The relationship between psychosocial work characteristics and fatigue and psychological distress.
To examine the associations between psychosocial work characteristics and fatigue in employees in the Maastricht Cohort Study. A second objective was to compare the relationships for fatigue versus psychological distress with these psychosocial work characteristics. The design was cross-sectional and included 11,020 employees who responded to the self-administered baseline questionnaire of the Maastricht Cohort Study. Fatigue was measured with the Checklist Individual Strength, a 20-item self-report instrument. Psychological distress was measured with the 12-item version of the General Health Questionnaire. Psychosocial work characteristics comprised: psychological demands, decision latitude, and social support at work as measured by the Job Content Questionnaire, as well as emotional demands at work, physical demands at work, job insecurity, and conflict with supervisor/co-worker, which were assessed with items from existing Dutch questionnaires. Low decision latitude and low social support at work were associated with fatigue in both men and women. Associations were also found between emotional demands at work, job insecurity, physical demands and conflict with supervisor and fatigue in men; and high psychological demands and fatigue in women. As regards psychological distress, there was no association with low decision latitude, but strong associations with emotional demands and conflict with supervisor in both genders. The study provides strong support for associations between psychosocial work characteristics and fatigue in men and women, even after adjustment for psychological distress. Moreover, it suggests some differential effects of psychosocial work characteristics on fatigue and psychological distress.


Multicystic encephalomalacia: CT appearance and pathological correlation.
Perinatal insults, including anoxia, may lead to a form of cerebral necrosis designated multicystic encephalomalacia. This common condition is characterized by (a) moderate atrophic ventricular dilatation, (b) intact ventricular walls with thickened subependymal glial layer, (c) multiple cysts of irregular size and shape distributed throughout the cerebral white matter and the inner layers of the cortex bilaterally, and (d) relative sparing of the orbital surfaces of the frontal lobes, the temporal lobes below the superior temporal gyri, the basal ganglia, the cerebellar hemispheres, and the spinal cord (except for secondary degeneration of corticospinal tracts).


Muscarinic receptor stimulation and cyclic AMP-dependent effects in guinea-pig ventricular myocardium.
1. The effect of carbachol on force of contraction, contraction duration, intracellular Na+ activity and cyclic AMP content was studied in papillary muscles of the guinea-pig exposed to isoprenaline or the phosphodiesterase inhibitor 3-isobutyl, 1-methyl xanthine (IBMX). The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. 2. Isoprenaline (10 nM) and IBMX (100 microM) produced comparable positive inotropic effects of 9.8 and 9.7 mN, respectively. Carbachol (3 microM) attenuated the inotropic effects by 82% (isoprenaline) and by 79% (IBMX). The shortening of contraction duration which accompanied the positive inotropic effect of isoprenaline (by 14.9%) and of IBMX (by 22.4%) was not significantly affected by 3 microM carbachol. 3. The positive inotropic effect of 10 nM isoprenaline and of 100 microM IBMX was accompanied by an increase in cellular cyclic AMP content of 58 and 114%, respectively. Carbachol (3 microM) failed to reduce significantly the elevated cyclic AMP content of muscles exposed to either isoprenaline or IBMX. 4. In the quiescent papillary muscle, isoprenaline (10 nM) and IBMX (100 microM) reduced the intracellular Na+ activity by 28 and 17%, respectively. This decline was not influenced by the additional application of 3 microM carbachol. 5. The results demonstrate that muscarinic antagonism in guinea-pig ventricular myocardium exposed to cyclic AMP-elevating drugs is restricted to force of contraction. The underlying mechanism does not apparently involve the cytosolic signal molecule cyclic AMP.


Standardized evaluation of nine instruments for self-monitoring of blood glucose.
Instruments for self-monitoring of blood glucose (SMBG) should undergo a standardized evaluation including a user-test before being marketed. In this study the results from standardized evaluations of nine different SMBG instruments are presented, and the standardized evaluation is discussed. Approximately 80 diabetes patients using three lots of test strips participated in each evaluation. Half of the patients were educated in how to use the meter, and the evaluations were carried out by both medical laboratory technologists (MLTs) and patients. Questionnaires were used to assess the user manual and the user-friendliness of the instrument. The imprecision obtained by the patients (coefficients of variation [CVs] of 3.2-8.1%) were generally higher compared to that by the MLT (CVs of 2.3-5.9%). Three of the nine instruments did not achieve the quality goal based on the recommendation in the International Organization for Standardization's ISO 15197 guideline in the hands of diabetes patients. The bias from the comparison method ranged from -10.4% to +3.2%. There were significant lot-to-lot variations and hematocrit effects for some of the instruments. Temperature difference between the instruments and the test strip caused deterioration of the quality in one instrument. The user-friendliness was in general acceptable. The quality of instruments for SMBG seems to have improved during recent years, although there are still analytical problems. A standardized evaluation protocol is necessary and should be regularly revised taking into account the development of new technology and the needs of the patients.


[The expression and significance of Pin1 and CyclinD1 in adult papilloma of larynx].
To study the expression and relationship of Pin1 and CyclinD1 in adult papilloma of larynx, and the effect of both in laryngeal papilloma's canceration. Ninety-two cases of paraffin section with immunoperoxidase (SP) staining method was used to detect the distribution of Pin1 and CyclinD1 in 10 cases of laryngeal normal epithelial tissue, 39 cases of laryngeal papilloma, 27 cases of laryngeal papilloma with middle, severe atypical hyperplasia and 16 cases of laryngeal carcinoma. The distribution of Pin1 and CyclinD1 increased gradually from laryngeal normal epithelial tissue to laryngeal carcinoma (P<0.05); No difference of the expression of CyclinD1 (not including Pin1, for Pin1, P=0.009) was found between laryngeal papilloma and laryngeal papilloma with middle, severe atypical hyperplasia (P>0.0125), but there had significant difference of the expression of Pin1 and CyclinD1 among the rest groups; There was significantly direct correlation between the expression of Pin1 and CyclinD1 (P<0.05). The hyper-expressions of Pin1 and CyclinD1 may play a key role in laryngeal papilloma's malignant change. Pin1 up-regulating the expressions of cyclinD1 possibly participate in its malignant change.


Comparison of narrow-band imaging with autofluorescence imaging for endoscopic detection of squamous cell carcinoma of the tonsil.
Early detection of mucosal neoplastic lesions is crucial for a patient's prognosis. This has led to the development of effective optical endoscopic diagnostic methods such as narrow band imaging (NBI) and autofluorescence (AFI). Independent of each other, both of these methods were proven useful in the detection of mucosal neoplasias. There are limited reported data comparing both methods for oropharyngeal cancer diagnostics. The aim of the study was to compare NBI and AFI endoscopic visualization of signs in identifying tonsillar squamous cell carcinoma (SCC) and assessing its extent and to determine whether the score was related to the evaluator's experience. Patients with tonsillar SCC underwent endoscopic pharyngeal examination using NBI and AFI. Fiftyseven video sequences of examinations of lesions proven to be SCC were evaluated by three reviewers. The accuracy of determination of lesion extent and visualization of its endoscopic signs of malignancy were evaluated. Endoscopic visualization of tumour spread was significantly better using AFI than NBI (p = 0.0003). No significant difference was found between NBI and AFI in the visualization of endoscopic malignancy determining signs (p = 0.1405). No significant difference was found among the three reviewers in the visualization of tumour spread and for identifying malignancy-determining signs in NBI endoscopy or AFI endoscopy. The results show that AFI obtained better results for assessing the extent of tonsillar cancers than NBI. Both methods were proven to be equal in the visualization of endoscopic malignancy-determining signs. Both are useful even for less experienced evaluators.


Increases of dissolved organic carbon in temperate and boreal lakes in Quebec, Canada.
Increases in dissolved organic carbon (DOC) concentrations have been reported in surface waters worldwide in the last 10 to 20 years. The causes behind these increases have been attributed to many factors, including climate change and decreasing depositions of atmospheric sulphate (SO₄²⁻). Trends in DOC concentrations and their potential causal factors were examined in a network of 30 lakes lying in undisturbed temperate and boreal catchments in the province of Quebec, Canada. Temporal trends in lake DOC concentrations were analysed with the seasonal Kendall test. For each lake, the variation in DOC concentration over time was assessed in light of the variation in SO₄²⁻ concentration in precipitation, air temperature, precipitation and solar radiation using the forward stepwise multiple regression. Between 1989 and 2006, significant increases in DOC were observed in most of the lakes, the mean rate of change being 0.05 mg L(-1) year(-1). Lake DOC concentrations were significantly explained by different models that yielded a variance explanation ranging from 13% to 77%. The models included long-term temperature variables (i.e. averaged over intervals of 10 years), short-term precipitation variables (i.e. summed over intervals 6 months), radiation (i.e. ice-free period prior to the DOC observation) and precipitation SO₄²⁻ concentration as explanatory variables. Temporal changes in DOC concentrations seem more consistent with the evolution of climate parameters rather than SO₄²⁻ concentrations despite the fact that most lakes were in the process of recovery, showing increases in pH.


[Immediate prosthetic management of surgically treated maxillary lesions].
In accordance with a method previously published - in which undercut areas in the region of resection are utilized for retaining the denture - a modified method is presented permitting immediate prosthetical care for operated maxillary defects despite fresh wound surfaces and constrictio maxillarum.


Da Vinci SP radical prostatectomy: a multicentric collaboration and step-by-step techniques.
Several techniques of robotic-assisted radical prostatectomy (RARP) using the da Vinci SP (SP) have been described since its clearance by the FDA (Food and Drug Administration) in 2018 (1, 2). Even with the expanding literature about this robot, the SP technology has been restricted to a few centers in the US and Asia due to the recent release of this robot in the marked.3 In this scenario, we provided, in this video compilation, a consensus of SP referral centers describing the current approaches and techniques of da Vinci SP Radical prostatectomy (SP-RARP). We have illustrated five different techniques, including transperitoneal, extraperitoneal, Retzius-sparing, transvesical, and transperineal (4-6). Each surgery demonstrated crucial steps from the trocar placement until anastomosis. All approaches follow anatomic concepts and landmarks to minimize positive surgical margins, optimize oncological outcomes and promote optimal functional recovery. The trocar placement and the use of an assistant port were selected according to the operative technique of each institution. None of these surgeries had intra- or postoperative complications, and the pain management until discharge was controlled without using narcotics. All patients were discharged in less than 16 hours of surgery. Robotic-assisted radical prostatectomy performed with the da Vinci SP is feasible and safe with optimal perioperative outcomes. Five different approaches were described in this video compilation, and we believe that the technical details provided by this multicentric collaboration are crucial for centers willing to initiate the SP approach to radical prostatectomy.


