Pitting corrosion inhibition of aluminum 2024 by Bacillus biofilms secreting polyaspartate or gamma-polyglutamate.
Pitting corrosion of aluminum 2024 in Luria Bertani medium was reduced by the secretion of anionic peptides by engineered and natural Bacillus biofilms and was studied in continuous reactors using electrochemical impedance spectroscopy. Compared to sterile controls, pitting was reduced dramatically by the presence of the biofilms. The secretion of a 20 amino acid polyaspartate peptide by an engineered Bacillus subtilis WB600/pBE92-Asp biofilm slightly reduced the corrosion rate of the passive aluminum alloy at pH 6.5; however, the secretion of gamma-polyglutamate by a Bacillus licheniformis biofilm reduced the corrosion rate by 90% (compared to the B. subtilis WB600/pBE92 biofilm which did not secrete polyaspartate or gamma-polyglutamate). The corrosion potential ( E(corr)) of aluminum 2024 was increased by about 0.15-0.44 V due to the formation of B. subtilis and B. licheniformis biofilms as compared to sterile controls. The increase of E(corr) and the observed prevention of pitting indicate that the pitting potential ( E(pit)) had increased. This result and the further decrease of corrosion rates for the passive aluminum alloy suggest that the rate of the anodic metal dissolution reaction was reduced by an inhibitor produced by the biofilms. Purified gamma-polyglutamate also decreased the corrosion rates of aluminum 2024.


Ferritin expression modulates cell cycle dynamics and cell responsiveness to H-ras-induced growth via expansion of the labile iron pool.
Repression or overexpression of ferritin accelerated or retarded cell cycling respectively, via changes in the cellular labile iron pool (LIP). A rise in LIP is caused by ferritin repression enhanced growth, induced by H-ras, and reverted growth arrest is induced by dominant negative H-ras. The studies indicate that repression of ferritin expression provides a mechanism by which certain oncogenes lead to cell growth stimulation.


A case of caffeine-induced coronary artery vasospasm of a 17-year-old male.
The intentional consumption and use of stimulants, such as caffeine, are known to have numerous interactions with the human cardiovascular system. Ex vivo studies have shown caffeine-induced vasoconstriction of coronary arteries (Forman et al. in Ann Emerg Med 29:178-180, 1997). We report on a case of a 17-year-old male who presented with angina and an abnormal electrocardiogram (ECG) concerning for ST elevation myocardial infarct. He was found to have diffuse ECG changes and markedly elevated cardiac enzymes. A transthoracic echocardiogram revealed a reduced left ventricular (LV) systolic function as well as segmental wall motion abnormalities consistent with an ischemic insult. The patient admitted to consuming near lethal doses of caffeine immediately preceding his angina. He was diagnosed with coronary vasospasms as a result of stimulant use. During hospitalization, ECG changes resolved, cardiac enzymes started trending downward, and LV systolic function returned to normal, all consistent with stunned myocardium that fully recovered. This case strongly suggests that overuse of stimulants, such as caffeine, should be considered in patients presenting with coronary vasospasms, particularly in teenagers and young adults.


Post-translational glutamylation and tyrosination in tubulin of tritrichomonads and the diplomonad Giardia intestinalis.
Glutamylated and tyrosinated tubulin were localized in Giardia intestinalis and selected trichomonads of the Tritrichomonadinae subfamily, using specific monoclonal antibodies directed at each of the post-translational modifications. Analysis was carried out using indirect immunofluorescence microscopy. Although trichomonad tubulins remained unlabeled by anti-tyrosine tubulin (TUB-1A2), the presence of the glutamylation motif (GT 335) was confirmed and found to differ in distribution among tritrichomonads. Tritrichomonas muris was most heavily labeled with GT 335, while T. foetus was the least so. Like trichomonads, Giardia was unreactive to anti-tyrosine tubulin; however, the GT 335 antibody produced marked fluorescence in Giardia trophozoites. This study is the first to report immunofluorescent localization of tubulin glutamylation in Giardia and confirms previously reported mass spectrometry data.


Household Prevalence of Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale in the Democratic Republic of the Congo, 2013-2014.
In a cross-sectional molecular study in the Democratic Republic of the Congo, 78% of households had ≥1 member infected with Plasmodium falciparum, Plasmodium vivax, and/or Plasmodium ovale spp.; 47% of children and 33% of adults tested positive for ≥1 species. Risk factors varied by species and age group.


[Feminism and interventions with women; an experience with female alcoholics and drug abusers at Domremy Trois-Rivieres].
With the advent of feminist ideology, women believed they could fashion made-to-measure tools to end their oppression and emancipate themselves. However, passing from ideology to practice has led to a certain number of difficulties. On the other hand, the feminist viewpoint has made a major and undeniable contribution to society. This article discusses the trials and tribulations as well as the successes of feminist practice.


Quality performance in the physician's office.
Because neither the physicians nor their office staffs are trained laboratorians, the reliability of test results from physician's office testing is of major concern. In this article, potential errors in laboratory testing are discussed, and a comprehensive quality-assurance program is presented.


Confirmation of the structure of nisin and its major degradation product by FAB-MS and FAB-MS/MS.
FAB-MS has been applied to the analysis of a nisin complex and FAB-MS and FAB-MS/MS data from the major component used to provide confirmation of the amino sequence and positions of the sulphur-bridged rings in these highly modified peptides.


PP2A holoenzymes negatively and positively regulate cell cycle progression by dephosphorylating pocket proteins and multiple CDK substrates.
Cell cycle progression is negatively regulated by the retinoblastoma family of pocket proteins and CDK inhibitors (CKIs). In contrast, CDKs promote progression through multiple phases of the cell cycle. One prominent way by which CDKs promote cell cycle progression is by inactivation of pocket proteins via hyperphosphorylation. Reactivation of pocket proteins to halt cell cycle progression requires dephosphorylation of multiple CDK-phosphorylated sites and is accomplished by PP2A and PP1 serine/threonine protein phosphatases. The same phosphatases are also implicated in dephosphorylation of multiple CDK substrates as cells exit mitosis and reenter the G1 phase of the cell cycle. This review is primarily focused on the role of PP2A and PP1 in the activation of pocket proteins during the cell cycle and in response to signaling cues that trigger cell cycle exit. Other functions of PP2A during the cell cycle will be discussed in brief, as comprehensive reviews on this topic have been published recently (De Wulf et al., 2009; Wurzenberger and Gerlich, 2011).


Outcome of incomplete systemic lupus erythematosus after 10 years.
The objective was to identify cases of incomplete systemic lupus erythematosus (SLE) within a defined population in southern Sweden, risk factors for development of complete SLE (> or = 4 classification criteria) and study outcome of the patients. During prospective retrieval of SLE cases within a defined population in southern Sweden, 28 patients (26 women, two men) with incomplete SLE (< 4 ACR criteria) were identified between 1981 and 1992. All patient records were reviewed and clinical and laboratory data were extracted from standardized formats. Organ damage was defined according to the SLICC/ACR damage index. During follow-ups, 16 of 28 patients developed complete SLE (median 13 years; range 10-20 years). The time to develop complete SLE varied between one and ten years with a median time of 5.3 years. Three patients were anti-DNA positive at inclusion; only one of them developed complete SLE. False positive Wasserman reaction and anti-cardiolipin antibodies (aCl) were only found in patients who developed complete SLE (P < 0.04; Fisher exact test). Six patients had malar rash from the start and they all had complete SLE at follow-up (P < 0.04; Fisher exact test). Of eight patients with arthritis, three developed complete SLE. Thrombocytopenia was only found in two patients, both developing complete disease. At follow-up, patients that developed complete SLE had high SLICC damage scores (mean 1.5) compared with patients that remained as incomplete SLE (mean 0.16). In conclusion, in this follow-up study of patients with incomplete SLE 57% developed complete disease after a median time of 5.3 years. Malar rash and aCl were predictors of complete SLE. Individuals that developed complete SLE were more prone to organ damage.


Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats.
Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats. Male SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits. The marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance. The results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage.


Esophageal rupture diagnosed with bedside ultrasound.
A 69-year-old man presented to the emergency department with hematemesis, hypotension, tachycardia, and hypothermia. The emergency physician performed a bedside ultrasound of the chest, heart, and abdomen. The heart was unable to be visualized in the parasternal, apical, or subxiphoid windows, and free fluid and particulate matter were visualized in the chest and abdomen. The inability to visualize the heart in the normal cardiac windows suggested a diagnosis of pneumopericardium. Based upon the patient's presenting symptoms and ultrasound findings, an esophageal perforation was suspected. Esophageal perforation is a medical emergency. Deterioration and death due to sepsis can occur within hours of presentation [6]. Although there is a great deal of literature discussing the diagnosis of esophageal perforation by chest radiograph, computed tomography (CT), and esophagography, there are no articles on the role of ultrasound. Esophageal perforation may result in the communication of air between the esophagus and pericardium and the leakage of gastric contents into the chest and peritoneal cavity. The presence of air in the pericardial sac results in nonvisualization of the heart on ultrasound. Fluid in the chest and abdomen may be visualized in the posterior upper abdominal windows. Although these ultrasound findings alone are not entirely specific for esophageal perforation, when coupled with a high index of suspicion due to the patient presentation, ultrasound can be one of the most portable, readily available, low-cost, and minimally invasive techniques to make the diagnosis of esophageal perforation.


