Experimental Voltammetry Analyzed Using Artificial Intelligence: Thermodynamics and Kinetics of the Dissociation of Acetic Acid in Aqueous Solution.
Artificial intelligence (AI) is used to quantitatively analyze the voltammetry of the reduction of acetic acid in aqueous solution generating thermodynamic and kinetic data. Specifically, the variation of the steady-state current for the reduction of protons at a platinum microelectrode as a function of the bulk concentration of acetic acid is recorded and analyzed giving data in close agreement with independent measurements, provided the AI is trained with accurate and precise knowledge of diffusion coefficients of acetic acid, acetate ions, and H+.


The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmic disorder with a highly malignant clinical course. Exercise-stress test is the first-line approach to diagnose suspected individuals. We sought to elucidate the value of exercise-stress test for predicting mutations and future cardiac events in CPVT-family relatives. The present study included 67 asymptomatic relatives (24 ± 15 years) of 17 genetically positive CPVT probands, who underwent exercise-stress test without any medication and genetic testing. Exercise-stress test, which was considered positive with the induction of ventricular tachycardia or premature ventricular contractions consisting of bigeminy or couplets, was positive in 17 relatives (25%). Genetic analysis disclosed mutations in 16 of these 17 relatives (94%) and in 16 of the 50 relatives (32%) with negative exercise-stress test; the sensitivity and specificity for a positive genotype were 50 and 97%, respectively (P< 0.001). Among 32 mutation carriers, cardiac events occurred in 7 of the 16 relatives with positive and 2 of the 16 relatives with negative exercise-stress test during the follow-up period of 9.6 ± 3.8 years, and four with positive and two with negative stress test were not on regular beta-blocker treatment at these events. In the 16 relatives with positive stress test, those on beta-blocker treatment demonstrated a trend of lower cardiac event rate (Log-rank P= 0.054). In asymptomatic relatives of CPVT probands, exercise-stress test can be used as a simple diagnostic tool. Nevertheless, because of the low sensitivity for predicting mutations and future cardiac events in those with negative stress test, genetic analysis should be performed to improve patient management.


Aortic valve replacement with the pulmonary autograft: mid-term results.
The purpose of this study is to assess the mid-term results of aortic valve replacement with the pulmonary autograft. From October 1993 through September 2003, 153 patients with aortic valve disease (81 rheumatic and 72 non-rheumatic), with a mean age of 28 +/- 14.2 years underwent the Ross procedure with root replacement technique and right ventricular outflow tract reconstruction using a homograft. Associated procedures included mitral valve repair (n = 19), open mitral commissurotomy (n = 15), tricuspid valve repair (n = 2), homograft mitral valve replacement (n = 2), and subaortic membrane resection (n = 1). Early mortality was 6.5% (10 patients). Mean follow-up was 77 +/- 42 months (range, 7 to 132 months; median, 90 months). One hundred, twenty-one survivors (84.6%) had no significant aortic regurgitation. Reoperation was required in 10 patients for autograft dysfunction alone (n = 3), infective endocarditis (n = 2), autograft dysfunction with failed mitral valve repair (n = 3), and failed mitral valve repair alone (n = 2). No reoperations were required for the pulmonary homograft. There were 8 late deaths. Actuarial and reoperation-free survival at 90 months were 91.% +/- 3.5%, 95.3% +/- 2.7%, in non-rheumatics and 86.1 +/- 3.9%, 90.5 +/- 3.7% in rheumatics, respectively. Freedom from significant aortic stenosis or regurgitation was 91.5 +/- 2.8% in non-rheumatics and 80.6 +/- 4.8% in rheumatics. Event-free survival was 86.2 +/- 4.9% in non-rheumatics and only 68.9 +/- 5.3% in rheumatics. The Ross procedure is not recommended for young patients (< 30 years) with rheumatic heart disease. It provides satisfactory hemodynamic and clinical results in properly selected patients. Important autograft dilatation was not observed in our patients.


Effects of aging on regional cerebral blood flow assessed by using technetium Tc 99m hexamethylpropyleneamine oxime single-photon emission tomography with 3D stereotactic surface projection analysis.
Although many previous reports have described age-related changes in regional cerebral blood flow (rCBF), none has used 3D stereotactic surface projection (3D-SSP) analysis, which is able to detect subtle and significant changes in rCBF. The subjects were 31 healthy volunteers (16 men and 15 women; 50-79 years of age) without abnormal MR imaging and MR angiographic findings, cognitive impairment, or depression. For each subject, rCBF was evaluated by using technetium Tc 99m-radiolabeled hexamethylpropyleneamine oxime single-photon emission CT. Maps of rCBF were compared among different age groups (50-59, 60-69, and 70-79 years of age) by using 3D-SSP. The mean z score for each gyrus was calculated for each age group by using a recently developed stereotactic extraction estimation method. Significant age-related reductions in rCBF were seen in the bilateral cingulate gyri, left inferior gyrus, bilateral medial frontal gyri, left subcallosal gyrus, and left superior temporal gyrus. Extensive and constant reduction in rCBF occurred with increasing age in the bilateral anterior cingulate gyri, and the mean z score for this region was the highest among all the regions examined. The 3D-SSP analysis revealed that the greatest reduction in rCBF occurred within the bilateral anterior cingulate gyri in normal middle-aged and older subjects.


Identification of an active-site residue in yeast invertase by affinity labeling and site-directed mutagenesis.
Deglycosylated yeast invertase is irreversibly inactivated by conduritol B epoxide (CBE), an active-site-directed reagent. The inactivated enzyme contained 0.8 mol of CBE/mol of invertase monomer suggesting that the inactivation results from the modification of a single amino acid residue. Peptic digestion of [3H]CBE-labeled invertase followed by reverse phase column chromatography yielded two labeled peptides, both located at the amino-terminal end of the enzyme. Sequence analyses of these peptides revealed that Asp-23 is the modified residue. The role of Asp-23 in the catalytic process was investigated by changing it to Asn using site-directed mutagenesis of the SCU2 gene. The mutant enzyme was basically inactive, confirming a role for Asp-23 in the catalytic process.


A Comparison of the LigaSure and harmonic scalpel in thyroid surgery: a single institution review.
During the last few years, many surgeons have begun to utilize the LigaSure device or Harmonic scalpel to perform thyroid surgery. Several papers have demonstrated the benefits of these devices compared with traditional hand-tying techniques. The purpose of this study was to examine our institution's experience with the LigaSure device and Harmonic scalpel during thyroid surgery and to compare mean operative times and complications associated with each device. A retrospective chart review was performed on all patients who underwent thyroid surgery using the LigaSure device or Harmonic scalpel at a single institution between December 2005 and August 2009. Charts were reviewed for patient demographics, mean operative time, length of stay, and complications, such as transient recurrent laryngeal nerve injury, hypocalcemia, and hematoma formation. A total of 231 patients were included in the study, of whom 123 underwent total thyroidectomy and 108 underwent lobectomy. There was a significant decrease in the operative time for both thyroidectomies and lobectomies when the Harmonic scalpel was utilized. In regard to complications, there was no statistically significant difference in the number of transient and permanent recurrent laryngeal nerve injuries, percentage of patients developing hypocalcemia, or rate of hematoma development. In this study, there was no difference in the rate of complications between the two devices. However, the use of the Harmonic scalpel significantly decreased operative time for both thyroidectomies and thyroid lobectomies compared with the LigaSure device.


Human hepatitis B viral e antigen and its precursor P20 inhibit T lymphocyte proliferation.
The hepatitis B virus (HBV) Precore protein is processed through the secretory pathway directly as HBeAg or with the generation of an intermediate (P20). Precore gene has been shown to be implicated in viral persistence, but the functions of HBeAg and its precursors have not been fully elucidated. We show that the secreted proteins HBeAg and P20 interact with T cell surface and alter Kit-225 and primary T cells proliferation, a process which may facilitate the establishment of HBV persistence. Our data indicate that the N-terminal end of Precore is important for these inhibitory effects and exclude that they are dependent on the association of HBeAg and P20 with two characterized cell surface ligands, the Interleukin-1 Receptor Accessory Protein and gC1qR (present study).


Hormesis commonly observed in the assessment of aneuploidy in yeast.
Extensive dose response studies have assessed the potential of toxic chemical agents to induce aneuploidy in the yeast model. An assessment of such findings revealed that hormetic-like biphasic dose responses were commonly observed. A preliminary estimate of the frequency of the hormetic responses using a priori entry and evaluative criteria was approximately 65-80%.


Assessment of the esophageal pressure in gastroesophageal reflux disease by the local regression.
Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. It is characterized by excessive reflux of gastric content (acid, pepsin, etc.) into the esophagus causing symptoms (heartburn, acid regurgitation, etc.) and mucosal inflammation and injuries. GERD occurs when the lower esophageal sphincter (LES) has a low resting pressure and stomach contents leak back, or reflux, into the esophagus. Therefore, the accurate measurement of the LES pressure is of great importance for the diagnosis of GERD. The LES pressure signal, involving severe respiratory contamination and motion artifacts, demands specific capabilities not provided by conventional data analysis methods. Recently, local regression has proved to be a very attractive technique to the nonparametric regression in statistics. In this contribution we apply the ideas of local regression to develop strategies for selecting smoothing parameters of local linear squares estimators, and present its application on the extraction of the LES pressure in GERD. The results from both extensive simulations and real data demonstrate the ability of local regression to characterize the LES pressure, which is consistent with the clinical observation.