Spared nerve injury causes motor phenotypes unrelated to pain in mice.
Most animal models of neuropathic pain use targeted nerve injuries quantified with motor reflexive measures in response to an applied noxious stimulus. These motor reflexive measures can only accurately represent a pain response if motor function in also intact. The commonly used spared nerve injury (SNI) model, however, damages the tibial and common peroneal nerves that should result in motor phenotypes (i.e., an immobile or "flail" foot) not typically captured in sensory assays. To test the extent of these issues, we used DeepLabCut, a deep learning-based markerless pose estimation tool to quantify spontaneous limb position in C57BL/6J mice during tail suspension following either SNI or sham surgery. Using this granular detail, we identified the expected flail foot-like impairment, but we also found SNI mice hold their injured limb closer to the body midline compared to shams. These phenotypes were not present in the Complete Freunds Adjuvant model of inflammatory pain and were not reversed by multiple analgesics with different mechanisms of action, suggesting these SNI-specific phenotypes are not directly related to pain. Together these results suggest SNI causes previously undescribed phenotypes unrelated to altered sensation that are likely underappreciated while interpreting preclinical pain research outcomes.


Women's use of physical and nonphysical self-defense strategies during incidents of partner violence.
Two incidents of partner violence are investigated using qualitative methodology to discover strategies women use to protect themselves and examine women's use of violence. Data were collected from 447 women (age 18 or older) from 7 domestic violence programs and 5 substance use disorder treatment programs in a midwestern state. Women were found to have developed numerous self-protection strategies, some using nonphysical means only, others using physical means only, and others combining nonphysical and physical means. Women often used a variety of strategies in the same incident. Few women initiated violence against partners. Implications for theory and research are discussed.


Introducing HPV triage into the English cervical cancer screening program: consequences for participation.
To predict the likely impact of adding human papillomavirus (HPV) triage for minor abnormalities on participation in the English cervical cancer screening program. Contingent valuations of the existing Pap program and a possible HPV-augmented screening program, obtained from questionnaires completed by 1141 women in east-central England. The value of participating in Pap screening was negatively associated with age, positively associated with educational level, and positively associated with the level of household income. Higher levels of worry about cervical cancer were associated with higher valuations of screening. Adding HPV-based triage to the Pap program lowered the value of screening participation for only two women, whereas for the sample as a whole, it increased the average valuation by about 47 percent. Supposedly-negative characteristics of HPV testing, when described, were expected to trigger psychosocial concerns in respondents and thereby give rise to significant decreases in valuations of participating in a Pap-plus-HPV program. For most women, however, such information changed their valuations of participation in screening little, if at all. Accepting the proposition that higher contingent valuations indicate stronger behavioural preferences, our results offer insubstantial grounds for believing that the inclusion of HPV triage would detrimentally affect participation in Pap screening for cervical cancer.


The Role of Crosstalk between AR3 and E2F1 in Drug Resistance in Prostate Cancer Cells.
Drug resistance is one of the most prevalent causes of death in advanced prostate cancer patients. Combination therapies that target cancer cells via different mechanisms to overcome resistance have gained increased attention in recent years. However, the optimal drug combinations and the underlying mechanisms are yet to be fully explored. The aim of this study is to investigate drug combinations that inhibit the growth of drug-resistant cells and determine the underlying mechanisms of their actions. In addition, we also established cell lines that are resistant to combination treatments and tested new compounds to overcome the phenomenon of double drug-resistance. Our results show that the combination of enzalutamide (ENZ) and docetaxel (DTX) effectively inhibit the growth of prostate cancer cells that are resistant to either drug alone. The downregulation of transcription factor E2F1 plays a crucial role in cellular inhibition in response to the combined therapy. Notably, we found that the androgen receptor (AR) variant AR3 (a.k.a. AR-V7), but not AR full length (AR-FL), positively regulates E2F1 expression in these cells. E2F1 in turn regulates AR3 and forms a positive regulatory feedforward loop. We also established double drug-resistant cell lines that are resistant to ENZ+DTX combination therapy and found that the expression of both AR3 and E2F1 was restored in these cells. Furthermore, we identified that auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, overcame drug resistance and inhibited the growth of drug-resistant prostate cancer cells both in vitro and in vivo. This proof-of-principle study demonstrates that targeting the E2F1/AR3 feedforward loop via a combination therapy or a multi-targeting drug could circumvent castration resistance in prostate cancer.


New insight on antimicrobial therapy adjustment strategies for gram-negative bacterial infection: A cohort study.
Gram-negative bacterial infections, especially multidrug-resistant (MDR) bacterial infection, are becoming a serious threat to public health. Although it is widely accepted that both appropriate initial empirical therapy and targeted therapy are important, but for patients needing therapy adjustment, few studies have explored whether adjustment strategy based on microbiologic susceptibility test (MST) brings better outcome compared with empirical adjustment.A total of 320 patients with gram-negative bacterial infection (airway, blood, or pleural effusion) were selected and a prospective cohort study was conducted. Baseline characteristics and outcomes (microbiologic, clinical, and economic) were documented during follow-up.MDR and nosocomial infections were common among subjects. Initial therapies consistent with MST could result in reduced in-hospital mortality, treatment failure rate, infection-related death, percentages of patients needing therapy adjustment, and daily hospitalization cost with increased successful treatment rate compared with inconsistent with MST, and microbiologic outcomes were also better with appropriate therapies.For patients needing therapy adjustment, relying on MST gained no significant benefit on mortality, clinical, or microbiologic outcomes compared with depending on clinical experience. But for patients with MDR infection, adjustment relying on MST gained more benefit than non-MDR infection.Appropriate initial therapy significantly improved the prognosis of patients with gram-negative bacterial infections, but improvement was not that obvious for patients needing therapy adjustment which was based on MST compared with clinical experience, and more beneficial effects of adjustment relying on MST were obtained for patients with MDR bacterial infection.


Metabolomics Identifies Distinctive Metabolite Signatures for Measures of Glucose Homeostasis: The Insulin Resistance Atherosclerosis Family Study (IRAS-FS).
Metabolomics provides a biochemical fingerprint that, when coupled with clinical phenotypes, can provide insight into physiological processes. Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Analysis of 733 plasma metabolites from the Insulin Resistance Atherosclerosis Family Study. Community based. One thousand one hundred eleven Mexican Americans. Dynamic measures were obtained from the frequently sampled intravenous glucose tolerance test and included insulin sensitivity and acute insulin response to glucose. Basal measures included homeostatic model assessment of insulin resistance and β-cell function. Insulin sensitivity was associated with 99 metabolites (P < 6.82 × 10-5) explaining 28% of the variance (R2adj) beyond 28% by body mass index. Beyond branched chain amino acids (BCAAs; P = 1.85 × 10-18 to 1.70 × 10-5, R2adj = 8.1%) and phospholipids (P = 3.51 × 10-17 to 3.00 × 10-5, R2adj = 14%), novel signatures of long-chain fatty acids (LCFAs; P = 4.49 × 10-23 to 4.14 × 10-7, R2adj = 11%) were observed. Conditional analysis suggested that BCAA and LCFA signatures were independent. LCFAs were not associated with homeostatic model assessment of insulin resistance (P > 0.024). Acute insulin response to glucose was associated with six metabolites; glucose had the strongest association (P = 5.68 × 10-16). Homeostatic model assessment of β-cell function had significant signatures from the urea cycle (P = 9.64 × 10-14 to 7.27 × 10-6, R2adj = 11%). Novel associations of polyunsaturated fatty acids (P = 2.58 × 10-13 to 6.70 × 10-5, R2adj = 10%) and LCFAs (P = 9.06 × 10-15 to 3.93 × 10-7, R2adj = 10%) were observed with glucose effectiveness. Assessment of the hyperbolic relationship between insulin sensitivity and secretion through the disposition index revealed a distinctive signature of polyunsaturated fatty acids (P = 1.55 × 10-12 to 5.81 × 10-6; R2adj = 3.8%) beyond that of its component measures. Metabolomics reveals distinct signatures that differentiate dynamic and basal measures of glucose homeostasis and further identifies new metabolite classes associated with dynamic measures, providing expanded insight into the metabolic basis of insulin resistance.


Intravenous lipid emulsion and high-dose insulin as adjunctive therapy for propranolol toxicity in a pediatric patient.
The concurrent use of intravenous lipid emulsion (ILE) and high-dose insulin (HDI) for the management and treatment of propranolol toxicity in a pediatric patient is described. A seven-month-old infant (weight, 6.1 kg) was admitted to a hospital emergency department with lethargy and bradycardia after an unintentional overdose of propranolol suspension, which had been prescribed several days previously for treatment of a scalp hemangioma. Notable physical examination and laboratory findings were as follows: blood pressure, 121/84 mm Hg (normal range, 90 ± 30/60 ± 10 mm Hg); heart rate, 62 beats/min (normal range, 100-150 beats/min); respiratory rate, 24 breaths/min (normal range, 25-35 breaths/min); oxygen saturation, 100% on room air; and rectal temperature, 35.7 °C (normal range, 36.6-38.0 °C). The patient was lethargic. Treatment included i.v. fluid boluses of 0.9% sodium chloride injection and i.v. boluses and continuous infusions of HDI, dextrose, and ILE. After the completion of these treatments, hemodynamic stability was regained. The case is believed to be the first reported case in which a pediatric patient less than one year of age regained hemodynamic stability after administration of ILE and HDI rescue therapy. Monitoring blood glucose frequently with HDI is essential to avoid hypoglycemia. The rationale for using ILE and HDI for reversal of drug toxicities is discussed. A symptomatic pediatric patient with acute propranolol toxicity exhibited clinical improvement with the administration of ILE in conjunction with HDI.


