Travel burden and geographic access to health care among children with cancer in Saudi Arabia.
Travel burden has a substantial psychosocial impact and financial strain on childhood cancer patients and their families. To study the geographic distribution of childhood cancer and assess the travel burden for care in Saudi Arabia. This was a cross-sectional multi-institutional study that enrolled 1657 children with cancer who were diagnosed between 2011 and 2014. Cancer type/stage, city/region of residence, and city/region of treating centre were recorded. Travel burden was measured based on a 1-way distance in kilometres from the city centre to the treatment institution. This study was supported by Sanad Children's Cancer Support Association. Diagnosis was leukaemia (45.2%), non-CNS solid tumours (30.2%), lymphoma (12.3%), CNS tumours (11.8%) and histiocytosis (0.5%). Childhood cancer centres were in the same city as where the patients lived in 652 (39.3%) cases, same region but different city in 308 (18.6%), different regions in 613 (37%), and not known in 84 (5.1%). The mean 1-way travel distance for patients who lived in different regions was 790 (range, 116-1542) km. A total of 536 (32%) patients lived ≥ 400 km and 216 (13%) > 1000 km from the treatment centre. Among 642 patients with acute lymphoblastic leukaemia who required 2-3 years of therapy, 197 (31%) lived ≥ 400 km and 94 (15%) >1000 km from the treatment centre. Nearly two thirds of patients with childhood cancer lived in different cities than the treatment centres, including one third of patients who lived ≥ 400 km away. There is a need to develop strategies to improve access to childhood cancer care.


Results of osteotomy, open reduction, and internal fixation for late-presenting malunited intra-articular fractures of the base of the middle phalanx.
To present our results in the treatment of late-presenting impaction fractures of the base of the middle phalanx treated by osteotomy with full exposure of the articular surface to restore the normal anatomy. Eleven patients with a malunited (impacted) fracture of the base of the middle phalanx were treated by osteotomy more than 5 weeks after the injury. All fractures had varying degrees of impaction, comminution, and dorsal subluxation. The malunited joint surface was visualized by dislocating the joint by hyperextension (shotgun approach). The restoration of the cup-shape contour of the middle phalangeal base was accomplished by osteotomy and mobilization of small osteochondral fragments. Rigid fixation was performed by cerclage wire, screws, or a combination of these. A distal radius bone graft was placed beneath disimpacted fragments in 9 of the 11 procedures. Ten of 11 patients were followed-up for more than than 1 year. One patient with a volar lateral impaction fracture was lost to follow-up study 4 weeks after the surgery and was excluded from the results. All patients except 1 achieved a functional range of motion of the proximal interphalangeal joint. Moderate limitations of the distal interphalangeal joint motion were common. Grip and thumb-affected finger tip pinch strengths were 95% and 90%, respectively, of the healthy side. The average pain level (as rated on a visual analog scale of 0-10) improved from a preoperative score of 9.1 to a postoperative score of 0.8. One patient was somewhat dissatisfied; all other patients were satisfied or very satisfied. All returned to their previous work at an average of 13 weeks after surgery. Favorable results have been achieved in this challenging scenario in the short- and middle-term in 9 of 10 patients. Previous surgery and moderate to severe wearing of the cartilage of the proximal phalanx head negatively affected the results.


Protein disorder, prion propensities, and self-organizing macromolecular collectives.
Eukaryotic cells are partitioned into functionally distinct self-organizing compartments. But while the biogenesis of membrane-surrounded compartments is beginning to be understood, the organizing principles behind large membrane-less structures, such as RNA-containing granules, remain a mystery. Here, we argue that protein disorder is an essential ingredient for the formation of such macromolecular collectives. Intrinsically disordered regions (IDRs) do not fold into a well-defined structure but rather sample a range of conformational states, depending on the local conditions. In addition to being structurally versatile, IDRs promote multivalent and transient interactions. This unique combination of features turns intrinsically disordered proteins into ideal agents to orchestrate the formation of large macromolecular assemblies. The presence of conformationally flexible regions, however, comes at a cost, for many intrinsically disordered proteins are aggregation-prone and cause protein misfolding diseases. This association with disease is particularly strong for IDRs with prion-like amino acid composition. Here, we examine how disease-causing and normal conformations are linked, and discuss the possibility that the dynamic order of the cytoplasm emerges, at least in part, from the collective properties of intrinsically disordered prion-like domains. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly.


Discovery of novel aminoquinazolin-7-yl 6,7-dihydro-indol-4-ones as potent, selective inhibitors of heat shock protein 90.
A novel class of Hsp90 inhibitors, structurally distinct from previously reported scaffolds, was developed from rational design and optimization of a compound library screen hit. These aminoquinazoline derivatives, represented by compound 15 (SNX-6833) or 1-(2-amino-4-methylquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one, selectively bind to Hsp90 and inhibit its cellular activities at concentrations as low as single digit nanomolar.


Stimulation of mammalian adenylate cyclase activity with guanosine 5'-tetraphosphate and other guanine nucleotides.
Guanosine 5'-tetraphosphate (GTP4) stimulated mammalian adenylate cyclase activity at concentrations down to 1 micronM. Greater stimulatory activity was apparent with lung than with heart, brain or liver from the rat. At a concentration of 0.1 mM, GTP4 stimulated lung adenylate cyclase activity from rat, guinea pig and mouse about four-fold. Other guanine nucleotides such as GTP, GDP, GMP, guanosine 3',5'-monophosphate and 5'-guanylylimidodiphosphate (GMP.PNP) also stimulated mammalian adenylate cyclase activity. EMP.PNP irreversibly activated, whereas GTP4 and GTP reversibly activated adenylate cyclase. Adenosine 5'-tetraphosphate (ATP4) stimulated rat lung and liver but inhibited rat heart and brain adenylate cyclase activities. Lung from guinea pig and mouse were not affected by ATP4. The formation of cyclic AMP by GTP4-stimulated rat lung adenylate cyclase was verified by Dowex-50 (H+), Dowex 1-formate and polyethyleneimine cellulose column chromatography. GTP4 was at least three times more potent than 1-isoproterenol in stimulating rat lung adenylate cyclase activity. The beta-adrenergic receptor antagonist propranolol blocked the effect of 1-isoproterenol but not that of GTP4, thus, suggesting that GTP4 and beta-adrenergic agonists interact with different receptor sites on membrane-bound adenylate cyclase. Stimulation of rat lung and liver adenylate cyclase activities with 1-isoproterenol was potentiated by either GTP4 or GMP.PNP, thus indicating that GTP4 resembles other guanine nucleotides in their capacity to increase the sensitivity of adenylate cyclase to beta-adrenergic agonists. Stimulation of adenylate cyclase activity by guanine derivatives requires one or more free phosphate moieties on the 5 position of ribose, as no effect was elicited with guanine, guanosine, guanosine 2'-monophosphate, guanosine 3'-monophosphate or guanosine 2',5'-monophosphate. Ribose, ribose 5-phosphate, phosphate and pyrophosphate were inactive. Pyrimidine nucleoside mono-, di-, tri- and tetraphosphates elicited negligible effects on mammalian adenylate cyclase activity.


Reversible inhibition of cellular metabolism by ribavirin.
The broad spectrum antiviral drug ribavirin (Virazole, 1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits cellular macromolecular synthesis as well as cell division in eucaryotic cells. The concentration and time dependence have been studied. One-hour treatment with 25 muM ribavirin or 18 h with 2 muM inhibited the deoxyribonucleic acid synthesis to 50%. Higher concentrations of ribavirin were required to obtain a similar inhibition of ribonucleic acid and protein synthesis. This effect on cell metabolism and cell division can be reversed by removing the drug from the cells.


Evidence for a discrete charge effect within lipid bilayer membranes.
A high amplitude voltage step technique has been used to meausre the surface density of dipicrylamine anions adsorbed at the surfaces of lipid bilayer membranes. Accompanying low amplitude measurements have determined the relaxation time for transient current flow across the membranes, a parameter governed by the height of the central energy barrier which dipicrylamine anions must cross in moving from one membrane surface to the other. Measured relaxation times and surface charge densities have been related by a quasi-continuum model of the discrete charge effect, which predicts that the membrane central barrier height will increase with increasing density of adsorbed surface charge. The experimentally determined relationship is in satisfactory agreement with the predictions of the model. The model does not provide a complete description of the membrane/solution interface, however, because it cannot be applied to the description of previously measured isotherms for the adsorption of dipicrylamine anions onto bilayer membranes surfaces. Possible reasons for this discrepancy are discussed.


Loss of miR-637 promotes cancer cell stemness via WASH/IL-8 pathway and serves as a novel prognostic marker in esophageal squamous cell carcinoma.
Esophageal carcinoma is the highly lethal cancer in the world, predominantly in some areas of East Asia. We previously reported that overexpression of cytoskeleton regulator Wiskott-Aldrich syndrome protein and SCAR Homolog (WASH) associates with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism and clinical significance involved in WASH overexpression have not been fully elucidated. Bioinformatics analysis and luciferase reporter assay were used to predict and validate miR-637 as a regulator of WASH in ESCC cell lines. qRT-PCR, Western blotting and ELISA assays were performed to examine RNA expression and protein levels, respectively. Next, the biological functions of miR-637 were explored by tumor sphere formation assay in vitro and nude mouse tumor xenograft in vivo. Finally, we evaluated the association of miR-637 levels with clinical features in ESCC patients. We identified miR-637 as a WASH-targeting miRNA. miR-637 mimic strongly attenuated the downstream IL-8 production and tumor sphere formation in esophageal cancer cells, whereas miR-637 inhibitor displayed an opposite effect. IL-8 could facilitate stem-like properties and partially rescue the phenotypes induced by miR-637 mimic. Furthermore, miR-637 inhibitor dramatically promoted IL-8 expression and cancer stemness properties in a WASH-dependent manner. Ectopic expression of miR-637 also inhibited tumor growth in a mouse model. Clinically, low expression of miR-637 was observed in tumor tissues and the low expression levels of miR-637 were correlated with poor survival of ESCC patients. In particular, plasma miR-637 could be used as a noninvasive biomarker for ESCC patients. These results implicate the potential application of miR-637 for diagnosis and prognosis of esophageal cancer.