Current state of career placement and employment opportunities for Doctor of Pharmacy graduates: A cross-sectional analysis from a college of pharmacy, Saudi Arabia.
Traditionally, graduates from colleges of pharmacy in Saudi Arabia work mainly in hospital settings, and only a few graduates work in other practice settings. However, several initiatives and national plans have recently been introduced to facilitate employment in community pharmacies and the pharmaceutical industry/companies. Consequently, the objectives of this study were to explore the current state of career placement, type of employment sectors, and practice settings that Doctor of Pharmacy (PharmD) graduates join based on recent developments in the profession. This study is a cross-sectional, descriptive study. The target population was PharmD graduates from Unaizah College of Pharmacy, Qassim University, Saudi Arabia. Consequently, all 162 graduates from three recent cohorts (2018-2020) were contacted to participate in this survey. A total of 157 graduates participated in this study, yielding a response rate of 96.91 %. Of the participants, 92 (58.6 %) were female graduates. The overall rate of employment was 84.7 %. Moreover, a higher proportion of male graduates than female graduates (97.1 % versus 73.7 %, P = 0.006) were employed. In this study, the three main sectors that the graduates joined were the pharmaceutical industry and companies (41.2 %), community pharmacies (29.4 %), and medical cities, hospitals and clinics (23.5 %). In addition, almost the same proportions of male and female graduates joined the pharmaceutical industry and companies (40.3 % versus 42.1 %). However, a higher proportion of male graduates than female graduates joined community pharmacies (32.3 % versus 26.3 %). Conversely, a higher proportion of female graduates joined medical cities, hospitals and clinics compared to male graduates (28.1 % versus 19.4 %). The current employment of PharmD graduates in the job market is generally high, but further improvement could be made, especially for female graduates. Moreover, the study findings showed that jobs are shifting toward community pharmacies and the pharmaceutical industry. Therefore, we believe that decision-makers in pharmacy education and curriculum developers must consider these trends and ensure that there is adequate preparation for careers in community pharmacy practice and other sectors of the profession in the curriculum.


Sex attractants for six clearwing and tineid species (Lepidoptera, Sesiidae and Tineidae) from Kazakhstan and Lithuania.
Sex attractants for 3 Sesiidae and 3 Tineidae moth species in West-Kazakhstan and Lithuania were discovered by field screening tests of (3Z,13Z)-, (3E,13Z)- and (2E,13Z)-octadecadien-1-ols and their acetates as well as of some binary mixtures of these compounds. Total amount of chemicals was 0.3 mg/dispenser. Males of Synanthedon serica were attracted by a 5:5 mixture of 3E,13Z-18:OAc and 2E,13Z-18:OAc, Chamaesphecia bibioniformis by a 9:1 mixture of 3Z,13Z-18:OAc and 3E,13Z-18:OAc, Paranthrene tabaniformis by a 1:9 mixture of 3Z,13Z-18:OH and 3E,13Z-18:OH, Tinea nonimella by a 1:9 mixture of 3E,13Z-18:OH and 2E,13Z-18:OH, Monopis monachella by a 1:9 mixture of 3Z,13Z-18:OH and 2E,13Z-18:OH, and Nemaxera betulinella by a 9:1 mixture of 2E,13Z-18:OAc and the corresponding alcohol. The periods of attraction to the traps were registered for males of S. serica and Ch. bibioniformis and were found to occur at 15-18 and 15-17 o'clock, local time, respectively.


Pharmacokinetics and pharmacodynamics of BIBT 986, a novel small molecule dual inhibitor of thrombin and factor Xa.
Current anticoagulant development focuses on agents with predictable pharmacokinetic and pharmacodynamic (PD) properties. BIBT 986 is a novel potent anticoagulant with a dual mechanism of action: it competitively inhibits factor (F) Xa and FIIa. To determine the safety, tolerability, pharmacokinetics (PK) and PD of BIBT 986 following intravenous infusion in healthy male volunteers. In three randomized, double-blind, placebo-controlled trials, subjects were administered by intravenous infusion escalating doses of BIBT 986 for up to 32 h. BIBT 986 concentrations were determined in plasma and urine samples by high pressure liquid chromatography tandem mass spectrometry. Pharmacodynamic response was assessed by measuring the changes in blood coagulation times. Activated partial thromboplastin time, International Normalized Ratio, thrombin time and ecarin clotting time were determined and compared with baseline results. In all three studies, intravenous infusion of BIBT 986 was safe and well tolerated. BIBT 986 exhibited linear PK over the dose range tested. Clearance was about 8 L h(-1) and V(ss) about 50 L. Apparent steady state concentrations were reached within 24 h, indicating a dominant half-life of about 6 h. The terminal half-life of BIBT 986 was approximately 12 h. Renal excretion contributes approximately 50% to total elimination. Overall interindividual variability in pharmacokinetic and PD parameters was < 40%. There was a linear correlation between plasma concentrations and PD responses, suggesting excellent predictability. BIBT 986 is the first small molecule of a novel class of anticoagulants that potently and directly inhibits both coagulation FXa and thrombin. It has predictable pharmacokinetic and PD characteristics.


Instruments for the identification of patients in need of palliative care: protocol for a systematic review of measurement properties.
The objective of this review is to provide a comprehensive overview of the psychometric properties of available clinician-reported instruments developed to identify patients in need of general and specialized palliative care in acute care settings. Identification of patients in need of palliative care has been recognized as an area where many health care professionals need guidance. Differentiating between patients who require general palliative care and patients with more complex conditions who need specialized palliative care is particularly challenging. To our knowledge, no dedicated instruments are available to date to assist health care professionals to make this identification. Included studies will report on i) instruments aiming to identify patients in need of palliative care, ii) adult patients in need of palliative care in acute-care settings, iii) clinician-reported outcome measures, or iv) the development process or one or more of its measurement properties. Studies conducted in intensive care units, emergency departments, or nursing homes will be excluded. We will search for studies published in English and French in a variety of sources, including Embase, Medline Ovid SP, PubMed, CINAHL EBSCO, Google Scholar, government websites, and hospice websites. All citations will be screened and selected by two independent reviewers. Data extraction, quality assessment, and syntheses of included studies will be performed according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria. PROSPERO CRD42020150074.


Role of hepsin in factor VII activation in zebrafish.
Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish.


[Pathogenesis of large vessel vasculitis].
Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are two granulomatous vasculitis affecting large arteries that present specific epidemiological and clinical features. Their pathogenesis is not fully understood but major advances have been obtained during the last years, thus allowing the emergence of new therapeutic strategies. GCA and TA develop on a specific genetic background but share some similarities regarding the immunological pathways involved in their pathogenesis. The trigger of these diseases is not clearly identified but it is thought that an infectious agent could activate and lead to the maturation of dendritic cells that are localized in the adventitia of arteries. Then, the cells of the adaptative immune response are recruited and activated: CD4 T cells that polarize into Th1 and Th17 cells, cytotoxic CD8 T cells and Natural Killer cells. Furthermore, the T regulatory cells (Treg) are decreased both in GCA and TA. Humoral immune response seems also to be involved, especially in TA. Then, the cytokines produced by T lymphocytes (especially IL-17 and IFN-γ) trigger the recruitment and activation of monocytes and their differentiation into macrophages and multinuclear giant cells that produce IL-1β and IL-6 that are responsible for general symptoms of GCA and TA, and cytotoxic mediators and growth factors that trigger the remodeling of the arterial wall leading to aneurysms and ischemic manifestations of GCA an TA.


Trend of the incidence of lumbar disc herniation: decreasing with aging in the elderly.
Compelling evidence has shown that the incidence of lumbar disc herniation (LDH) increases with age. In this study, retrospective clinical analysis of 601 cases of LDH has been conducted to investigate the role of age in the incidence of LDH in the elderly. The aim of the study is to investigate the relationship between the process of aging and the occurrence of LDH in old adults. Clinical cases (n = 601) of LDH were retrospectively analyzed. The imaging examination with computed tomography and/or magnetic resonance imaging showed the occurrence of degeneration in LDH patients over 65 years of age. The most common site of LDH is toward the bottom of the spine at L4-L5 and/or L5-S1. The incidence of LDH drops with age in the elderly, especially after the age of 80 years. There is an obvious decrease in LDH in the elderly female. A decreasing incidence of LDH with aging occurs in the elderly. This investigation indicates that aging is not a contributor to the performance of LDH in the elderly although the incidence of LDH is proportional to age.


Retracted: Degree of the Hazards of Silver-Containing Dressings on MRSA-Infected Wounds in Sprague-Dawley and Streptozotocin-Induced Diabetic Rats.
The Editor and Publisher regretfully have to retract the following two publications due to faulty study design.


Stabilized coronavirus spike stem elicits a broadly protective antibody.
Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive β-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies.


Possibility of steroid therapy without pacemaker implantation in patients with sarcoidosis presenting atrioventricular block.
Atrioventricular Block (AVB) is one of the common manifestations in cardiac sarcoidosis (CS). Although pacemaker implantation is generally recommended in patients with CS complicated by symptomatic AVB, some case reports have shown that they can be managed by steroid therapy without pacemaker implantation. The aim of this study was to evaluate the feasibility and effectiveness of steroid therapy without pacemaker implantation in patients with CS complicated by symptomatic AVB. We performed medical record review of consecutive ten CS patients who admitted Nippon Medical School Hospital for symptomatic second or third degree AVB between April 2015 and March 2021. Of the studied population, steroid therapy before pacemaker implantation was feasible in three patients with second degree AVB. Two of them showed subsequent recovery of atrioventricular conduction to 1:1, and they were managed by steroid therapy without pacemaker. The remaining one patient showed no improvement of atrioventricular conduction and required pacemaker implantation. Seven patients with third degree AVB required device implantation (pacemaker; n = 7, cardiac resynchronization therapy defibrillator; n = 1) before steroid therapy mainly because of hemodynamic instability. Steroid therapy without pacemaker implantation might be feasible, and possibly be effective in patients with CS presenting second degree AVB. However, the feasibility is limited in patients with third degree AVB.


The co-occurrence of anxiety disorders in African American parents and their children.
This study examined the co-occurrence of anxiety disorders, specifically the relationship between parent and youth anxiety, in a community-based sample of 100 African American parents and their biological child between the ages of 6 and 17 years. Data were provided by both the parent and child. Parents completed the Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) Client Version about their own experiences with anxiety and related disorders and the Parent version for the child's experiences. Children were administered the ADIS-IV Child version to assess their experiences with anxiety and related disorders. Fifty-five parents met criteria for at least one anxiety disorder while 34 children met criteria for at least one anxiety disorder. Two logistic regressions were subsequently conducted to predict the presence of any form of psychopathology from the ADIS-IV and the presence of an anxiety disorder in African American offspring. Results indicated that African American offspring with an anxious parent were 4 times more likely to meet criteria for both an anxiety disorder and other forms of psychopathology.