Takayasu's arteritis.
Takayasu's arteritis is a rare disease that causes arterial inflammation with resulting stenosis or aneurysm of affected vessels. It primarily affects young females and has a predilection for the aorta, its primary branches, and the pulmonary arteries. Patients may present with symptoms of organ ischemia, such as stroke or claudication, or with signs of arterial stenosis, such as absent pulses or asymmetric blood pressures. Most patients require chronic immunosuppressive therapy to control inflammation. The foundation of therapy is glucocorticoids, which are often used in combination with other immunosuppressive agents, such as methotrexate, azathioprine, or mycophenolate mofetil. The goal of systemic therapy is to induce and maintain disease remission, often defined as the absence of new arterial lesions, lack of systemic symptoms, and ability to taper prednisone to less than 10 mg/d. Promising results have been seen with the use of agents directed against tumor necrosis factor in patients who have failed to maintain remission with standard therapies. Revascularization procedures such as percutaneous transluminal angioplasty (PTA) or bypass grafting are reserved for patients who have critical organ ischemia or severe extremity claudication. Bypass grafting has a lower restenosis rate than PTA and is the preferred method of restoring blood flow to affected organs. Frequent laboratory testing is recommended to monitor for drug toxicity and signs of disease relapse. At each clinic visit, physicians should auscultate for bruits over primary arterial branches and evaluate for asymmetry between arm and leg blood pressures. Biannual radiographic imaging with magnetic resonance or CT angiography is helpful to examine for evidence of new aortic aneurysms or arterial stenoses.


Multicentre oncology clinical trials in primary health care in Cuba: evaluation of programme implementation in Villa Clara Province, 2010-2020.
The Center of Molecular Immunology of Cuba has developed a programme for the conducting of multicentre oncology clinical trials in primary healthcare centres since 2009. To evaluate the ability to conduct oncology clinical trials in primary health care. A longitudinal, prospective, analytical study was developed between July 2010 and August 2020 in the Villa Clara province. Structure, process, and outcome indicators were evaluated by the methods of a structured interview, direct observation, documentary observation, and databases analysis. The investigators' curricula vitae, the investigator site file, minutes of workshops, the monitoring reports, the clinical trial training records, and databases were employed as sources of information. The following criteria were considered adequate: when the indicator met the standard; and not adequate: when the indicator did not meet the standard. The six structure indicators reached adequate results and showed that the programme has allowed building of capacities to conduct clinical trials in primary care. The eight processes indicators and two outcome indicators were considered adequate too. Trials conducted in primary care showed better indicators of patient recruitment than secondary care. Both scenarios showed similar behaviour for the process indicators: retention, protocol compliance, and safety. Survival and satisfaction with health services were also comparable in both scenarios. The evaluation of the programme showed adequate indicators for conducting oncology clinical trials in primary care in Villa Clara and these were comparable to those determined in the secondary care.


Glucose increases spontaneous platelet aggregation in whole blood.
Glucose (10-50 mM) added to samples of citrated whole blood increased the spontaneous platelet aggregation (SPA) that was observed upon stirring the samples, in a dose-dependent but time-independent manner. EDTA prevented and also reversed the SPA that occurred in the presence of glucose. Galactose, fructose and 2-deoxyglucose, but not sorbitol and sucrose, had effects on SPA similar to those of glucose. The effect of glucose on SPA in whole blood could not be specifically inhibited by tetramethylene glutaric acid (an inhibitor of aldose reductase). SPA was not affected by pentoxifylline, but was markedly reduced by chlorpromazine. We previously found that glucose, galactose, fructose and 2-deoxyglucose, but not sorbitol and sucrose, render red blood cells more fragile, and the results obtained in the present study provide further evidence that glucose as well as other reducing sugars potentiate SPA in whole blood by liberating ADP or other aggregating material from red blood cells.


Common patterns of violence experiences and depression and anxiety among adolescents.
A considerable amount of research has examined violence experiences and psychopathology; however, few studies have examined how multiple settings and experiences of violence are associated with major depressive disorder (MDD) and generalized anxiety disorder (GAD). The sample included 2,345 adolescents from a community-based sample in the US. The mean age was 14 years at the time that violence experiences in the home, school, and neighborhood were reported; psychiatric outcomes were assessed 2 years later using the Diagnostic Interview Schedule for Children. We applied latent class analysis to identify adolescents with common patterns of violence exposure and obtained adjusted prevalence ratios for the associations between violence classes and psychopathology. A four-class model was selected based on fit statistics and meaningfulness, and adolescents were categorized into four classes: low violence, home violence, neighborhood violence/traumatic news, and multiple settings of violence. Relative to adolescents in the low violence class, risk of MDD for adolescents in the home violence, neighborhood violence/traumatic news, and multiple settings classes was 1.62, 1.47, and 2.44 times higher, respectively (p values <0.05); risk for GAD was 1.61 and 2.87 times higher for adolescents in the neighborhood violence/traumatic news and multiple settings classes, respectively (p values <0.05). Exposure to a high level of violence-within a single domain or multiple domains-poses significant risk for MDD and GAD, and risk increases with high exposure in multiple domains. Thus, pervasive exposure to violence is associated with the highest risk for the development of psychopathology. Based on these results, prevention and treatment efforts should target adolescents exposed to violence in multiple settings.


Towards a typology of relapse: a preliminary report.
This paper outlines an empirical investigation into alcoholic relapse. The model underlying this work hypothesized that relapse in alcoholics is an interaction between (1) situations seen as dangerous in precipitating relapse, (2) the behaviours available within the individuals' repertoire to cope with these situations, (3) the perceived effectiveness of these "coping" behaviours and (4) the degree of alcohol dependence. The results of a "principal components" analysis indicated that "dangerous situations" or relapse precipitants could be categorized as (1) an unpleasant affect, (2) external events and euphoric feelings, (3) social anxiety and (4) lessened cognitive vigilance. Except for "external events", these relapse precipitants seemed to be associated with certain styles of coping, with varying degrees of effectiveness. The therapeutic implications of these findings are discussed in the context of designing treatment regimes geared towards more effective coping behaviours given specific types of situations.


[Management of heart failure: a challenge for healthcare systems].
Heart failure is a highly prevalent disorder associated with increased mortality, repeated and lengthy hospitalization, and disability. Major progress has been made in the treatment of chronic heart failure associated with a reduced ejection fraction, through the development of neuromodulators such as angiotensin-converting-enzyme inhibitors, betablockers, angiotensin receptor blockers, mineralocorticoid receptor antagonists and, more recently, the bradycardic agent ivabradine. By contrast, little or no progress has been made in the management of acute heart failure or of heart failure with a preserved ejection fraction. New treatment modalities, including drugs, devices, and other novel approaches are currently being developed with the aim of reducing morbidity and/or mortality and improving the quality of life of patients with these disorders, which are a major burden for healthcare systems.


Match play demands of 11 versus 11 professional football using Global Positioning System tracking: Variations across common playing formations.
This study aimed to examine Global Positioning System (GPS) determined movement patterns across the 5 most common playing formations (4-4-2; 4-3-3; 3-5-2; 3-4-3; 4-2-3-1) employed in 11 versus 11 football match play in England. Elite male footballers (n=46) were monitored over the course of a season; total distance (TD), high speed running (HSR), high metabolic load distance (HMLD), high speed accelerations (Acc) and decelerations (Dec) data was collected for analysis. It was found that 3-5-2 formation elicited higher TD (10528±565m, p=0.05), HSR (642±215m, p=0.001), and HMLD (2025±304m, p=0.001) than all other formations and above average Acc and Dec (34±7, p=0.036 and 57±10, p=0.006), with 4-2-3-1 eliciting the highest Acc and Dec (38±8 and 61±12). Positional data showed that CM in 4-3-3 covered >11% TD than in 4-4-2 (p=0.012). FW in 3-5-2 covered >45% HSR than in 4-2-3-1 (p=0.004). CM in 4-3-3 covered >14% HMLD than in 4-4-2 (p=0.367). FW in 4-3-3 performed >49% accelerations than in 4-2-3-1 (p=0.293). WD in 3-5-2 performed >20% more decelerations than in 4-4-2 (p=0.161). This study is important for coaches understanding, that positional physical characteristics are influenced by the demands of playing in different formations during match play.


Association between Takayasu arteritis and latent or active Mycobacterium tuberculosis infection: a systematic review.
Takayasu arteritis (TA) is a granulomatous vasculitis of large vessels with unknown aetiopathogenesis. An association between TA and tuberculosis (TB) has been suggested by several authors. The objective of this study was to perform a systematic review of the literature on the association of Mycobacterium tuberculosis (MT) infection in patients with TA. The research was conducted using the PUBMED/Medline and LILACS databases including studies published until June 2019 and using the descriptors "takayasu arteritis", "tuberculosis", "mycobacterium tuberculosis", "purified protein derivate" (PPD), "mantoux test", "quantiferon tb gold", and "interferon gamma release assay" (IGRA). A total of 113 publications were found, but only 38 publications were included after the pre-established criteria were applied. The results were divided into (1) active TB in adolescents with TA: 13 cases; (2) active TB in adults with TA: 116 cases, with a prevalence ranging from 6.3 to 20%, including a South Korean study of 267 cases of TA that found a prevalence of active TB of 17.7%; (3) latent TB in TA patients: the most widely used method was PPD, and only one study compared PPD with IGRA; the prevalence ranged from 20 to 82%; (4) findings that indicate TB in arterial biopsy or autopsies: 5 studies, with different results ranging from an absence of MT DNA in the aortic tissue to 70% positivity; and (5) immunological studies that evaluated the presence of antimycobacterial antibodies and heat shock proteins in TA patients. Although most of the studies show a high prevalence of TB, it is not possible to establish a causal relationship. We suggest that greater care be taken with latent TB screening in patients who are TA candidates for immunosuppressive therapy.


Building and Participating in a Simulation: Exploring a Continuing Education Intervention Designed to Foster Reflective Practice Among Experienced Clinicians.
Engaging health professionals in the processes of first building and then participating in simulations has not yet been explored. This qualitative study explored the experience of building and participating in a simulation as an educational intervention with experienced clinicians. Pediatric rehabilitation clinicians, along with a patient facilitator and standardized patients, created simulations and subsequently participated in a live simulation. The educational content of the simulation was culturally sensitive communication. We collected participants' perspectives about the process from individual journal entries and focus groups. A thematic analysis of these data sources was conducted. Participants described a process of building and participating in a simulation that provided: 1) a unique opportunity for clinicians to reflect on their current practice; 2) a venue to identify different perspectives through discussion and action in a group; and 3) a safe environment for learning. The combined process of building and participating in a simulation stimulated reflection about the clinicians' own abilities in culturally sensitive communication through discussion, practice, and feedback. It provided a safe environment for participants to share their multiple perspectives and to develop new ways of communicating. This type of educational intervention may contribute to the continuing education of experienced clinicians in both academic and community settings.


