Economic feasibility of interventions targeted at decreasing piglet perinatal and pre-weaning mortality across European countries.
Piglet perinatal and pre-weaning mortality is a welfare problem causing economic losses in pig production. In this study, the effects of housing and management interventions on the economic result of sow enterprises representing six European countries (Belgium, Denmark, Finland, Germany, The Netherlands and Spain) were tested. Interventions concerned: (1) installing mechanical ventilation, (2) re-designing of the gestation unit, (3) drying and warming newborn piglets, (4) providing enrichment for gestating sows, including high-fiber dietary supplementation and point-source objects, and (5) music provision and backscratching of sows in the farrowing unit. A bio-economic model was used to determine the effects of interventions on economic outcomes during the nursery phase and to calculate a maximum cost of 1%-point reduction in perinatal and pre-weaning mortality, irrespective of the intervention type. Biological parameters were set according to previous observational and experimental studies. Interventions 1-4 were expected to decrease perinatal mortality, defined as stillbirths and deaths occurring within the first 48 h of postnatal life. Intervention 5 was expected to decrease pre-weaning mortality. Interventions increased fixed (1-3) and variable costs (3-5). We hypothesized that housing and management interventions would have a positive economic effect. Piglet mortality can be decreased in various ways. Interventions concerning ventilation and re-designing of the gestation unit (1 and 2) were the most beneficial in countries with low housing costs and high perinatal mortality. Drying and warming newborn piglets (3) resulted in varying economic results, with the highest increase in profits obtained in a country with low labor costs and high litter size. Interventions providing sows with enrichment and human-animal interaction (4 and 5) were effective across varying conditions. Regardless of intervention type, policies aiming at 1%-point reduction in perinatal and pre-weaning mortality could cost from €0.2 to €0.5 (average €0.4) and from €0.4 to €0.5 (average €0.5) per piglet, respectively, depending on productions conditions. To decrease piglet mortality, farmers should consider low input interventions, such as those targeting appropriate behavior. Our results suggest that providing enrichment or increasing human-animal interaction pays off and brings positive economic result even when piglet mortality is marginally reduced.


Computerized Clinical Training Simulations with Virtual Clients Abusing Alcohol: Initial Feasibility, Acceptability, and Effectiveness.
Although masters-level social work students typically build clinical skills via role-playing with their peers or instructors, several innovative training simulations are emerging in the literature that may enhance existing skill-building methodologies. We evaluated the initial feasibility, acceptability, usability, and effectiveness of three computerized simulations (two cognitive behavioral therapy, one motivational interviewing) during an interpersonal practice course among 22 students in a Master of Social Work program accredited by the Council on Social Work Education. Trainees repetitively practiced their clinical skills with virtual clients while receiving feedback via real-time nonverbal cues, transcript review, and performance assessment across pre-specified theoretical learning objectives. Across the three simulations, at least 86.4% of students completed the required protocol and completed M = 468.95 (SD = 178.27) minutes of simulated sessions. Students improved their scores (range 0 to 100) across all the simulations from M = 63.41 (SD = 11.13) to M = 93.64 (SD = 3.24). Students found the simulations to be acceptable with strong usability. Paired sample t-tests revealed students reported greater self-efficacy in general clinical skills, exploration skills, insight skills, and action skills between pre-test and post-test after completing the simulations (all p < 0.001). Students reported that the clinical skills learned from the simulations translated into successful interactions with real-world clients during their field placements. We discuss the results of this initial feasibility study within the context of simulation-based learning and the potential for broader implementation within MSW programs.