Production of branched-chain aroma compounds by Propionibacterium freudenreichii: links with the biosynthesis of membrane fatty acids.
Short branched-chain fatty acids (BCFAs) are cheese flavour compounds, which result from the conversion of branched-chain amino acids (BCAAs). In Swiss cheese, the production of short BCFAs is mainly performed by Propionibacterium freudenreichii and is strain dependent. Our aim was to investigate the possible links between the biosynthesis of short BCFAs and membrane BCFAs in P. freudenreichii. Short and membrane BCFAs were analysed by gas chromatography-mass spectrometry. Two strains differing in their capacities to release short BCFAs were selected. Tri-deuterated-labelled leucine was used in both strains as a precursor of short extracellular iso-BCFAs and of membrane iso-BCFAs. The proportions of anteiso : iso BCFAs synthesized varied as function of the BCAAs provided in the growth medium, from 72 : 28 to 100 : 0, with leucine and valine, and with isoleucine as sole BC precursors, respectively. The branching pattern of short BCFAs exactly matched that of membrane BCFAs, whatever the exogenous BCAAs provided. The biosynthesis of short BCFAs is closely related to that of membrane BCFAs in P. freudenreichii. The biosynthesis of short BCFAs in P. freudenreichii depends more on the strain than on the presence of exogenous BC precursors.


Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A.
Neutrophil diapedesis is an immediate step following infections and injury and is driven by complex interactions between leukocytes and various components of the blood vessel wall. Here, we show that perivascular mast cells (MC) are key regulators of neutrophil behaviour within the sub-endothelial space of inflamed venules. Using confocal intravital microscopy, we observe directed abluminal neutrophil motility along pericyte processes towards perivascular MCs, a response that created neutrophil extravasation hotspots. Conversely, MC-deficiency and pharmacological or genetic blockade of IL-17A leads to impaired neutrophil sub-endothelial migration and breaching of the pericyte layer. Mechanistically, identifying MCs as a significant cellular source of IL-17A, we establish that MC-derived IL-17A regulates the enrichment of key effector molecules ICAM-1 and CXCL1 in nearby pericytes. Collectively, we identify a novel MC-IL-17A-pericyte axis as modulator of the final steps of neutrophil diapedesis, with potential translational implications for inflammatory disorders driven by increased neutrophil diapedesis.


Evaluation of the diagnostic value of plasma copper levels in cattle.
Copper (Cu) is an essential trace element. Depletion of liver-Cu stores leads to clinical or sub-clinical Cu deficiency. Our objective was to evaluate plasma-Cu levels as a diagnostic test for the assessment of Cu status in cattle. We used liver-Cu levels as the gold standard. The chosen cutoff for plasma Cu was 9 mmol/l; two different cutoffs were chosen for liver-Cu: 20 and 10 microg/g dry matter (DM). When 20 microg/g DM of liver Cu was the cutoff, plasma Cu had sensitivity=69% (58, 79) and specificity=84% (74, 93). The same values if the cutoff in liver was 10 microg/g were 92 (82, 100) and 73% (64, 82), respectively. ROC curves showed that the best cutoff to be used for plasma Cu was 8.26 mmol/l; however, no significant improvement was found in sensitivity or specificity. We concluded that interpretation of plasma-Cu levels significantly varies with the liver-Cu cutoff.


Delayed-type skin reactions in bursectomized or thymectomized chickens.
Chickens can easily be induced to develop delayed-type skin reactions to oxazolone when animals are sensitized 7 days before the challenge. The reaction is quantitated by assessing the increase in wattle thickness: maximum reactions occur 24 h after challenge. The reaction is inhibited by neonatal thymectomy or bursectomy; these findings therefore suggest also an important B-derived component in delayed hypersensitivity to oxazolone.


Formation of oxyadenine metabolites in the rabbit after intravenous administration of adenine.
Adenine, 8-oxyadenine, and 2,8-dioxyadenine were analyzed, by Dowex-50 column chromatography, in rabbit urine four hours after IV infusion of the following doses of adenine in mg/kg: 2, 4, 8.75, 17.5, 35, 70, 140 and 210. The average excretion in mole percentage of the dose was: adenine, 11.1; 8-oxyadenine, 6.1; and 2,8-dioxyadenine, 6.2. The percentage of excretion of 8-oxyadenine and of 2,8-dioxyadenine was unrelated to the dose of adenine. At doses of adenine of 35 mg/kg and above more than 80 per cent of the 2,8-dioxyadenine in the urine was in the form of microscopic pale yellow spherical particles. The particulate 2,8-dioxyadenine was found in the kidney in a very small amount at the dose of 70 mg/kg and in much greater quantities at 140 and 210 mg/kg.


Isoform specificity of monoclonal hybridoma antibodies to quail skeletal muscle myosin subunits.
Monoclonal antibodies to adult quail breast muscle myosin (QBM) have been prepared and characterized using a solid phase enzyme linked immunosorbent assay and immunoblot procedures. One antibody (QBM-1) is directed against an epitope in the rod portion of the myosin heavy chain while another (QBM-2) binds exclusively to a conserved portion of the two alkali light chains of fast muscle myosin. Both of these antibodies cross-react with myosin from myotubes cultured in vitro but do not recognize non-muscle myosin. The application of these antibodies to the study of myogenesis is discussed.


Interaction characteristics of Plexin-B1 with Rho family proteins.
Plexin-B1 regulates various cellular processes interacting directly with several Rho proteins. Molecular details of these interactions are, however, not well understood. In this study, we examined in vitro and in silico the interaction of the Rho binding domain (B1RBD) of human Plexin-B1 with 11 different Rho proteins. We show that B1RBD binds in a GTP-dependent manner to Rac1, Rac2, Rac3, Rnd1, Rnd2, Rnd3, and RhoD, but not to RhoA, Cdc42, RhoG, or Rif. Interestingly, Rnd1 competitively displaces the Rac1 from B1RBD but not vice versa. Structure-function analysis revealed a negatively charged loop region, called B1L(31), which may facilitate a selective B1RBD interaction with Rho proteins.


Thermotropic phase transitions of phosphatidylcholines with odd-numbered n-acyl chains.
Diacyl phosphatidylcholines with n-C13, -C15, -C17 and -C19 saturated acyl chains have been synthesized and their phase transitions in the presence of excess water monitored by differential thermal analysis. The C15-, C17- and C19-diacyl species show gel to liquid-crystalline transitions and pretransitions like those of the even-chain phosphatidylcholines. A plot of the main phase transition temperature, Tc, vs. acyl chain length is a smooth curve on which the Tc values of both odd- and even-chain species fall, while a similar plot for the pretransition temperature, Tp, shows significant alternation of Tp between odd- and even-chain species. Consideration of these results in terms of the physical basis of the odd-even alternation of phase transition temperatures in homologous series of paraffinic compounds suggests that the acyl chains of disaturated phosphatidylcholines are tilted with respect to the bilayer normal below Tp but become perpendicular to the bilayer surface above the pretransition temperature.


[Subtypes of foot-and-mouth disease virus type A. Genetic markers of clones obtained from 4 strains isolated in Argentina between 1961 and 1970].
The results obtained studying the genetic markers g, t and rtc of different clones of subtypes of foot-and-mouth disease virus type A are presented in this paper. The subtypes were isolated during outbreaks of foot and mouth disease in Argentine. No significative differences among the subtypes were observed with the t marker. For the other markers, the results seem to indicate a gradual change related with the serological variation. Because of their sensibility to guanidine hidrochloride, it is possible to conclude that the studied clones do not belong to the so called European strains.


Neuroprotection by 7-nitroindazole against iron-induced hippocampal neurotoxicity.
(1) Iron plays an important role in maintaining normal brain function. In some neurodegenerative disorders including Parkinson's and Alzheimer's disease, iron levels rise in the brain. It is known that higher iron levels induce neuronal hyperactivity and oxidative stress. A body of evidence indicates a relationship between neuronal death and nitric oxide (NO). The aim of present study was to evaluate the effects of NO produced by neuronal nitric oxide synthase (nNOS) on iron-induced neuronal death. (2) Animals were classified into four groups: control, iron, iron+7-nitroindazole, and iron+vehicle. Rats in iron, iron+7-nitroindazole, and iron+vehicle groups received intracerebroventricular (i.c.v.) FeCl3 injection (200 mM, in 2.5 microl). Rats belonging to control groups received the same amount of saline into the cerebral ventricles. All animals were kept alive for 10 days following the operation. Animals in iron+7-nitroindazole group received intraperitoneal 7-nitroindazole (30 mg/kg/day) injections once a day during this period, while the rats belonging to vehicle group received daily intraperitoneal injection of peanut oil. After 10 days, rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using the standard histological techniques. (3) The total number of neurons in hippocampus of all rats was estimated with the unbiased stereological techniques. Results of present study show that 7-nitroindazole decreased mean neuron loss from 43% to 11%. Treatment of peanut oil alone did not affect iron-induced hippocampal cell loss with respect to iron group values. (4) Findings of our study suggest that 7-nitroindazole may have neuroprotective effects against iron-induced hippocampal neurotoxicity by inhibiting nNOS.


Application of online teaching mode combining case studies and the MOOC platform in obstetrics and gynecology probation teaching.
To explore the application effect of the clinical basic integration teaching mode constructed by case studies and the MOOC platform in obstetrics and gynecology internship teaching in the face of public health emergencies. One hundred ten clinical medical students of grade 2020 were selected as the experimental group, and 110 clinical medical students of grade 2021 were selected as the control group. The experimental group adopted the online teaching mode combined with case studies and the MOOC platform, while the control group adopted the offline traditional probation teaching method. Comprehensive test and questionnaire were used to evaluate and compare the teaching effect of the two groups of students. The experimental group was found to be superior to the control group in the quality assessment of complete medical record writing and the ability assessment of diagnosis and analysis of typical obstetrics and gynecology cases (P < 0. 05). However, the score of professional knowledge was lower than that of the control group (P < 0. 05). The results of questionnaire survey showed that the satisfaction of the experimental group in stimulating learning interest, enhancing problem solving ability, enhancing communication and clinical thinking ability, enhancing team cooperation awareness and independent innovation ability was higher than that of the control group (P < 0.01). The satisfaction of teacher-student interaction was also better (P < 0.05). However, in terms of strengthening theoretical understanding, the satisfaction of the experimental group was lower than that of the control group, but with no significant difference (P > 0.05). During the epidemic period, we designed a new online teaching mode, which can be applied to the probation teaching of obstetrics and gynecology. In our study, compared with traditional offline teaching, the new online teaching mode could improve students' ability of case writing and case analysis. However, more teaching practice is needed to complete this online teaching mode.