Characterization and genome sequencing of phage Abp1, a new phiKMV-like virus infecting multidrug-resistant Acinetobacter baumannii.
While screening for alternative antibiotics against multidrug-resistant Acinetobacter baumannii, we isolated a virulent A. baumannii bacteriophage Abp1. Transmission electron microscopy revealed that the phage had an icosahedral head with a short tail and should be classified as a member of the Podoviridae family. SDS-PAGE showed that Abp1 contained at least one major and nine minor proteins. In a single-step growth test, we demonstrated that Abp1 had a latent period of 10 min and a burst size of 350. Abp1 also had a relatively narrow host range. The entire genome was sequenced, and the final assembly yielded a 42,185 bp, linear, double-stranded DNA molecule with a G+C content of 39.15 % and containing 54 putative genes. Among these genes, 26 were functionally known, leaving 28 unknown putative genes. Abp1 is a new member of the phiKMV-like virus subgroup of the T7 group; its genome sequence is very similar to that of the A. baumannii phage phiAB1.


Bullying at 8 years and violent offenses by 31 years: the Finnish nationwide 1981 birth cohort study.
This study explored the associations between bullying perpetration and victimization at 8 years of age and violent offenses by the age of 31. Data were obtained for subjects enrolled in a population-based longitudinal birth cohort study. In 1989, 5813 8-year-old children (attrition 3.4%), and their parents and teachers, were surveyed about bullying. When 5405 subjects (attrition 10.2%) were 15-31 years of age, violent offenses were extracted from the Finnish National Police Register. We analyzed the data by sex and categorized bullying perpetration and victimization by frequency. Violent offenses were categorized by severity. Cox regression analyses estimated the hazard ratios (HRs) and 95% confidence intervals (95% CIs). When they were compared to males who had not been bullies at 8 years of age, frequent male bullies had an increased hazard for violent offenses (adjusted HR 3.01, 95% CI 2.11-4.33) and severe violent offenses (adjusted HR 2.86, 95% CI 1.07-7.59) as adults, even when the data were controlled for them being victims, parental education level, family structure and child psychopathology. Frequent female bullies also had an increased hazard for violent offenses, compared to those who had not bullied others (adjusted HR 5.27, 95% CI 1.51-18.40). Frequent male bullying was associated with higher odds for violent offenses compared to only bullying sometimes. Being a victim was not associated with violent offenses. Preventing childhood bullying could reduce violent offenses by both sexes.


Critical evaluation of kinetic schemes for coagulation.
Two well-established numerical representations of the coagulation cascade either initiated by the intrinsic system (Chatterjee et al., PLOS Computational Biology 2010) or the extrinsic system (Butenas et al., Journal of Biological Chemistry, 2004) were compared with thrombin generation assays under realistic pathological conditions. Biochemical modifications such as the omission of reactions not relevant to the case studied, the modification of reactions related to factor XI activation and auto-activation, the adaptation of initial conditions to the thrombin assay system, and the adjustment of some of the model parameters were necessary to align in vitro and in silico data. The modified models are able to reproduce thrombin generation for a range of factor XII, XI, and VIII deficiencies, with the coagulation cascade initiated either extrinsically or intrinsically. The results emphasize that when existing models are extrapolated to experimental parameters for which they have not been calibrated, careful adjustments are required.


Secondary elephant trunk fixation with endovascular stent grafting for extensive/multiple thoracic aortic aneurysm.
Four patients who underwent secondary elephant trunk fixation by endovascular stent grafting are presented and the advantage of this method to treat multiple/extensive thoracic aortic aneurysm is discussed. In two of them, the elephant trunk installation has been performed at another hospital for extensive aortic aneurysm. In two other patients, the aortic arch replacement and the elephant trunk installation were performed through median sternotomy, initially for multiple aortic lesions, including both arch and descending aorta. No neurological deficit, stroke nor spinal cord injury was encountered during the follow-up period (24-40 months). The diameter of the aneurysms decreased markedly in three patients. In one patient, the aneurysm expanded gradually and type II endoleak was treated by coil embolization. In one patient, who showed marked shrinkage of the aneurysm, the stent graft kinked mildly. Based on the low mortality rate of well-established aortic arch surgery, concomitant elephant trunk installation which was followed by the secondary fixation with endovascular stent grafting might be useful to treat multiple/extensive thoracic aneurysm from distal arch to descending aorta.


Corrosion mitigation in desalination plants by ammonium-based ionic liquid.
CuNi (90:10) alloy is widely used in desalination plants. CuNi alloy corrosion in sulfide-containing seawater is the fundamental problem in the desalination industry. Here we have confronted this difficulty by using ammonium-based ionic liquid (Diethyl (2-methoxyethyl)-methyl ammonium Bis(fluorosulfonyl)imide) [DEMEMA][FSI]. The results revealed that the [DEMEMA][FSI] can suppress Cu-Ni alloy corrosion in a solution of (3.5% NaCl + 10 ppm sulphide) with an efficiency of 98.4% at 120 ppm. This has been estimated by electrochemistry and gravimetry. Furthermore, [DEMEMA][FSI] inhibits the growth of sulfate-reducing bacteria SRB in saline water. Surface morphology testing confirmed [DEMEMA][FSI] adsorption on Cu-Ni surface alloys. In addition, quantum calculations have been used to theoretically predict inhibition efficiency [DEMEMA][FSI].


The Japanese Respiratory Society guidelines may reduce unnecessary chest computed tomography in patients with pneumonia requiring hospitalization: A retrospective study.
With the abundance of CT scanners in Japan, doctors can easily order CT scans to diagnose pneumonia. The Japanese Respiratory Society (JRS) guidelines uniquely recommend conditions for which additional CT scans should be considered at the time of diagnosis of pneumonia, a feature not found in other guidelines. In this study, we aimed to evaluate the usefulness of the recommendations in a bid to reduce the number of unnecessary CT examinations. We retrospectively reviewed the electronic medical records of consecutive patients with pneumonia hospitalized between April 2016 and March 2017 to extract patients' backgrounds and clinical courses. Conformity with the JRS guideline recommendations was also examined. In the patients who did not meet the recommendations, we investigated the proportion of them for whom an additional CT scan influenced the clinical decisions. Finally, we evaluated whether there was a difference in hospital stay depending on the additional chest CT at the time of admission. We included 363 hospitalized patients with pneumonia. Chest CT scan was performed in 306 patients (84.3%), of whom 186 (60.8%) did not meet the JRS guideline recommendations. Chest CT revealed findings requiring a change in treatment strategy in only 14 (7.5%) of the 186 patients. Among the 240 patients (66.1%) who did not meet the recommendations, no statistically significant difference was observed in the hospital stay or mortality between patients with and without CT scans. Adherence to the JRS guideline recommendations may reduce the excessive use of CT scans in the diagnosis of pneumonia.


Systemic Therapies for the Management of Non-Clear Cell Renal Cell Carcinoma: What Works, What Doesn't, and What the Future Holds.
Non-clear cell renal cell carcinoma (nccRCC) is a broad term that refers to a diverse group of tumors, each with its own distinct biologic and therapeutic profile. The management of nccRCCs is often based on extrapolating data from clinical trials in the more common clear cell renal cell carcinoma, but our emerging prospective and retrospective clinical experience in nccRCC allows us to make more precise recommendations tailored to each histology. The systemic therapy options for metastatic nccRCC include targeted therapies such as tyrosine kinase inhibitors, immune checkpoint inhibitors, and, for specific rare subtypes, cytotoxic chemotherapy. Each nccRCC histology may respond differently to these regimens, which makes accurate pathologic diagnosis imperative. In the present review, we discuss the available clinical and biological data that can help guide systemic therapy recommendations for specific nccRCC subtypes.


Brain responses to micro-machined silicon devices.
Micro-machined neural prosthetic devices can be designed and fabricated to permit recording and stimulation of specific sites in the nervous system. Unfortunately, the long-term use of these devices is compromised by cellular encapsulation. The goals of this study were to determine if device size, surface characteristics, or insertion method affected this response. Devices with two general designs were used. One group had chisel-shaped tips, sharp angular corners, and surface irregularities on the micrometer size scale. The second group had rounded corners, and smooth surfaces. Devices of the first group were inserted using a microprocessor-controlled inserter. Devices of the second group were inserted by hand. Comparisons were made of responses to the larger devices in the first group with devices from the second group. Responses were assessed 1 day and 1, 2, 4, 6, and 12 weeks after insertions. Tissues were immunochemically labeled for glial fibrillary acidic protein (GFAP) or vimentin to identify astrocytes, or for ED1 to identify microglia. For the second comparison devices from the first group with different cross-sectional areas were analyzed. Similar reactive responses were observed following insertion of all devices; however, the volume of tissue involved at early times, <1 week, was proportional to the cross-sectional area of the devices. Responses observed after 4 weeks were similar for all devices. Thus, the continued presence of devices promotes formation of a sheath composed partly of reactive astrocytes and microglia. Both GFAP-positive and -negative cells were adherent to all devices. These data indicate that device insertion promotes two responses-an early response that is proportional to device size and a sustained response that is independent of device size, geometry, and surface roughness. The early response may be associated with the amount of damage generated during insertion. The sustained response is more likely due to tissue-device interactions.


Study on shear behavior of kaolinite contaminated by heavy metal Cu (II).
Numerous studies have shown that the invasion of the chemicals plays an important role on the geomechanical properties of the soil. This article aims to investigate the shear behavior of contaminated soil by laboratory tests and develop an extended shear strength model on the basis of the experimental results. In order to explicitly evaluate the effect of solution concentration on the shear strength behavior of soil, the remolded samples of kaolinite mixed with different concentrations of CuCl2 solutions were prepared to carry out a series of consolidated-undrained triaxial shear strength tests. The results indicate that different CuCl2 solution concentrations have significant influence on the shear strength property of kaolinite. With the increase of CuCl2 solution concentration, the shear strength of soil displays a declining tendency, and the strength properties including cohesion and internal friction angle are also reduced, which indicates the Cu (II) that existed in the soil samples has deteriorated the soil strength strongly. Based on the experimental results, an extended Mohr-Coulomb strength model for contaminated soils has been proposed by introducing osmotic suction as a macro variable parameter. The conclusions in this study can provide reference for pollution prevention of existing and future foundations.