Ex vivo gene delivery of platelet-derived growth factor increases 0-2A progenitors in adult rat spinal cord.
The O-2A progenitor cell, which serves as a stem cell for the myelinating oligodendrocyte, has been implicated as a major target for radiation-induced spinal cord injury. In an attempt to increase the number of O-2A cells in the spinal cord, we applied an ex vivo gene therapy procedure for delivering platelet derived growth factor (PDGF). Recombinant fibroblasts expressing PDGF A chain were injected into the cisterna magna of adult rats, which resulted in cell seeding of the subarachnoid space of the cervical spinal cord. The number of O-2A progenitors in the cervical spinal cord was then assessed with an in vitro clonogenic assay. O-2A cells were found to be increased 8 days after recombinant cell injection, and they remained elevated up to at least 14 days. Analysis of O-2A colonies indicated that the implantation of PDGF-expressing cells increased the number of O-2A progenitors without affecting their in vitro proliferation potential or differentiation capacity. These data suggest that implantation of PDGF-expressing cells in the subarachnoid space of the cervical spinal cord may influence a stem cell population critical to the repair of demyelinated lesions.


Techniques and outcome of retrograde crural artery revascularization.
In complex popliteal to infrapopliteal occlusions, an endovascular recanalization attempt can fail in a substantial number of cases. The additional use of a retrograde approach seems feasible and safe and can favorably modify this failure rate. However, this is a technique that requires training and is associated with a learning curve. Although this technique is widely practiced among experienced endovascular specialists, the literature contains reports of less than 100 of these cases. We present our experience with the retrograde approach for the treatment of complex tibial arterial disease. Insights into the technical aspects of the procedure and optimal case selection are discussed.


AIDS-related lymphadenopathies.
Lymphoid proliferations in the acquired immunodeficiency syndrome reflect the profound immunologic imbalances induced by the lymphotropic human immunodeficiency virus, and comprise a range of lymphoproliferative disorders from benign lymphadenopathy to malignant lymphoma. Persistent generalized lymphadenopathy (PGL) is associated with a frequently debilitating complex of clinical symptoms and waxing and waning lymphadenopathy. Biopsies of lymph nodes, bone marrow, and other involved tissues show a spectrum of abnormal lymphoid proliferations, with eventual lymphoid depletion, lymphadenopathic Kaposi's sarcoma, and malignant lymphoma. Although individual features of AIDS-related lymphadenopathy may not be specific, the constellation of histologic, immunologic, and ultrastructural findings is highly characteristic of the disorder and useful as a predictor of clinical course. Malignant lymphomas that develop within this setting of multicloncal B cell expansion and impaired immune surveillance have distinctive clinical, histologic, and molecular biologic parameters.


[Biomechanical properties of epithelial mesenchymal transition in idiopathic pulmonary fibrosis].
Idiopathic pulmonary fibrosis (IPF) is a progressive scar-forming disease with a high mortality rate that has received widespread attention. Epithelial mesenchymal transition (EMT) is an important part of the pulmonary fibrosis process, and changes in the biomechanical properties of lung tissue have an important impact on it. In this paper, we summarize the changes in the biomechanical microenvironment of lung tissue in IPF-EMT in recent years, and provide a systematic review on the effects of alterations in the mechanical microenvironment in pulmonary fibrosis on the process of EMT, the effects of mechanical factors on the behavior of alveolar epithelial cells in EMT and the biomechanical signaling in EMT, in order to provide new references for the research on the prevention and treatment of IPF.


[Spectrum and frequency of mitochondrial 12S rRNA variants in the Chinese subjects with nonsynrdomic hearing loss in Zhejiang Province].
Mitochondrial DNA (mtDNA) mutations are one of the important causes of deafness. In particular, the 12S rRNA gene is the hot spots for mutations associated with both aminoglycoside ototoxicity and nonsyndromic deafness. In this report, a total of 318 Chinese pediatric hearing-impaired subjects were recruited from otology clinics in the Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of 12S rRNA gene. Mutational analysis identified 34 variants in the 12S rRNA gene in this cohort. The incidences of the known deafness-associated 1555A>G, 1494C>T and 1095T>C mutations were 9.1%, 0.6% and 1.25% in this cohort, respectively. Other mtDNA variants were evaluated by structural and phylogenetic analysis. Of these, the 839A>G and 1452T>C variants could confer increased sensitivity to aminoglycosides or nonsyndromic deafness as they were not present in 449 Chinese controls and localized at highly conserved nucleotides of the 12S rRNA. However, other variants appeared to be polymorphisms. These data further support the idea that mitochondrial 12S rRNA is one of major targets for aminoglycoside ototoxicity. These data have been providing valuable information to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.


Statistical mechanics study of the introduction of a vaccine against COVID-19 disease.
By the end of 2020, a year since the first cases of infection by the Covid-19 virus have been reported; several pharmaceutical companies made significant progress in developing effective vaccines against the Covid-19 virus that has claimed the lives of more than 10^{6} people over the world. On the other hand, there is growing evidence of re-infection by the virus, which can cause further outbreaks. In this paper, we apply statistical physics tools to examine theoretically the vaccination rate required to control the pandemic for three different vaccine efficiency scenarios and five different vaccination rates. Also, we study the effect of temporal restrictions or reliefs on the pandemic's outbreak, assuming that re-infection is possible. When examining the efficiency of the vaccination rate of the general population in preventing an additional outbreak of the disease, we find that a high vaccination rate (where 0.3% of the population is vaccinated daily, which is equivalent to ≈10^{6} vaccine doses in the United States daily) is required to gain control over the spread of the virus without further restrictions.


Clinical management of iron deficiency anemia in adults: Systemic review on advances in diagnosis and treatment.
Global burden disease studies point out that one of the top cause-specific anemias is iron deficiency (ID). Recent advances in knowledge of iron homeostasis have shown that fragile patients are a new target population in which the correction of ID might impact their morbidity, mortality and quality of life. We did a systematic review using specific search strategy, carried out the review of PubMed database, Cochrane Database of systemic reviews and international guidelines on diagnosis and clinical management of ID from 2010 to 2016. The International guidelines were limited to those with peer-review process and published in journal present in citation index database. The eligible studies show that serum ferritin and transferrin saturation are the key tests in early decision-making process to identify iron deficiency anemia (IDA). The clinician has to carefully consider fragile and high-risk subset of patients such as elders or individuals with chronic diseases (i.e chronic kidney disease, inflammatory bowel disease, chronic heart failure). Treatment is based on iron supplementation. Infusion route should be preferentially considered in frail patients especially in the view of new iron available formulations. The available evidences indicate that (i) recurrent IDA should always be investigated, considering uncommon causes; (ii) IDA might worse the performance and the clinical outcome of fragile and high-risk patients and require an intensive treatment.


Effects of dopamine D3 receptor antagonists on spontaneous and agonist-reduced motor activity in NMRI mice and Wistar rats: comparative study with nafadotride, U 99194A and SB 277011.
Studies investigating the role of the dopamine D3 receptor in the regulation of motor activity of rodents have used several ligands; however, there have been few comparative studies using agonist-antagonist interactions. In the present study, we compared the effects of dopamine D3 antagonists with different levels of selectivity over D2 receptors (nafadotride, U 99194A and SB 277011) on motor activity as well as on agonist-induced hypoactivity, in mice and rats. Horizontal and vertical movements were measured in photocell activity cages. 7-Hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) and PD 128907 were used as dopaminergic agonists. Both dose-dependently inhibited motor activity in mice and vertical activity in rats, while decreasing horizontal activity of rats at doses of 0.01 and 0.1 mg/kg s.c., with no effect (7-OH-DPAT) or stimulation (PD 128907) at the 1 mg/kg dose. In mice habituated to the activity cage, nafadotride (0.1-3 mg/kg i.p.) caused a dose-dependent decrease in motor activity but did not affect the hypomotility evoked by either 7-OH-DPAT (0.1 mg/kg) or PD 128907 (0.1 mg/kg). In habituated rats it had no significant effect on motor activity and was not able to antagonize the hypoactivity caused by PD 128907 (0.1 mg/kg s.c.). U 99194A (5, 10 and 20 mg/kg s.c.) dose-dependently and significantly increased motor activity in mice and inhibited the effects of both agonists. In rats, nafadotride produced considerable motor stimulation and significantly inhibited the PD 128907-induced decrease in horizontal, but not in vertical, activity. SB 277011 (15-45 mg/kg p.o.) significantly increased motor activity in mice and partially blocked the action of 7-OH-DPAT on vertical, but not on horizontal, activity while against PD 128907, its significant inhibitory effect was restricted to a single dose (20 mg/kg). In habituated rats, SB 277011 (13.5, 20 and 30 mg/kg p.o.) exerted no significant effects on motor activity and did not antagonize the hypoactivity caused by PD 128907. Considerable species differences and movement-type differences (horizontal versus vertical) were observed between the effects of the tested dopamine D2/D3 ligands on motor activity in rodents. The antagonists also differed markedly in the robustness of their action. The poorly D3 selective antagonist, nafadotride, had little effect on motor behaviour. The moderately selective U 99194A exerted marked stimulatory effects on motility, and potently inhibited the actions of agonists. SB 277011, a highly selective dopamine D3 receptor antagonist, showed limited ability to influence the motor activity of rodents.