Antibiotic and antibiotic-resistant gene loads in swine slurries and their digestates: Implications for their use as fertilizers in agriculture.
The spread of antibiotic resistance in bacteria is a matter of global concern, and the identification of possible sources of the associated genetic elements (antibiotic resistance genes -ARGs-, components of the horizontal gene transfer mechanism), is becoming an urgent need. While the transmission of ARGs in medical settings have been adequately characterized, ARG propagation in agroecosystems remains insufficiently studied. Particularly crucial is the determination of potential risks associated to the use of swine slurries and related products as component of organic fertilizers, an increasingly used farming practice. We determined ARGs and antibiotic loads analysed from swine slurries and digestates from eight farms from Catalonia (NE Spain), and compared the results with their microbiome composition. Both ARGs and antibiotic were conspicuous in farm organic wastes, and the levels of some antibiotics exceeded currently accepted minimum inhibitory concentrations. Particularly, the presence of high loads of fluoroquinolones was directly correlated to the prevalence of the related qnrS1 ARG in the slurry. We also found evidence that ARG loads were directly correlated to the prevalence of determined bacterial taxa (Actinobacteria, Proteobacteria, Spirochaeta), a parameter that could be potentially modulated by the processing of the raw slurry prior to their use as fertilizer.


Review: Extragastric diseases and Helicobacter pylori.
The involvement of Helicobacter pylori infection in many extra-gastroduodenal manifestations remains a fascinating field of investigation. However, for several of these supposed associations, the potential pathogenic mechanism remains unclear. The present review highlights the main associations of H pylori with extra-gastroduodenal manifestations reported during the last year. We searched for the most relevant studies on this topic, published between April 2019 and March 2020, identified using the term "Helicobacter" in the MEDLINE/Pubmed database. Consistent data emerged from studies investigating metabolic syndrome and ischaemic cardiovascular diseases. Other reported fields of investigation were hepatology, especially focused on non-alcoholic steatohepatitis, neurology, including Parkinson's disease and Alzheimer's disease, as well as dermatology. Inflammatory bowel disease (IBD), that comprises Crohn's disease and ulcerative colitis, may originate from a dysregulation of the host's immune response to commensal bacteria in individuals with genetic predisposition. The reduction of biodiversity and other specific imbalances in the faecal microbiome composition of IBD patients compared to that of healthy controls support this hypothesis. In this context, an inverse correlation between H pylori infection and IBD prevalence has been confirmed. Similar results were found in patients with kidney diseases and allergic manifestations. There are indications of the possible involvement of H pylori infection in metabolic syndrome and ischaemic cardiovascular diseases. However, due to a series of factors linked to study designs and the multifactorial pathogenesis of some diseases, further studies are needed.


Fcγ receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab.
To assess the association between a single nucleotide polymorphism in the gene of FCGR3A and the response to treatment with rituximab (RTX) in rheumatoid arthritis (RA). SMART is a randomised open trial assessing two strategies of re-treatment in patients responding to 1 g infusion of RTX with methotrexate on days 1 and 15 after failure, intolerance or contraindication to tumour necrosis factor (TNF) blockers. Among the 224 patients included, 111 could be genotyped and were included in an ancillary study of SMART. Univariate and multivariate analyses adjusted on disease activity score on 28 joints were performed to assess whether FCGR3A-158V/F polymorphism was associated with European League Against Rheumatism response at week 24. Among the 111 patients, 90 (81%) were responders of whom 30 (27%) were good responders. V allele carriage was significantly associated with a higher response rate (91% of responders vs 70%, OR 4.6 (95% CI 1.5 to 13.6), p=0.006). These results were also confirmed in rheumatoid factor-positive patients (93% vs 74%, p=0.025). In multivariate analysis, V allele carriage was independently associated with response to RTX (OR 3.8 (95% CI 1.2 to 11.7), p=0.023). The 158V/F polymorphism of FCGR3A seems to influence the response to RTX in patients with RA after failure, intolerance or contraindication to TNF blockers.


Morphine produces circuit-specific neuroplasticity in the bed nucleus of the stria terminalis.
The bed nucleus of the stria terminalis (BST) is a brain structure located at the interface of the cortex and the cerebrospinal trunk. The BST is a cluster of nuclei organized in a complex intrinsic network that receives inputs from cortical and subcortical sources, and that sends a widespread top-down projection. There is growing evidence that the BST is a key component in the neurobiological basis of substance abuse. In the present study, the regulation of excitatory inputs onto identified neurons in the BST was examined in rats treated chronically with morphine. Neurons projecting to the ventral tegmental area (VTA) were identified by retrograde transport of fluorescent microspheres and recorded in the whole-cell voltage clamp configuration in brain slices. Selective excitatory inputs to these neurons were electrically evoked with electrodes placed in the medial and lateral aspects of the dorsal BST. The chronic morphine treatment selectively increased AMPA-dependent excitatory postsynaptic currents in a subset of inputs activated by dorso-lateral stimulation in the BST. Inputs activated by medial stimulation were not affected by morphine. Likewise, the inputs to neurons that did not project to the VTA were not changed by morphine. Altogether, these results extend the understanding of neuronal circuits intrinsically sensitive to drugs of abuse within the BST.


Minimally Invasive Interhemispheric Approach for Giant Olfactory Groove Meningioma: Technical Note.
Skull base tumors, such as large olfactory groove meningiomas (OGMs), are a challenge for neurosurgeons. However, the tendency to reduce invasive surgeries is gaining more adepts. We describe a minimally invasive interhemispheric approach with a falx window for microsurgical resection of the giant OGM as a technical note. A minimal medial frontal craniotomy measuring 3-5 cm in size is performed, and an interhemispheric approach is combined with an opening in the falx to improve microsurgical resection of the giant OGM. The technique and more details are described. A minimally invasive interhemispheric approach with a falx window was performed in this case. Gross total resection of the OGM was possible with minimal brain retraction. Simpson grade I was achieved, and there was a good outcome on the postoperative recovery period of the patient, with vision improvement, preservation of olfaction, and no other complications. The minimally invasive interhemispheric approach with a falx window is effective and safe for giant OGM with a good outcome for the patient. The opening in the falx improves the interhemispheric pathway and allows gross total resection with minimal brain retraction and low morbidity.


Effects of whole body vibration on outer hair cells' hearing response to distortion product otoacoustic emissions.
Whole body vibration (WBV) is one of the most vexing problems in industries. There is a debate about the effect of WBV exposure on hearing system as vibration-induced hearing loss. The purpose of this study was to investigate outer hair cells' (OHCs') hearing response hearing response to distortion product otoacoustic emissions (DPOAEs) in rabbits exposed to WBV. It was hypothesized that the DPOAE response amplitudes (A(dp)) in rabbits exposed to WBV would be lower than those in control rabbits not exposed to WBV. New Zealand white (NZW) rabbits as vibration group (n = 6, exposed to WBV in the z-axis at 4-8 Hz and 1.0 ms(-2) root mean square for 8 h per day during five consecutive days) and NZW rabbits as control group (n = 6, not exposed to any WBV) were participated. A(dp) and noise floor levels (L(nf)) were examined on three occasions: day 0 (i.e., baseline), day 8 (i.e., immediately 1 h after exposure), and day 11 (i.e., 72 h following exposure) with f(2) frequencies ranging from 500 to 10,000 Hz and primaries L(1) and L(2) levels of 65 and 55 dB sound pressure level, respectively. Main effects were statistically found to be significant for group, time, and frequency (p < 0.05). DPOAE amplitudes were significantly larger for rabbits exposed to WBV, larger on day 8 and larger for mid to high f(2) frequencies (at and above 5,888.50 Hz). Main effects were not statistically found to be significant for ear (p > 0.05). Also, four statistically significant interactions including time by ear, time by frequency, group by frequency, and group by time were detected (p < 0.05). Contrary to the main hypothesis, DPOAE amplitudes were significantly larger for rabbits exposed to WBV. WBV exposure significantly led to enhanced mean A(dp) at mid to high frequencies rather than at low ones.


Application of Machine Learning Models to Predict Recurrence After Surgical Resection of Nonmetastatic Renal Cell Carcinoma.
Predictive tools can be useful for adapting surveillance or including patients in adjuvant trials after surgical resection of nonmetastatic renal cell carcinoma (RCC). Current models have been built using traditional statistical modelling and prespecified variables, which limits their performance. To investigate the performance of machine learning (ML) framework to predict recurrence after RCC surgery and compare them with current validated models. In this observational study, we derived and tested several ML-based models (Random Survival Forests [RSF], Survival Support Vector Machines [S-SVM], and Extreme Gradient Boosting [XG boost]) to predict recurrence of patients who underwent radical or partial nephrectomy for a nonmetastatic RCC, between 2013 and 2020, at 21 French medical centres. The primary end point was disease-free survival. Model discrimination was assessed using the concordance index (c-index), and calibration was assessed using the Brier score. ML models were compared with four conventional prognostic models, using decision curve analysis (DCA). A total of 4067 patients were included in this study (3253 in the development cohort and 814 in the validation cohort). Most tumours (69%) were clear cell RCC, 40% were of high grade (nuclear International Society of Urological Pathology grade 3 or 4), and 24% had necrosis. Of the patients, 4% had nodal involvement. After a median follow-up of 57 mo (interquartile range 29-76), 523 (13%) patients recurred. ML models obtained higher c-index values than conventional models. The RSF yielded the highest c-index values (0.794), followed by S-SVM (c-index 0.784) and XG boost (c-index 0.782). In addition, all models showed good calibration with low integrated Brier scores (all integrated brier scores <0.1). However, we found calibration drift over time for all models, albeit with a smaller magnitude for ML models. Finally, DCA showed an incremental net benefit from all ML models compared with conventional models currently used in practice. Applying ML approaches to predict recurrence following surgical resection of RCC resulted in better prediction than that of current validated models available in clinical practice. However, there is still room for improvement, which may come from the integration of novel biological and/or imaging biomarkers. We found that artificial intelligence algorithms could better predict the risk of recurrence after surgery for a localised kidney cancer. These algorithms may help better select patients who will benefit from medical treatment after surgery.