Neural responses to threat and reward and changes in inflammation following a mindfulness intervention.
Mindfulness meditation has been shown to reduce distress and increase well-being among individuals with chronic disease, including breast cancer survivors. However, the neural correlates of these changes and their links with inflammatory biology are not yet known. The present study examined whether a mindfulness meditation intervention was associated with changes in neural responses to threat and reward from pre- to post-intervention, and whether those neural changes were associated with changes in markers of inflammation in breast cancer survivors. This was a single-arm trial of a standardized, validated 6-week mindfulness meditation intervention. Participants were 20 women who had been diagnosed and treated for early-stage breast cancer. Participants provided peripheral blood samples and underwent a 90-minute neuroimaging scan before and after the intervention, with a focus on tasks known to elicit activity in threat- and reward-related neural regions. There were significant changes in neural responses to the two tasks of interest from pre to post-intervention (ps < 0.042). Participants showed significant reductions in amygdala activity in response to threatening images and significant increases in ventral striatum activity to rewarding images from pre- to post-intervention. Although changes in amygdala activity were not correlated with inflammatory markers, increases in ventral striatum activity were correlated with decreases in circulating concentrations of the proinflammatory cytokine IL-6 and the inflammatory marker CRP. These results, while preliminary, suggest that while a mindfulness meditation intervention can alter neural responses to both threat and nonsocial reward-related stimuli, changes in neural reward activity may be more closely linked to changes in circulating levels of inflammation.


Interactions of the major effective components in Shengmai formula with breast cancer resistance protein at the cellular and vesicular levels.
Shengmai Formula (SMF) is one of the traditional Chinese medicine representative formulas and is widely used for the treatment of cardio- and cerebrovascular disease. Previous studies demonstrated that the major effective ingredients in SMF can interact with each other based on some uptake transporters. However, the role of the efflux transporter breast cancer resistance protein (BCRP) in these interactions involving SMF remains unclear. The purpose of this study was to investigate the interactions of the major active components of SMF with BCRP and the compatibility mechanism of these complex components in SMF based on BCRP. We selected 4 main fractions, including ginseng total saponins (GTS), ophiopogon total saponins (OTS), ophiopogon total flavonoids (OTF), and fructus schisandrae total lignans (STL), and 12 bioactive components, including ginsenosides Re, Rd, Rb1, and Rg1, ophiopogonins D and D', methylophiopogonanones A and B, schizandrins A and B, and schizandrols A and B to explore the interactions of SMF with BCRP in LLC-PK1 and LLC-PK1/BCRP cells and BCRP membrane vesicles. The results showed that ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A can be transported by BCRP into LLC-PK1/BCRP cells. Schisandrol B exhibited a markedly inhibitory effect on the transport function of BCRP and can significantly inhibit the uptake of methylophiopogonanone B and schizandrin A into LLC-PK1/BCRP cells. In "Inside-Out" BCRP membrane vesicles, BCRP mediated the transport of ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A, with Km values of 111.9 ± 31.26 μM, 82.01 ± 16.72 μM, 57.06 ± 8.789 μM, and 37.19 ± 6.512 μM, respectively. GTS, STL, ginsenosides Rd and Rb1, and schisandrol B were potent inhibitors of BCRP and showed different degrees of inhibition on the transport of ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A via BCRP. In conclusion, GTS, STL, ginsenosides Rd and Rb1, and schizandrol B are potential inhibitors of BCRP. Ginsenosides Re and Rg1, methylophiopogonanone B, and schizandrin A are potential substrates of BCRP, and their transport, which is mediated by BCRP, may be inhibited by potential inhibitors in SMF. There are potential interactions of these main effective components of SMF at the cellular and vesicular levels that are mediated by BCRP. The interplay of these bioactive components based on BCRP may be an important compatibility mechanism in SMF.


Adherence of Randomized Controlled Trials to Consolidated Standards of Reporting Trials 2010 Guidelines: A Survey of Randomized Controlled Trials Published in 2011-2016 in 3 Periodontology Journals.
To assess the quality of reporting of randomized controlled trials (RCTs) in the Journal of Clinical Periodontology (JCP), Journal of Periodontology (JOP), and Journal of Periodontal Research (JPR), published in the years 2011 until 2016, using Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines. A thorough search of PubMed for RCTs published between January 2011 and December 2016 in the three journals was carried out. The CONSORT 2010 checklist (36 questions) was used to evaluate the adherence of these RCTs to these guidelines. A modified CONSORT score was calculated and categorized as "perfect" (100%), "excellent" (80%-99%), "good" (60%-79%), "modest" (40%-59%), and "poor" (<40%). A total of 369 RCTs were published in the three periodontology journals from 2011 until 2016. Based on the modified CONSORT score among all the RCTs, title, abstract, and introduction sections of the included RCTs showed good adherence to the CONSORT 2010 guidelines (60%-79%), whereas the adherence was poor for half the items in methodology (<40%), results (<40%), and discussion (40%). The highest modified CONSORT score was obtained for the trials published in the JCP from 2011 to 2016, whereas the lowest score was achieved by the RCTs in the JPR. Overall, none of the RCTs in any of the journals were perfect in reporting the trials as per the guidelines. Almost half of the RCTs in the JCP showed good adherence (51.1%), whereas almost three-fourths of the RCTs in the JOP (72%) and JPR (82.7%) showed modest to poor adherence as per the reporting guidelines (P < .001). Among the three periodontology journals assessed, the JCP showed better adherence than the JOP and JPR from 2011 until 2016.


A practical guide for pharmacists to establish a transitions of care program in an outpatient setting.
To improve understanding of the logistics of transitions of care (TOC) clinics and to provide guidance to pharmacists in developing and implementing a new TOC clinic or improving an existing one. Outpatient TOC clinic within an ambulatory care practice. Two general internal medicine practices collaborated with a university health system to create an interdisciplinary TOC clinic to improve quality and continuity of patient care. The clinic accommodates any patients of the practice who are not able to get an appointment with their primary care physician within 1 to 2 weeks of discharge from any hospital. Physician residents, an attending physician, a clinical pharmacist, a nurse, medical assistants, and a social worker (if necessary) are involved in the patient's care during the transition process. Pharmacists can play a vital role in developing and implementing a TOC clinic or enhancing a current one. There are many logistical components to consider in developing a clinic, and this article provides guidance in the various steps required in creating a clinic, including support and coordination, personnel, workflow, operations, reimbursement, marketing, metrics, and measures. This tool may help pharmacists implement or enhance an outpatient TOC clinic to improve patient care, quality, and continuity.


Jogging or walking--comparison of health effects.
The present study compared the different health effects of 6 months' endurance training at two exercise intensities. Seventy-five nonsmoking, sedentary men were randomly assigned to either a home-based, unsupervised exercise program of 4 x 30 min/wk jogging at an intensity of 75% VO2max (n = 28), or of 6 x 30 min/wk walking at an intensity of 50% VO2max (n = 28), or to an inactive control group (n = 19). Exercise adherence and injuries related to exercise training as well as changes in endurance capacity, body fat, and serum lipids were assessed. After 6 months, joggers and walkers showed a similar increase in VO2max as measured by a maximal bicycle ergometer test (2.9 +/- 4.1 ml/kg min, P < 0.01 and 2.5 +/- 5.7 ml/kg min, P < 0.5, respectively). There were no significant changes in blood lipids in either group, although results revealed a significant association between the amount of training (i.e., kilometers exercised) and the increase in high-density lipoprotein-cholesterol (HDL-C) in joggers (Pearson's r = 0.42, P < 0.05). In walkers, a significant association between the amount of exercise and the decrease in sum of skinfolds and the waist-hip ratio was observed (Pearson's r = -0.48 and -0.45, P < 0.05 for both). The adherence rate was similar for both training groups with respect to the prescribed intervention goal with an average of 90 +/- 41 min/wk (joggers) and 121 +/- 72 min/wk (walkers) spent on endurance training.(ABSTRACT TRUNCATED AT 250 WORDS)


Dysmegakaryopoiesis, a clue for an early diagnosis of familial platelet disorder with propensity to acute myeloid leukemia in case of unexplained inherited thrombocytopenia associated with normal-sized platelets.
We report dysmegakaryopoiesis in a case of familial platelet disorder with predisposition to acute myeloid leukemia (familial platelet disorder/acute myeloid leukemia phenotype Mendelian Inheritance in Man number 601 399). Slight reduction of the number of megakaryocytes with high nucleocytoplasmic ratio, strongly basophilic cytoplasm and poorly lobulated nuclei are suggestive of megakaryocytic dysplasia.


Next-generation sequencing-aided precise diagnosis of Stickler syndrome type I.
To explore an early, rapid and precise diagnosis of Stickler syndrome type I (STL1) and to enrich the spectrum of COL2A1 mutations in the Chinese population, which is poorly studied at present. In the current study, we analysed 115 patients with high myopia by next-generation sequencing and identified five STL1 patients from four unrelated Chinese families. The clinical features of all patients were reviewed in detail. Four variants of COL2A1 were identified, including two novel variants (c.1435delG and c.184delG) and two previously reported variants (c.1221+1G>A and c.1030C>T). Three variants caused premature termination codons which were common in STL1. In addition, we proposed a new diagnostic tactic to improve early diagnostics of STL1 in patients. In this study, our findings expanded the spectrum of COL2A1 mutations with two novel variants and provided a new diagnostic tactic for reference, which was of great significance. Precise diagnosis on the basis of clinical manifestations and genetic testing will become the gold standard to diagnose inherited ocular disorders or syndromes in the future.


Effects of estrogen on serum leptin levels and leptin mRNA expression in adipose tissue in rats.
In this study, we examined changes in serum leptin levels during the estrus cycle and the role of estrogen in these changes. We measured serum leptin levels during normal estrus cycles in intact rats and estradiol-17beta (E2)-induced artificial estrus cycles in ovariectomized rats. Serum leptin levels increased 1.6-fold from 4.2 +/- 0.2 ng/ml during diestrus stage 2 to 6.7 +/- 0.9 ng/ml during proestrus stage during the 4-day estrus cycle. During the E2-induced estrus cycle, serum leptin levels increased 2.3-fold from 2.3 +/- 0.1 ng/ml at estrus to 5.4 +/- 1.2 ng/ml at proestrus. E2 also increased serum leptin concentrations and leptin mRNA expression in adipose tissue of immature rats. These findings suggest that increased serum leptin induced by estrogen during proestrus may trigger the preovulatory release of luteinizing hormone. Furthermore, our findings indicate that estrogen has a positive effect on leptin production in adipose tissue.