Biophysical ordering transitions underlie genome 3D re-organization during cricket spermiogenesis.
Spermiogenesis is a radical process of differentiation whereby sperm cells acquire a compact and specialized morphology to cope with the constraints of sexual reproduction while preserving their main cargo, an intact copy of the paternal genome. In animals, this often involves the replacement of most histones by sperm-specific nuclear basic proteins (SNBPs). Yet, how the SNBP-structured genome achieves compaction and accommodates shaping remain largely unknown. Here, we exploit confocal, electron and super-resolution microscopy, coupled with polymer modeling to identify the higher-order architecture of sperm chromatin in the needle-shaped nucleus of the emerging model cricket Gryllus bimaculatus. Accompanying spermatid differentiation, the SNBP-based genome is strikingly reorganized as ~25nm-thick fibers orderly coiled along the elongated nucleus axis. This chromatin spool is further found to achieve large-scale helical twisting in the final stages of spermiogenesis, favoring its ultracompaction. We reveal that these dramatic transitions may be recapitulated by a surprisingly simple biophysical principle based on a nucleated rigidification of chromatin linked to the histone-to-SNBP transition within a confined nuclear space. Our work highlights a unique, liquid crystal-like mode of higher-order genome organization in ultracompact cricket sperm, and establishes a multidisciplinary methodological framework to explore the diversity of non-canonical modes of DNA organization.


Effects of clozapine and fluphenazine treatment on responses to m-chlorophenylpiperazine infusions in schizophrenia.
To explore serotonin function in patients with schizophrenia during typical and atypical neuroleptic treatment. We hypothesized that clinically relevant doses of the atypical neuroleptic clozapine would attenuate responses to the serotonin agonist m-chlorophenylpiperazine (m-CPP). m-CPP or placebo was administered intravenously over 90 seconds to patients who had been receiving no medications for at least 3 weeks. m-CPP was also administered during treatment with the typical neuroleptic fluphenazine and the atypical neuroleptic clozapine. Fifteen inpatients (two women and 13 men) who met DSM-III-R criteria for chronic schizophrenia (n = 13) or schizoaffective disorder (n = 2) participated in the study. Mean age (+/- SD) was 33.8 +/- 8.0 years. Measures of m-CPP effects included plasma cortisol and prolactin, body temperature, and the Brief Psychiatric Rating Scale (BPRS). The final BPRS total score at approximately 12 weeks of treatment was used to assess response to clozapine. m-CPP infusion significantly increased plasma cortisol and prolactin levels in drug-free patients. There was a range of behavioral responses while drug-free, but no statistically significant effects on BPRS total or BPRS factor scores. Clozapine treatment significantly blocked neuroendocrine responses to m-CPP, whereas fluphenazine had no effect. Clozapine also appeared to attenuate behavioral responses. These results demonstrate that clozapine treatment has potent serotonin antagonist effects in patients with schizophrenia. This may be related to clozapine's therapeutic effects since patients with greater cortisol response to m-CPP while drug-free had a better subsequent response to clozapine.


Assessment of global and regional left ventricular diastolic function in hypertensive heart disease using automated border detection techniques.
Acoustic quantification (AQ) and color kinesis (CK) are techniques that involve automated detection and tracking of endocardial borders. These methods are useful for the evaluation of global and regional left ventricular (LV) systolic function and more recently have been applied to evaluating LV diastolic performance. Assessment of diastolic dysfunction in hypertensive heart disease is a relevant clinical issue in which these techniques have proven useful. The diastolic portion of left atrium and LV AQ area waveforms are frequently abnormal in patients with left ventricular hypertrophy (LVH). Left ventricular AQ curves consistently demonstrate reduced rapid filling fraction (RFF) and peak rapid filling rate (PRFR), elevated atrial filling fraction (AFF), peak atrial filling rate (PAFR), and reductions in the ratio PRFR/PAFR. Acoustic quantification complements traditional Doppler echocardiographic evaluation of global diastolic function. Many patients with significant LVH and normal Doppler diastolic parameters can be identified as having diastolic dysfunction with AQ. In addition, CK has allowed the evaluation of regional diastolic performance in hypertensive patients. Regional filling curves obtained from CK have demonstrated that endocardial diastolic motion is commonly delayed and heterogeneous in patients with LVH.


Recapitulation of prostate tissue cell type-specific transcriptomes by an in vivo primary prostate tissue xenograft model.
Studies of the normal functions and diseases of the prostate request in vivo models that maintain the tissue architecture and the multiple-cell type compartments of human origin in order to recapitulate reliably the interactions of different cell types. Cell type-specific transcriptomes are critical to reveal the roles of each cell type in the functions and diseases of the prostate. A primary prostate tissue xenograft model was developed using fresh human prostate tissue specimens transplanted onto male mice that were castrated surgically and implanted with a device to maintain circulating testosterone levels comparable to adult human males. Endothelial cells and epithelial cells were isolated from 7 fresh human prostate tissue specimens and from primary tissue xenografts established from 9 fresh human prostate tissue specimens, using antibody-conjugated magnetic beads specific to human CD31 and human EpCAM, respectively. Transcriptomes of endothelial, epithelial and stromal cell fractions were obtained using RNA-Seq. Global and function-specific gene expression profiles were compared in inter-cell type and inter-tissue type manners. Gene expression profiles in the individual cell types isolated from xenografts were similar to those of cells isolated from fresh tissue, demonstrating the value of the primary tissue xenograft model for studies of the inter-relationships between prostatic cell types and the role of such inter-relationships in organ development, disease progression, and response to drug treatments.


Genetic influences in individual susceptibility to noise: a review.
Individual animals and humans show differing susceptibility to noise damage even under very carefully controlled exposure conditions. This difference in susceptibility may be related to unknown genetic components. Common experimental animals (rats, guinea pigs, chinchillas, cats) are outbred-their genomes contain an admixture of many genes. Many mouse strains have been inbred over many generations reducing individual variability, making them ideal candidates for studying the genetic modulation of individual susceptibility. Erway et al. (1993) demonstrated a recessive gene associated with early presbycusis in the C57BL/6J inbred mouse. A series of studies have shown that mice homozygous for Ahl allele are more sensitive to the damaging effects of noise. Recent work has shown that mice homozygous for Ahl are not only more sensitive to noise, but also are probably damaged in a different manner by noise than mice containing the wild-type gene (Davis et al., 2001). Recent work in Noben-Trauth's lab (Di Palma et al., 2001) has shown that the wild-type Ahl gene codes for a hair cell specific cadherin. Cadherins are calcium dependent proteins that hold cells together at adherins junctions to form tissues and organs. The cadherin of interest named otocadherin or CDH23, is localized to the stereocillia of the outer hair cells. Our working hypothesis, suggests that otocadherin may form the lateral links between stereocilia described by Pickles et al (1989). Reduction of, or missing otocadherin weakens the cell and may allow stereocilia to be more easily physically damaged by loud sounds and by aging.


Molecular identification of Candida species isolated from gastro-oesophageal candidiasis in Tehran, Iran.
The aim of this investigation is identification of Candida strains isolated from patients with gastro-oesophageal candidiasis in Tehran, Iran. Gastro-oesophageal candidiasis is a rare infection and appears mainly in debilitated or immunocompromised patients. Colonization by Candida spp. may occur in this region and the organism can remain for several months or years in the absence of inflammation. The main infection symptom is the presence of white plaques in gastro-oesophageal surface. C. albicans remains the most prevalent Candida spp. identified in gastrointestinal candidiasis. Regarding differences in susceptibilities to antifungal drugs among Candida spp., identification of isolates to the species level is significant to quick and appropriate therapy. A total of 398 patients underwent gastrointestinal endoscopy during February 2012 to October 2014 were included in the present study. Histological sections from all endoscopic gastric and oesophageal biopsies were prepared, stained with Periodic acid-Schiff (PAS), and examined for the presence of fungal elements. Part of the biopsy sample was sub-cultured on sabouraud glucose agar. The genomic DNA of each strain was extracted using FTA(®) Elute MicroCards. Molecular identification of Candida isolates was performed by PCR-RFLP technique with the restriction enzyme HpaII. Twenty-one out of 398 cases (5.2%) were found to have gastro-oesophageal candidiasis. Candida albicans was the main strain isolated from clinical samples (90.5%), followed by C. glabrata (4.7%), and C. parapsilosis (4.7%). Due to varying antifungal susceptibility of Candida spp. careful species designation for clinical isolates of Candida was recommended by a rapid and meticulous method like PCR-RFLP.


[Echo-guided puncture of intraprostatic cysts].
The occurrence of an obstruction of the ejaculatory ducts, in spite of its rarity, must be considered by the Urologists in the screening of the etiologic causes of obstructive azoospermia. Nowadays, the diagnostic approach, which includes the biochemical study of seminal plasma and prostatic ultrasound, often leads to the preoperative recognition of the site of obstruction. Various surgical and endoscopic techniques have been adopted for the treatment of ejaculatory duct obstructions in different historical periods. Herein we describe our experience that starts from 1979. 17 infertile patients with intraprostatic cysts and 2 with a stenosis of the veru montanum were treated by us following these criteria: 9 azoospermic patients underwent scrototomy and endoscopy; 10 patients with a severe oligozoospermia underwent echo-guided puncture of an intraprostatic cyst. The patients were placed in the lithotomy position, a 16 G needle was adopted and by means ultrasound was possible to follow the needle entering the cyst. When no spermatozoa was detected in the cystic liquid, sclerosing agents (Sodium-tetradecyl-sulphate 30 mg in 1 l.) was introduced. This easy procedure was carried out on outpatients in local anaesthesia. One out of ten oligozoospermic patients had to repeat the echo-guided puncture of intraprostatic cyst as the first attempt had been followed by recurrence. Eight out of ten subfertile patients who had undergone percutaneous echo-guided treatment had longer than 1 year follow-up: in seven cases an increase in sperms number and motility was obtained; in one case sperm count remained unmodified. In three cases the partners became pregnant.


Water sorption and solubility of methacrylate resin-based root canal sealers.
The water sorption and solubility characteristics of three contemporary methacrylate resin-based endodontic sealers, EndoREZ, Epiphany, and InnoEndo, were compared with those obtained from Kerr EWT, Ketac-Endo (positive control), GuttaFlow, and AH Plus (both negative controls). Ten disks of each material were dehydrated in Drierite for 24 h and weighed to constant dry mass. They were placed in water and weighed periodically until maximum water sorption was obtained. The disks were dehydrated again to determine their mass loss (solubility) at equilibrium. Epiphany exhibited the highest apparent water sorption (8%) followed by Ketac-Endo (6.2%), InnoEndo (3.4%), EndoREZ (3.0%), AH Plus (1.1%), GuttaFlow (0.4%), and Kerr EWT (0.3%). Significantly higher solubility (3.5-4%) were observed for all three methacrylate resin-based sealers and Kerr EWT (3.95%), compared with Ketac-Endo (1.6%), AH Plus (0.16%), and GuttaFlow (0.13%). American Dental Association specifications require<3% solubility for endodontic sealers. Only Ketac-Endo, AH Plus, and GuttaFlow met that criterion.