Age criteria for polysomnography and inpatient management for adenotonsillectomy.
Clinical practice guidelines (CPG) by the American Academy of Otolaryngology recommend that children <2yo with sleep disordered breathing (SDB) undergo preoperative polysomnography (PSG) and children <3yo be admitted following adenotonsillectomy (TA) for inpatient management. As the rationale for preoperative PSG and postoperative admission in the CPG are the same, there is an inconsistency in the age recommendations between <2yo and two to three-years-old (2-3yo). This study compared the characteristics of <2yo versus 2-3yo patients undergoing workup and treatment for SDB, with the goal of determining whether 2-3yo should be classified with <2yo. Case series with retrospective review. Boston Medical Center, a tertiary academic hospital. Patients ≤3yo who underwent PSG 2015 to 2019 were identified using a filter through the electronic medical record. 448 patients underwent PSG. Bivariate analysis via Pearson chi-square test and multivariate analysis via multinomial logistic regression were performed using SPSS. Of the 427 patients included in this study, 217 patients were in the age group of <2yo while 210 patients were in the age group of 2-3yo. Severity of OSA (p = 0.069) and surgical outcomes (defined by presence or resolution of OSA on follow-up PSG) (p = 0.260) were similar between the two groups. Children <2yo were more likely to have smaller tonsils (p < 0.024) than 2-3yo. Characteristics, such as severity of OSA, were similar between the age groups. Further studies should be conducted to determine if consideration should be taken for routine preoperative PSG children <3yo. IV.


Polydioxanone thread insertion in combination with radio frequency treatment does not exhibit synergistic efficacy: Animal study with pigs.
Polydioxanone (PDO) thread insertion and monopolar radio frequency (RF) treatment are two common antiaging modalities. The efficacy and safety profile of PDO in combination with RF treatment is unknown. To investigate pathological changes in skin in response to PDO + RF treatment in an animal model. PDO threads were implanted into the skin of young white domestic pigs. RF treatment was performed on the PDO insertion sites 2 weeks after the PDO procedure. Skin biopsies were taken at 6 and 12 weeks after PDO for histological examination. Both PDO and PDO + RF treatments induced the fibrous granular formation surrounding the PDO threads. There were more exaggerated inflammatory responses such as development of nodular panniculitis and adipocyte necrosis in the skin at 6 weeks after PDO + RF as compared with PDO alone, which was largely resolved at 12 weeks. All treatments led to thickened and replicated interlobular septa, many of which were connected to the collagenous network in dermis. In all treatment groups, the cross-sectional areas of the dermal collagenous bundles were significantly increased at both endpoint times as compared with the baseline level. PDO + RF treatment did not lead to increases in neocollagenesis as compared with PDO or RF treatment alone. Our data showed that RF and PDO induced comparable levels of collagen remodeling in the skin. PDO + RF treatment did not exhibit evident synergistic effects of derma collagen remodeling but rather amplified the inflammatory responses in the skin. Therefore, combined treatment is not recommended.


[Diagnosis and treatment of liver injuries and their sequelae].
The authors studied 222 cases of closed and open injuries to the liver and, in addition, had 5 patients who were treated for sequelae of injury (hemobilia, abscesses, biliary fistula of the liver). The diagnosis of open injuries to the liver is established without great difficulties; laparocentesis and laparoscopy are indicated in closed injury. The volume of the operation is determined by the character of the damage: closure of the hepatic wound proves sufficient in most patients; surgical debridement is necessary in deep extensive wounds; resection of the liver is resorted to in disturbed blood supply. The high postoperative mortality rate is due to the fact that 71.8% of patients had concurrent injuries of the liver, other abdominal organs, organs of other cavities, central nervous system, and the locomotor apparatus.


Lung metastasis after pneumonectomy: Is there a place for surgery?
Resection of the contralateral lung after primary total pneumonectomy is a real surgical option for patients with secondary lung disease.


Geographic patterns in the flight ability of a monophagous beetle.
The migratory ability of a monophagous insect, Tetraopes tetraophthalmus (Coleoptera: Cerambycidae), was measured in ten populations in each of two regional types. In the first region, a river valley, populations were abundant and close together; in the second regional type, mountainous and peripheral areas, populations were uncommon and far apart. The data revealed that regional variation in migratory behavior occurred along two dimensions. Regions differed not only in the mean migratory ability of individuals (1st dimension) but in the amount of variation between populations (2nd dimension). Whereas river valley populations were found to be uniformly sedentary, mountainous and peripheral populations were found to be heterogeneous, some being very vagile, others being very sedentary. In the mountainous and peripheral areas, small and sparse populations were more vagile than large dense populations. The site to site variation in the mountainous and peripheral areas was due exclusively to females. In these areas, the mean migratory ability of females in a population was positively correlated with mean body size of the females, and inversely correlated with populations density. The data are consistent with the FLY hypothesis for this species (long distance migraters=Females, Large, and Young). Taken together, the geographical patterns support the "founding hypothesis" of migration. According to this theory, the inevitable selection against migration within populations is balanced by periodic extinctions of the populations and the founding of new populations by migrating individuals.


Assessment of Treatment-Relevant Immune Biomarkers in Psoriasis and Atopic Dermatitis: Toward Personalized Medicine in Dermatology.
Immunologically targeted therapies have revolutionized the treatment of inflammatory dermatoses, including atopic dermatitis and psoriasis. Although immunologic biomarkers hold great promise for personalized classification of skin disease and tailored therapy selection, there are no approved or widely used approaches for this in dermatology. This review summarizes the translational immunologic approaches to measuring treatment-relevant biomarkers in inflammatory skin conditions. Tape strip profiling, microneedle-based biomarker patches, molecular profiling from epidermal curettage, RNA in situ hybridization tissue staining, and single-cell RNA sequencing have been described. We discuss the advantages and limitations of each and open questions for the future of personalized medicine in inflammatory skin disease.


Fatty acid elongation in the biosynthesis of (Z)-10-heptadecen-2-one and 2-tridecanone in ejaculatory bulb microsomes of Drosophila buzzatii.
A fatty acid chain elongation process is involved in incorporation of saturated and unsaturated fatty acyl-CoA esters into 2-tridecanone and (Z)-10-heptadecen-2-one by Drosophila buzzatii. The microsomal fraction from mature male ejaculatory bulbs is chain-length specific and requires malonyl-CoA (or acetyl-CoA, if acetyl-CoA carboxylase were present) for the chain elongation step to 2-ketones. Decarboxylation of the proposed intermediate beta-ketoacid results in 2-ketone biosynthesis. Incubation of the microsomes with the acetyl-CoA carboxylase inhibitor avidin indicated that acetyl-CoA carboxylase was present in the microsomal preparations; however, washing of the microsomal preparation removed the acetyl-CoA carboxylase activity. Fatty acyl-CoA esters were also chain elongated to produce fatty acids two and four carbons longer, suggesting that the enzymes for normal fatty acid chain elongation are also present in the microsomal fraction from ejaculatory bulbs. How much, if any, of this fatty acid chain elongation system is used for 2-ketone biosynthesis is yet to be determined.


Colonization characteristics of bacterial communities on microplastics compared with ambient environments (water and sediment) in Haihe Estuary.
The bacterial communities on microplastics in marine and freshwater environments have been described by many studies. However, the migration and transportation processes of bacterial communities on microplastics in estuarine areas remain unclear. In this study, the bacterial communities on three substrates (microplastics, surface water and sediment) in estuarine areas (the Haihe Estuary (HHE) in Bohai Bay, China) were investigated based on 16S rRNA sequencing. The mean OTUs of the three substrates - water, microplastics and sediments - were 1091, 2213 and 3419, respectively. The partitioning of the OTUs among the three substrates indicated that the microplastics could be messengers facilitating the bacterial transportation between water and sediment. According to nMDS and relative abundance analyses, it was found that the microplastics enriched the particular bacteria (e.g., Halobacteriaceae and Pseudoalteromonadaceae) and weakened the influence of environmental variation. In addition, taxonomic and metabolic-pathway analyses indicated that the abundance of potentially pathogenic bacteria (e.g., Pseudomonas and Bacillus) on microplastics was significantly higher than that in the ambient environment. Meanwhile, the microplastic polymer types had little effect on the abundance and structure of the bacterial communities. Compared with surface water and sediments, microplastics could be a good habitat for bacterial communities and could lead to potential ecological risks because of the high stability, pathogenicity and stress tolerance of the bacterial communities on microplastics.


Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy.
In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+).n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group.


Spatial and temporal variations of river nitrogen exports from major basins in China.
Provincial-level data for population, livestock, land use, economic growth, development of sewage systems, and wastewater treatment rates were used to construct a river nitrogen (N) export model in this paper. Despite uncertainties, our results indicated that river N export to coastal waters increased from 531 to 1,244 kg N km(-2) year(-1) in the Changjiang River basin, 107 to 223 kg N km(-2) year(-1) in the Huanghe River basin, and 412 to 1,219 kg N km(-2) year(-1) in the Zhujiang River basin from 1980 to 2010 as a result of rapid population and economic growth. Significant temporal changes in water N sources showed that as the percentage of runoff from croplands increased, contributions of natural system runoff and rural human and livestock excreta decreased in the three basins from 1980 to 2010. Moreover, the nonpoint source N decreased from 72 to 58 % in the Changjiang River basin, 80 to 67 % in the Huanghe River basin, and 69 to 51 % in the Zhujiang River basin, while the contributions of point sources increased greatly during the same period. Estimated results indicated that the N concentrations in the Changjiang, Huanghe, and Zhujiang rivers during 1980-2004 were higher than those in the St. Lawrence River in Canada and lower than those in the Thames, Donau, Rhine, Seine, and Han rivers during the same period. River N export will reduce by 58, 54, and 57 % for the Changjiang River, Huanghe River, and Zhujiang River in the control scenario in 2050 compared with the basic scenario.