Ultrastructural changes in myotendinous nerve endings induced by injection of botulinum toxin into the extraocular muscle.
The myotendinous nerve endings located in the extraocular muscles are considered as proprioceptors. The proprioception of extraocular muscles can be altered if botuminium toxin, which is widely used for the treatment of strabismus, damages the endings. The purpose of this study is to investigate the ultrastructural changes in myotendinous nerve endings after injection of botulinum toxin into the extraocular muscles. Under general anesthesia, 5 IU of botulinum toxin (0.1 ml) were injected into the superior and medial rectus muscles of one eye in each of 12 cats, and 0.1 ml of normal saline was injected into the muscles of the other eye. The myotendinous junction was harvested in four cats each at 1, 4, and 12 weeks after injection and examined using electron microscopy. The myotendinous junctions of four normal uninjected cats were also examined as a control group. There were no morphological differences between the control group and saline injection group. In the botox injection group, separation of the myelin sheath and an increase in neurofilaments in axons of myelinated and unmyelinated nerve fibers were observed 1 week after injection and persisted until 12 weeks. Around the terminal nerve endings, incomplete Schwann cells with axonal exposure were observed, and fibroblast-like changes in Schwann cells were detected. These findings were not observed in the control group. Injection of botulinum toxin into the extraocular muscle induced ultrastructural changes in the myotendinous nerve endings. The possibility that those changes might diminish the proprioceptive abilities of the extraocular muscle should be considered when botulinum toxin is used for the treatment of strabismus.


The Bacillus subtilis menCD promoter is responsive to extracellular pH.
Activation kinetics of a Bacillus subtilis menaquinone biosynthetic gene promoter (the menCD promoter) were measured during growth and sporulation, with the aid of a menCD'-lacZ translational gene fusion. Transient maximal activation was seen shortly after the end of exponential growth in unbuffered complex medium containing a low glucose concentration. These activation kinetics were correlated with transient acidification of the medium under conditions permitting TCA cycle function during the post-exponential period, while mutations that blocked TCA cycle function (cit mutants) were associated with sustained acidification and promoter activation during this period. In cit+ strains, buffering of the medium to pH 5.7 caused sustained maximal activation, while buffering to pH 7.2 prevented enhancement of activation. The menCD promoter appears to be responsive to extracellular acidic pH.


Reduced GeO2 Nanoparticles: Electronic Structure of a Nominal GeOx Complex and Its Stability under H2 Annealing.
A nominal GeOx (x ≤ 2) compound contains mixtures of Ge, Ge suboxides, and GeO2, but the detailed composition and crystallinity could vary from material to material. In this study, we synthesize GeOx nanoparticles by chemical reduction of GeO2, and comparatively investigate the freshly prepared sample and the sample exposed to ambient conditions. Although both compounds are nominally GeOx, they exhibit different X-ray diffraction patterns. X-ray absorption fine structure (XAFS) is utilized to analyse the detailed structure of GeOx. We find that the two initial GeOx compounds have entirely different compositions: the fresh GeOx contains large amorphous Ge clusters connected by GeOx, while after air exposure; the Ge clusters are replaced by a GeO2-GeOx composite. In addition, the two GeOx products undergo different structural rearrangement under H2 annealing, producing different intermediate phases before ultimately turning into metallic Ge. In the fresh GeOx, the amorphous Ge remains stable, with the GeOx being gradually reduced to Ge, leading to a final structure of crystalline Ge grains connected by GeOx. The air-exposed GeOx on the other hand, undergoes a GeO2→GeOx→Ge transition, in which H2 induces the creation of oxygen vacancies at intermediate stage. A complete removal of oxides occurs at high temperature.


Phylogenetic relationships of some Microsporum and Arthroderma species inferred from mitochondrial DNA analysis.
Thirty-eight strains of 12 Microsporum and 10 Arthroderma (Nannizzia) species were investigated by analysis of mitochondrial DNA with 6 restriction enzymes, and classified into 13 genetic groups. The phylogenetic tree of the 13 groups thus established was constructed. On the tree, M. audouinii, M. langeronii, M. rivalieri, M. distortum, M. equinum, M. ferrugineum and A. otae comprise one genetic group and are suggested to be the same species. A. gypseum, A. fulvum, M. duboisii, M. ripariae, A. incurvatum, A. persicolor and A. obtusum are clustered on one of five boughs of the tree indicating their close relation. A. racemosum and A. cajetani are also closely related.


Enhancement of site specific delivery of diloxanide furoate as an antiamoebic drug.
The basic aim of the present research work is to deliver the diloxanide furoate (DF) at specific area using pectin microspheres. The microspheres were prepared by spray drying method and cross-linked by zinc acetate. Different concentrations of polymer (pectin 0.5-3%) and cross-linking agent (0-3% w/v in a mixture of ethanol:water) are taken to optimize the entrapment efficiency, swelling behavior, size and first 6h in-vitro release in simulated gastric fluids. Optimized formulation was characterized in the terms of in-vitro release, in-vivo drug disposition in various organs and in the blood of Sprague-Dawley albino rats and in-vivo gastrointestinal tract transit behavior using X-ray imaging method on albino rabbits. Findings suggested that microspheres containing a concentration of polymer (2% w/v) have average size of 100-500 μm, entrapment efficiency 85.82 ± 0.5 with swelling index 18.77 ± 5.21. In-vitro results and in-vivo gastric transit behavior (using X-ray imaging) have shown no release in first 3-6h that proved the colon specific delivery of DF. The results also suggested that the above approach have not only site specific delivery, but it improves the conversion of active drug by increasing the enzyme mediated hydrolytic degradation of DF due to the presence of polysaccharide polymer:water gel complex.


Emergency coronary artery bypass grafting for cardiogenic shock due to left main coronary artery obstruction caused by Kawasaki disease in a 4-year-old boy.
We describe the case of a 4-year-old boy whose clinical course after Kawasaki disease resulted in coronary artery bypass grafting (CABG) due to acute myocardial infarction (AMI) causing cardiogenic shock. He had developed an ischemic cardiomyopathy due to severe localized stenosis of the left main coronary artery (LCA) and went into cardiogenic shock due to AMI on the day before a scheduled operation. He underwent successful emergency CABG within 4 h of MI. Postoperatively his neurological status was intact. This is the first report of a successful emergency CABG in a small child with cardiogenic shock due to LCA occlusion. CABG should be undertaken in small patients when appropriate indications exist, if bodyweight is >10 kg.


Development of peptide and small-molecule HIV-1 fusion inhibitors that target gp41.
It has been 25 years since the development of the first efficient HIV-1/AIDS treatment. Scientists now know more about the HIV-1 infection life cycle, and more than 30 antiretroviral drugs have been developed, including HIV-1 fusion inhibitors. Fundamental work was begun in the early 1990s and led to the development of a novel class of anti-HIV-1 drugs, culminating in a peptide known as T20, which is currently the only HIV-1 fusion inhibitor approved by the US Food and Drug Administration. However, more work needs to be done to perfect the development of peptide and small-molecule HIV fusion inhibitors, particularly those that target gp41. Herein we present a brief overview of the development of this class of anti-HIV-1 drug by focusing on the achievements, challenges, and lessons learned. We cite hallmark studies of the past and comment on future drug development.


An analysis of molecular interactions involved in the assembly of tropomyosin tactoids.
Arrangements of parallel and antiparallel tropomyosin molecules are examined for residue interactions which might explain the paracrystal forms observed by electron microscopy. Molecular arrays which produce interaction maxima and corresponding computer graphics-simulated staining patterns are compared with observd electron micrographs. The best correlation of interactions with staining pattern occurs when cationic bridging of acid residues is maximized and supported by favourable ion pair interactions. In the antiparallel case, two main maxima occur and appear to correspond to divalent ion tactoids which have been previously reported. For the Cohen-Longley Mg2+ tactoid the best fit is obtained with a molecular overlap of 201 residues and an end overlap of 17-18 residues (based on a rational 287 peptide sequence). Secondary maxima correspond to other known tactoid forms. Binding of tropomyosin molecules to actin may involve hydrogen bonding to six serine residues which occur at approx. 40-residue intervals.


Effect of sea tangle extract on the quality characteristics of reduced-salt, low-fat sausages using pre-rigor muscle during refrigerated storage.
The aim of this study was to investigate quality characteristics of reduced-salt, low-fat pork sausage (PS) using pre-rigor muscle and sea tangle extract (STE) to reduce salt level of sausages during refrigerated storage. Pork ham was prepared with pre-rigor and post-rigor muscle from the local market. Sausages using post-rigor muscle were manufactured with the 1.5% of salt content, and samples with pre-rigor muscle were processed by different salt concentrations (0.8%). Accordingly, PSs were prepared in 4 treatments (REF, PS with 1.5% of salt using post-rigor muscle; CTL, PS with 0.8% of salt using pre-rigor muscle; TRT1, PS with 0.8% of salt and 5% of STE using pre-rigor muscle; TRT2, PS with 0.8% of salt and 10% of STE using pre-rigor muscle). For the evaluation of quality characteristics and shelf-life of reduced-salt PS, pH and color values, cooking loss (%), expressible moisture (%), textural properties, lipid oxidation (thiobarbituric reactive substances), protein denaturation (volatile basic nitrogen), and microbiological analysis (total plate counts and Enterobacteriaceae counts) were determined. The pH and temperature of pre-rigor raw pork ham were higher than those of post-rigor pork ham. Hardness of TRT2 was higher than that of REF or CTL. TRT2 had higher gumminess and chewiness than CTL. TRT1 and TRT2 had lower volatile basic nitrogen than CTL. Total plate counts of TRT2 were lower than those of CTL. Expressible moisture values of TRT1 and TRT2 were similar to those of REF. The addition of STE into PS improved functional properties and shelf-life of PS. Reduced-salt PS containing pre-rigor muscle and STE had similar functional properties to those of regular-salt ones, while containing approximately 47% less salt compared to regular-salt level.


Antimicrobial activity and synergism of some substituted flavonoids.
Natural and synthetic substituted chalcones, flavones and flavanones were tested for antibacterial activity. In order to determine synergism, new combinations of substituted flavonoids against Staphylococcus aureus, Escherichia coli and Enterobacter aerogenes were assayed. The results allow us to establish relationships between antimicrobial effect of the compounds and membrane structures of these microorganisms. When flavonoid combinations were employed a stronger effect was found against E. coli than against S. aureus. This fact is due to the existence of porins in the outer membrane of G(-)-bacteria. The compound that acts as enhancer acts by blocking the charges of amino acids in the porins and thus facilitates the passage of the other compound by diffusion into the bacterial cell.