Extramammary myofibroblastoma of the oral cavity.
Myofibroblastoma is a rare, benign mesenchymal tumor first described as a neoplasm of the breast. Extramammary myofibroblastoma is a histopathologically and genetically identical lesion occurring outside the breast. Herein is presented a case of extramammary myofibroblastoma arising in the oral cavity. A 59-year-old woman presented with a 1.5 cm nodule on the buccal surface of the lower lip. Wide local excision was performed. Histopathologic examination revealed haphazard fascicles of monomorphic spindle cells with hyalinized collagen bundles without fat. The spindled cells were diffusely positive for CD34, and focally for progesterone receptor. Desmin, smooth muscle actin, estrogen receptor, androgen receptor, S100, and STAT6 were negative. Rb1 expression was lost in tumor cells. Thus, the diagnosis of extramammary myofibroblastoma was made. Differential diagnoses include spindle-cell lipoma and angiofibroma. All three tumors are members of the 13q14 deletion/RB1 loss family. Indolent but locally aggressive (solitary fibrous tumor, desmoid fibromatosis) and frankly malignant (low-grade peripheral nerve sheath tumor, dermatofibrosarcoma protuberans) entities can be excluded by immunohistochemistry and careful microscopic examination. Extensive sampling extramammary myofibroblastoma is important to exclude the possibility of malignancy. Clinicians and pathologists alike should be aware of this entity and its potential to arise rarely in unusual locations.


Victor McKusick and his short course.
The Short Course in Human and Mammalian Genetics and Genomics (aka the "Short Course" or the "Bar Harbor course") is one of Victor McKusick's landmark contributions to medical genetics. Conceived in 1959 as a way to increase the contribution of genetic advances to medicine, it has directly affected more than 7000 students and 600 participating faculty from around the world. Now, more than 10 years after his death, it continues to be a vibrant disseminator of genetics, and genomics knowledge for medicine, a catalytic agent for ongoing research and a source of collegiality in our field. What an extraordinary gift!


The transcription factor T-box 3 regulates colony-stimulating factor 1-dependent Jun dimerization protein 2 expression and plays an important role in osteoclastogenesis.
Colony-stimulating factor 1 (CSF1) is known to promote osteoclast progenitor survival, but its roles in osteoclast differentiation and mature osteoclast function are less well understood. In a microarray screen, Jun dimerization protein 2 (JDP2) was identified as significantly induced by CSF1. Recent reports indicate that JDP2 is required for normal osteoclastogenesis and skeletal metabolism. Because there are no reports on the transcriptional regulation of this gene, the DNA sequence from -2612 to +682 bp (relative to the transcription start site) of the JDP2 gene was cloned, and promoter activity was analyzed. The T box-binding element (TBE) between -191 and -141 bp was identified as the cis-element responsible for CSF1-dependent JDP2 expression. Using degenerate PCR, Tbx3 was identified as the major isoform binding the TBE. Overexpression of Tbx3 induced JDP2 promoter activity, whereas suppressing Tbx3 expression substantially attenuated CSF1-induced transcription. Suppressing Tbx3 in osteoclast precursors reduced JDP2 expression and significantly impaired RANKL/CSF1-induced osteoclastogenesis. A MEK1/2-specific inhibitor was found to block CSF1-induced JDP2 expression. Consistent with these data, JDP2(-/-) mice were found to have increased bone mass. In summary, CSF1 up-regulates JDP2 expression by inducing Tbx3 binding to the JDP2 promoter. The downstream signaling cascade from activated c-Fms involves the MEK1/2-ERK1/2 pathway. Tbx3 plays an important role in osteoclastogenesis at least in part by regulating CSF1-dependent expression of JDP2.


Enantioselective addition of vinylzinc reagents to aldehydes catalyzed by modular ligands derived from amino acids.
[reaction: see text] A series of N-acylethylenediamine-based ligands were synthesized from Boc-protected amino acids. The ligands were screened for the ability to catalyze the asymmetric addition of vinylzinc reagents to aldehydes. Three sites of diversity on the ligands were optimized for this reaction using a positional scanning approach. The optimized ligand 3d was found to catalyze the formation of 15 different (E)-allylic alcohols with enantioselectivities that ranged from 52 to 91% ee and yields that ranged from 40 to 90%. This ligand was especially effective for the reaction of aromatic aldehydes with vinylzinc reagents derived from bulky terminal alkynes. Ligand 3d catalyzed the addition of (E)-(3,3-dimethylbut-1-enyl)(ethyl)zinc to 2-naphthaldehyde to give (R,E)-4,4-dimethyl-1-(naphthalene-1-yl)pent-2-en-1-ol in 89% ee. The ee of this product could be increased to 97% through a single recrystallization.


Hexaazatrinaphthylene Derivatives: Efficient Electron-Transporting Materials with Tunable Energy Levels for Inverted Perovskite Solar Cells.
Hexaazatrinaphthylene (HATNA) derivatives have been successfully shown to function as efficient electron-transporting materials (ETMs) for perovskite solar cells (PVSCs). The cells demonstrate a superior power conversion efficiency (PCE) of 17.6 % with negligible hysteresis. This study provides one of the first nonfullerene small-molecule-based ETMs for high-performance p-i-n PVSCs.


Differential tumor infiltration by T-cells characterizes intrinsic molecular subtypes in breast cancer.
Molecular subtypes of breast cancer and presence of tumor-infiltrating immune cells have both been implicated as important predictive and prognostic factors for improved risk stratification and treatment individualization of breast cancer patients. Their association, however, has not been studied in detail. The aim of this study was to evaluate the expression of the T cell markers CD8, FoxP3, CD3 and ζ-chain in molecular subtypes of the invasive margin and tumor center of breast cancer and corresponding sentinel nodes and to deduct prognostic information from these findings. Tumor and sentinel node sections from 177 patients with primary, invasive, unilateral early-stage breast cancer were stained by immunohistochemistry and T-cell phenotypes quantified manually. Clinical data were collected from medical records. The degree of T-cell infiltration and expression of all markers differed significantly among the molecular subtypes, being highest in non-luminal, more aggressive tumors: more T-cell infiltration and higher expression of all markers were associated with hormone receptor negativity, higher proliferation and higher histological grades, but also with larger tumor size. Basal-like tumors, and most remarkably their tumor centers, hosted the highest number of FoxP3+ T-cells with an unfavorable ratio to cytotoxic CD8+ T-cells. T-cell infiltration was generally higher in the invasive margin than the tumor center. A scoring system based on densities of CD3 and CD8 could significantly separate molecular subtypes (p < 0.001). Thus, immunological patterns with functional implications within each subtype are associated with prognostic factors. These findings should be further validated in studies using larger patient populations and longer follow-up.


Perceived barriers to children's active commuting to school: a systematic review of empirical, methodological and theoretical evidence.
Active commuting to school (ACS) may increase children's daily physical activity and help them maintain a healthy weight. Previous studies have identified various perceived barriers related to children's ACS. However, it is not clear whether and how these studies were methodologically sound and theoretically grounded. The purpose of this review was to critically assess the current literature on perceived barriers to children's ACS and provide recommendations for future studies. Empirically based literature on perceived barriers to ACS was systematically searched from six databases. A methodological quality scale (MQS) and a theory utilization quality scale (TQS) were created based on previously established instruments and tailored for the current review. Among the 39 studies that met the inclusion criteria, 19 (48.7%) reported statistically significant perceived barriers to child's ACS. The methodological and theory utilization qualities of reviewed studies varied, with MQS scores ranging between 7 and 20 (Mean =12.95, SD =2.95) and TQS scores from 1 to 7 (Mean =3.62, SD =1.74). A detailed appraisal of the literature suggests several empirical, methodological, and theoretical recommendations for future studies on perceived barriers to ACS. Empirically, increasing the diversity of study regions and samples should be a high priority, particularly in Asian and European countries, and among rural residents; more prospective and interventions studies are needed to determine the causal mechanism liking the perceived factors and ACS; future researchers should include policy-related barriers into their inquiries. Methodologically, the conceptualization of ACS should be standardized or at least well rationalized in future studies to ensure the comparability of results; researchers' awareness need to be increased for improving the methodological rigor of studies, especially in regard to appropriate statistical analysis techniques, control variable estimation, multicollinearity testing, and reliability and validity reporting. Theoretically, future researchers need to first ground their investigations in theoretical foundations; efforts should be devoted to make sure theories are used thoroughly and correctly; important theoretical constructs, in particular, need to be conceptualized and operationalized appropriately to ensure accurate measurement. By reviewing what has been achieved, this review offered insights for more sophisticated ACS studies in the future.


Mitochondria-targeted antioxidant supplementation improves 8 km time trial performance in middle-aged trained male cyclists.
Exercise increases skeletal muscle reactive oxygen species (ROS) production, which may contribute to the onset of muscular fatigue and impair athletic performance. Mitochondria-targeted antioxidants such as MitoQ, which contains a ubiquinone moiety and is targeted to mitochondria through the addition of a lipophilic triphenylphosphonium cation, are becoming popular amongst active individuals as they are designed to accumulate within mitochondria and may provide targeted protection against exercise-induced oxidative stress. However, the effect of MitoQ supplementation on cycling performance is currently unknown. Here, we investigate whether MitoQ supplementation can improve cycling performance measured as time to complete an 8 km time trial. In a randomized, double-blind, placebo-controlled crossover study, 19 middle-aged (age: 44 ± 4 years) recreationally trained (VO2peak: 58.5 ± 6.2 ml·kg- 1·min- 1, distance cycled per week during 6 months prior to study enrollment: 158.3 ± 58.4 km) male cyclists completed 45 min cycling at 70% VO2peak followed by an 8 km time trial after 28 days of supplementation with MitoQ (20 mg·day- 1) and a placebo. Free F2-isoprostanes were measured in plasma samples collected at rest, after 45 min cycling at 70% VO2peak and after completion of the time trial. Respiratory gases and measures of rating of perceived exertion (RPE) were also collected. Mean completion time for the time trial was 1.3% faster with MitoQ (12.91 ± 0.94 min) compared to placebo (13.09 ± 0.95 min, p = 0.04, 95% CI [0.05, 2.64], d = 0.2). There was no difference in RPE during the time trial between conditions (p = 0.82) despite there being a 4.4% increase in average power output during the time trial following MitoQ supplementation compared to placebo (placebo; 270 ± 51 W, MitoQ; 280 ± 53 W, p = 0.04, 95% CI [0.49, 8.22], d = 0.2). Plasma F2-isoprostanes were lower on completion of the time trial following MitoQ supplementation (35.89 ± 13.6 pg·ml- 1) compared to placebo (44.7 ± 16.9 pg·ml- 1 p = 0.03). These data suggest that MitoQ supplementation may be an effective nutritional strategy to attenuate exercise-induced increases in oxidative damage to lipids and improve cycling performance.