COVID-19 Public Stigma Scale (COVID-PSS): development, validation, psychometric analysis and interpretation.
Amid the COVID-19 pandemic, social stigma towards COVID-19 infection has become a major component of public discourse and social phenomena. As such, we aimed to develop and validate the COVID-19 Public Stigma Scale (COVID-PSS). National-based survey cross-sectional study during the lockdown in Thailand. We invited the 4004 adult public to complete a set of measurement tools, including the COVID-PSS, global fear of COVID-19, perceived risk of COVID-19 infection, Bogardus Social Distance Scale, Pain Intensity Scale and Insomnia Severity Index. Factor structure dimensionality was constructed and reaffirmed with model fit by exploratory and confirmatory factor analyses and non-parametric item response theory (IRT) analysis. Psychometric properties for validity and reliability were tested. An anchor-based approach was performed for classifying the proper cut-off scores. After factor analysis, IRT analysis and test for model fit, we created the final 10-item COVID-PSS with a three-factor structure: stereotype, prejudice and fear. Face and content validity were established through the public and experts' perspectives. The COVID-PSS was significantly correlated (Spearman rank, 95% CI) with the global fear of COVID-19 (0.68, 95% CI 0.66 to 0.70), perceived risk of COVID-19 infection (0.79, 95% CI 0.77 to 0.80) and the Bogardus Social Distance Scale (0.50, 95% CI 0.48 to 0.53), indicating good convergent validity. The correlation statistics between the COVID-PSS and the Pain Intensity Scale and Insomnia Severity Index were <0.2, supporting the discriminant validity. The reliability of the COVID-PSS was satisfactory, with good internal consistency (Cronbach's α of 0.85, 95% CI 0.84 to 0.86) and test-retest reproducibility (intraclass correlation of 0.94, 95% CI 0.86 to 0.96). The proposed cut-off scores were as follows: no/minimal (≤18), moderate (19-25) and high (≥26) public stigma towards COVID-19 infection. The COVID-PSS is practical and suitable for measuring stigma towards COVID-19 in a public health survey. However, cross-cultural adaptation may be needed.


Surgical Outcomes, Health Care Utilization, and Costs Associated with Staple Line Buttressing Among Primary Sleeve Gastrectomy Patients.
Staple line buttressing is a method of reinforcing surgical staple lines using buttress materials. This study evaluated surgical outcomes, hospital utilization, and hospital costs associated with staple line buttressing among patients who underwent primary laparoscopic sleeve gastrectomy (PLSG) in the United States. This was a retrospective cohort study using Premier Healthcare Database data from January 1, 2012 to December 31, 2017. Patients aged ≥ 18 years who underwent PLSG were selected and assigned to buttress or non-buttress cohorts based on the use of buttress material during their hospitalization for PLSG (index). Propensity score matching (PSM) was conducted to balance patient demographic and clinical characteristics between the cohorts. Generalized estimating equation models were used to compare the clinical and economic outcomes of the matched buttress and non-buttress users during the index hospitalization. A total of 38,231 buttress and 27,349 non-buttress patients were included in the study. After PSM, 24,049 patients were retained in each cohort. Compared with non-buttress cohort, the buttress cohort patients had a similar rate of in-hospital leaks (0.28% vs 0.39%; p = 0.160) and a lower rate of bleeding (1.37% vs 1.80%, p = 0.015), transfusion (0.56% vs 0.77%, p = 0.050), and composite bleeding/transfusion (1.57% vs 2.04%, p = 0.019). Total costs ($12,201 vs $10,986, p < 0.001) and supply costs ($5366 vs $4320, p < 0.001) were higher in the buttress cohort compared with the non-buttress cohort. Staple line buttressing was associated with an improvement in complication rates for bleeding and transfusion. Total and supply costs were higher in the buttress cohort, necessitating further research into cost-effective buttressing materials.


