck or the uptake is empirically considered too small. By quantification, ablation is considered complete if neck uptake is < 1%. Further radioiodine therapy is considered necessary only if neck uptake exceeds 1% of the administered dose. Both visual assessment and quantification of thyroid bed uptake were applied to 46 scans after diagnostic or therapeutic doses of 131I had been administered to 25 patients who were being followed up for follicular or papillary carcinoma of the thyroid. The results were compared to assess the effect of either method on determining the need for a further ablative dose of 131I. Visual assessment overestimated thyroid bed uptake in 10 of 46 (22%) of the scans. Bearing in mind the unpleasantness of radioiodine ablation and the potential for bone marrow toxicity, it is recommended that quantification of neck uptake should be routinely performed as a guide to completeness of ablation and to determine the need for a therapeutic dose of the isotope. This should help to avoid unnecessary radioiodine treatment in patients with thyroid cancer.


Applying the workload indicators of staffing needs method in nursing health workforce planning: evidences from four hospitals in Vietnam.
Vietnam has encountered difficulties in ensuring an adequate and equitable distribution of health workforce. The traditional staffing norms stated in the Circular 08/TT-BYT issued in 2007 based solely on population or institutional size and do not adequately take into consideration the variations of need such as population density, mortality and morbidity patterns. To address this problem, more rigorous approaches are needed to determine the number of personnel in health facilities. One such approach is Workload Indicators of Staffing Need (WISN) developed by the World Health Organization (WHO), a facility-based workforce planning method that assists managers in defining the responsibilities of different workforce categories and improving the appropriateness and efficiency of a staff mix. This study applied the WISN approach and was employed in 22 clinical departments at four hospitals in Vietnam between 2015 and 2018. 22 targeted group discussions involving nurses were conducted. Hospital personnel records have been retrieved. The data were analyzed according to WISN instructions. Of the 22 departments, there was a shortage of 1 to 2 nurses in 10 departments, with WISN ratios ranging between 0.88 and 0.95. Only 01 clinical colleges at Can Tho Hospital lacked 05 nurses, facing a high workload with a WISN ratio of 0.78. Administrative time represented 20-40% of the total work time of a nurse. In comparison, nurses at Can Tho Hospital spent time on administration from 24 onwards. 5-41.7% of their working time while nurses at Thanh Hoa Hospital spent 21-33%. The application of the WISN enabled health managers to analyze the workload of nurses, calculate staffing needs, and thus effectively contribute to the workforce planning process. It is expected that the results of this research will encourage the use of the WISN tool in other hospitals and health facilities across the health system. At provincial and national levels, this study provides important evidence to help policy makers develop guidelines for personnel norms for health facilities in the context of limited resources, while the existing regulation is no longer appropriate.


Characterization of the muscle involvement in dynamin 2-related centronuclear myopathy.
Centronuclear myopathy (CNM) is a slowly progressive congenital myopathy characterized by abnormal centrally located nuclei in a large number of muscle fibres. Recently, different missense mutations affecting the middle domain of the dynamin 2 (DNM2) have been shown to cause autosomal dominant CNM. In order to better define the phenotype of DNM2-related CNM, we report here on the clinical and muscle imaging findings of 10 patients harbouring DNM2 mutations. DNM2-CNM is characterized by slowly progressive muscular weakness usually beginning in adolescence or early adulthood. In addition to bilateral ptosis, our data show that distal muscle weakness often exceeds proximal involvement. Furthermore, electrophysiological investigations frequently demonstrated signs of mild axonal peripheral nerve involvement, and electromyographical examination may show neuropathic changes in addition to the predominant myopathic changes. These features overlap with findings seen in the phenotype of DNM2-related autosomal dominant Charcot-Marie-Tooth disease type 2B. In all 10 DNM2-CNM patients, muscle computer tomography assessment showed a consistent pattern of muscular involvement and a characteristic temporal course with early and predominant distal muscle involvement, and later affection of the posterior thigh compartment and gluteus minimus muscles. The recognition of this specific imaging pattern of muscle involvement--distinct to the reported patterns in other congenital myopathies--may enable a better selection for direct genetic testing.


Light-dependant biostabilisation of sediments by stromatolite assemblages.
For the first time we have investigated the natural ecosystem engineering capacity of stromatolitic microbial assemblages. Stromatolites are laminated sedimentary structures formed by microbial activity and are considered to have dominated the shallows of the Precambrian oceans. Their fossilised remains are the most ancient unambiguous record of early life on earth. Stromatolites can therefore be considered as the first recognisable ecosystems on the planet. However, while many discussions have taken place over their structure and form, we have very little information on their functional ecology and how such assemblages persisted despite strong eternal forcing from wind and waves. The capture and binding of sediment is clearly a critical feature for the formation and persistence of stromatolite assemblages. Here, we investigated the ecosystem engineering capacity of stromatolitic microbial assemblages with respect to their ability to stabilise sediment using material from one of the few remaining living stromatolite systems (Highborne Cay, Bahamas). It was shown that the most effective assemblages could produce a rapid (12-24 h) and significant increase in sediment stability that continued in a linear fashion over the period of the experimentation (228 h). Importantly, it was also found that light was required for the assemblages to produce this stabilisation effect and that removal of assemblage into darkness could lead to a partial reversal of the stabilisation. This was attributed to the breakdown of extracellular polymeric substances under anaerobic conditions. These data were supported by microelectrode profiling of oxygen and calcium. The structure of the assemblages as they formed was visualised by low-temperature scanning electron microscopy and confocal laser microscopy. These results have implications for the understanding of early stromatolite development and highlight the potential importance of the evolution of photosynthesis in the mat forming process. The evolution of photosynthesis may have provided an important advance for the niche construction activity of microbial systems and the formation and persistence of the stromatolites which came to dominate shallow coastal environments for 80% of the biotic history of the earth.