Exposure to a farm environment is associated with T helper 1 and regulatory cytokines at age 4.5 years.
Farm exposure has been shown to protect from childhood asthma and allergic diseases, but underlying immunological mechanisms are not clear yet. To explore whether farming lifestyle determines cytokine profile of peripheral blood mononuclear cells (PBMCs) of 4.5-year-old children (n = 88) from the Finnish PASTURE birth cohort study. We analysed regulatory (IL-10, IL-2), T helper 1 (Th1)-associated (IL-12, IFN-γ), inflammatory (IL-1β, TNF, CXCL8) and Th2-associated (IL-13) cytokines in unstimulated PBMCs and after a short-term (5 h) stimulation with lipopolysaccharide (LPS). Specific farm exposures (stables, hay barn, farm milk) at age 4 years were assessed from questionnaires. The unstimulated PBMCs of farm children produced more IL-10 (GMR 1.22, P = 0.032), IL-12 (GMR 1.24, P = 0.012) and IFN-γ (GMR 1.24, P = 0.024) than those of non-farm children. Also, specific farm exposures were associated with higher spontaneous production of cytokines. The number of specific farm exposures tended to be dose dependently associated with higher spontaneous production of IFN-γ (test for trends, P = 0.013) and lower LPS-induced production of TNF (test for trends, P = 0.025). Farming lifestyle seemed to be associated with increased spontaneous production of Th1 and regulatory cytokines. Decreased TNF responses to short-term LPS stimulation in farm-exposed children may imply tolerogenic immune mechanisms. These novel findings might contribute to the asthma and allergy protection in farm environment.


Expression of genes related to the human erbB, erbA, pdgf and pdgf-r in tumors of different etiology in Xiphophorus.
The melanoma determining Tu locus of the teleost Xiphophorus contains an accessory gene, x-erbB*a, which is closely related to the EGF receptor gene family, and is probably oncogenic. x-erbB*a exists in allelic forms that are specific for distinct Tu-loci, and shows high homology to a non-allelic non-oncogenic counterpart x-erbB*i which is transcribed into mRNA of 4.6 kb in non-tumorous and tumorous tissues of fish harboring and lacking Tu. Expression of a 4.0-kb mRNA in tumors (melanoma and fibrosarcoma) of different etiology is strictly correlated with the inheritance of X. maculatus x-erbB*a alleles; transcripts of 8.0 kb were detected in melanoma and carcinoma of fish harboring a certain x-erbB*a of X. variatus. The expression of the putative x-erbB*a transcripts parallels the stage of malignancy of the tumor. The expression of the xiphophorine EGF receptor gene (x-erbB) was detected in almost all tumors, is strongly enhanced in carcinoma, and is positively correlated with the degree of malignancy of melanoma and fibrosarcoma. Some tumors show expression of erbA-related genes. The PDGF receptor mRNA is expressed in all tumors analyzed and shows enhanced expression in malignant tumors of neurogenic, epithelial and mesenchymal origin. Expression of x-pdgf was observed in several cases of melanoma, but more frequently in carcinoma and fibrosarcoma. We conclude that x-erbB*a might be involved in initiation of tumors of different cellular origin and etiology in fish harboring Tu, as well as in the determination of the malignancy of the tumor. Furthermore, we assume that x-erbB*i, x-erbB, x-pdgf and x-pdgf-r play a role in secondary events in tumorigenesis by, e.g., conferring a selective growth advantage to the tumor cells.


Proton beam radiation induces DNA damage and cell apoptosis in glioma stem cells through reactive oxygen species.
Glioblastoma multiforme (GBM) is among the most lethal of human malignancies. Most GBM tumors are refractory to cytotoxic therapies. Glioma stem cells (GSCs) significantly contribute to GBM progression and post-treatment tumor relapse, therefore serving as a key therapeutic target; however, GSCs are resistant to conventional radiation therapy. Proton therapy is one of the newer cancer treatment modalities and its effects on GSCs function remain unclear. Here, by utilizing patient-derived GSCs, we show that proton radiation generates greater cytotoxicity in GSCs than x-ray photon radiation. Compared with photon radiation, proton beam irradiation induces more single and double strand DNA breaks, less H2AX phosphorylation, increased Chk2 phosphorylation, and reduced cell cycle recovery from G2 arrest, leading to caspase-3 activation, PARP cleavage, and cell apoptosis. Furthermore, proton radiation generates a large quantity of reactive oxygen species (ROS), which is required for DNA damage, cell cycle redistribution, apoptosis, and cytotoxicity. Together, these findings indicate that proton radiation has a higher efficacy in treating GSCs than photon radiation. Our data reveal a ROS-dependent mechanism by which proton radiation induces DNA damage and cell apoptosis in GSCs. Thus, proton therapy may be more efficient than conventional x-ray photon therapy for eliminating GSCs in GBM patients.


Chemically Bonded α-Fe2 O3 /Bi4 MO8 Cl Dot-on-Plate Z-Scheme Junction with Strong Internal Electric Field for Selective Photo-oxidation of Aromatic Alcohols.
Inferior contact interface and low charge transfer efficiency seriously restrict the performance of heterojunctions. Herein, chemically bonded α-Fe2 O3 /Bi4 MO8 Cl (M=Nb, Ta) dot-on-plate Z-scheme junctions with strong internal electric field are crafted by an in situ growth route. Experimental and theoretical results demonstrate that the internal electric field provides a powerful driving force for vectorial migration of photocharges between Bi4 MO8 Cl and α-Fe2 O3 , and the interfacial Fe-O bond not only serves as an atomic-level charge flow highway but also lowers the charge transfer energy barrier, thereby accelerating Z-scheme charge transfer and realizing effective spatial charge separation. Impressively, α-Fe2 O3 /Bi4 MO8 Cl manifests a significantly improved photocatalytic activity for selective oxidation of aromatic alcohols into aldehydes (Con. ≥92 %, Sel. ≥96 %), with a performance improvement of one to two orders of magnitude. This work presents atomic-level insight into interfacial charge flow steering.


Results of newborn screening for galactose metabolic disorders.
A screening strategy has been used which uses the Paigen and Beutler methods for the determination of galactose and galactose-1-phosphate. A blood spot test for epimerase has also been developed. In the last 10 years, 265,019 samples from newborns have been tested by these methods. Among the 154 screening positives, we have detected seven cases of epimerase-deficient galactosaemia (Type III), seven cases of Duarte/galactosaemia heterozygotes, 48 cases of other various types of heterozygotes, four cases of persistent hypergalactosaemia, three cases of hepatitis and one case of congenital atresia of the bile duct. These results indicate that our screening system has effectively detected the infants with galactose metabolic disorders.


[The basic minimum set of data in primary care. A Delphi study].
The term basic minimal unit of data in primary care is used for those essential data required so that all primary care professionals may carry out their work. The results of a study performed with the Delphi technique about the basic unit of data by 35 Spanish physician are reported. The results are distributed in three areas: clinical interview (12 basic data were considered), clinical history (27 essential data) and health care performance (19 minimal data).


Trypanosoma acomys (Wenyon, 1909): reproductive forms and course of parasitemia in the natural host Acomys cahirinus (Desmarest, 1819).
Trypanosoma acomys (Stercoraria, Trypanosomatidae) was studied in the laboratory-bred spiny mouse Acomys cahirinus. Only trypomastigotes were found in peripheral blood, whereas the thymus of experimentally infected A. cahirinus showed amastigote syncytial reproductive forms whose nuclei of nuclei ranged from 2 to 128. These reproductive forms were detected 9-10 days after the i.p. injection of spiny mice with trypanosomes obtained from primary lung cultures. Transitional trypomastigote-like forms were observed in the thymus; no reproductive or diving forms were encountered in any other tissue, including blood. The course of the parasitemia in spiny mice inoculated i.p. with 1.2 x 10(6) parasites from 26- to 32-day-old cultures initiated from infected lungs was studied. A similar, characteristic pattern was observed in both male and female hosts. Four phases were recognized: latent, logarithmic, stationary, and decline. These phases ended on days 2, 14, 98, and 154 postinoculation, respectively. The decline phase was gradual and the parasites could not be detected by day 154 postinoculation. In contrast, inoculation from older cultures (35-50 days old) showed longer latent and logarithmic phases, a shorter stationary phase, and a sharp drop in parasite density during the decline phase; the parasites were not detected in the peripheral blood by 120 days postinoculation.


Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports.
The process of generating 'signals' of possible unrecognized hazards from spontaneous adverse drug reaction reporting data has been likened to looking for a needle in a haystack. However, statistical approaches to the data have been under-utilised. Using the UK Yellow Card database, we have developed and evaluated a statistical aid to signal generation called a Proportional Reporting Ratio (PRR). The proportion of all reactions to a drug which are for a particular medical condition of interest is compared to the same proportion for all drugs in the database, in a 2 x 2 table. We investigated a group of newly-marketed drugs using as minimum criteria for a signal, 3 or more cases, PRR at least 2, chi-squared of at least 4. The database was used to examine retrospectively 15 drugs newly-marketed in the UK, with the highest levels of ADR reporting. The method identified 481 signals meeting the minimum criteria during the period 1996-8. Further evaluation of these showed that 70% were known adverse reactions, 13% were events which were likely to be related to the underlying disease and 17% were signals requiring further evaluation. Proportional reporting ratios are a valuable aid to signal generation from spontaneous reporting data which are easy to calculate and interpret, and various refinements are possible.


Germline copy number variation of genes involved in chromatin remodelling in families suggestive of Li-Fraumeni syndrome with brain tumours.
Germline alterations of the tumour suppressor TP53 gene are detected approximately in 25% of the families suggestive of Li-Fraumeni syndrome (LFS), characterised by a genetic predisposition to a wide tumour spectrum, including soft-tissue sarcomas, osteosarcomas, premenopausal breast cancers, brain tumours, adrenocortical tumours, plexus choroid tumours, leukaemia and lung cancer. The aim of this study was to determine the contribution of germline copy number variations (CNVs) to LFS in families without detectable TP53 mutation. Using a custom-designed high-resolution array CGH, we evaluated the presence of rare germline CNVs in 64 patients fulfilling the Chompret criteria for LFS, but without any detectable TP53 alteration. In 15 unrelated patients, we detected 20 new CNVs absent in 600 controls. Remarkably, in four patients who had developed each brain tumour, the detected CNV overlap the KDM1A, MTA3, TRRAP or SIRT3 genes encoding p53 partners involved in histone methylation or acetylation. Focused analysis of SIRT3 showed that the CNV encompassing SIRT3 leads to SIRT3 overexpression, and that in vitro SIRT3 overexpression prevents apoptosis, increases G2/M and results in a hypermethylation of numerous genes. This study supports the causal role of germline alterations of genes involved in chromatin remodelling in genetic predisposition to cancer and, in particular, to brain tumours.