[The encyclopedia of Etienne Binet (1621), medicine and dentistry].
This jesuit, humanist devotee is the author of many spiritualism written works and of an "Essay des Merveilles de Nature" (Essay on Nature's Marvels), original book of personal observations. Concerning Odontology, BINET still belongs to Middle-Age, failing to recognize anatomy and esthetics, in spite of Renaissance.


[Giant diverticulum of the colon. Apropos of 2 cases].
Two cases of giant colonic diverticulum are reported. Clinical and radiological features are described. Surgery is absolutely necessary.


The accuracy of noninvasive cardiac output and pressure measurements with finger cuff: a concise review.
The present review aims to summarize literature on the accuracy of the finger cuff method to measure cardiac output (CO) and blood pressure, its ability to track hemodynamic changes, and to predict fluid responsiveness. Finger cuff is an easy-to-use hemodynamic monitoring technique. Different devices are currently available, which provide continuous arterial blood pressure (Finapress), whereas only ClearSight (previously known as Nexfin; BMEYE) provides an estimate of CO. In most studies, the criteria for clinical interchangeability (for CO) were not met, when compared with the currently used invasive monitoring systems such as uncalibrated CO via a radial artery line, and calibrated CO either via a pulmonary artery catheter or a femoral artery catheter connected to the PiCCO (Pulsion Medical Systems) or VolumeView (Edwards Lifesciences) devices. In particular, ClearSight obtained CO seems to be less accurate in patients with a low CO. However, in most patients, ClearSight is able to track hemodynamic changes induced by a fluid challenge or passive leg raising test. We will discuss in this review the relevant literature with regard to validation of the finger cuff technique for both arterial blood pressure and CO. The finger cuff method provides a reasonable estimate of CO and blood pressure, which does not meet the criteria for clinical interchangeability with the currently used invasive devices.


A biomechanical comparison of short segment long bone fracture fixation techniques: single large fragment plate versus 2 small fragment plates.
To determine whether using 2 small fragment plates (3.5 mm screw size) side by side is biomechanically superior to the use of 1 large fragment plate (4.5 mm screw size), in the fixation of "short segments" in long bone fractures. Fiber-filled epoxy bone surrogates were plated across 1-cm gaps with 3 different constructs. Six surrogates were fixed using 2 side-by-side 3.5-mm waisted compression plates and six 3.5-mm screws, 6 surrogates were fixed using one 4.5-mm waisted compression plate and two 4.5-mm screws, and 6 surrogates were fixed using one 3.5-mm waisted compression plate and three 3.5-mm screws. These constructs then underwent cyclic axial compression in 100-N increments until 500 N was reached. Then, they underwent cyclic cantilever bending at 2 Hz and at a 23.6 N·m moment until fatigue failure occurred. Also, a single load to failure test was performed in cantilever bending to evaluate plate strength. The cumulative gap length change after 500 cycles of loading up to 500 N was 3.4% ± 0.4% for the 3.5 mm double plate construct, 9.5% ± 1.4% for the 4.5 mm single plate construct, and 14.4% ± 0.9% for the 3.5 mm single plate construct. In cantilever bending, the 3.5 mm double plate construct failed after 15,345 ± 2493 cycles, the 4.5 mm single plate construct failed after 2713 ± 1811 cycles, and the 3.5 mm single plate construct failed in its first cycle. In single load to failure testing, the load at offset yield was higher in the 3.5 mm double plate construct than the 4.5 mm single plate construct. This study suggests that in situations where anatomy or other limitations limit the length of bone segments available for fixation, it may be preferable to use 2 small plates with more screws rather than 1 large plate with few screws.


Ultrasound examination of tendons.
This article reviews the type of equipment used in sonography of the tendons, the method of approach in viewing normal tendon anatomy, and the sonographic appearance in pathologic conditions of the tendons. The role of ultrasound in follow-up studies is also emphasized because of its noninvasive nature.


Mechanism of transcription regulation by Acinetobacter baumannii HpaR in the catabolism of p-hydroxyphenylacetate.
HpaR is a transcription regulator in the MarR family that controls the expression of the gene cluster responsible for conversion of p-hydroxyphenylacetate to pyruvate and succinate for cellular metabolism. Here, we report the biochemical and structural characterization of Acinetobacter baumannii HpaR (AbHpaR) and its complex with cognate DNA. Our study revealed that AbHpaR binds upstream of the divergently transcribed hpaA gene and the meta-cleavage operon, as well as the hpaR gene, thereby repressing their transcription by blocking access of RNA polymerase. Structural analysis of AbHpaR-DNA complex revealed that the DNA binding specificity can be achieved via a combination of both direct and indirect DNA sequence readouts. DNA binding of AbHpaR is weakened by 3,4-dihydroxyphenylacetate (DHPA), which is the substrate of the meta-cleavage reactions; this likely leads to expression of the target genes. Based on our findings, we propose a model for how A. baumannii controls transcription of HPA-metabolizing genes, which highlights the independence of global catabolite repression and could be beneficial for metabolic engineering toward bioremediation applications. DATABASES: The structural data that support these findings are openly available in the wwPDB at https://doi.org/10.2210/pdb7EL2/pdb and https://doi.org/10.2210/pdb7EL3/pdb for AbHpaR and AbHpaR-DNA complex, respectively.


Vindication, virtue, and vitriol: A study of online engagement and abuse toward British MPs during the COVID-19 pandemic.
COVID-19 has given rise to a lot of malicious content online, including hate speech, online abuse, and misinformation. British MPs have also received abuse and hate on social media during this time. To understand and contextualise the level of abuse MPs receive, we consider how ministers use social media to communicate about the pandemic, and the citizen engagement that this generates. The focus of the paper is on a large-scale, mixed-methods study of abusive and antagonistic responses to UK politicians on Twitter, during the pandemic from early February to late May 2020. We find that pressing subjects such as financial concerns attract high levels of engagement, but not necessarily abusive dialogue. Rather, criticising authorities appears to attract higher levels of abuse during this period of the pandemic. In addition, communicating about subjects like racism and inequality may result in accusations of virtue signalling or pandering by some users. This work contributes to the wider understanding of abusive language online, in particular that which is directed at public officials.


Use of mupirocin ointment in the treatment of secondarily infected dermatoses.
A double-blind, randomized, vehicle-controlled study was conducted to evaluate the safety and efficacy of 2% mupirocin ointment in the treatment of secondarily infected dermatoses. One hundred six patients were enrolled, 92 of whom were evaluable for efficacy. There was a significantly greater rate of eradication of Staphylococcus aureus and total pathogens in mupirocin-treated patients than in control subjects. Analysis of the clinical data relative to all pathogens showed a significant difference in skin infection evaluations performed at the interim and follow-up visits, which favored the mupirocin-treated groups. In those patients infected with S. aureus or Streptococcus pyogenes, there was a significant difference at end-point that favored mupirocin in seven clinical ratings and the skin infection evaluation at follow-up. Mild local adverse effects were noted in a small percentage of patients in each group. Mupirocin appears to be safe and effective for the treatment of secondarily infected dermatoses, especially in those infections caused by Staphylococcus aureus.


A rapid and simple resazurin assay to detect minimum inhibitory concentrations of first-line drugs for Mycobacterium tuberculosis isolated from cerebrospinal fluid.
Central nervous system tuberculosis (CNS-TB) is a devastating manifestation of TB. The most common form of CNS-TB is tuberculous meningitis. Drug-resistant TB poses a major threat to the control of TB worldwide. Timely treatment dramatically improves the outcome. Colorimetric techniques for drug susceptibility testing based on the oxidation-reduction principle give results quick and are less expensive. The objectives of this study were to compare the susceptibility of Mycobacterium tuberculosis isolated from cerebrospinal fluid to four first-line drugs using the MGIT automated mycobacterial detection system and the resazurin assay (RA) as well as to estimate the minimum inhibitory concentrations (MICs) by RA. A total of 42 M. tuberculosis isolates were analysed for their susceptibilities by MGIT and RA. Of the 42 isolates, 35 gave concordant results with both methods. Agreement between the two tests for streptomycin and rifampicin was 100% with a Fleiss' kappa (κ) value of 1, whereas for isoniazid and ethambutol agreement was 92.86% and 90.48%, respectively, with κ values of 0.853 and 0.738. The RA appears to be a good alternative to the automated MGIT technique in resource-limited settings.


A rapid RNA extraction method from oil palm tissues suitable for reverse transcription quantitative real-time PCR (RT-qPCR).
Cetyltrimethylammonium bromide (CTAB) is the preferred detergent in RNA extraction of oil palm tissues. However, the CTAB-based protocol is time-consuming. In this study, a combination of the CTAB-based method and silica-based purification reduced the extraction time from two days to five hours. Quality of total RNA from 27 different tissues of oil palm was shown to have an RNA integrity number (RIN) value of more than seven. The extracted RNA was evaluated by RT-qPCR using three reference oil palm genes (GRAS, CYP2, and SLU7) and three putative mesocarp-specific transcripts annotated as WRKY DNA-binding protein 70 (WRKY-70), metallothionein (MT) and pentatricopeptide repeat (PPR) genes. Tissue-specific expression profiling across complete developmental stages of mesocarp and vegetative tissues was determined in this study. Overall, the RNA extraction protocol described here is rapid, simple and yields good quality RNAs from oil palm tissues.