Alternative competition-induced digestive strategies yield equal growth, but constrain compensatory growth in red-eyed treefrog larvae.
Compensatory growth is well documented across taxa and provides a fitness advantage to animals who would otherwise reach a smaller reproductive size. We investigated the role of competition-induced gut plasticity in facilitating a compensatory response in red-eyed treefrog larvae. We reared larvae at low, medium, and high densities with different per capita resources, environments known to produce individuals with long and short guts. We then transferred larvae to competitively equal environments to determine if longer guts provided an advantage when resources became available. We predicted that larvae from higher densities with longer guts would exhibit hyperphagia and compensatory growth. We measured growth over 1-week, as well as the time to and size at metamorphosis. To assess mechanisms underlying the growth response, we measured diet transit time and intake. Growth, development, and metamorph snout-vent length did not differ between larvae with long and short guts. Instead, different gut lengths were associated with dramatically different feeding strategies. Medium- and high-density larvae fed at rates far below what their guts could accommodate. However, the combination of low intake and longer guts extended diet transit times, presumably increasing digestibility. This unexpected strategy achieved the same results as that of low-density larvae, which ate twice as much food, but passed it more quickly through a shorter gut. The lack of a compensatory response may be attributed to the costs of accelerated growth and weak seasonal time constraints in the tropics. This suggests that although compensatory growth is widespread among animals, expression of the response may vary with environmental context. J. Exp. Zool. 323A: 778-788, 2015. © 2015 Wiley Periodicals, Inc.


On Examining Residential Segregation in Rural Gadag, Karnataka, India: The Case of the Banjara Tandas.
Residential segregation of settlements on caste lines is common across Indian villages. Banjara settlements or tandas are an extreme form of residential segregation, rooted in colonial history and India's complex caste system, and an outcome of structural discrimination. This analysis examines the structural discrimination of tandas in the distribution of various infrastructure and compares it with the villages in proximity to it. A cross-sectional comparative study of infrastructure was conducted in Banjara tandas and villages in Gadag district, Karnataka, India. Composite scores were computed for various infrastructure and discriminant analysis done to classify tandas and villages. The villages have better physical infrastructure such as paved roads, multiple water supply sources, and better drains and amenities such as the community water filter, ration shop, veterinary center, milk society, banks, post office, and health facilities compared to tandas. Discriminant analysis indicated that social infrastructural indicators of health and education (Discriminant function coefficient -0.8689), followed by transportation (Discriminant function coefficient -0.3576) and water supply (Discriminant function coefficient -0.2939), are the most significant discriminating factors between tanda and villages. This disadvantage indicates structural discrimination that is a continuation of the stigma and labeling perpetrated upon them historically and the complex caste system in Indian societies.


Postjunctional alpha 2-adrenoceptors in pial arteries of anesthetized newborn pigs.
The purpose of this study was to characterize the nature of the postjunctional alpha-adrenoceptors (alpha 1 versus alpha 2) in the cerebral circulation of anesthetized newborn pigs. Diameters of pial arteries in anesthetized piglets, 1-6 days old, were examined using a 'closed' cranial window. We examined sympathetically mediated constriction of pial arteries in the presence and absence of alpha 1- (prazosin) or alpha 2- (yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Initial experiments demonstrated that prazosin and yohimbine attenuated constriction of pial arteries during topical administration to the pial surface of phenylephrine and clonidine, respectively. In one group, electrical stimulation of the ipsilateral superior cervical ganglion reduced pial arterial diameter from 176 +/- 26 (mean +/- SEM) to 153 +/- 24 microns, and this response was unaffected by prior administration of prazosin. In a second group, sympathetic nerve stimulation reduced pial arterial diameter from 175 +/- 23 to 148 +/- 19 microns, and this response was abolished by prior administration of yohimbine. After administration of yohimbine, pial arteries still constricted in response to topical phenylephrine and arterial hypertension. We conclude that sympathetic nerve stimulation in anesthetized newborn pigs constricts pial arteries via alpha 2-adrenoceptors.


Diosmin 600 in adjunction to rivaroxaban reduces the risk of post-thrombotic syndrome after femoropopliteal deep vein thrombosis: results of the RIDILOTT DVT study.
To assess the efficacy and safety of long-term diosmin 600 therapy added to rivaroxaban and elastic compression stockings (ECS) in patients with femoropopliteal deep vein thrombosis (DVT). This single-center, open-label randomized clinical trial RIDILOTT DVT enrolled patients with their first femoropopliteal DVT confirmed by duplex ultrasound scan (DUS). Participants were randomly allocated to the control group (standard treatment with rivaroxaban for six months and ECS for 12 months) or the experimental group (standard treatment with the additional use of diosmin 600 mg once daily for 12 months). Patients were followed for 12 months. The primary outcome was post-thrombotic syndrome (PTS), according to the Villalta Score (≥5). The secondary outcomes were deep vein recanalization, chronic venous disease (CVD) progression, the severity of PTS (Villalta), and CVD (VCSS), quality of life (CIVIQ-20), venous thromboembolism recurrence, and adverse event (AE). Ninety patients were randomized (45 per group). There were 56 men and 34 women with a mean age of 57.8±13.4 years, and 69% had clinically unprovoked DVT. PTS frequency at 12 months was significantly lower (8.9% vs. 48.9%) in the experimental group compared with control one (relative risk, 0.14; 95% confidential interval, 0.04-0.43, P<0.001). Adding diosmin 600 was associated with quicker and complete vein recanalization, lower CVD progression rate, and lower Villalta, VCSS, and CIVIQ-20 scores. There was no difference in recurrent DVT or AE. Adjunctive use of diosmin 600 to rivaroxaban and ECS in patients with femoropopliteal DVT can improve the clinical and ultrasound outcomes after 12 months of treatment.


Pathology of idiopathic dystonia: findings from genetic animal models.
Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions. In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain. The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia. Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia. Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are describe. This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dt(sz)), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease. Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder. Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder.


The jumping plant-lice of the Neotropical genus Tainarys (Hemiptera: Psylloidea) associated with Anacardiaceae.
The Neotropical psyllid genus Tainarys Brèthes, 1920 is revised to include 14 extant and one fossil species from Dominican amber. Eight species are described as new, viz. Tainarys aroeira sp. nov., T. atra sp. nov., T. hapla sp. nov., T. myracrodrui sp. nov., T. nigricornis sp. nov., T. didyma sp. nov. and T. orientalis sp. nov. from Brazil, the last two also from Uruguay, as well as T. lozadai sp. nov. from Peru. The fifth instar immatures are described for nine species. †Vicinilura Klimaszewski, 1996, erected for the fossil †V. reposta Klimaszewski, 1996 and previously synonymised with Leurolophus Tuthill, 1942, is synonymised here (syn. nov.) with Tainarys and †V. reposta is transferred to become †Tainarys reposta (Klimaszewski), comb. nov. The descriptions are supplemented by illustrations and keys for the identification of adults and immatures. Phylogenetic relationships between species are investigated with a cladistic analysis using 22 adult and six immature morphological characters. The analysis resulted in a single most parsimonious, fully resolved tree. The fossil species is nested within the genus rather than being the sister taxon of the remainder of species. The extant species are restricted to the subtropical and temperate parts of South America. Three pairs of sister clades display an east‒west South American and one a midwest‒southern Brazilian geographical vicariance. Host plants are confirmed for nine and likely for another four species. They are Astronium, Haplorhus, Myracrodruon, Schinopsis and Schinus (Anacardiaceae). All Tainarys species appear to be oligophagous inducing irregular leaf curls on their hosts.


Making two-level standards work in legacy communication frameworks.
The research presented deals with the problem of how information technology can support the interconnection of medical information systems in practice. We apply a two-part structural standard that consists of a fixed Information Reference (IR) Model, and an Archetype Reference (AR) Model that uses the structures of the IR model. A very important problem with the real-world application of such a two-level model is that the high level (abstract) entities, structures and their connections must be somehow translated into lower level equivalents that legacy database information systems can actually use to program their standardised interface. Our choice for the lower level medium is XML, such that the standard appears as an XSD schema that can be used, in the usual way, to validate a message document. To test the viability of the above paradigm, we developed an archetype-XSD translator tool in the form of Protégé/OWL plugins and tested it on an industrial interface for exchanging medical episodes (MedQuery), using an implementation of openEHR. We found that the most important features: Containment, Cardinality, Named references to other instances, and References to external terminologies, could all be mapped to standard XSD constructs. We also developed a validator plugin to check external references. We plan to put the system at work in a heterogeneous medical messaging system (a descendant of the Budapest based MediNet system) in the near future.