Multiple benign juvenile melanoma.
Multiple benign juvenile melanoma is a rare entity, seen primarily in children. Two 3-year-old patients who developed multiple juvenile melanomas in areas of congenital hyperpigmentation are presented. The distinct clinical presentations of this lesion are discussed, and its ultrastructure is described.


Nao-Fu-Cong ameliorates diabetic cognitive dysfunction by inhibition of JNK/CHOP/Bcl2-mediated apoptosis in vivo and in vitro.
Chinese herbal compound Nao-Fu-Cong (NFC) has been mainly used to treat cognitive disorders in Traditional Chinese Medicine (TCM). The present study aimed to investigate whether its neuroprotective effects might be related to the inhibition of JNK/CHOP/Bcl2-mediated apoptosis pathway or not. We randomly assigned STZ (60 mg·kg-1)-induced diabetic rats into control group, diabetic model group and NFC groups (low-dose, medium-dose and high-dose). The primary culture of hippocampal neurons were transferred into different culture media on the third day. The cells were then divided into control group, high-glucose group, NFC (low-dose, medium-dose and high-dose) groups, CHOP si-RNA intervention group, JNK pathway inhibitor SP600125 group and oxidative stress inhibitor N-acetylcysteine (NAC) group. NFC significantly improved the cognitive function of diabetic rats, and had neuroprotective effect on hippocampal neurons cultured in high glucose. Further research results showed that NFC could reduce the apoptosis of hippocampal neurons in rats with diabetic cognitive dysfunction. NFC had inhibitory effects on CHOP/JNK apoptosis pathway induced by high glucose, and also decreased the levels of ROS and increased the mitochondrial membrane potential. These suggested that the neuroprotective effect of NFC might be related to the inhibition of CHOP and JNK apoptotic signaling pathways, and the cross pathway between oxidative stress and mitochondrial damage pathway.


Alterations of DNA methylation and expression of genes related to thyroid hormone metabolism in colon epithelium of obese patients.
Colorectal cancer is common among obese individuals. The purpose of the current study was to determine changes in DNA methylation status and mRNA expression of thyroid hormone receptor beta (THRB), as a tumor suppressor, and thyroid hormone inactivating enzyme, type 3 deiodinase (DIO3) genes, in human epithelial colon tissues of healthy obese individuals. Colon biopsies were analyzed by methylation sensitive-high resolution melting (MS-HRM) to investigate promoter methylation of DIO3 and THRB, and by quantitative real-time polymerase chain reaction to assay expression of DIO3 and THRB mRNA on eighteen obese and twenty-one normal-weight healthy men. There was no significant difference in mean methylation levels at the THRB promoter region between the two groups. Nevertheless, obesity decreased THRB expression levels, significantly (P < 0.05; fold change: 0.19). Furthermore, obesity attenuated DNA methylation (P < 0.001) and enhanced mRNA expression of DIO3 (P < 0.05; fold change: 3). Our findings suggest that obesity may alter expression of THRB and DIO3 genes through epigenetic mechanism. Alterations of THRB and DIO3 expressions may predispose colon epithelium of obese patients to neoplastic transformation.


Subarachnoid haematoma after spinal anaesthesia mimicking transient radicular irritation: a case report and review.
I report a patient with a spinal subarachnoid haematoma after difficult spinal anaesthesia who presented with symptoms of radicular irritation, and who recovered with conservative management. Subarachnoid haematoma is rare after spinal anaesthesia; a literature review found nine cases. In the majority of these cases, spinal anaesthesia had been difficult and unsuccessful. Other risk factors included antiplatelet and anticoagulant therapy, and direct spinal cord trauma. All the previous cases required decompressive laminectomy.


Facial emotion recognition in adolescent depression: The role of childhood traumas, emotion regulation difficulties, alexithymia and empathy.
Facial emotion recognition (FER) is crucial for effective social competency, and problems in this skill are linked depression during adolescence. In this study, we aimed to find the rates of FER accuracy for negative (fearful, sad, angry, disgusted), positive (happy, surprised), and neutral emotions, and the possible predictors of FER skill for most confusing emotions. A total of 67 drug-naive adolescents with depression (11 boys, 56 girls; 11-17 years) were recruited for the study. The facial emotion recognition test, childhood trauma questionnaire and basic empathy, difficulty of emotion regulation, and Toronto alexithymia scales were used. The analysis demonstrated that adolescents have more difficulties in recognizing negative emotions when compared the positive ones. The most confusing emotion is fear (39.8% of fear was recognized as surprise). Boys have lower fear recognition skill than girls and higher childhood emotional abuse, physical abuse, emotional neglect, and difficulty in describing feelings to predict lower fear recognition skill. For sadness recognition skill, emotional neglect, difficulty in describing feelings, and depression severity were the negative predictors. Emotional empathy has a positive effect on disgust recognition skill. Our findings demonstrated that impairment of FER skill for negative emotions is associated with childhood traumas, emotion regulation difficulties, alexithymia, and empathy symptoms in adolescent depression.


Use of measurement audit in outcomes management.
With the growing emphasis on accountability in mental health services, outcomes management strategies are gaining popularity. However, for these techniques to be credible, it is necessary to ensure the reliability of clinical data. In other words, outcomes measures must accurately reflect the actual status of service recipients. This article presents the use of the measurement audit as one means of monitoring and improving the reliability of outcomes measurements. The methods and findings from an audit of crisis assessment workers for children in state custody are presented. Clinical assessments completed at the time of service were compared with assessments using the same measure completed via retrospective file review. Findings suggest generally good reliability, 0.72 overall, with some variation by provider and type of information.


Acute nonlymphocytic leukemia.
The authors review the advances of the last decade in bone marrow culture cytogenetics and immunology that have aided in understanding the pathophysiology of acute nonlymphocytic leukemia and they also discuss the major strides in treatment that have occurred.


Prolyl hydroxylase and collagen biosynthesis in rat liver following varying degrees of partial hepatectomy.
Prolyl hydroxylase activity and collagen biosynthesis have been measured at intervals following 2 extents of hepatic resection in rats. Prolyl hydroxylase activity is validated as a measure of collagen biosynthesis. The levels rise to a peak at 72 h and thereafter decline. The implications for the process of liver regeneration are discussed.


Oxidation of HDAC4 by Nox4-derived H2O2 maintains tube formation by endothelial cells.
NADPH oxidases produce reactive oxygen species that differ in localization, type and concentration. Within the Nox family only Nox4 produces H2O2 which can directly oxidize cysteine residues. With this post-translational modification, activity, stability, localization and protein-protein interactions of the affected protein is altered. Nox4 controls differentiation, cellular homeostasis and prevents inflammation. Therefore, is likely that epigenetic mechanisms contribute to the effects of Nox4. One group of epigenetic modifiers are class IIa histone deacetylases (HDACs). We hypothesize that Nox4-derived H2O2 oxidizes HDACs and analyzed whether HDACs can be differentially oxidized by Nox4. As an artificial system, we utilized HEK293 cells, overexpressing Nox4 in a tetracycline-inducible manner. HDAC4 was oxidized upon Nox4 overexpression. Additionally, Nox4 overexpression increased HDAC4 phosphorylation on Ser632. H2O2 disrupted HDAC4/Mef2A complex, which de-represses Mef2A. In endothelial cells such as HUVECs and HMECs, overexpression of HDAC4 significantly reduced tube formation. Overexpression of a redox insensitive HDAC4 had no effect on endothelial tube formation. Treatment with H2O2, induction of Nox4 expression by treatment of the cells with TGFβ and co-overexpression of Nox4 not only induced phosphorylation of HDAC4, but also restored the repressive effect of HDAC4 for tube formation, while overexpression of a redox dead mutant of Nox4 did not. Taken together, Nox4 oxidizes HDAC4, increases its phosphorylation, and eventually ensures proper tube formation by endothelial cells.


Strategies in vineyard establishment to face global warming in viticulture: a mini review.
Different technological solutions are developing in the wine industry to mitigate the negative effects of the current global warming to mainly achieve wines with a lower alcohol content. These proposed solutions mostly act at the oenological level and are focused on intervening in the raw material to be transformed; that is, on reducing the concentration of sugar in the must using filtration techniques or also on wine dealcoholizing by physical processes. These techniques are intended to offer solutions and respond to new consumer expectations, but they may be considered too artificial to be widely accepted. In this way, viticultural strategies may offer a natural solution to obtain grapes with low sugar content, maximizing their quality by delaying ripening. This mini review surveys the viticultural strategies that can be applied in the establishment of a vineyard - that is, when it comes to planting of a new vineyard - such as vineyard altitude, latitude, orientation, and slope, as well as rootstock, variety, clone, training system, and row orientation and slope, with the aim to mitigate the negative effects of climate change on grape and wine quality and to delay grape maturation. Finally, we propose a ponderation of the strategies discussed to contextualize its importance to face global warming in viticulture. © 2020 Society of Chemical Industry.


In silico characterization of fructosyl peptide oxidase properties from Eupenicillium terrenum.
Fructosyl peptide oxidase (FPOX) enzyme from Eupenicillium terrenum has a high potential to be applied as a diagnostic enzyme. The aim of the present study is the characterization of FPOX from E. terrenum using different bioinformatics tools. The computational prediction of the RNA and protein secondary structures of FPOX, solubility profile in Escherichia coli, stability, domains, and functional properties were performed. In the FPOX protein, six motifs were detected. The d-amino acid oxidase motif was found as the most important motif that is a FAD-dependent oxidoreductase. The cysteines including 97, 154, 234, 280, and 360 showed a lower score than -10 that have a low possibility for participitation in the formation of the SS bond. The 56.52% of FPOX amino acids are nonpolar. Random coils are dominant in the FPOX sequence, followed by alpha-helix and extended strand. The fpox gene is capable of generating a stable RNA secondary structure (-423.90 kcal/mol) in E. coli. FPOX has a large number of hydrophobic amino acids. FPOX showed a low solubility in E. coli which has several aggregation-prone sites in its 3-D structure. According to the scores, the best mutation candidate for increasing solubility was the conversion of methionine 302 to arginine. The melting temperature of FPOX based on its amino acid sequence was 55°C to 65°C. The amounts of thermodynamic parameters for the FPOX enzyme were -137.4 kcal/mol, -3.59 kcal/(mol K), and -6.8 kcal/mol for standard folding enthalpy, heat capacity, and folding free energy, respectively. In conclusion, the in silico study of proteins can provide a valuable method for better understanding the protein properties and functions for use in our purposes.