Mito-nuclear discordance within Anthozoa, with notes on unique properties of their mitochondrial genomes.
Whole mitochondrial genomes are often used in phylogenetic reconstruction. However, discordant patterns in species relationships between mitochondrial and nuclear phylogenies are commonly observed. Within Anthozoa (Phylum Cnidaria), mitochondrial (mt)-nuclear discordance has not yet been examined using a large and comparable dataset. Here, we used data obtained from target-capture enrichment sequencing to assemble and annotate mt genomes and reconstruct phylogenies for comparisons to phylogenies inferred from hundreds of nuclear loci obtained from the same samples. The datasets comprised 108 hexacorals and 94 octocorals representing all orders and > 50% of extant families. Results indicated rampant discordance between datasets at every taxonomic level. This discordance is not attributable to substitution saturation, but rather likely caused by introgressive hybridization and unique properties of mt genomes, including slow rates of evolution driven by strong purifying selection and substitution rate variation. Strong purifying selection across the mt genomes caution their use in analyses that rely on assumptions of neutrality. Furthermore, unique properties of the mt genomes were noted, including genome rearrangements and the presence of nad5 introns. Specifically, we note the presence of the homing endonuclease in ceriantharians. This large dataset of mitochondrial genomes further demonstrates the utility of off-target reads generated from target-capture data for mt genome assembly and adds to the growing knowledge of anthozoan evolution.


When can complete regression of low-grade gastric lymphoma of mucosa-associated lymphoid tissue be predicted after helicobacter pylori eradication?
Recent studies suggest that primary low-grade gastric lymphomas of mucosa-associated lymphoid tissue (MALT) are cured in many cases between 1 and 18 months after H. pylori eradication. The aim of this study is to elucidate when complete regression (CR) of MALT lymphoma can be histologically predicted after H. pylori eradication. Twenty-one patients with low-grade gastric MALT lymphoma were treated with triple therapy (amoxicillin, clarythromycin and proton pump inhibitor) for 14 days. Subsequently, they were followed up by sequential endoscopy and biopsy (number of biopsy specimens for each endoscopy is 3-8, with an average of 4) from 91 to 657 days (average: 309 +/- 165 days). Eradication of H. pylori infection was achieved in all patients. Nine patients were free of lymphoma at 1 to 2 months after eradication and remained in CR at 163-657 days. Twelve patients showed residual lymphoma at 1 to 2 months after eradication. Five out of 12 patients revealed only one or two small foci of lymphoma-cell aggregation and showed a high incidence (80%) of CR at the latest biopsy (135-434 days, average 276 +/- 115 days after eradication), while seven patients showed diffuse remains of lymphoma cells and indicated CR in only one case (14%) at 362 days, partial regression in five cases at 130-431 days (average 227 +/- 114 days), and no change in one case at 91 days after eradication. : These results suggest that CR of low-grade MALT lymphoma can be predicted at 1 to 2 months after eradication therapy by checking histological changes of MALT lymphoma cells.


Umbelliferone prevents isoproterenol-induced myocardial injury by upregulating Nrf2/HO-1 signaling, and attenuating oxidative stress, inflammation, and cell death in rats.
The role of oxidative injury and inflammatory response in cardiovascular diseases and heart failure has been well-acknowledged. This study evaluated the protective effect of umbelliferone (UMB), a coumarin with promising radical scavenging and anti-inflammatory activities, on myocardial injury induced by isoproterenol (ISO) in rats. Rats received 50 mg/kg UMB orally for 14 days and 85 mg/kg ISO twice at an interval of 24 h. Administration of ISO elevated serum troponin I, creatine kinase-MB and lactate dehydrogenase, and caused histopathological alterations, including degeneration, fatty vacuolation, myolysis, and atrophy of myocardial fibers. Malondialdehyde (MDA), nitric oxide (NO), nuclear factor-kappaB (NF-κB) p65, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were increased, whereas reduced glutathione (GSH), superoxide dismutase (SOD), and catalase were decreased in ISO-administered rats. UMB effectively ameliorated myocardial injury, alleviated cardiac function markers, MDA, NO, NF-κB p65, and the inflammatory mediators, and enhanced cellular antioxidants. Bax, caspase-3, and 8-OHdG were decreased, and Bcl-2 was increased in ISO-administered rats treated with UMB. In addition, UMB upregulated nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 in the heart of ISO-administered rats. In conclusion, UMB can protect the myocardium from oxidative injury, inflammatory response, and cell death induced by ISO by upregulating Nrf2/HO-1 signaling and antioxidants.


Evaluation of phytoextracting cadmium and lead by sunflower, ricinus, alfalfa and mustard in hydroponic culture.
Soil contaminated with heavy metals cadmium (Cd) and lead (Pb) is hard to be remediated. Phytoremediation may be a feasible method to remove toxic metals from soil, but there are few suitable plants which can hyperaccumulate metals. In this study, Cd and Pb accumulation by four plants including sunflower (Helianthus annuus L.), mustard (Brassica juncea L.), alfalfa (Medicago sativa L.), ricinus (Ricinus communis L.) in hydroponic cultures was compared. Results showed that these plants could phytoextract heavy metals, the ability of accumulation differed with species, concentrations and categories of heavy metals. Values of BCF (bioconcentration factor) and TF (translocation factor) indicated that four species had dissimilar abilities of phytoextraction and transportation of heavy metals. Changes on the biomass of plants, pH and Eh at different treatments revealed that these four plants had distinct responses to Cd and Pb in cultures. Measurements should be taken to improve the phytoremediation of sites contaminated with heavy metals, such as pH and Eh regulations, and so forth.


An ¹⁸F-FDG PET study of cervical muscle in parkinsonian anterocollis.
The underlying etiology of parkinsonian anterocollis has been the subject of recent debate. The purpose of this study is to test the hypothesis that anterocollis in parkinsonian syndromes is associated with dystonia of the deep cervical flexors (longus colli and capitis). Eight patients with anterocollis, six in the setting of parkinsonism and two primary cervical dystonia control subjects with anterocollis underwent prospective structured clinical evaluations (interview, examination and rating scales), systematic electromyography of the cervical extensor musculature and (18)F-FDG PET/CT studies of cervical muscles to examine evidence of hypermetabolism or overactivity of deep cervical flexors. Subjects with parkinsonian anterocollis were found to have hypermetabolism of the extensor and sub-occipital muscles but not in the cervical flexors (superficial or deep). EMG abnormalities were observed in all evaluated patients, but only one patient was definitely myopathic. Meanwhile, both dystonia controls exhibited hypermetabolism of cervical flexors (including the longus colli). In conclusion, we were able to demonstrate hypermetabolism of superficial and deep cervical flexors with muscle (18)F-FDG PET/CT in dystonic anterocollis patients, but not in parkinsonian anterocollis patients. The hypermetabolic changes seen in parkinsonian anterocollis patients in posterior muscles may be compensatory. Alternative explanations for anterocollis include myopathy of the cervical extensors, or unbalanced rigidity of the cervical flexors, but this remains to be proven.


Mediated Effects of Perceived Competence on Youth Physical Activity and Sedentary Behavior.
This study evaluates whether physical activity (PA) and sedentary behavior (SB) are influenced by a common mediating relationship. A total of 1,552 participants in 3rd to 12th grade completed an online survey that included assessments of PA at school (PAS), PA at home (PAH), and SB as well as a battery of psychosocial variables (i.e., attraction to PA and perceived competence). Perceived competence had a direct positive effect on PA and a negative effect on SB. These associations were consistently (but partially) mediated by attraction to PA; however, the indirect effect (IE) of perceived competence was stronger for PAH (IE = .27, p < .05) than for PAS (IE = .07, p < .05), or SB (IE = .13, p < .05). This study revealed some direct effects and IEs of perceived competence on PAS, PAH, and SB through attraction to PA as the mediator. PA and SB may be influenced by some common underlying psychosocial mediators.


Effect of the chronic ingestion of chlorimipramine and desipramine on the hole board response to acute stresses in male rats.
The effect of the chronic ingestion of chlorimipramine (CI) or desipramine (DS) on the alterations of hole board behavior caused by a model stress (2 IP injections of physiological saline) and by a short restraint stress (5 min) is analyzed in this study. The experimental groups ingested about 3 mg/kg/24 hr CI or DS for 15 days. Then some experimental and control rats were assigned to control of drug effects on baseline activity. The remaining rats were submitted to saline stress (Experiment I) or restraint stress (Experiment II). The baseline scores of hole board locomotion, head dipping, grooming and defecation were not affected by DS treatment but locomotion slightly increased in the CI treated group. Saline stress impaired significantly head dipping and caused excessive grooming in control rats. The CI treatment induced almost full protection against these behavioral effects of saline stress but DS treatment was ineffective. Restraint stress was found to cause a pronounced inhibition of head dipping as well as a great increase of the scores of grooming in the control group. The CI treatment clearly attenuated these effects of restraint but DS treatment was not effective. The results suggest that male rats treated chronically with CI tolerated both acute stresses better than untreated rats, and that a similar treatment with DS did not provide protection against the effect of such stresses on hole board responding. Inasmuch as CI and DS have different relative potency at noradrenergic and serotonergic systems, it is speculated that this might be in part responsible for their differences as stress protectors.