Clinicopathological, Radiological, and Molecular Features of Primary Lung Adenocarcinoma with Morule-Like Components.
Morule-like component (MLC) was a rare structure in primary lung adenocarcinoma. We aimed to reveal the clinicopathological, radiological, immunohistochemical, and molecular features of lung adenocarcinoma with MLCs. Twenty lung adenocarcinomas with MLCs were collected, and computed tomographic and histological documents were reviewed. Immunohistochemistry, targeted next-generation sequencing, and Sanger sequencing for β-catenin gene were performed. There were 9 lepidic adenocarcinomas, 8 acinar adenocarcinomas, 2 papillary adenocarcinomas, and 1 minimally invasive adenocarcinoma. Most patients (16/17) were shown a pure solid nodule, and 1 patient was shown a partly solid nodule on chest computed tomography (CT). Nine cases were accompanied with micropapillary components, and 3 were with cribriform components in which 2 suffered a worse prognosis. No significant association was found between the MCLs and the overall survival of lung adenocarcinoma (P = 0.109). The MLCs were often arranged in whorled or streaming patterns. The cells in MLCs showed syncytial and mild appearance. The MLCs were positive for E-cadherin, CK7, TTF-1, napsin-A, vimentin, and β-catenin (membrane), and negative for CK5/6, p40, p63, Synaptophysin, chromogranin A, and Cdx-2. EGFR mutation, ALK-EML4 fusion, HER2 amplification, and PIK3CA mutation were detected in 16 cases, 2 cases, 1 case, and 1 case, respectively. EGFR mutation was more frequent in adenocarcinomas with MLCs than those without MLCs (P = 0.040). β-catenin gene mutation was not detected in any patients. MLC is often observed in the background of acinar, lepidic, and papillary adenocarcinomas. Lung adenocarcinomas with MLCs tend to appear as a solid mass on CT and harbor EGFR gene mutations. The micropapillary components and cribriform components may cause poor prognosis of lung adenocarcinomas with MLCs. Vimentin is always positive in MLCs, and it is a useful marker for the identification of MLCs.


Studies on purified rheumatoid synovial collagenase in vitro and in vivo.
Rheumatoid synovial collagenase obtained from culture medium can be separated by Sephadex gel filtration into two peaks of enzyme activity. These have been designated as fast-moving and slow-moving rheumatoid synovial collagenases on the basis of their electrophoretic mobility on polyacrylamide gels. The slow-moving rheumatoid synovial collagenase has been highly purified by affinity chromatography on collagen conjugated to Sepharose and used to prepare a monospecific anti-synovial collagenase antiserum. The antiserum against rheumatoid synovial collagenase has permitted the demonstration of immunoreactive collagenase in extracts of rheumatoid synovial tissue that have no detectable enzymatic activity. Collagenase has also been detected immunologically in enzymatically inactive culture medium from the first 24 hr of culture. Recovery of collagenase activity appears to be related to the chromatographic separation of the enzyme from serum antiproteases. The demonstration of collagenase in vivo in rheumatoid synovium adds further support for the concept that the enzyme is present in tissue at levels that are of significance in the pathogenesis of rheumatoid arthritis. In addition, rheumatoid synovial collagenase and human skin collagenase show complete immunologic identity when reacted with monospecific antiserum prepared against either of these purified enzymes, indicating that organ specificity between these two human collagenases is unlikely.


On-chip microfluidic biosensor using superparamagnetic microparticles.
In this paper, an integrated solution towards an on-chip microfluidic biosensor using the magnetically induced motion of functionalized superparamagnetic microparticles (SMPs) is presented. The concept of the proposed method is that the induced velocity on SMPs in suspension, while imposed to a magnetic field gradient, is inversely proportional to their volume. Specifically, a velocity variation of suspended functionalized SMPs inside a detection microchannel with respect to a reference velocity, specified in a parallel reference microchannel, indicates an increase in their non-magnetic volume. This volumetric increase of the SMPs is caused by the binding of organic compounds (e.g., biomolecules) to their functionalized surface. The new compounds with the increased non-magnetic volume are called loaded SMPs (LSMPs). The magnetic force required for the manipulation of the SMPs and LSMPs is produced by current currying conducting microstructures, driven by a programmable microcontroller. Experiments were carried out as a proof of concept. A promising decrease in the velocity of the LSMPs in comparison to that of the SMPs was measured. Thus, it is the velocity variation which determines the presence of the organic compounds in the sample fluid.


Physical examination skills training: Faculty staff vs. patient instructor feedback-A controlled trial.
Standardized patients are widely used in training of medical students, both in teaching and assessment. They also frequently lead complete training sessions delivering physical examination skills without the aid of faculty teaching staff-acting as "patient instructors" (PIs). An important part of this training is their ability to provide detailed structured feedback to students which has a strong impact on their learning success. Yet, to date no study has assessed the quality of physical examination related feedback by PIs. Therefore, we conducted a randomized controlled study comparing feedback of PIs and faculty staff following a physical examination assessed by students and video assessors. 14 PIs and 14 different faculty staff physicians both delivered feedback to 40 medical students that had performed a physical examination on the respective PI while the physicians observed the performance. The physical examination was rated by two independent video assessors to provide an objective performance standard (gold standard). Feedback of PI and physicians was content analyzed by two different independent video assessors based on a provided checklist and compared to the performance standard. Feedback of PIs and physicians was also rated by medical students and video assessors using a questionnaire consisting of 12 items. There was no statistical significant difference concerning overall matching of physician or PI feedback with gold standard ratings by video assessment (p = .219). There was also no statistical difference when focusing only on items that were classified as major key steps (p = .802), mistakes or parts that were left out during physical examination (p = .219) or mistakes in communication items (p = .517). The feedback of physicians was significantly better rated than PI feedback both by students (p = .043) as well as by video assessors (p = .034). In summary, our study demonstrates that trained PIs are able to provide feedback of equal quantitative value to that of faculty staff physicians with regard to a physical examination performed on them. However, both the students and the video raters judged the quality of the feedback given by the physicians to be significantly better than that of the PIs.


Is Extracorporeal Shockwave Therapy Combined With Isokinetic Exercise More Effective Than Extracorporeal Shockwave Therapy Alone for Subacromial Impingement Syndrome? A Randomized Clinical Trial.
Study Design Single-blind randomized trial. Background Extracorporeal shockwave therapy (ESWT) has been shown to produce good results in the treatment of subacromial impingement syndrome (SAIS). The efficacy of a combined administration of ESWT and isokinetic exercise (IE) has not yet been studied. Objectives To evaluate the efficacy of focused ESWT combined with IE for the rotator cuff versus focused ESWT alone in the treatment of SAIS. The secondary objective was to assess the isokinetic torque recovery (external rotation at 210°/s, 180°/s, and 120°/s). Methods Thirty participants with SAIS were randomly assigned to a focused-ESWT group or focused ESWT-plus-IE group. Subjects of both groups received 3 treatment sessions of focused ESWT over a period of 10 days. Participants in the second group also received IE for 10 therapy sessions. Outcome measures were the Constant-Murley score (CMS), the visual analog scale (VAS), and isokinetic parameters (peak torque and total work calculated from 5 repetitions) measured with the isokinetic test. Subjects were assessed at baseline, 10 days after the last treatment session with focused ESWT, and after 2 months of follow-up. Results At 2 months posttreatment, participants in the focused ESWT-plus-IE group showed significantly less pain (focused-ESWT VAS, 3.4 ± 0.8 versus focused ESWT-plus-IE VAS, 1.5 ± 0.5; P<.001) and greater improvement in functionality (focused-ESWT CMS, 75.9 ± 6.7 versus focused ESWT-plus-IE CMS, 92.1 ± 6.3; P<.001) and muscle endurance than the subjects in the focused-ESWT group. Conclusion In subjects with SAIS, combined administration of focused ESWT and IE for the rotator cuff resulted in greater reduction of pain, as well as superior functional recovery and muscle endurance in the short to medium term, compared with ESWT alone. Level of evidence Therapy, 2b. unregistered 2011 trial. J Orthop Sports Phys Ther 2016;46(9):714-725. Epub 5 Aug 2016. doi:10.2519/jospt.2016.4629.


MERGE: A Multinational, Multicenter Observational Registry for Myeloproliferative Neoplasms in Asia, including Middle East, Turkey, and Algeria.
Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal disorders of the bone marrow, and are associated with a high disease burden, reduced quality of life (QOL), and shortened survival. This multinational, multicenter, non-interventional registry "MERGE" was initiated with an objective to collect data on the epidemiological indices of classical Ph-MPNs, existing treatment patterns, and impact of MPNs on health-related QOL in various countries/regions in Asia, including the Middle East, Turkey, and Algeria. Of the 884 eligible patients with MPNs, 169 had myelofibrosis (MF), 301 had polycythemia vera (PV), 373 had essential thrombocythemia (ET), and 41 had unclassified MPNs. The median age was 58 years (range, 47-66 years), and 50% of patients were males. The prevalence and incidence of MPNs were estimated to be 57-81 and 12-15 per 100 000 hospital patients per year over the last 4 years, respectively, in these countries. Total symptom score (mean [standard deviation; SD]) at baseline was highest in patients with MF (23.5 [17.47]) compared with patients with ET (14.6 [14.26]) and PV (16.6 [14.84]). Patients with ET had a lower mean (SD) number of inpatient visits (0.9 [0.77] days), and patients with MF had more outpatient visits (5.2 [3.17] days) on an average, compared with the entire MPN group. The study showed that patients with MPNs have a severe disease burden and reduced QOL. A discordance between physician and patient perception of symptom assessment was observed in this study (International clinical trials registry ID: CTRI/2014/05/004598).


Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.
Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.


Bone inflammation and chronic recurrent multifocal osteomyelitis.
Chronic recurrent multifocal osteomyelitis (CRMO) is a sporadic condition of inflammatory bone pain that occurs as recurrent flares because of osteomyelitis, which presents in the form of multiple aseptic foci. The estimated prevalence of CRMO is 1-2 per million, affecting mostly children, in the age group of 2 to 17. Main symptoms of CRMO are bone inflammation and pain, which are generally worse at night. Other symptoms seen on radiographs indicate osteolytic lesions surrounded by sclerosis, at later stages of the disease. Markers of inflammation, viz. tumor necrosis factor a and C-reactive protein are elevated in many cases. Because of similar symptoms, differential diagnosis is needed to confirm CRMO from infectious osteomyelitis, bone tumors, and other diseases. The genetic component is likely in some cases such as Majeed syndrome, deficiency of IL-1 antagonist, etc. Imaging is the essential part of diagnosing CRMO, and magnetic resonance imaging of the whole body is the most widely used and recommended method for the evaluation of multiple foci, as compared to radiography for reasons of sensitivity as well as prevention of excessive exposure of affected children to radiation. CRMO is considered an autoimmune and auto-inflammatory disorder, but its precise pathophysiology is not clear. Current treatment options are non-steroid anti-inflammatory drugs like naproxen, as the primary choice, and the bisphosphonates such as pamidronate as the second choice, to counter the symptoms and to reduce bone lesions. The surgical option is the choice for recalcitrant cases, even though recurrence may still be a problem.