Isolation of Actinomyces species and Eikenella corrodens from patients with chronic diffuse sclerosing osteomyelitis.
Cultures from 26 patients with chronic diffuse sclerosing osteomyelitis of the mandible were studied. In most cases there was a mutualistic infection involving any one of the known human Actinomyces species together with Eikenella corrodens. In a few cases, Arachnia species were substituted for Actinomyces and gram-negative anaerobes for E corrodens. The specific culture protocol used to identify these organisms from clinical specimens is described. Taxonomic and experimental evidence that supports an infectious etiology are presented.


Characterization of the stage(s) in the virus replication cycle at which the host-cell specificity of the feline parvovirus subgroup is regulated in canine cells.
Feline panleukopenia virus (FPLV), mink enteritis virus (MEV), and canine parvovirus (CPV) are classified as a host-range variants. They show different host-range specificity in vivo and host-cell specificity in vitro. For instance, FPLV and MEV cannot grow or can grow only inefficiently in canine cell lines such as MDCK and the canine fibroma cell line A72. Here we have studied the mechanism(s) by which the different cell tropism is mediated in vitro. When FPLV or MEV was inoculated to A72 cells, viral DNA replicated slightly, few viral-antigen-positive cells were detected, and the culture fluid contained the threshold level of infectivity. On the other hand, when an infectious molecular clone of MEV (pMEV) was introduced into A72 cells, viral DNA replicated efficiently, and the culture fluid of pMEV-transfected cells contained much higher infectivities than that of MEV-infected cells. In spite of the restrictive growth in A72 cells, MEV could bind to A72 cells as efficiently as CPV. No detectable viral RNA was produced in MEV-infected A72 cells. In contrast, efficient viral transcription occurred in pMEV-transfected A72 cells. These results suggest that the restrictive infections of MEV and FPLV in A72 cells are not mediated by the attachment of the virus to the cells or by the events occurring after the viral transcription. It appears to be caused by the stage(s) in the virus replication cycle, which exists between a postadsorptional step required for virus penetration and the initiation of viral transcription.


The Society of Thoracic Surgeons General Thoracic Surgery Database: 2020 Update on Outcomes and Research.
The Society of Thoracic Surgeons General Thoracic Surgery Database (GTSD) remains the largest and most robust thoracic surgical database in the world. The GTSD provides participant sites with risk-adjusted performance reports for benchmarking and facilitates quality improvement initiatives. In addition the GTSD provides several mechanisms for high-quality research using data from over 283 participant sites and nearly 620,000 procedures since its inception in 2002. Participant sites are audited at random annually to ensure continued completeness and accuracy of the GTSD. In 2020 the GTSD migrated to a cloud-based interactive data platform, and the Task Force continues to refine the data collection form to decrease data entry burden while maintaining data quality, granularity, and relevance. This report provides an update on outcomes, volume trends, and database improvements as well as a summary of research productivity resulting from the GTSD over the preceding year.


Protocol for cell type-specific labeling, enrichment, and proteomic profiling of plasma proteins in mice.
Secreted polypeptides represent a fundamental axis of intercellular communication. Here, we present a protocol for the cell type-specific biotinylation, enrichment, and proteomic profiling of secreted plasma proteins directly in mice. This protocol uses conditional "turn-on" adeno-associated viruses expressing an endoplasmic reticulum-targeted biotin ligase to globally biotinylate proteins of the secretory pathway in a cell type-specific manner. Biotinylated secreted proteins can be directly purified from blood plasma and analyzed by SDS-PAGE gel or shotgun proteomics. For complete information on the generation and use of this protocol, please refer to Wei et al. (2021).


A prospective comparative study of the efficacy of conventional Lichtenstein versus self-adhesive mesh repair for inguinal hernia.
Lichtenstein repair has been the gold standard in inguinal hernia surgery. The aim of this study was to investigate the role of mesh fixation in terms of postsurgical chronic pain and recurrence. Sixty patients with primary inguinal hernias were treated between March 2007 and December 2008. Thirty patients underwent conventional Lichtenstein repair while a self-adhesive mesh was used for the second group. The primary outcome parameters were the rate of recurrence and chronic pain. The operating time, postoperative pain, complications, and time when patients returned to work were recorded. Fifty-one patients completed the survey. Early pain scores were lower in the self-adhesive mesh group. The main advantage of the self-adhesive mesh was the shorter operating time (23.70 ± 5.57 vs 36.90 ± 11.36, P = 0.006). Both techniques were almost identical in terms of long-term chronic pain (P = 0.294), and the rates of recurrence at the end of a median of 31 months' follow-up were identical. Self-adhesive mesh repair of inguinal hernias is superior to the conventional Lichtenstein method in terms of shorter operative time and less pain in the early postoperative period. The rates of chronic pain and recurrence are similar with the suture-fixed repairs.


A new method for detecting histamine release.
Glass microfibres have been found to bind histamine with high affinity and selectivity. A new test for measuring basophil histamine release has been developed using the glass microfibres as a solid phase. Glass microfibres are crushed and fixed to the bottom of microtitre plates with a water-soluble glue. Histamine release is performed in the glass microfibre -prepared microtitre plates by challenging 100 microliter washed blood with 20 microliter antigen per well for 90 min at 37 degrees C. Released histamine is bound with high affinity to the glass microfibres , since 90% of histamine in the solution is adsorbed to the fibres. After incubation the microtitre plate is washed with H2O to remove cells and interfering substances. Fibre-bound histamine is detected by the fluorometric o-phthaldialdehyde method. The sensitivity of the assay is 0.63 ng histamine, 2 HCl and the histamine standard curve is linear up to at least 5 ng histamine, 2 HCl. Optimal conditions for the new assay are described. After challenge with anti-Ige a comparison with the conventional histamine release from Ficoll-Hypaque-isolated leukocytes showed almost identical results.


Smoking-related subjective and physiological changes: pre- to postpuff and pre- to postcigarette.
Twenty-six female regular smokers participated in two sessions, smoking a cigarette and drinking for comparison a cup of coffee in each. Cardiovascular, electromyogram (EMG), motor activity, and electroencephalogram (EEG) parameters were assessed before and after smoking a cigarette or drinking a cup of coffee. The same variables were averaged for 5-s periods preceding, during, and following the first six puffs and sips. As the expected psychophysiological changes might be related to pleasure, the experimental design included both pleasant-tasting coffee and cigarettes and preparations manipulated to be unpleasant. Comparing pre/post consumption and pre/post puffing changes, heart rate increased as expected pre/post a cigarette but not pre/post puffing. On the other hand, there was no change in heart rate pre/post a cup of coffee but a transient increase pre/post sipping. The pre/post puffing and pre/post sipping changes in the EEG power distribution were similar for both drugs, occurred already in anticipation of puffing and sipping, and qualitatively suggested sedation as opposed to the pre/post cigarette arousing effects. These results might explain the observations of subjective tranquilizing effects during the consumption of a stimulant. Although the taste manipulations produced significant subjective effects, they did not influence the anticipatory effects.


[Drug treatment of dermatological disorders. Aspects to consider from an andrological perspective].
Dermatologists administer a broad spectrum of systemic medications. However, our current knowledge of potential risks to male fertility is still limited, particularly with the new emerging therapies in dermato-oncology. Individual differences in susceptibility and a history of andrological disorders influence prognostic values. For fertility protection, a thoughtful selection of medication and/or sperm cryopreservation remain the best options.


Flow diverter embolization device for endovascular treatment of ruptured blister and wide necked very small aneurysms.
Ruptured blood blisters (BBA) and very small, wide necked aneurysms (VSA) remain challenging lesions to treat due to their small size, wide necks, and thin, fragile walls. In the present study, we reviewed our experience with these aneurysms treated by flow diversion. A total of 18 patients with hemorrhage due to a ruptured BBAs and VSAs, treated with flow diversion between July 2014 and March 2016 were included in this study. We analyzed clinical and radiographic outcomes. A total of 12 (66.7%) VSAs and 6 (33.3%) BBAs were treated with flow diversion. Fifteen (83.3%) and three (16.7%) aneurysms were located on the internal carotid artery and the basilar artery, respectively. On admission, a GCS score of 15 and WFNS grade 1 were found in 14 (77.7%) patients, 3 patients had an admission GCS of 13 and WFNS grade 2, one had an admission GCS of 8 and WFNS of 4. Fisher CT grades 2, 3, and 4 were observed in 11 (61.1%), 1 (5.6%), and 6 (33.3%) patients, respectively. Flow diversion was performed on average 5.6 days after onset of hemorrhage. 6 months post-intervention angiography showed complete obliteration of the aneurysms in all patients. Our findings indicate that flow diversion in the acute and subacute phase of hemorrhage is a reliable treatment for reducing complications in patients with BBAs and VSAs. In patients with poor clinical presentation it might be reasonable to delay treatment until the first signs of recovery become apparent.


The absence of a role for the carbohydrate moiety in the binding of apolipoprotein B to the low density lipoprotein receptor.
The binding of low density lipoprotein (LDL) to fibroblasts occurs through apolipoprotein B, a glycoprotein. The role of the carbohydrate in binding was assessed in two ways: (1) LDL, freed of sialic acid and most of the glucosamine and hexoses by digestion with a mixture of glycosidases, bound to fibroblasts as does native LDL. (2) The glycopeptides liberated from apoprotein B by trypsin and pronase failed to inhibit LDL binding to fibroblasts. Apparently the carbohydrate moiety of LDL does not interact with the plasma membrane receptor.