Mutations of amino acids in the DNA-recognition domain of Epstein-Barr virus ZEBRA protein alter its sub-nuclear localization and affect formation of replication compartments.
ZEBRA, a transcription factor and DNA replication protein encoded by the Epstein-Barr virus (EBV) BZLF1 gene, plays indispensable roles in the EBV lytic cycle. We recently described the phenotypes of 46 single amino acid substitutions introduced into the DNA-recognition region of ZEBRA [Heston, L., El-Guindy, A., Countryman, J., Dela Cruz, C., Delecluse, H.J., and Miller, G. 2006]. The 27 DNA-binding-proficient mutants exhibited distinct defects in their ability to activate expression of the kinetic classes of viral genes. Four phenotypic variants could be discerned: wild-type, defective at activating Rta, defective at activating early genes, and defective at activating late genes. Here we analyze the distribution of ZEBRA within the nucleus and the localization of EA-D (the viral DNA polymerase processivity factor), an indicator of the development of replication compartments, in representatives of each phenotypic group. Plasmids encoding wild-type (WT) and mutant ZEBRA were transfected into 293 cells containing EBV-bacmids. WT ZEBRA protein was diffusely and smoothly distributed throughout the nucleus, sparing nucleoli, and partially recruited to globular replication compartments. EA-D induced by WT ZEBRA was present diffusely in some cells and concentrated in globular replication compartments in other cells. The distribution of ZEBRA and EA-D proteins was identical to WT following transfection of K188R, a mutant with a conservative change. The distribution of S186A mutant ZEBRA protein, defective for activation of Rta and EA-D, was identical to WT, except that the mutant ZEBRA was never found in globular compartments. Co-expression of Rta with S186A mutant rescued diffuse EA-D but not globular replication compartments. The most striking observation was that several mutant ZEBRA proteins defective in activating EA-D (R179A, K181A and A185V) and defective in activating lytic viral DNA replication and late genes (Y180E and K188A) were localized to numerous punctate foci. The speckled appearance of R179A and Y180E was more regular and clearly defined in EBV-positive than in EBV-negative 293 cells. The Y180E late-mutant induced EA-D, but prevented EA-D from localizing to globular replication compartments. These results show that individual amino acids within the basic domain influence localization of the ZEBRA protein and its capacity to induce EA-D to become located in mature viral replication compartments. Furthermore, these mutant ZEBRA proteins delineate several stages in the processes of nuclear re-organization which accompany lytic EBV replication.


Modelling cadmium contamination in paddy soils under long-term remediation measures: Model development and stochastic simulations.
A pollutant accumulation model (PAM) based on the mass balance theory was developed to simulate long-term changes of heavy metal concentrations in soil. When combined with Monte Carlo simulation, the model can predict the probability distributions of heavy metals in a soil-water-plant system with fluctuating environmental parameters and inputs from multiple pathways. The model was used for evaluating different remediation measures to deal with Cd contamination of paddy soils in Youxian county (Hunan province), China, under five scenarios, namely the default scenario (A), not returning paddy straw to the soil (B), reducing the deposition of Cd (C), liming (D), and integrating several remediation measures (E). The model predicted that the Cd contents of soil can lowered significantly by (B) and those of the plants by (D). However, in the long run, (D) will increase soil Cd. The concentrations of Cd in both soils and rice grains can be effectively reduced by (E), although it will take decades of effort. The history of Cd pollution and the major causes of Cd accumulation in soil were studied by means of sensitivity analysis and retrospective simulation.


Distribution of Kawasaki Disease Coronary Artery Aneurysms and the Relationship to Coronary Artery Diameter.
We investigated how the diameter of coronary artery aneurysm (CAA) relates to the distribution immediately after Kawasaki disease (KD). Two hundred and four pts (155 males and 49 females) who had undergone selective coronary angiography (CAGs) less than 100 days after the onset of KD were studied. We measured the maximum diameter of each artery segment in the initial CAGs. We analyzed the relationship between the maximum diameters and the distribution of CAA. We divided the patients into four groups based on the maximum CAA diameter in each patient (large(L) ≥8 mm, medium(M) ≥6 and <8 mm, small(S) ≥4 and <6 mm, very small(VS) <4 mm) and counted the affected segments. There were 87, 61, 36, and 20 patients in groups L, M, S, VS, respectively. The number of segments with CAA in each group was L 6 ± 2, M 4 ± 2, S 2 ± 2, VS 2 ± 1. The number of affected segments in L was significantly more than M, and a large value for L indicated that involvement was significantly more likely to be bilateral. The larger the maximum diameter of CAA, the more extensive disease involvement and the more likely to be bilateral. A large maximum CAA can also indicate coronary involvement in the longitudinal directions. It is an important charcteristic in distribution of CAA caused by KD vasculitis.