DHPC strongly affects the structure and oligomerization propensity of Alzheimer's Aβ(1-40) peptide.
Alzheimer's disease (AD) is thought to depend on the deleterious action of amyloid fibrils or oligomers derived from β-amyloid (Aβ) peptide. Out of various known Aβ alloforms, the 40-residue peptide Aβ(1-40) occurs at highest concentrations inside the brains of AD patients. Its aggregation properties critically depend on lipids, and it was thus proposed that lipids could play a major role in AD. To better understand their possible effects on the structure of Aβ and on the ability of this peptide to form potentially detrimental amyloid structures, we here analyze the interactions between Aβ(1-40) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). DHPC has served, due to its controlled properties, as a major model system for studying general lipid properties. Here, we show that DHPC concentrations of 8 mM or higher exert dramatic effects on the conformation of soluble Aβ(1-40) peptide and induce the formation of β-sheet structure at high levels. By contrast, we find that DHPC concentrations well below the critical micelle concentration present no discernible effect on the conformation of soluble Aβ, although they substantially affect the peptide's oligomerization and fibrillation kinetics. These data imply that subtle lipid-peptide interactions suffice in controlling the overall aggregation properties and drastically accelerate, or delay, the fibrillation kinetics of Aβ peptide in near-physiological buffer solutions.


Mgs1 function at G-quadruplex structures during DNA replication.
The coordinated action of DNA polymerases and DNA helicases is essential at genomic sites that are hard to replicate. Among these are sites that harbour G-quadruplex DNA structures (G4). G4s are stable alternative DNA structures, which have been implicated to be involved in important cellular processes like the regulation of gene expression or telomere maintenance. G4 structures were shown to hinder replication fork progression and cause genomic deletions, mutations and recombination events. Many helicases unwind G4 structures and preserve genome stability, but a detailed understanding of G4 replication and the re-start of stalled replication forks around formed G4 structures is not clear, yet. In our recent study, we identified that Mgs1 preferentially binds to G4 DNA structures in vitro and is associated with putative G4-forming chromosomal regions in vivo. Mgs1 binding to G4 motifs in vivo is partially dependent on the helicase Pif1. Pif1 is the major G4-unwinding helicase in S. cerevisiae. In the absence of Mgs1, we determined elevated gross chromosomal rearrangement (GCR) rates in yeast, similar to Pif1 deletion. Here, we highlight the recent findings and set these into context with a new mechanistic model. We propose that Mgs1's functions support DNA replication at G4-forming regions.


Impact of dried skim milk in production diets on Lactobacillus and pathogenic bacterial shedding in growing-finishing swine.
To determine the possible effects of inclusion of dried skim milk (DSM) in swine diets on indigenous Lactobacillus spp. and Escherichia coli, and its potential for controlling pathogen shedding and affect animal growth in growing-finishing swine. Animals were fed over three dietary phases to match production needs from age 10-14 weeks, 14-18 weeks and 18-22 weeks. For each feeding phase, diets were formulated to contain 0 or 10% DSM (balanced for metabolizable energy and true ileal digestible amino acids). Animals were weighed every 2 weeks and faecal samples were collected from 40 animals (20 with DSM and 20 without DSM) at week 10 (d 0 on diets), 14, 18 and 22 of age, and were analysed for Lactobacillus spp., Enterobacteriaceae, coliforms, E. coli, Salmonella, Campylobacter and E. coli O157:H7. At the start of the study (week 10), faecal bacterial counts (log10 CFU g(-1) faeces) were 9.55, 7.26, 7.01 and 6.93 for Lactobacillus, Enterobacteriaceae, coliforms and E. coli populations respectively. The Enterobacteriaceae, coliform and E. coli populations decreased through week 14 and 18, but were higher in animals fed with the DSM diet compared with the basal diet without DSM. The Lactobacillus populations at weeks 14 and 18 were lower in the animals fed the diet without DSM, whereas feeding DSM maintained the Lactobacillus counts from week 10. At week 22, populations of Enterobacteriaceae, coliforms and E. coli were >week 18 for the animals fed the diet without DSM, less change was observed with the feeding of DSM, and no differences between the diets were observed at week 22. However, in week 22 the animal gain was positively correlated with Lactobacillus numbers and negatively correlated with E. coli numbers. Subtraction of the E. coli population (log10) from the Lactobacillus population (log10) yielded a positive value termed 'effective'Lactobacillus that correlated well with animal gain and may better define a beneficial function in the intestine. Salmonella were detected in over 60% of the animals at week 10 and 14, and <20% at week 18 and 22. Campylobacter were detected rarely at weeks 10, 14 and 18, but were found in 25% of the animals at week 22. The DSM did not affect Salmonella or Campylobacter shedding, but examination of individual animals over the entire experiment indicated that fewer recurring incidences of Salmonella shedding occurred in animals that maintained higher Lactobacillus. In addition, at week 22, Salmonella and Campylobacter shedding was associated with lower levels of effective Lactobacillus and lower animal weight gains. The DSM did not directly affect the animal performance or pathogen shedding via the Lactobacillus spp. population at any phase of production. However, analysis of data from all animals revealed that faecal Lactobacillus affected Salmonella shedding and in the finishing phase, animal growth and pathogen shedding also were affected, as reflected by the 'effective'Lactobacillus-associated observations. In the swine intestine, any benefits from gastrointestinal Lactobacillus may be compromized by the E. coli population, and this antagonism may explain responses observed with prebiotics or probiotics in some swine.


Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery: a randomized placebo-controlled, double-blind study.
Skeletal trauma and immobilization are well-known risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE). While prophylaxis against thromboembolic complications has become routine after major orthopedic surgery, whether or not prophylaxis after minor surgery and lower limb immobilization is necessary is still under debate. In a double-blind, placebo-controlled study, 272 consecutive patients were randomized to receive either thromboprophylaxis with Dalteparin (n = 136) or placebo (n = 136) for 5 weeks after ankle fracture surgery. All patients received 1 week of initial treatment with Dalteparin before randomization. A unilateral phlebography was performed when the cast was removed. The overall incidence of DVT was 21% (95% CI: 13-29%) in the Dalteparin group and 28% (CI: 19- 37%) in the placebo group (risk ratio = 0.8, CI: 0.6-1.1; p = 0.3). The incidence of proximal DVTs was 4% and 3%, respectively. No major bleeding occurred. We found no significant difference in the incidence of DVT between the 2 treatment groups and our results do not support prolonged thromboprophylaxis. The overall incidence of DVT was high, reflecting the potential risk of PE and post-thrombotic syndrome after ankle fracture surgery. Most of the DVTs were asymptomatic, however, and were located in distal veins.


Curriculum development on the human rights of people with disabilities for future medical education: using a modified Delphi.
In order for doctors to effectively provide medical services to patients with disabilities, an understanding of this population is necessary, along with the knowledge, attitudes, and technical abilities necessary to address health problems associated with each type of disability. One way of doing this is by educating doctors about disabilities and ensuring their frequent contact with people with disabilities while they are in medical school. Therefore, this study aimed to develop a systematic medical education curriculum to enhance doctors' understanding of people with disabilities. The authors conducted a systematic literature review to develop and verify the basic framework of the educational content and curriculum. Two surveys were also developed using the Delphi method to evaluate the adequacy and necessity of educational topics. Items with a content validity ratio equal to or greater than the minimum value were considered valid. Survey panels comprised academic experts and health care practitioners who were working with people with disabilities. We conducted two surveys, one for a basic and the other for an advanced course, in which 13 to 16 respondents took part. The authors selected 13 topics for the 'Basic Introductory Course' and included general educational content on the health rights of people with disabilities focused on improving students' knowledge of disabilities. The authors also selected 12 topics for the 'Care and Communication for Patients with Disabilities Course' designed to improve students' understanding of interviewing and communicating with patients with disabilities. In Korea, disability has received little attention in the medical curriculum to date. The curriculum developed in this study provides preliminary data for guiding future directions in medical education and developing specific support plans for an education that promotes people with disabilities' health rights.


Attitudes of Palliative Care Specialists Toward Assessing Sexual Dysfunction in Patients With Cancer.
The sexual health of patients is frequently neglected. To evaluate the attitudes and beliefs of palliative care providers toward discussing the presence of sexual dysfunction (SD) in patients with cancer METHODS: In this pilot study, an anonymous survey was conducted among palliative care professionals about their attitudes toward discussing SD RESULTS: Forty-nine (89%) palliative care providers completed the survey. Thirty-four (69%) responded that they rarely or never discussed sexuality with their patients and most believed it is the oncologist's responsibility. The top reasons for not discussing SD were that the patient did not raise the issue, lack of time and the presence of a third party. The majority acknowledged the need of more training and that printed materials would be helpful. Palliative care providers infrequently address the presence of SD among patients with cancer. Additional training and routine screening for SD might help addressing this problem.


Four diseases of disarray in public health.
The Institute of Medicine's report The Future of Public Health stated that "public health is in disarray" (Washington, DC: National Academy Press, 1988). I describe four "diseases" of this disarray: "hardening of the categories," "hypocommitment to training," "tension headache between prevention and treatment," and "cultural incompetence." We must step outside the focus on problems and risk factors to use epidemiology to define health status positively and to identify health enhancing factors. This conference should catalyze innovative, holistic, culturally competent studies that will improve our well-being.


The ultrastructure of lymphadenosis benigna cutis (pseudolymphoma cutis).
In an ultrastructural study supplementing previous histological, cytochemical and immunocytological investigations of lymphadenosis benigna cutis, the tumor is shown to consist mainly of two cell types: Lymphocytes and macrophagocytic (reticulum?) cells. The tendency to spontaneous regression is manifested on the ultrastructural level by pronounced degenerative alterations.


Inhibition of the genotoxicity of bleomycin by superoxide dismutase.
Bleomycin was found to be cytotoxic and mutagenic in the CHO/HGPRT forward mutation assay. Approximately 50% cell mortality was achieved after a 1-h exposure to 10 micrograms/ml BLM. Bleomycin was also found to induce mutation to thioguanine resistance in a dose-dependent manner. Both the cyto- and geno-toxicity resulting from BLM exposure could be reduced by the prior addition of superoxide dismutase, implicating a role for activated oxygen metabolites in the mechanism of toxicity of bleomycin.