The cost-effectiveness of expanded testing for primary HIV infection.
Primary infection with the human immunodeficiency virus (HIV) is a major factor in the HIV epidemic. Most patients become symptomatic and seek care, but seldom are they tested or is their condition diagnosed. The objectives of this study are to determine whether it is cost-effective to expand testing for primary HIV infection to a larger cohort of patients, and, if so, which diagnostic assay is most cost-effective. We undertook a cost-effectiveness analysis of testing a hypothetical cohort of more than 3 million outpatients with fever and other viral symptoms regardless of HIV risk factors using 3 diagnostic assays: p24 antigen enzyme immunosorbent assay (EIA), HIV-1 RNA assay, and third-generation HIV-1 EIA. Antiretroviral therapy was started when the CD4 cell count decreased to 350/microL. Outcome measures were the incremental cost-effectiveness of the diagnostic assays, number of cases identified, cases avoided in sexual partners, and threshold prevalence. For sensitivity analyses, we used 50,000 dollars as the threshold for cost-effectiveness. At the baseline prevalence of 0.66%, p24 antigen EIA testing was the most cost-effective option at a cost of 30,800 dollars per quality-adjusted life-year gained when compared with no testing. There were 17,054 cases identified, and infection was avoided in 435 partners. Probabilistic sensitivity analysis, in which the estimates for all variables are varied simultaneously, determined that expanded testing with p24 antigen EIA compared with no testing had a 67% probability of being cost-effective at the baseline prevalence and a 71% probability at a prevalence of 1%. Expanded testing for primary HIV infection with p24 antigen EIA may be a sound expenditure of health care resources.


miR-21-5p renal expression is associated with fibrosis and renal survival in patients with IgA nephropathy.
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN. In the context of IgAN, we aimed to analyze the role of miR-21-5p, miR-214-3p and miR-199a-5p, three established "fibromiRs" involved in renal fibrosis. Fifty-six IgAN biopsy specimens were retrospectively scored according to Oxford classification. Renal expression of miR-21-5p, miR-214-3p and miR-199a-5p were significantly associated with T score (miR-21-5p T0 RQ median = 1.23, T1 RQ = 3.01, T2 RQ = 3.90; miR-214-5p T0 RQ = 1.39, T1 RQ = 2.20, T2 RQ = 2.48; miR-199a-5p T0 RQ = 0.76, T1 RQ = 1.41, T2 RQ = 1.87). miR-21-5p expression was associated with S score (S0 RQ median = 1.31, S1 RQ = 2.65), but not miR-214-3p nor miR-199a-5p. In our cohort, poor renal survival was associated with high blood pressure, proteinuria and elevated creatininemia, as well as T and S scores. Moreover, renal expression of miR-21-5p, miR-214-3p were associated with renal survival. In conclusion, miR-21-5p, miR-214-3p and miR-199a-5p are three "fibromiRs" involved in renal fibrosis in the course of IgAN and miR-21-5p and miR-214-3p are associated with renal survival.


Table top relocation test--New clinical test for posterolateral rotatory instability of the elbow.
We describe a new clinical test for assessment of posterolateral rotatory instability. This has been assessed in 8 patients who have been diagnosed with posterolateral rotatory instability. Six of these have undergone surgical reconstruction of the lateral ulnar collateral ligament, and the clinical test has subsequently been negative with resolution of their symptoms.


Photodynamic activity of liposome-delivered Cd-texaphyrin using tumor-bearing nude mice.
Photodynamic effects in bladder-tumor bearing nude mice induced by a krypton ion laser (752.5 nm) after i.v. application of liposome-delivered cadmium texaphyrin were investigated. Cd-texaphyrin possesses strong absorption transitions in the far red spectral region (around 760 nm) and a high quantum efficiency of singlet oxygen production. No therapeutic effects were obtained using irradiation 24 hours after administration of the sensitizer, whereas phototreatment 2 hours after application led to significant tumor reduction. This corresponds well with studies on fluorophore-labeled liposomes indicating highest tumor accumulation 1-2 hours after administration. However, the induced cytotoxic effects were lower than those of HpD.


Modeling Variation in Empathic Sensitivity Using Go/No-Go Social Reinforcement Learning.
Recent advances in computational behavioral modeling can help rigorously quantify differences in how individuals learn behaviors that affect both themselves and others. But social learning remains understudied in the context of understanding individual variation in social phenomena like aggression, which is defined by persistent engagement in behaviors that harm others. We adapted a go/no-go reinforcement learning task across social and non-social contexts such that monetary gains and losses explicitly impacted the subject, a study partner, or no one. We then quantified participants' (n = 61) sensitivity to others' rewards, sensitivity to others' losses, and the Pavlovian influence of expected outcomes on approach and avoidance behavior. Results showed that subjects learned in response to punishments and rewards that affected their partner in a way that was computationally similar to how they learned for themselves, consistent with the possibility that social learning engages empathic processes. Further supporting this interpretation, an individualized model parameter that indexed sensitivity to others' punishments was inversely associated with trait antisociality. Modeled sensitivity to others' losses also mapped onto post-task motivation ratings, but was not associated with self-reported trait empathy. This work is the first to apply a social reinforcement learning task that spans affect and action requirement (go/no-go) to measure multiple facets of empathic sensitivity. The online version contains supplementary material available at 10.1007/s42761-022-00119-4.


In-line Raman spectroscopy for characterization of an industrial poultry raw material stream.
In this work, we evaluated the feasibility of Raman spectroscopy as an in-line raw material characterization tool for industrial process control of the hydrolysis of poultry rest raw material. We established calibrations (N = 59) for fat, protein, ash (proxy for bone) and hydroxyproline (proxy for collagen) in ground poultry rest raw material. Calibrations were established in the laboratory using poultry samples with high compositional variation. Samples were measured using a wide area illumination Raman probe at varying working distance (6 cm, 9 cm, 12 cm) and probe tilt angle (0°, 30°) to mimic expected in-line variations in the measurement situation. These moderate variations did not significantly affect performance for any analytes. The obtained calibrations were tested in-line with continuous measurements of the ground poultry by-product stream at a commercial hydrolysis facility over the course of two days. Measurements were acquired under demanding conditions, e.g. large variations in working distance. Reasonable estimates of compositional trends were obtained. Validation samples (N = 19) were also reasonably well predicted, with RMSEPcorr = [0.14, 1.37, 2.36, 1.51]% for hydroxyproline, protein, fat and ash, respectively. However, there were indications that further calibration development and robustification of pre-processing would be advantageous, particularly with respect to hydroxyproline and protein models. It is the authors' impression that with such efforts, potentially in combination with development of practical measurement setup, the use of Raman spectroscopy as a process control tool for the hydrolysis of poultry rest raw materials is within reach.


Women authorship in radiology research in France: An analysis of the last three decades.
The aim of this study was to evaluate the evolution of women authorship in France and to analyze the recent trends of the evolution of gender differences in French academic radiology. A retrospective bibliometric analysis was performed by searching for articles published in Diagnostic and Interventional Imaging (Diagn Interv Imaging) and in Journal de Radiologie (J Radiol) in Pubmed over the last three decades. For each of these articles, we determined the gender of the first and last author. The specific radiological field of each article was also determined. The proportion of women authors has significantly increased from 12% in 1984 to 34% in 2014 (P<0.0001) for the first authors and from 11% (11/96) in 1984 to 20% (38/193) in 2014 for last authors (P =0.03). Women authorship in Diagnostic and Interventional Imaging has increased over the last years together with the proportion of women first authors. However, the fraction of women last authors is still underrepresented. More women need to become leaders in radiological research to contribute to stimulate women authorship.


Apomorphine in the evaluation of dopaminergic function in man.
1. Apomorphine (Apo), a short acting dopamine (DA) receptor agonist, stimulates growth hormone (GH) secretion, decreases prolactin secretion, induces yawning, penile erections and other physiological effects in man. An effect on behavior, movement disorders and alcoholism has also been described. 2. Apo-mediated responses are used to evaluate DA function in psychiatric and neurological disorders. Many of the studies in schizophrenia using the GH response to Apo as an index of central DA function are difficult to interpret because of failure to control for key variables. 3. The GH response to Apo is a useful system to evaluate the effects of various drugs including peptides which may not cross the blood brain barrier on DA function in man. 4. Apo is a potent sedative. Specific antimanic, antischizophrenic, and anticraving effects in alcoholics have not been convincingly demonstrated. Side effects of Apo and failure to use active placebo make double-blind studies difficult. 5. Apo improves parkinsonian symptoms and certain forms of reflex epilepsy but beneficial effects in other involuntary movement disorders requires further documentation. 6. Apo may be a useful agent to evaluate DA function in impotent patients and predict a therapeutic response to long-acting dopaminergic agents. 7. Impairment of DA function may play a role in diabetic impotence. 8. The development of a simple polygraphic method to monitor the yawning response to Apo may facilitate clinical studies on the basic physiology of yawning in man and the use of the yawning response as a measure of central DA function in schizophrenia and other clinical disorders. 9. The use of Apo with 18F-fluorodeoxyglucose positron emission tomography to examine regional DA function in man opens up a promising area of research. 10. Though long-acting orally active aporphine DA agonists and antagonists have been developed the problem of tolerance may limit their therapeutic potential.


Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of doxorubicin, suppressing its adverse effect.
The ultimate goal of cancer chemotherapy is to achieve a cure without causing any adverse effects. We have developed a pH-sensitive redox nanoparticle (RNP(N)), which disintegrates under acidic conditions and exposes nitroxide radicals, leading to strongly scavenging reactive oxygen species (ROS). After intravenous administration of RNP(N) to tumor bearing mice, it effectively accumulated in tumors due to the leaky neovascular and immature lymphatic system and scavenged ROS, resulting in suppression of inflammation and activation of NF-кB, after disintegration of RNP(N) in the tumors. Pre-administration of RNP(N) prior to treatments with anticancer agents, doxorubicin, to tumor-bearing mice significantly suppressed the progression of tumor size, compared to low-molecular weight 4-hydroxy-TEMPO. Interestingly, the administration of RNP(N) suppressed adverse effects of doxorubicin to normal organs due to the scavenging ROS and suppression of inflammation, which was confirmed by reduction in lactate dehydrogenase and creatine phosphokinase activities in plasma. RNP(N) is thus anticipated as a novel and ideal adjuvant for cancer chemotherapy.


Guillain-Barré Syndrome: A Variant Consisting of Facial Diplegia and Paresthesia with Left Facial Hemiplegia Associated with Antibodies to Galactocerebroside and Phosphatidic Acid.
BACKGROUND A rare variant of Guillain-Barré syndrome (GBS) consists of facial diplegia and paresthesia, but an even more rare association is with facial hemiplegia, similar to Bell's palsy. This case report is of this rare variant of GBS that was associated with IgG antibodies to galactocerebroside and phosphatidic acid. CASE REPORT A 54-year-old man presented with lower left facial palsy and paresthesia of his extremities, following an upper respiratory tract infection. Physical examination confirmed lower left facial palsy and paresthesia of his extremities with hyporeflexia of his lower limbs and sensory loss of all four extremities. The differential diagnosis was between a variant of GBS and Bell's palsy. Following initial treatment with glucocorticoids followed by intravenous immunoglobulin (IVIG), his sensory abnormalities resolved. Serum IgG antibodies to galactocerebroside and phosphatidic acid were positive in this patient, but not other antibodies to glycolipids or phospholipids were found. Five months following discharge from hospital, his left facial palsy had improved. CONCLUSIONS A case of a rare variant of GBS is presented with facial diplegia and paresthesia and with unilateral facial palsy. This rare variant of GBS may which may mimic Bell's palsy. In this case, IgG antibodies to galactocerebroside and phosphatidic acid were detected.