Arbuscular mycorrhizal fungi community in soils under desertification and restoration in the Brazilian semiarid.
Soil desertification has a significant social, economic, and environmental impact worldwide. Mycorrhizal diversity remains poorly understood in semiarid regions impacted by desertification, especially in Brazilian drylands. More importantly, positive impacts of grazing exclusion on mycorrhizal communities are still incipient. Here, we hypothesized that overgrazing changes the structure of Arbuscular Mycorrhizal Fungi (AMF) community compared to native areas and, grazing exclusion is effective to restore the AMF community. Thus, we analyzed the status of AMF community in soils under desertification (overgrazing) and restoration (twenty-years of grazing exclusion) in the Brazilian semiarid. AMF-spores were extracted via humid decantation methodology, morphologically classified, and alpha diversity metrics were calculated. Soil samples were chemically, and physically characterized and multivariate statistical analyses were applied to verify the impact of soil degradation and restoration on AMF-community. Briefly, native, and restored areas presented higher contents of organic matter, phosphorus, microbial carbon, and β-glucosidase activity. However, degraded soil showed higher Al3+, Na+, and bulk soil density values. The abundance of AMF spores was higher in restored soil, followed by degraded and native vegetation, and Shannon's diversity index was significantly higher in restored soils, followed by native vegetation. AMF-spores were classified into four families (Gigasporaceae > Acaulosporaceae > Glomeraceae > Ambisporaceae). Ambisporaceae was closed correlated with degraded soil, mainly with Al3+, Na+, and bulk soil density properties. On the other hand, Acaulosporaceae and Glomeraceae were positively correlated with native vegetation and restored soil, respectively, thereby improving Shannon index, richness, enzyme activity, and soil respiration. Thus, grazing exclusion, in long term, can be a good strategy to restore AMF-diversity in soils in the Brazilian semiarid.


Muscle-nerve ephaptic excitation in some repetitive after-discharges.
We describe high frequency muscular repetitive after-discharges (MRDs), induced by maximal or near maximal electrical nerve stimulation, in 5 patients suffering from different peripheral neuropathies. No MRDs were observed at rest or during voluntary contraction. In all the MRDs the interval between the onset of the M wave and the onset of the MRD did not change in relation to the nerve stimulation point; double supramaximal stimulation with adequate delay, delivered at the same nerve site, could suppress the MRDs. From the electrophysiological features the authors suggest an interpretative model: the muscular electric field of the M wave could reexcite ephaptically an intramuscular axon, with defective repolarizing capacity, producing a muscle-nerve reverberating loop.


Characterising and dissecting human perception of scene complexity.
Humans can effortlessly assess the complexity of the visual stimuli they encounter. However, our understanding of how we do this, and the relevant factors that result in our perception of scene complexity remain unclear; especially for the natural scenes in which we are constantly immersed. We introduce several new datasets to further understanding of human perception of scene complexity. Our first dataset (VISC-C) contains 800 scenes and 800 corresponding two-dimensional complexity annotations gathered from human observers, allowing exploration for how complexity perception varies across a scene. Our second dataset, (VISC-CI) consists of inverted scenes (reflection on the horizontal axis) with corresponding complexity maps, collected from human observers. Inverting images in this fashion is associated with destruction of semantic scene characteristics when viewed by humans, and hence allows analysis of the impact of semantics on perceptual complexity. We analysed perceptual complexity from both a single-score and a two-dimensional perspective, by evaluating a set of calculable and observable perceptual features based upon grounded psychological research (clutter, symmetry, entropy and openness). We considered these factors' relationship to complexity via hierarchical regressions analyses, tested the efficacy of various neural models against our datasets, and validated our perceptual features against a large and varied complexity dataset consisting of nearly 5000 images. Our results indicate that both global image properties and semantic features are important for complexity perception. We further verified this by combining identified perceptual features with the output of a neural network predictor capable of extracting semantics, and found that we could increase the amount of explained human variance in complexity beyond that of low-level measures alone. Finally, we dissect our best performing prediction network, determining that artificial neurons learn to extract both global image properties and semantic details from scenes for complexity prediction. Based on our experimental results, we propose the "dual information" framework of complexity perception, hypothesising that humans rely on both low-level image features and high-level semantic content to evaluate the complexity of images.


Proficiency tests in the determination of activity of radionuclides in radiopharmaceutical products measured by nuclear medicine services in 8 years of comparison programmes in Brazil.
Proficiency tests were applied to assess the performance of 74 nuclear medicine services in activity measurements of (131)I, (123)I, (99)Tc(m), (67)Ga and (201)Tl. These tests produced 913 data sets from comparison programmes promoted by the National Laboratory for Ionizing Radiation Metrology (LNMRI) from 1999 to 2006. The data were evaluated against acceptance criteria for accuracy and precision and assigned as Acceptable or Not acceptable accordingly. In addition, three other statistical parameters were used as complementary information for performance evaluation which related to normative requirements and to radionuclide calibrators. The results have shown a necessity to improve quality control procedures and unsatisfactory performances of radionuclide calibrators, which incorporate Geiger-Müller detectors.


Fetal liver infusion in acute myelogenous leukaemia.
Forty-five patients with acute myelogenous leukaemia (AML) received induction chemotherapy with either a conventional dose of cytarabine and daunorubicin (27 patients) or a low dose of cytarabine (18 patients). Maintenance chemotherapy was given to all responders. In 14 of 39 evaluable patients, infusion of fetal liver cells from 10-24 weeks old foetuses was given following induction as well as maintenance therapy. Six of 14 patients (43%) achieved a complete remission; 2 showed evidence of transient engraftment documented by analysis of sex chromosomes and RBC antigens (1 patient each). Fetal liver infusion within 6 days of completing induction chemotherapy appeared more effective than when given later. Five of 25 patients (20%) who did not receive fetal liver infusion achieved a complete remission. The present work suggests that fetal liver infusion given following induction chemotherapy may increase the remission rate in AML either by temporary engraftment or by accelerating the rate of haematological recovery.


Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study.
To evaluate the efficacy and safety of three dose levels of relugolix, a gonadotropin-releasing hormone receptor antagonist, compared with placebo and leuprorelin in women with endometriosis-associated pain. Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Hospitals and clinics. Adult premenopausal women with endometriosis who had dysmenorrhea and endometriosis-associated pelvic pain. During a 12-week treatment period, patients received relugolix 10 mg (n = 103), 20 mg (n = 100), or 40 mg (n = 103) as a daily oral dose; placebo (n = 97) as a daily oral dose; or leuprorelin 3.75 mg (n = 80) as a monthly subcutaneous injection. Primary endpoint was the change from baseline in mean visual analog scale score for pelvic pain during 28 days before the end of treatment. The mean changes in mean visual analog scale score for pelvic pain were -3.8 mm in the placebo group; -6.2, -8.1, and -10.4 mm in the relugolix 10-mg, 20-mg, and 40-mg groups; respectively; and -10.6 mm in the leuprorelin group. The major adverse events with relugolix were hot flush, metrorrhagia, menorrhagia, and irregular menstruation, and bone mineral density decrease in a dose-response manner, which were also observed in the leuprorelin group with a frequency comparable with that in the relugolix 40-mg group. Oral administration of relugolix alleviated endometriosis-associated pain in a dose-response manner and was generally well tolerated. Relugolix 40 mg demonstrated efficacy and safety comparable with those of leuprorelin. NCT01458301.


[Congenital laryngeal cyst: an uncommon cause of stridor in neonates].
Laryngeal cyst is a rare but generally benign lesion in the larynx. It may cause stridor and life-threatening airway obstruction in early infancy. We report the case of a neonate who developed respiratory distress 24h after birth in relation with materno-fetal infection. Airway obstruction was then suspected because of stridor. A laryngeal mass was discovered at the time of intubation. The infant experienced a nosocomial infection and died on day 14 of life before any surgical treatment. Autopsy concluded in an epiglottic congenital laryngeal cyst.


Monthly pattern of psychiatric morbidity and duration of stay among the patients admitted in Mental Hospital, a central level tertiary care hospital.
Psychiatric morbidity is a major public health problem in the world across developed and developing countries. There is a paucity of Nepalese studies on psychiatric morbidity. All the patients who were admitted in mental hospital, Lagankhel from 17th July 2009 to 16th July 2010 were included in this study. Information on their Socio-demographic profiles and hospital diagnosis was extracted from their clinical notes. Eight hundred and fifty two patients were included in this study. Fifty eight percent were males. More than sixty percent of the patients were aged between 21 and 40 years. Sixty patients were married. In terms of ICD 10 diagnosis, the most common diagnoses were Schizophrenia in 427 (50.1%), mood disorders in 286 (33.5%) and substance use disorder in 80 (9.3%). In terms of length of stay, majority of them (56.4%) had stayed for 0-14 days. Thus, there is a need to increase the awareness in the general public regarding the impact of mental illness and the need for timely treatment.


Biobehavioral factors in cancer pain.
Despite the presence of pathology in cancer pain, the pain experience in adult cancer patients cannot be totally explained by the extent of such pathology. Unlike chronic benign pain very little research on the role of biobehavioral factors has been conducted to help explain this paradox. The literature on the role of biobehavioral factors in the cancer pain experience is reviewed. A brief review of epidemiology and pathophysiology is presented. Following this, the biobehavioral literature was organized according to research on psychological characteristics and environmental factors. Research addressing affective, cognitive, behavioral and physiological reactions to pain was also discussed. Despite the paucity of studies, the review suggested the following: (1) personality factors do not appear to play a consistent role in the modulation of pain in cancer patients; (2) the work on environmental influences on cancer pain indicate a weak association between such factors as social network and pain intensity; (3) studies on affective state indicate minimal relationships to pain, and lastly, (4) studies on cognitive responses to pain in cancer patients and their influence on the pain experience have not been conducted. To date, in the areas where biobehavioral factors have been investigated, the findings appear modest. However, many potential variables, e.g., self-esteem, the role of family, the role of models, past or current work environments, social learning factors and responses to pain such as fear, somatization and reattribution have not been explored with cancer patients. While the influence of biobehavioral factors in adult cancer pain appear to be relatively modest, the literature is not extensive. Increased efforts at more precisely determining the input of such factors in cancer pain are warranted, particularly given the role of such variables in other recurrent and chronic pain states.