Trihydrogen cation with neon and argon: structural, energetic, and spectroscopic data from quartic force fields.
The argonium cation, ArH(+), has been previously detected in nature for the first time. This cation is believed to form through the gas-phase reaction of Ar(+) and H2. In this work, quantum chemical techniques show that the reaction of Ar and H3(+) may be a viable alternative or contributor to the creation of ArH(+) corroborating previous analysis. In order to further evaluate this claim, highly accurate quartic force field computations are used to produce spectroscopic data and anharmonic vibrational frequencies for ArH3(+) in its 18 isotopologues. NeH3(+) is also analyzed but has a low Ne-H3(+) dissociation barrier. Therefore, it less likely to be observed. Consequently, NeH(+) is also unlikely to be formed from NeH3(+) as it was also not from NeH2(+).


Ovarian adenosarcoma in a postmenopausal woman: Case report and review of literature.
Mullerian adenosarcoma is a rare malignancy that generally occurs in the uterine corpus but uncommonly, it may be found extrauterine. Ovarian adenosarcoma is extremely rare and often is presented in reproductive age women. Most of them are low grade and have à good prognosis except for adenosarcoma with sarcomatous overgrowth. A 77-year-old menopausal woman presented with abdominal discomfort. She had severe ascites and elevated levels of CA-125, CA 19-9, and HE4 tumor markers. Adenosarcoma with sarcomatous overgrowth was diagnosed after the histopathological examination of the surgical biopsy. The possibility of endometriosis transformation to malignancy even in postmenopausal women may warrant continuous follow-up for early diagnosis of ovarian cancer, this potentially fatal disease. More studies are needed to find the best therapeutic approach to adenosarcoma with sarcomatous overgrowth.


Potential mechanisms for functional changes in taste receptor cells following sodium deficiency in mammals.
Sodium is an essential nutrient for life, and its level in the body is tightly regulated. When sodium deficient, some mammals alter their behavior towards salt by avidly consuming it, even at concentrations animals typically choose to avoid. This change in acceptance is accompanied by a reduction in the response of the gustatory chorda tympani nerve to sodium solutions. More specifically, the response rate of the sodium-specialist units to NaCl stimulation is reduced following sodium deficiency or adrenalectomy. The initial transduction of the chemical signal is mediated, in part, by Na+ influx through epithelial Na+ channels in the apical membrane of taste cells that synapse with the specialist neurons. Circulating hormones like angiotensin II and adrenocorticotropin hormone, which are released in response to sodium deficiency and adrenalectomy, could regulate the activity of Na+ channels through G-protein linked second-messenger systems. These putative pathways are of interest because they have been described in mammalian taste receptor cells. The present review will summarize evidence linking some hormones of fluid homeostasis with the apparent attenuation of input from sodium-specialist neurons.


Impact of administrative state capacity determinants on sustainable healthcare.
Public administration implements government policies through prudent administrative practices and state capacity. Based on Asia's political and administrative proficiency and paradox, this study explores the administrative state capacity determinants-bureaucratic quality (BQ) and military in politics (MP)-and their interaction with sustainable public health quality (PHQ) in Asia from 2006 to 2020. With its focus on the scenario and Asian state administrative issues, Goal 04: Health and Well-being of Sustainable Development Goals has been the core aspect of state capacity and sustainable development. Applying the generalized method of moments (GMM) econometric estimation, the study finds that the high risk of poor BQ due to political pressures and policy inconsistency has significantly and negatively impacted PHQ in Asia. In contrast, by overtaking the administration, a high degree of MP and military dominancy has been a progressive force for PHQ in Asia. The interaction of BQ and MP negatively affects the state's social development due to conflict of interest and shredding policy outcomes. This is the first study that deals with the nexus between sustainable development and administrative state capacity determinants of Asia's public sector. The paper finds that an effective and prudent administrative collaboration and expertise-sharing between the bureaucracy and the military accelerates sustainable healthcare in Asia. Furthermore, the study believes that a healthy institutional collaboration will help overcome the development loopholes in Asia, promote PHQ, and accelerate regional development.


Tension gastrothorax.
Tension gastrothorax develops when the stomach herniated through a congenital diaphragmatic defect into the thorax is massively distended by trapped air. The authors present 5 cases and discuss the diagnostic and therapeutic management. Four children, aged 3, 4, 6, and 13 months, presented with progressive respiratory distress. In only 1 child was the diagnosis of tension gastrothorax established initially, and immediate insertion of a nasogastric tube led to complete resolution of respiratory distress symptoms. In the remaining 3 children, the initial chest radiograph was misread as tension pneumothorax. One of them developed cardiac arrest and was successfully resuscitated. In 2 patients, thoracostomy resulted in immediate respiratory improvement. Only on follow-up radiographic evaluation was diaphragmatic hernia with herniation of the stomach into the left hemithorax diagnosed. One child underwent diagnostic thoracoscopy revealing the correct diagnosis. All 4 children underwent uneventful repair of a classic Bochdalek hernia. The fifth child, aged 5 months, had sudden infant death. At autopsy tension gastrothorax was found. Tension gastrothorax is a life-threatening condition leading to acute and severe respiratory distress. The condition exhibits distinct radiographic features. Emergency decompression of the distended stomach should first be attempted via nasogastric tube. If this maneuver fails, decompression must be achieved either by needle puncture or by chest tube insertion into the stomach.


Baicalin suppresses Th1 and Th17 responses and promotes Treg response to ameliorate sepsis-associated pancreatic injury via the RhoA-ROCK pathway.
Recent studies have reported that the imbalance of T helper 1 cell (Th1), Th17 and regulatory T cell (Treg) have been confirmed to play a vital role in the development of sepsis and other inflammatory diseases. Baicalin (BA) has anti-inflammatory properties and improves survival in sepsis. We investigated whether baicalin could regulate Th1, Th17 and Treg responses to ameliorate sepsis-associated pancreatic injury through the ras homolog family member A (RhoA)-Rho kinase (ROCK) pathway. The sepsis model was established by using the cecal ligation and puncture (CLP) method. Fifty mice were randomly divided into five groups (n = 10): sham group, model group, low-dose group (BA-L, 100 mg/kg of baicalin), medium-dose group (BA-M, 200 mg/kg of baicalin) and highdose group (BA-H, 300 mg/kg of baicalin). The effects of baicalin on the pancreatic injury, on changes of Th1, Th17 and Treg cells in vivo and in vitro, on RhoA, ROCK1 and signal transducer and activator of transcription (STAT) signaling pathways, and on levels of interferon-γ (IFN-γ), interleukin-17 (IL-17) and IL-10 were examined. Treatment of the CLP mice with baicalin significantly reduced the extent, scope and severity of the pathological changes of sepsis-associated pancreatic injury. Baicalin evidently reduced Th1 and Th17 cells and increased Treg cells in peripheral blood, spleen, pancreatic tissue and significantly inhibited T-box protein expressed in T cells (T-bet), retinoic acid receptor-related orphan receptor γt (RORγt) and increased forkhead/winged helix transcription factor (Foxp3) expressions in the pancreatic tissue. Baicalin reduced the expressions of RhoA, ROCK1, phosphorylated STAT4 (p-STAT4), p-STAT3 and increased the expression of p-STAT5 in peripheral blood, spleen and pancreatic tissue. Baicalin reduced the expressions of IFN-γ and IL-17 and increased the IL-10 in serum and pancreatic tissue. Baicalin is capable of ameliorating sepsis-associated pancreatic injury and regulating Th1, Th17 and Treg responses in sepsis. The present study provided a potential adjunctive therapy for treating pancreatic injury in sepsis, and further study is needed to reveal its deeper mechanisms.


A monoclonal antibody against tetrodotoxin that reacts to the active group for the toxicity.
A monoclonal antibody against tetrodotoxin was produced. Tetrodotoxin coupled with keyhole limpet hemocyanin was used as an immunogen to BALB/c mice. These mice had no clinical signs for the toxicity of tetrodotoxin during the immunization. The reason may be that the guanidyl group of tetrodotoxin which is an important group for the toxicity was hidden by coupling with keyhole limpet hemocyanin. The monoclonal antibody was highly specific for tetrodotoxin and had no cross-reaction to tetrodotoxin derivatives, paralytic shellfish toxins, keyhole limpet hemocyanin and crude proteins from various organs of puffer fish. Also, tetrodotoxin was neutralized in vitro by this antibody. From the fact that the structural difference between tetrodotoxin and anhydro-tetrodotoxin is recognized by this antibody, it was suggested that this antibody reacted with the OH-groups on C-4 and/or C-9 of tetrodotoxin. In addition, the results from immunization and neutralization tests demonstrated that tetrodotoxin became non-toxic even when one of the active groups of tetrodotoxin was coupled by a molecule.


The influence of first pass metabolism on the development and validation of an IVIVC for metoprolol extended release tablets.
To investigate the influence of alpha-hydroxymetoprolol (AHM) and 4-(2-hydroxy-3-isopropylaminopropoxy)-phenylacetic acid (ACMB), both derived from its first pass metabolism of metoprolol, an in vitro in vivo correlation incorporating first pass metabolite data for metoprolol extended release formulations was developed. Three different releasing formulations (slow (S), moderate (M) and fast (F), 100 mg) of metoprolol were evaluated in a previously reported clinical study. The non-first pass effect (Non-FPE) in vitro in vivo correlation (IVIVC) was developed using a fraction of metoprolol dissolved and a fraction of total drug (metoprolol + metabolites) as the absorption data for various combinations of formulations (S/M/F, M/F, S/M, and S/F). Direct convolution approaches predicting metoprolol concentrations and indirect convolution predicting total drug concentrations (metoprolol + metabolites) were used to determine in vivo behavior. The Non-FPE IVIVC using the S/M/F formulations displayed the strongest relationship (r2 > 0.92). The IVIVC using the indirect approach was predictive of both the C(max) (prediction errors (PE) 4.77, 3.94 and 6.14%) and AUC (10.7, 11.0 and 11.3%) for metoprolol, AHM and ACMB. Poor predictability (PE > 40% for C(max) and AUC) was observed for metoprolol when using the direct methods. The predictability of the IVIVC using the indirect approach as compared to the direct method displays the influence of first pass metabolism on the development and evaluation of an IVIVC for a drug that displays a high extraction ratio. In addition, the indirect IVIVC allows for not only predicting the in vivo performance of the parent drug but also the metabolites formed via the first pass effect.