Chemical and genetic tools to explore S1P biology.
The zwitterionic lysophospholipid Sphingosine 1-Phosphate (S1P) is a pleiotropic mediator of physiology and pathology. The synthesis, transport, and degradation of S1P are tightly regulated to ensure that S1P is present in the proper concentrations in the proper location. The binding of S1P to five G protein-coupled S1P receptors regulates many physiological systems, particularly the immune and vascular systems. Our understanding of the functions of S1P has been aided by the tractability of the system to both chemical and genetic manipulation. Chemical modulators have been generated to affect most of the known components of S1P biology, including agonists of S1P receptors and inhibitors of enzymes regulating S1P production and degradation. Genetic knockouts and manipulations have been similarly engineered to disrupt the functions of individual S1P receptors or enzymes involved in S1P metabolism. This chapter will focus on the development and utilization of these chemical and genetic tools to explore the complex biology surrounding S1P and its receptors, with particular attention paid to the in vivo findings that these tools have allowed for.


Histaminergic modulation of hormonal control in the exocrine guinea-pig pancreas.
The effects of histamine upon secretin- or cholecystokinin (CCK)-evoked exocrine pancreatic secretion were investigated in the anaesthetised guinea pig. Histamine (0.1 mumol/kg/min) induced a slight increase in pancreatic juice flow and total protein release compared to saline controls. Secretin (0.5 pmol/kg/min) and CCK-8 (0.75 pmol/kg/min) evoked marked time course increases in both the rate of pancreatic juice flow and total protein output in the anaesthetised guinea pig. Administration of either secretin or CCK-8 simultaneously with histamine elevated the exocrine pancreatic secretion compared to the smaller response obtained when administered separately. These results indicate that histamine may play an important physiological role in modulating the hormonal control of exocrine guinea pig pancreas.


Suprapubic single-port approach for complicated diverticulitis.
Laparoscopic sigmoidectomy is the gold standard for elective surgical treatment of diverticulitis. A periumbilical single-port technique reduces the size of the access wound, usually to 3-4 cm. However, in the presence of large phlegmon or fistulae, the risk of conversion is higher and the extraction site might be enlarged. A suprapubic Pfannenstiel incision reduces the risk of incisional hernia compared to umbilical access and might provide the possibility to perform sigmoidectomy with a hybrid technique. The aim of the present study was to investigate the feasibility of laparoscopic sigmoidectomy through a single suprapubic transverse access for large diverticular phlegmon. Consecutive patients with a diverticular inflammatory mass ≥ 5 cm, with or without sigmoid-vesical fistula, were considered candidates for laparoscopic sigmoidectomy through a 5-cm single-port suprapubic (SPSP) access, extended (if required) to match the size of the inflammatory mass. Twenty patients underwent SPSP sigmoidectomy at our institution in April 2014-April 2017. All procedures were completed by SPSP access, with no intraoperative complications or need for additional trocar placement. Eight patients had a sigmoid-vesical fistula (bladder sutured in three patients). The splenic flexure was mobilized in nine patients. Median operative time was 178 min and median hospital stay was 5.5 days (iqr 4-6). Postoperative complications occurred in four patients and included one subcutaneous hematoma, one urinary tract infection, and two superficial wound infections. After a median follow-up time of 25 months (interquartile range 15-38), all patients experienced complete resolution of symptoms, with no incisional hernias reported. SPSP sigmoidectomy for diverticulitis is feasible and effective, minimizing the size of the access wound and avoiding increased risk of hernia. This approach might be especially valuable for the management of large diverticular phlegmon and sigmoid-vesical fistula.


The sialotranscriptome of adult male Anopheles gambiae mosquitoes.
Adult mosquitoes feed on sugary meals to obtain energy for flight and other activities, while anautogenous females take a blood meal to develop eggs. Accordingly, female but not male salivary glands possess several antihemostatic components to facilitate acquisition of blood, while both sexes have activities related to digestion of the sugar meal as well as antimicrobials to maintain meal integrity. Studies on adult female sialotranscriptomes indicated a set of approximately 70 proteins and peptides possibly secreted in saliva that presumably facilitate sugar and blood meals. Most of these proteins have no known function, so no assignment to blood or sugar feeding is possible. Microarray and RT-PCR studies attempted to identify sex specificity of these transcripts. Our present study complements the previous data set, comparing approximately 1000 randomly sequenced clones of a male adult salivary gland cDNA library with the female set. Statistically significant differences were found in 16 transcripts found exclusively in the female library, 4 transcripts significantly female enriched but also found in male glands, and 6 transcripts enriched in male glands. We additionally found a transcript in male salivary glands with a trypsin inhibitor-like (TIL) domain that we presume codes for an antimicrobial peptide; a novel defensin transcript was also found in the male sialotranscriptome. Supplemental tables can be found at.