Optimal Aspergillus fumigatus and Asp f 1 serum IgG cut-offs for the diagnosis of allergic bronchopulmonary aspergillosis.
The presence of IgG antibodies (Abs) to Aspergillus fumigatus (Af) is a crucial diagnostic criterion for allergic bronchopulmonary aspergillosis (ABPA). Although precipitation is traditionally used to document IgG Abs, anti-Af serum IgG levels can also be measured by enzyme immunoassay (EIA). However, there are insufficient data on the optimal cut-offs to assess diagnostic performance of the EIA method. This study aimed to determine cut-off levels of IgG binding crude Af extracts or recombinant Asp f 1 (by ImmunoCAP®) and to compare their efficacy for ABPA diagnosis with Af-precipitating Abs. The age distribution of levels of IgG to crude extracts of Af (Af-IgG) and recombinant Asp f 1 (Asp f 1-IgG) was established using sera from 694 healthy controls (HC). Receiver operating characteristic analysis for Af-IgG and Asp f 1-IgG levels for the purpose of ABPA diagnosis was performed in 306 Af-sensitized asthma patients (including 49 ABPA), and cut-offs were determined. An age-dependent decline in the levels of Af-IgG was observed in HC. Thus, cut-offs for Af-IgG levels were determined separately by age as 60 mg/L for patients aged <55 years, and 45 mg/L for those aged ≥55 years. For Asp f 1-IgG, 6.6 mg/L was set as the cut-off regardless of age. Although such IgG testing by EIA allowed a sufficiently good diagnostic performance, Af-precipitating Abs had better diagnostic applicability for ABPA. We determined cut-offs for Af-IgG and Asp f 1-IgG measured by EIA, which can be useful in clinical settings where precipitating Abs are unavailable.


30S ribosomal proteins cross-linked to 16S RNA by periodate oxidation followed by borohydride reduction.
Gel electrophoretic techniques have been used to reexamine the RNA-protein cross-linking reaction induced by periodate oxidation and borohydride reduction of 30S ribosomal subunits. The results show that a number of 30S ribosomal proteins become attached to intact 16S RNA by this method, in addition to those already published. It follows that this cross-linking technique as it stands is of little value as a topographical probe of the environment of the 3'-terminus of the 16S RNA.


Comparison of the in vitro and in vivo effects of retinoids either alone or in combination with cisplatin and 5-fluorouracil on tumor development and metastasis of melanoma.
Retinoids have previously been reported to inhibit proliferation of melanoma cell lines in vitro. However, the relative antimetastatic efficacy of various retinoids on melanoma in vivo is unknown. Therefore, we investigated the effects of different retinoids on the invasion and metastasis of murine melanoma B16-F10 cells in vitro and in vivo. Based on the findings, the antitumor effects of a selected retinoid either alone or in combination with cisplatin were also investigated in a preclinical mouse melanoma model. Cell proliferation and invasion analyses of murine melanoma B16-F10 cells were assessed in the presence of different retinoids, either alone or in combination with cisplatin (CDDP) or 5-fluorouracil (5-FU). Experimental lung metastasis assay was performed in this study to investigate the antimetastatic efficacy of retinoids. Additionally, a mouse melanoma model was used to assess the antitumor efficacy of a selected retinoid in combination with cisplatin. Retinoids showed significant antiproliferation and anti-invasion effects on murine melanoma B16-F10 cells. Pretreatment with retinoids increased the sensitivity to CDDP but not to 5-FU in in-vitro. Moreover, the number of metastatic colonies formed in the lungs of mice injected intravenously with B16-F10 cells was significantly reduced by injecting the respective retinoid once a day for 10 days. Treatment with a combination of cisplatin and 13-cis-retinoic acid resulted in a significant reduction in primary tumor size and the number of lung metastatic nodules in melanoma-bearing mice. These results suggest that retinoids not only exhibit antimetastatic effect, but also enhance the antitumor activity of cisplatin in vivo.


Essential steps in developing best practices to assess reflective skill: A comparison of two rubrics.
Medical education lacks best practices for evaluating reflective writing skill. Reflection assessment rubrics include the holistic, reflection theory-based Reflection-on-Action and the analytic REFLECT developed from both reflection and narrative-medicine literatures. To help educators move toward best practices, we evaluated these rubrics to determine (1) rater requirements; (2) score comparability; and (3) response to an intervention. One-hundred and forty-nine third-year medical students wrote reflections in response to identical prompts. Trained raters used each rubric to score 56 reflections, half written with structured guidelines and half without. We used Pearson's correlation coefficients to associate overall rubric levels and independent t-tests to compare structured and unstructured reflections. Reflection-on-Action training required for two hours; two raters attained an interrater-reliability = 0.91. REFLECT training required six hours; three raters achieved an interrater-reliability = 0.84. Overall rubric correlation was 0.53. Students given structured guidelines scored significantly higher (p < 0.05) on both rubrics. Reflection-on-Action and REFLECT offer unique educational benefits and training challenges. Reflection-on-Action may be preferred for measuring overall quality of reflection given its ease of use. Training on REFLECT takes longer but it yields detailed data on multiple dimensions of reflection that faculty can reference when providing feedback.


Retrospective study on the trajectories of lower limb volume after outpatient-based complex decongestive therapy in post-operative gynecological cancer patients with lymphedema.
To determine the effect of outpatient-based complex decongestive therapy in patients with secondary lower limb lymphedema (LLL) after gynecologic cancer surgery using group-based trajectory modeling (GBTM), and to examine factors predictive of the treatment course. This retrospective study included participants who underwent surgery for gynecological cancer with pelvic lymph node dissection and subsequently visited the outpatient clinic for the treatment of stage II LLL according to the International Society of Lymphology. The improvement rate of edema at the initial visit and 3, 6, and 12 months later was assessed by calculating the volume of the lower extremity using the circumferential method. For evaluation of the patterns of treatment course, logistic regression analysis was performed after group estimation by the trend of the treatment course using GBTM. A total of 148 women (mean age 60.6 years (standard deviation: 13.4 years)) were analyzed. Three improvement trajectories were identified: (1) no response group, with worsening rather than improvement (n = 26); (2) moderate response group, with a slow improvement rate (n = 89); and (3) high response group, with a high improvement rate (n = 33). In addition, adherence to compression therapy at 3 months post-intervention was found to be a predictor in the no response group. GBTM estimated that there are three patterns of the treatment course in patients with LLL after gynecologic cancer surgery. Adherence to compression therapy at 3 months post-intervention is a predictor of the treatment effectiveness.


Antinuclear antibodies and nuclear antigens in NZB myeloma ascitic fluids.
Approximately 5-10% of ascitic fluids from 411 NZB myeloma tumors were found to possess either antinuclear (ANA) or Coombs antibodies. Some fluids showed anti-SM specificity, which is thought to be unique to systemic lupus erythematosus (SLE). In addition, the ascitic fluids were found to contain large amounts of DNA and Sm autoantigens. Further passage of ANA-positive myelomas indicated that the autoantibodies were not products of the myeloma cells themselves. The sporadic appearance of unsuspected autoantibodies in ascitic fluids may cause confusion when working with myeloma or with hybridoma reagents. Furthermore, the development of SLE-specific anti-Sm antibodies in this context suggests parallels between myeloma development and autoimmunity.


Synthesis of a Diverse Library of N,N-Dimethylamino Containing Monomers Appropriate as Lipid Head Groups.
We report on the synthesis of a diverse library of N,N-dimethylamino containing monomers. Subjecting these monomers to Chabrier reaction conditions would yield lipids with polymerizable head groups. This library of lipid head groups is equipped with a variety of arm lengths containing reduction-oxidation polymerizable groups at the terminus.


Left bundle branch potential predicts better electrical synchrony in bradycardia patients receiving left bundle branch pacing.
Left bundle branch pacing (LBBP) is a novel physiological pacing technology. We aim to explore the relation between LBB potential (LBB Po) and left ventricular (LV) electrical/mechanical synchrony in bradycardia patients without heart failure (HF) receiving LBBP. A total of 62 patients undergoing LBBP were categorized by LBB Po: the LBB Po positive (+) group and the LBB Po negative (-) group. The perioperative electrocardiographic and echocardiography parameters related to cardiac synchrony were analyzed. There were 42 (67.74%) patients in the LBB Po (+) group and 20 patients in the LBB Po (-) group. Paced QRS duration (113.50 ± 17.65 ms vs. 123.40 ± 13.18 ms, P = 0.031) and stimulus left ventricular activation time (71.76 ± 3.53 ms vs. 74.45 ± 3.12 ms, P = 0.005) were shorter in the LBB Po (+) group than in the LBB Po (-) group. No significant differences in the LV mechanical synchrony (Ts-SD-12, 36.55 ± 19.76 vs. 39.95 ± 16.04, P = 0.505; PSD, 51.14 ± 17.69 vs. 45.65 ± 10.55, P = 0.205) between the two groups. There was not statistically difference in ventricular lead parameters measured intraoperative between the two groups. Compared with the LBB Po (-) group, the LBB Po (+) group showed a dramatically higher total procedure duration time (93.52 ± 9.18 min vs. 86.25 ± 10.54 min, p = 0.007) and fluoroscopy time for ventricle lead implantation (18.95 ± 3.43 min vs. 14.00 ± 3.16 min, p < 0.001). The appearance of LBB Po may suggest better electrical synchrony during LBBP, but similar in LV mechanical synchrony. However, the total operation duration and fluoroscopy time of ventricular lead implantation in the LBB Po (+) group were longer. Therefore, it may be unnecessary to deliberately recognize the LBB Po when it is difficult to detect LBB Po and meet the LBBP criterion.