Combined hyperlipidemia and hypertriglyceridemia in renal allograft recipients. Comparison with non-renal combined hyperlipidemic or hypertriglyceridemic patients and normal subjects.
In order to investigate the degree of similarity between renal transplant and non-renal combined hyperlipidemic and hypertriglyceridemic patients, serum and lipoprotein lipid compositions were compared in transplant and non-renal combined hyperlipidemic and in transplant and non-renal hypertriglyceridemic patients, and normal subjects. Although certain similarities were demonstrated, combined hyperlipidemia in transplants differed from that in non-renal patients in a number of respects: (1) LDL-triglyceride levels were increased to a greater extent in transplant than in non-renal patients in females, while LDL-phospholipid was elevated in male transplants only; (2) HDL-cholesterol levels were raised in transplants relative to non-renal patients in females, and relative to both non-renal patients and normal subjects in males; (3) a number of differences in lipoprotein-lipid ratios between transplant and non-renal patients were demonstrated for all three lipoprotein fractions. In hypertriglyceridemia, changes in lipoprotein-lipid levels were similar in transplant and non-renal patients with the exception of HDL-cholesterol levels, which were decreased in non-renal patients only. Furthermore, the ratio of esterified to free cholesterol in LDL and HDL was decreased in non-renal but not in transplant patients. The data presented demonstrate that, despite certain similarities, a number of the lipoprotein-lipid changes observed in transplant combined hyperlipidemia and in transplant hypertriglyceridemia differ from those observed in non-renal patients with similarly elevated serum lipids.


Taking charge of ventilator-associated pneumonia.
Target average length of stay and treatment costs to develop best practices for care of ventilator-associated pneumonia patients.


Evidence that apomorphine and (+)-amphetamine produce different types of circling in rats.
Apomorphine and (+)-amphetamine are known to produce circling in naive rats. Frame by frame analysis of videotape recordings of the behaviour of Wistar rats treated with a subcutaneous injection of apomorphine (1.1 mg/kg; n = 8) or (+)-amphetamine (0.5 and 1.0 mg/kg; n = 8 and n = 8) was used to study this behaviour in more detail. In line with previously reported studies, apomorphine was found to change the functioning of hindlimb stepping. In contrast, (+)-amphetamine was found to change the functioning of forelimb stepping. These data imply that apomorphine and (+)-amphetamine produce their drug-specific circling via different substrates within the brain.


Cancer and SOX proteins: New insight into their role in ovarian cancer progression/inhibition.
Transcription factors are potential targets in disease therapy, particularly in cancer. This is due to the fact that transcription factors regulate a variety of cellular events, and their modulation has opened a new window in cancer therapy. Sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) proteins are potential transcription factors that are involved in developmental processes such as embryogenesis. It has been reported that abnormal expression of SOX proteins is associated with development of different cancers, particularly ovarian cancer (OC). In the present review, our aim is to provide a mechanistic review of involvement of SOX members in OC. SOX members may suppress and/or promote aggressiveness and proliferation of OC cells. Clinical studies have also confirmed the potential of transcription factors as diagnostic and prognostic factors in OC. Notably, studies have demonstrated the relationship between SOX members and other molecular pathways such as ST6Ga1-I, PI3K, ERK and so on, leading to more complexity. Furthermore, SOX members can be affected by upstream mediators such as microRNAs, long non-coding RNAs, and so on. It is worth mentioning that the expression of each member of SOX proteins is corelated with different stages of OC. Furthermore, their expression determines the response of OC cells to chemotherapy. These topics are discussed in this review to shed some light on role of SOX transcription factors in OC.


Prestress due to dimensional changes caused by demineralization: a potential mechanism for microcracking in bone.
Microcracking in bone due to internal strains caused by mineralization is a possible mechanism of damage. Similar damage can be seen in other biological composites such as trees experiencing growth-related prestresses. Dimensional changes in cortical bone due to demineralization and experimental glycation were studied to test whether mineralization-related prestrains are consistent with observed microcracking patterns in bone. A microscopy technique that enables wet measurements of length and angle of milled bone specimens was used. Demineralization of bovine and human bones caused significant anisotropic changes in tissue size. Dimensional changes due to demineralization in bovine bone were prevented or reduced when collagen cross linking was increased by glycation. The dimensional changes of bone caused by demineralization are consistent with the hypothesis that mineralization-caused stresses in remodeling tissue can cause microcracks.


Acaricidal activity of Acmella oleracea (Asteraceae) extract against Rhipicephalus microplus: What is the influence of spilanthol?
The present study was carried out to evaluate and compare the acaricidal activity of different fractions of Acmella oleracea methanolic extract, containing 0.0 % (F1), 24.5 % (F2), 48.0 % (F3) and 100 % (F4) of spilanthol, on unfed larvae and engorged females from the same Rhipicephalus microplus population. To obtain these fractions, the crude extract was subjected to different extraction procedures using increasingly polarized solvents to isolate the spilanthol compound. The Larval Packet Test was used to evaluate acaricidal activity in unfed larvae at concentrations ranging from 0.2 to 25.0 mg/mL, while for engorged females, the Adult Immersion Test was performed at concentrations from 3.1 to 25.0 mg/mL. The F1 fraction showed no activity on unfed larvae, while a control percentage of 44.6 % was observed at a concentration of 25.0 mg/mL for engorged females. For unfed larvae, the F2 fraction resulted in 95.7 % mortality at a concentration of 1.6 mg/mL, with a control percentage of 92.7 % for engorged females at a concentration of 12.5 mg/mL. Fractions F3 and F4 had similar activity against unfed larvae, with mortality >84.0 % from the concentration of 0.8 mg/mL. This similarity between the fractions was also observed for engorged females from a concentration of 12.5 mg/mL, resulting a control percentage >94.0 %. These results demonstrate that the presence of spilanthol is an important factor for the acaricidal activity of A. oleracea extract. Fraction extracts with 24.5, 48 and 100 % of spilanthol have similar acaricidal activity on R. microplus.


Element decoupling of 7T dipole body arrays by EBG metasurface structures: Experimental verification.
Metasurfaces are artificial electromagnetic boundaries or interfaces usually implemented as two-dimensional periodic structures with subwavelength periodicity and engineered properties of constituent unit cells. The electromagnetic bandgap (EBG) effect in metasurfaces prevents all surface modes from propagating in a certain frequency band. While metasurfaces provide a number of important applications in microwave antennas and antenna arrays, their features are also highly suitable for MRI applications. In this work we perform a proof-of-principle experiment to study finite structures based on mushroom-type EBG metasurfaces and employ them for suppression of inter-element coupling in dipole transceive array coils for body imaging at 7T. We firstly show experimentally that employment of mushroom structures leads to reduction of coupling between adjacent closely-spaced dipole antenna elements of a 7T transceive body array, which reduces scattering losses in neighboring channels. The studied setup consists of two active fractionated dipole antennas previously designed by the authors for body imaging at 7T. These are placed on top of a body-mimicking phantom and equipped with the manufactured finite-size periodic structure tuned to have EBG properties at the Larmor frequency of 298MHz. To improve the detection range of the B1+ field distribution of the top elements, four additional elements were positioned along the bottom side of the phantom. Bench measurements of a scattering matrix showed that coupling between the two top elements can be considerably reduced depending on the distance to the EBG structure. On the other hand, the measurements performed on a 7T MRI machine indicated redistribution of the B1+ field due to interaction between the dipoles with the structure. When the structure is located just over two closely spaced dipoles, one can reach a very high isolation improvement of -14dB accompanied by a strong field redistribution. In contrast, when put at a certain height over the antennas the structure provides a moderate isolation improvement together with a slight increase of B1+ level. This study provides a tool for the decoupling of dipole antennas in ultrahigh field transceive arrays, possibly resulting in denser element placement and/or larger subject-element spacing.


Body size predicts the rate of contemporary morphological change in birds.
Variation in evolutionary rates among species is a defining characteristic of the tree of life and may be an important predictor of species' capacities to adapt to rapid environmental change. It is broadly assumed that generation length is an important determinant of microevolutionary rates, and body size is often used as a proxy for generation length. However, body size has myriad biological correlates that could affect evolutionary rates independently from generation length. We leverage two large, independently collected datasets on recent morphological change in birds (52 migratory species breeding in North America and 77 South American resident species) to test how body size and generation length are related to the rates of contemporary morphological change. Both datasets show that birds have declined in body size and increased in wing length over the past 40 y. We found, in both systems, a consistent pattern wherein smaller species declined proportionally faster in body size and increased proportionally faster in wing length. By contrast, generation length explained less variation in evolutionary rates than did body size. Although the mechanisms warrant further investigation, our study demonstrates that body size is an important predictor of contemporary variation in morphological rates of change. Given the correlations between body size and a breadth of morphological, physiological, and ecological traits predicted to mediate phenotypic responses to environmental change, the relationship between body size and rates of phenotypic change should be considered when testing hypotheses about variation in adaptive responses to climate change.