Effects of kinesiotaping versus non-steroidal anti-inflammatory drugs and physical therapy for treatment of pes anserinus tendino-bursitis: A randomized comparative clinical trial.
Pes anserinus tendino-bursitis is a condition caused by repetitive friction over the bursa or direct trauma to knee joint and it presents with proximal medial tibial pain and swelling. The aim of this study is to determine the effects of kinesiotaping in comparison with naproxen and physical therapy in treatment of pes anserinus tendino-bursitis. In a randomized comparative clinical trial 56 patients with clinical diagnosis of pes anserinus tendino-bursitis were randomly assigned to kinesiotaping and naproxen/physical therapy (28 patients in each group). Kinesiotaping on the tender area in the form of space-correction (lifting) technique was used and repeated for three times with a one-week interval. Another group received naproxen (250mg TID for 10 days) and ten sessions of daily physical therapy. The visual analog scale (VAS) was used for evaluation of pain. The depth of swelling of the area was measured with sonography before and after treatment. Wilcoxon signed ranks test has been used for determining the influence of interventions on pain (VAS) and swelling scores in each group. The ANCOVA (Analysis of covariance) test was applied for comparing the influence of interventions on VAS and swelling scores after adjustment for co-variables. At end of the study, 27 patients remained in the kinesiotaping group and 19 patients in naproxen/physical therapy group. Treatment with kinesiotaping significantly decreased the pain (P=0.0001) and swelling scores (P=0.0001) in comparison with naproxen/physical therapy after adjustment for baseline characteristics. Kinesiotaping was safe without any complications except for a mild local skin irritation in one patient. Kinesiotaping is more effective than naproxen plus physical therapy in reduction of pain and swelling in patients with pes anserinus tendino-bursitis. www.ClinicalTrials.gov identifier is NCT01680263.


XAFS spectra from reflectivity measurements.
The reflectivity of TiSi(2) films was measured as a function of photon energy E at the Ti K-edge region at a glancing angle theta close to the critical angle theta(C) of total reflection. TiSi(2) silicide films (about 30 nm thickness) were prepared by silicidation of Ti thin films deposited on Si(001) substrates. Since the Fresnel reflectivity R(theta,E) is a function of the dispersion delta(E) and of the absorption beta(E), the absorption beta(E) which carries the XAFS signal can be solved as beta(theta,delta,R) for observed reflectivity R and for estimated delta. The dispersion delta(E) is related to the absorption beta(E) by the Kramers-Kronig (K-K) relations since the refractive index is n(E) = 1 - delta(E) - ibeta(E). beta(E) was calculated from the observed reflectivity R(theta,E) using theoretical values for initial delta(E). Titanium K-edge XAFS for TiSi(2) was extracted from the reflectivity by 'ReflXAFS'.


Dendrimer-influenced supramolecular structure formation of block copolymers.
The water content-dependent supramolecular structure formation of polystyrene-block-poly(acrylic acid) (PS-b-PAA) copolymer in the presence of a fourth-generation amine-terminated poly(amido amine) dendrimer (PAMAM) is investigated by dynamic light scattering, turbidity measurements, and transmission electron microscopy. The solvent system for this study is a mixture of dioxane/THF and water. A very complex turbidity profile is observed with increasing water content in the system and is explained by the presence of various aggregated structures based on strong interactions between the amine-containing dendrimers and the poly(acrylic acid) blocks of the polymer. The onset of the self-assembly of single chains of PS-b-PAA (primary structure) into single and multiple dendrimer core inverse micelles (secondary structure) is detected as very low water contents of cw < 2% wt (cwc). These micelles consist of dendrimers coated with PAA blocks, which are connected to the corresponding PS chains that form the corona. Further addition of water leads to an association of these micelles into compound multiple dendrimer core inverse micelles (tertiary structure) in the range of cw = approximately 6 to approximately 10% wt. At still higher water content, some of the acrylic acid chains of the block copolymer move from the vicinity of the dendrimer to the outside of the aggregates, resulting in a decrease in the size of the formed structures and the acquisition of progressively increasing hydrophilic character of the aggregates. Multiple dendrimer core inverse onion micelles are formed, which agglomerate into compound multiple dendrimer core inverse onion micelles at cw = approximately 12 to approximately 18% wt. Above this water content, vesicular structures are formed. The complexity is unusual for block copolymer systems and illustrates the importance of strong interactions in structure formation.


A Study on User-Oriented Subjects of Child Abuse on Wikipedia: Temporal Analysis of Wikipedia History Versions and Traffic Data.
Many people turn to online open encyclopedias such as Wikipedia to seek knowledge about child abuse. However, the information available on this website is often disorganized and incomplete. The aim of this study is to analyze Wikipedia's coverage of child abuse and provide a more accessible way for users to browse child abuse-related content. The study explored the main themes and subjects related to child abuse on Wikipedia and proposed a multilayer user-oriented subject schema from the general users' perspective. The knowledge of child abuse on Wikipedia is presented in the child abuse-related articles on it. The study analyzed child abuse-related articles on Wikipedia, examining their history versions and yearly page views data to reveal the evolution of content and popularity. The themes and subjects were identified from the articles' text using the open coding, self-organizing map, and n-gram approaches. The subjects in different periods were compared to reveal changes in content. This study collected and investigated 241 associated Wikipedia articles and their history versions and traffic data. Four facets were identified: (1) maltreatment behavior (n=118, 48.9%); (2) people and environment (n=28, 11.6%); (3) problems and risks (n=33, 13.7%); and (4) protection and support (n=62, 25.7%). A total of 8 themes and 51 subjects were generated from the text, and a user-oriented subject schema linking the facets, themes, subjects, and articles was created. Maltreatment behavior (number of total views = 1.15 × 108) was the most popular facet viewed by users, while people and environment (number of total views = 2.42 × 107) was the least popular. The popularity of child abuse increased from 2010 to 2014 but decreased after that. The user-oriented subject schema provides an easier way for users to seek information and learn about child abuse. The knowledge of child abuse on Wikipedia covers the harms done to children, the problems caused by child abuse, the protection of children, and the people involved in child abuse. However, there was an inconsistency between the interests of general users and Wikipedia editors, and the child abuse knowledge on Wikipedia was found to be deficient, lacking content about typical child abuse types. To meet users' needs, health information creators need to generate more information to fill the knowledge gap.


cDNA structure of an insulin-related peptide in the Pacific oyster and seasonal changes in the gene expression.
Insulin-related peptide cDNA was characterized in the Pacific oyster Crassostrea gigas. It was determined that three transcripts with differing lengths of 3'-untranslated region (3'-UTR) were expressed in the visceral ganglia. The insulin-related peptide cDNA contained a number of AUUUA motifs that were typical of adenylate/uridylate-rich elements in the 3'-UTR. The deduced preprohormone was a polypeptide of 161 residues and showed a conformation typical of preprohormones of the insulin superfamily, which included conserved amino acids necessary to adopt the globular insulin structure. The expression of the three different transcripts was variable throughout the year, with the highest expression observed in March and lower expression in November and July. The expression of the shortest mRNA in March was about tenfold higher than in July, while the expression of the longest transcript varied approximately twofold during the year. The accumulation of glycogen in the soft body rapidly increased in October and November, and robust body growth and gametogenetic development occurred in March to May. The period of the highest expression of the oyster insulin-related peptide gene corresponded to the onset of body growth and gametogenetic development, but did not overlap with the period of glycogen accumulation. This is the first report that fully details the structure and expression of the insulin-related peptide gene in bivalves.


Medical contraindications to implant therapy: part I: absolute contraindications.
In order to ensure implant success, it is essential to select patients who do not possess local or systemic contraindications to therapy. Hence, it is the purpose of this paper to review the medical diseases that reportedly preclude conventional dental implant treatment. Absolute contraindications to implant rehabilitation include recent myocardial infarction and cerebrovascular accident, valvular prosthesis surgery, immunosuppression, bleeding issues, active treatment of malignancy, drug abuse, psychiatric illness, as well as intravenous bisphosphonate use. Any of these conditions bar elective oral surgery, and require judicious monitoring by the physician as well as the dental provider. Noncompliance to the suggested protocol may, in the worst possible case, result in patient mortality.


Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison.
Despite recent genetic advances and numerous ongoing therapeutic trials, malignant melanoma remains fatal, and prognostic factors as well as more efficient treatments are needed. The development of such research strongly depends on the availability of appropriate models recapitulating all the features of human melanoma. The concept of comparative oncology, with the use of spontaneous canine models has recently acquired a unique value as a translational model. Canine malignant melanomas are naturally occurring cancers presenting striking homologies with human melanomas. As for many other cancers, dogs present surprising breed predispositions and higher frequency of certain subtypes per breed. Oral melanomas, which are much more frequent and highly severe in dogs and cutaneous melanomas with severe digital forms or uveal subtypes are subtypes presenting relevant homologies with their human counterparts, thus constituting close models for these human melanoma subtypes. This review addresses how canine and human melanoma subtypes compare based on their epidemiological, clinical, histological, and genetic characteristics, and how comparative oncology approaches can provide insights into rare and poorly characterized melanoma subtypes in humans that are frequent and breed-specific in dogs. We propose canine malignant melanomas as models for rare non-UV-induced human melanomas, especially mucosal melanomas. Naturally affected dogs offer the opportunity to decipher the genetics at both germline and somatic levels and to explore therapeutic options, with the dog entering preclinical trials as human patients, benefiting both dogs and humans.