Laboratory-based versus non-laboratory-based World Health Organization risk equations for assessment of cardiovascular disease risk.
The WHO model has laboratory-based and non-laboratory-based versions for 10-year risk prediction of cardiovascular diseases. Due to the fact that in some settings, there may not be the necessary facilities for risk assessment with a laboratory-based model, the present study aimed to determine the agreement between laboratory-based and non-laboratory-based WHO cardiovascular risk equations. In this cross-sectional study, we used the baseline data of 6796 individuals without a history of cardiovascular disease and stroke who participated in the Fasa cohort study. The risk factors of the laboratory-based model included age, sex, systolic blood pressure (SBP), diabetes, smoking and total cholesterol, while the non-laboratory-based model included age, sex, SBP, smoking and BMI. Kappa coefficients was used to determine the agreement between the grouped risk and Bland-Altman plots were used to determine the agreement between the scores of the two models. Sensitivity and specificity of non-laboratory-based model were measured at the high-risk threshold. In the whole population, the agreement between the grouped risk of the two models was substantial (percent agreement = 79.0%, kappa = 0.68). The agreement was better in males than in females. A substantial agreement was observed in all males (percent agreement = 79.8%, kappa = 0.70) and males < 60 years old (percent agreement = 79.9%, kappa = 0.67). The agreement in males ≥ 60 years old was moderate (percent agreement = 79.7%, kappa = 0.59). The agreement among females was also substantial (percent agreement = 78.3%, kappa = 0.66). The agreement for females < 60 years old, (percent agreement = 78.8%, kappa = 0.61) was substantial and for females ≥ 60 years old, (percent agreement = 75.8%, kappa = 0.46) was moderate. According to Bland-Altman plots, the limit of agreement was (95%CI: -4.2% to 4.3%) for males and (95%CI: -4.1% to 4.6%) for females. The range of agreement was suitable for both males < 60 years (95%CI: -3.8% to 4.0%) and females < 60 years (95%CI: -3.6% to 3.9%). However, it was not suitable for males ≥ 60 years (95% CI: -5.8% to 5.5%) and females ≥ 60 years (95%CI: -5.7% to 7.4%). At the high-risk threshold of 20% in non-laboratory and laboratory-based models, the sensitivity of the non-laboratory-based model was 25.7%, 70.7%, 35.7%, and 35.4% for males < 60 years, males ≥ 60 years, females < 60 years, and females ≥ 60 years, respectively. At the high-risk threshold of 10% in non-laboratory-based and 20% in laboratory-based models, the non-laboratory model has high sensitivity of 100% for males ≥ 60 years, females < 60 years, females ≥ 60 years, and 91.4% for males < 60 years. A good agreement was observed between laboratory-based and non-laboratory-based versions of the WHO risk model. Also, at the risk threshold of 10% to detect high-risk individuals, the non-laboratory-based model has acceptable sensitivity for practical risk assessment and the screening programs in settings where resources are limited and people do not have access to laboratory tests.


Correction: Honey Bee Inhibitory Signaling Is Tuned to Threat Severity and Can Act as a Colony Alarm Signal.
[This corrects the article DOI: 10.1371/journal.pbio.1002423.].


Onset of action of a topical antihistamine as assessed by histamine challenge-induced plasma exudation responses.
Although usually administered orally, antihistamines are available also for topical use in allergic rhinitis. Information on onset of action of these drugs is incomplete. To examine onset of action of topical cetirizine-dinitrate on plasma exudation evoked by repeated nasal histamine challenges. A liposome formulation of cetirizine-dinitrate (2.44 mg per nasal cavity) was delivered via a nasal spray device as 2 consecutive actuations per nasal cavity in a placebo-controlled design. The nasal mucosal surface was challenged and lavaged with a histamine solution (100 microg/mL) 5, 15, 25, and 55 minutes after each treatment. In addition, the mucosa was lavaged with saline before each treatment. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation (luminal entry) of plasma. Histamine produced significant increases in nasal lavage fluid levels of alpha2-macroglobulin at all observation points (5 through 55 minutes after treatment). Nasal cetirizine-dinitrate significantly inhibited this response at 5 and 15 minutes after treatment. The effect of topical cetirizine-dinitrate, as established by histamine challenge-induced mucosal exudation of plasma, has an early onset (ie, within 5 to 10 minutes).


Assisted reproduction in Indonesia: policy reform in an Islamic culture and developing nation.
This article considers how religious and economic factors shape assisted reproductive technology (ART) policy in Indonesia, the world's most populous Muslim country. Infertility clinic policies are grounded on both the views of the country's powerful Islamic coalition and those of the worldwide Islamic community. Indonesian government officials, physicians, and Islamic scholars have expressed concern over who can use ART and which procedures can be performed. Indonesia has also faced economic challenges related to ART, including inadequate health insurance coverage, inequitable access to ART, and maintenance of expensive ART infrastructure. The prohibitive price of infertility treatment and regional differences in the provision of health care prohibit most Indonesians from obtaining ART. In the absence of a shift in religious mores and a rapid reduction in poverty and inequality, Indonesia will need to adopt creative means to make ART both more available and less necessary as a solution to infertility. This paper suggests policy reforms to promote more affordable treatment methods and support preventative health programmes to reduce infertility rates. This country-specific analysis of the laws and customs surrounding ART in Indonesia reveals that strategies to reduce infertility must be tailored to a country's unique religious and economic climate.


Predictive power of ejection fraction and renal failure in patients admitted for chest pain without ST elevation in the troponin era.
Ejection fraction (EF) and renal failure (RF) are powerful predictors of mortality in patients with myocardial infarction (MI). There are limited data assessing the predictive value of EF and RF compared with clinical variables in patients without ST elevation using troponin as the diagnostic MI criteria. Consecutive patients admitted from the emergency department underwent serial assessment of cardiac markers, including troponin I. Abnormal EF was defined as < 50%; RF, as creatinine clearance (CrCl) < 60 mL/min. Multivariate analysis was used to compare clinical variables, CrCl, and EF for predicting short- and long-term outcomes. A total of 3074 patients had EF assessed. Mild to moderately reduced EF and CrCl were present in 639 (21%) and 582 (19%) patients, with 403 (13%) and 233 (7.6%) having severe systolic dysfunction and severe RF, respectively. Abnormal EF and RF were both present in 13% of patients (1-year mortality 26%), whereas 52% had both normal EF and CrCl (1-year mortality 3.2%). The presence of either systolic dysfunction or RF increased mortality 3- to 4-fold compared with patients without either. The most important multivariate predictors of 1-year mortality were EF (OR 2.6 [95% CI 1.7-3.8, P < .0001]) and CrCl (OR 2.8 [95% CI 1.8-4.2, P < .0001]). Both RF and EF are strong predictors of cardiac mortality in patients admitted for exclusion of MI. Prediction models that do not include these 2 variables will underestimate risk.


Correction to Estimation of Gas Holdup Using the Gassed to Ungassed Power Ratio of an Oxygen-Water System in a Stirred and Sparged Tank Contactor.
[This corrects the article DOI: 10.1021/acsomega.0c02292.].


Gastric cardiac carcinomas involving the esophagus are more adequately staged as gastric cancers by the 7th edition of the American Joint Commission on Cancer Staging System.
The aim of this study was to compare the 7th with the 6th edition of the American Joint Commission on Cancer Staging System for prognostic stratification of gastric cardiac carcinomas involving the esophagus. We retrospectively compared differences in pathological stages with patient survival between the 7th and the 6th staging systems in 142 consecutive resection cases of this cancer. Patient median age was 65 years. The male-female ratio was 3.3. The epicenter of all tumors was within 5 cm below the gastroesophageal junction. The median tumor size was 5.0 cm. Most tumors (79%) were typical adenocarcinomas and the rest showed uncommon histology types. Using the guidelines for gastric cancer, this group of cancer was better stratified by the 7th than the 6th edition of the staging system, especially for pathological nodal (pN) and overall stage pIIIC. Patients with celiac axis nodal disease had the 5-year survival rate worse than those staged at pN3A and pIIIA. Patients staged at pT3 and pN3B had the 5-year survival rate worse than those at pM1 and pIV. We showed that the overall stage of gastric cardiac carcinomas was better stratified by gastric than by esophageal cancer grouping. We conclude that these tumors are better stratified with the 7th than the 6th edition of the gastric staging system, especially for pIII cancers, and better staged by the new gastric than esophageal cancer staging system. We propose that the staging of these tumors be reverted to gastric grouping and combine pT3 and pN3B into the overall stage pIV.


Solution structure of antimicrobial peptide esculentin-1c from skin secretion of Rana esculenta.
Granular glands in the skins of frogs synthesize and secrete a remarkably diverse range of peptides capable of antimicrobial activity. These anuran skin antimicrobial peptides are commonly hydrophobic, cationic and form an amphipathic α-helix in a membrane mimetic solution. Recently, they have been considered as useful target molecules for developing new antibiotics drugs. Esculentin-1c is a 46-amino acid residue peptide isolated from skin secretions of the European frog, Rana esculenta. It displays the most potent antimicrobial activity among bioactive molecules. Esculentin-1c has the longest amino acids among all antimicrobial peptides. The present study solved the solution structure of esculentin-1c in TFE/water by NMR, for the first time. We conclude that this peptide is comprised of three α-helices with each helix showing amphipathic characteristics, which seems to be a key part for permeating into bacterial membranes, thus presenting antimicrobial activity.


The cyclic AMP-dependent protein kinase A pathway is involved in progesterone effects on calcitonin secretion from TT cells.
It is well known that gonadal steroid hormones influence the level of plasma calcitonin (CT), but the mechanism by which progesterone affects CT secretion is not clear. Immortalized TT cells are a reliable model system for studying the endocrine function of human parafollicular cells. In the present study, the effects of progesterone on CT secretion were examined in TT cells. TT cells were incubated in medium containing vehicle (DMSO), progesterone or BSA-progesterone for 60 or 150 min, and then the levels of CT in the medium, progesterone receptors, cAMP accumulation and CT mRNA expression were measured. To study the correlation between progesterone effects and the cAMP-dependent protein kinase A (PKA) pathway, cell lysates or cells in 24-well plates were treated with either vehicle or progesterone plus RU486, SQ22536, KT5720, or 3-isobutyl-1-methylxanthine. Then, adenylyl cyclase and protein kinase A (PKA) activities were measured in the cell lysates, and the CT levels were measured in the medium from the 24-well plate. The activated cAMP response element binding protein (P-CREB) was also measured by immunofluorescence. Administration of 1 microM progesterone or 500 nM BSA-progesterone increased the secretion of CT by 381% and 100%, respectively. Progesterone receptors A and B were downregulated by progesterone treatment. The cAMP concentration, adenylyl cyclase and PKA activity, CT mRNA expression, and nuclear P-CREB concentrations all showed an increase after progesterone treatment. RU486, SQ22536 and KT5720 inhibited the progesterone-stimulated effects. These results suggest that a cAMP-dependent PKA pathway is involved in progesterone-stimulated effects on CT secretion from TT cells.