A Janus supramolecular hydrogel prepared by one-pot method for wound dressing.
Despite the adhesive hydrogels have gained progress and popularity, it is still an enormous challenge to develop a smart adhesion hydrogel for clinical medicine, which is an asymmetric adhesion hydrogel with on-demand detachment. Motivated by the thermal phase transition mechanism of gelatin, we have synthesized a Janus supramolecular hydrogel dressing with skin temperature-triggered adhesion by a simple one-pot process. This hydrogel has asymmetric and controllable adhesion, which not only can become the external objects barrier but also can achieve repeated adhesion and on-demand detachment triggered by temperature in tens of seconds. This hydrogel presents great mechanical performance (compressive strain of 65 %, 1.38 MPa) owing to the presence of supramolecular interactions in the hydrogel. Additionally, this hydrogel exhibits excellent antibacterial activity and biocompatibility. The synergistic effect of modified gelatin and ionic liquid greatly facilitates wound healing of full-thickness skin with high wound healing efficiency (98.45 %). Therefore, thanks to all these advantages, the Janus supramolecular hydrogel can be applied for wound management and treatment, which has huge potential in healing skin wounds.


The Incidence and Risk Factors Associated With the Need for Fasciotomy in Tibia and Forearm Fractures: An Analysis of the National Trauma Data Bank.
The aims of this study were to analyze a large national trauma database to determine the incidence of, risk factors for, and outcomes after a fasciotomy of the lower leg or forearm after fracture. Data from the National Trauma Data Bank for the years 2004-2016 were analyzed, and we identified 301,351 patients with forearm fractures and 369,237 patients with tibial fractures. Risk factors, length of stay (LOS), and mortality were assessed to determine associations with an injury that required a fasciotomy. A total of 1.22% of the forearm fractures and 3.79% of the tibial fractures had a fasciotomy. Patients with a fasciotomy were more likely to have invasive procedures (P < 0.0001); have injuries resulting from machinery, motor vehicle collisions, and firearms (P < 0.0001); and smoke, use drugs, and/or alcohol (P < 0.05) compared with patients who did not undergo fasciotomies. Fasciotomy procedures were associated with longer LOS and higher mortality rate (P < 0.05). The incidence of a fasciotomy is less than 5% in tibia or forearm fractures. Patients who underwent fasciotomy have higher energy injuries, increased alcohol or drug use, higher rates of surgical interventions, and increased LOS. Furthermore, having a fasciotomy is associated with increased mortality rate. When counseling patients and evaluating surgeon/hospital performance, fasciotomies can serve as an indicator and modifier for a more complex trauma pathology. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


[Dementia-specific characteristics of patients with fall-related femur fractures : A case study based on routine hospital data of patients with unspecified dementia].
A fall-related femur fracture is one of the most frequent reasons for hospital admission of patients with dementia. The aim of the study was to identify dementia-specific characteristics of patients with fall-related femur fractures and additionally an unspecified dementia in order to gain further knowledge about this particular patient group. A descriptive explorative case study with a single case-embedded design based on routine hospital data from a university hospital was performed. A total number of 34 patient records from 2015 were analyzed. In the embedded unit of analysis I the data of selected items of the nursing assessment AcuteCare (ePA-AC©) were descriptively analyzed for the time of admission and discharge. In the embedded unit of analysis II a summarizing inductive content analysis was conducted. The results of the embedded unit of analysis I showed that this patient group is characterized by a high need for care, changes of cognition and behavioral symptoms. The status of cognition, behavior and reciprocity as well as the self-care index stagnated or deteriorated in many patients from admission to discharge. The embedded unit of analysis II identified observable (social)behavior, (non)compliance and orientation as central dementia-specific characteristics. The results reflect the complexity of the care situation of patients with unspecified dementia in acute care hospitals. The results showed that a higher awareness for this particular patient group is needed to improve outcomes.


Skin blood flow dynamics and its role in pressure ulcers.
Pressure ulcers are a significant healthcare problem affecting the quality of life in wheelchair bounded or bed-ridden people and are a major cost to the healthcare system. Various assessment tools such as the Braden scale have been developed to quantify the risk level of pressure ulcers. These tools have provided an initial guideline on preventing pressure ulcers while additional assessments are needed to improve the outcomes of pressure ulcer prevention. Skin blood flow function that determines the ability of the skin in response to ischemic stress has been proposed to be a good indicator for identifying people at risk of pressure ulcers. Wavelet spectral and nonlinear complexity analyses have been performed to investigate the influences of the metabolic, neurogenic and myogenic activities on microvascular regulation in people with various pathological conditions. These findings have contributed to the understanding of the role of ischemia and viability on the development of pressure ulcers. The purpose of the present review is to provide an introduction of the basic concepts and approaches for the analysis of skin blood flow oscillations, and present an overview of the research results obtained so far. We hope this information may contribute to the development of better clinical guidelines for the prevention of pressure ulcers.


In vitro toxicity evaluation in the development of new anticancer drugs-genistein glycosides.
In vitro cytotoxicity tests currently in use applied in the developmental stages of anticancer drug discovery are able to select the most potent compounds, but are not predictive of their potential toxicity. In this study, we have demonstrated the applicability of neutral red uptake assay using mouse fibroblasts Balb/c 3T3 cell line (3T3 NRU assay) for in vitro toxicity testing of newly synthesized genistein glycosides, the compounds that appear to show anticancer activity. We have also proven the compatibility of in-house 3T3 NRU assay with the prediction model for acute rodent oral toxicity testing, endorsed by NIEHS-ICCVAM workshop. The combined results from the cytotoxicity and the in vitro toxicity tests facilitated the selection of the most promising genistein derivatives, compounds G21 and G23, which were the most active and selective towards cancer cells. The comparison of predicted LD50 values revealed that almost all genistein derivatives are at least two-fold less toxic than the chemotherapeutics currently used in cancer therapy, which is very promising for this new group of compounds.


Chemically engineered glycan-modified cancer vaccines to mobilize skin dendritic cells.
Dendritic cell (DC)-targeting vaccines show great promise in increasing antitumor immunity. Glycan-engineered vaccines facilitate both DC targeting and increased uptake by DCs for processing and presentation to CD4+ and CD8+ T cells to induce tumor-specific T-cell responses. However, the complexity of various DC subsets in skin tissues, expressing different glycan-binding receptors that can mediate vaccine uptake or drainage of vaccines via lymphatics directly to the lymph node-resident DCs, complicates the success of vaccines. Moreover, the influx of inflammatory immune cells to the site of vaccination, such as monocytes that differentiate to DCs and coexpress glycan-binding receptors, may contribute to the strength of DC-targeting glycovaccines for future clinical use.


Correction to: Distribution and human health hazard appraisal with special reference to chromium in soils from Peenya industrial area, Bengaluru City, South India.
[This corrects the article DOI: 10.1007/s40201-021-00757-z.].


Comparison of different annotation tools for characterization of the complete chloroplast genome of Corylus avellana cv Tombul.
Several bioinformatics tools have been designed for assembly and annotation of chloroplast (cp) genomes, making it difficult to decide which is most useful and applicable to a specific case. The increasing number of plant genomes provide an opportunity to accurately obtain cp genomes from whole genome shotgun (WGS) sequences. Due to the limited genetic information available for European hazelnut (Corylus avellana L.) and as part of a genome sequencing project, we analyzed the complete chloroplast genome of the cultivar 'Tombul' with multiple annotation tools. Three different annotation strategies were tested, and the complete cp genome of C. avellana cv Tombul was constructed, which was 161,667 bp in length, and had a typical quadripartite structure. A large single copy (LSC) region of 90,198 bp and a small single copy (SSC) region of 18,733 bp were separated by a pair of inverted repeat (IR) regions of 26,368 bp. In total, 125 predicted functional genes were annotated, including 76 protein-coding, 25 tRNA, and 4 rRNA unique genes. Comparative genomics indicated that the cp genome sequences were relatively highly conserved in species belonging to the same order. However, there were still some variations, especially in intergenic regions, that could be used as molecular markers for analyses of phylogeny and plant identification. Simple sequence repeat (SSR) analysis showed that there were 83 SSRs in the cp genome of cv Tombul. Phylogenetic analysis suggested that C. avellana cv Tombul had a close affinity to the sister group of C. fargesii and C. chinensis, and then a closer evolutionary relationship with Betulaceae family than other species of Fagales. In this study, the complete cp genome of Corylus avellana cv Tombul, the most widely cultivated variety in Turkey, was obtained and annotated, and additionally phylogenetic relationships were predicted among Fagales species. Our results suggest a very accurate assembly of chloroplast genome from next generation whole genome shotgun (WGS) sequences. Enhancement of taxon sampling in Corylus species provide genomic insights into phylogenetic analyses. The nucleotide sequences of cv Tombul cp genomes can provide comprehensive genetic insight into the evolution of genus Corylus.


Prescreening of tumor samples for tumor-centric transcriptome analyses of lung adenocarcinoma.
Single-cell RNA sequencing (scRNA-seq) enables the systemic assessment of intratumoral heterogeneity within tumor cell populations and in diverse stromal cells of the tumor microenvironment. Gain of treatment resistance during tumor progression or drug treatment are important subjects of tumor-centric scRNA-seq analyses, which are hampered by scarce tumor cell portions. To guarantee the inclusion of tumor cells in the data analysis, we developed a prescreening strategy for lung adenocarcinoma. We obtained candidate genes that were differentially expressed between normal and tumor cells, excluding stromal cells, from the scRNA-seq data. Tumor cell-specific expression of the candidate genes was assessed via real-time reverse transcription-polymerase chain reaction (RT-PCR) using lung cancer cell lines, normal vs. lung cancer tissues, and lymph node biopsy samples with or without metastasis. We found that CEA cell adhesion molecule 5 (CEACAM5) and high mobility group box 3 (HMGB3) were reliable markers for RT-PCR-based prescreening of tumor cells in lung adenocarcinoma. The prescreening strategy using CEACAM5 and HMGB3 expression facilitates tumor-centric scRNA-seq analyses of lung adenocarcinoma.


Knotting of an epidural catheter: a case report.
Difficulty with removal of an epidural catheter is described due to formation of a knot near the end of the catheter. It is stressed that in the lumbar area an epidural catheter should never be inserted more than 5 cm into the epidural space, as curling with knot formation may occur. Removal may be attempted by pulling on the catheter if testing of a similar catheter indicates that it will withstand the tension. The patient and the spouse should be kept informed and involved in the decision-making for medico-legal reasons.