The implications of listening during political conversations for democracy.
There is a dearth of research on listening in the context of political conversation. Yet there is theoretical reason to believe that political listening could be an important pathway toward several democratically important outcomes including increased exposure to difference, mutual understanding, and decreased polarization. Unfortunately, listening in political contexts associated with deeply held moral beliefs and strong social identities may be among the most difficult settings for listening to flourish. On the other hand, listening is reciprocal within dyads and so a foothold of listening could, through subsequent social contagion, have potentially widespread effects. This article will review theory and research on political listening, as well as relevant scholarship on listening outside of the political domain.


Fungal endophytes associated with Viola odorata Linn. as bioresource for pancreatic lipase inhibitors.
As per the recent statistical reports of World Health Organisation (WHO), 13% of total global population is obese. Orlistat remains to be the only drug approved for the long term treatment of obesity. Recent findings highlighted severe adverse effects of orlistat that included hepatotoxicity, gall stones, kidney stones and acute pancreatitis. Therefore, search for new drug is required. The investigations based on endophytic natural products would prove pivotal in the global fight against this health issue. Obesity is associated with lipid metabolism involving pancreatic lipase enzyme. The inhibition of pancreatic lipase is demonstrated by using the extracts of endophytes isolated from Viola odorata Linn. In addition, endophytes were identified using ITS based rDNA sequencing. Present study involves the isolation and identification of 27 endophytes from V. odorata. All the endophytes were evaluated for lipase inhibitory activities. The extracts of seven endophytes exhibited lipase inhibitory activity with IC50 < 10 μg/mL. The extract of VOLF4 (Aspergillus sp.) displayed promising lipase inhibitory activity (IC50 3.8 μg/mL). The present study demonstrates that V. odorata harbors endophytic community with potent lipase inhibitory activity. VOLF4 is the potential endophyte. The extract of VOLF4 can be used to develop the potential drug to treat obesity.


[Furuncular myiasis caused by Dermatobia hominis. Fortuitous diagnosis on extemporaneous macroscopic analysis of an excised cutaneous nodule].
Furuncular myiasis is a parasitic disease caused by the development of human botfly larva in the skin. It affects people living in tropical countries and travelers returning from these countries and concerns a number of medical specialties. One form of treatment involves surgical extraction of the parasites. We report the case of a 47-year-old man returning from Guyana presenting two furuncle-like nodules of the skin on the right buttock and on the right shoulder blade. Extemporaneous intraoperative macroscopic examination of the buttock nodule resulted in diagnosis of myiasis caused by the human botfly, Dermatobia hominis. The diagnosis of furuncular myiasis is made primarily on clinical grounds and should be suspected on observation of an abscess in subjects returning from a tropical region. It is consequently rare to find D. hominis in biopsy specimens. In the present case, macroscopic examination showed an extremely rare image of the edge of the intact larva in a longitudinal cut, which to our knowledge has never been published to date.


Imaging of the Charcot foot.
Charcot foot is a serious problem that causes considerable morbidity and may lead to limb loss. Arriving at a definitive diagnosis can be challenging. Given the progressive, destructive nature of Charcot's arthropathy, this delay can result advancing deformity, ulceration, infection, and place the limb at risk for amputation. Although clinical signs and symptoms and historical information are crucial, this article focuses on the imaging modalities that can aid practitioners in arriving at an early diagnosis, and how to differentiate Charcot's arthropathy from osteomyelitis of the feet.


Etiology of Shoulder Arthritis in Young Patients.
The manifestation of glenohumeral arthritis in the young adult is a devastating occurrence that can be difficult to manage. This review details the many underlying etiologies including genetic causes, congenital abnormalities, glenohumeral instability, posttraumatic lesions, postcapsulorraphy arthropathy, osteonecrosis, intraarticular pain pump postoperative use, radiofrequency/thermal capsulorraphy treatments, septic arthritis/infection, and inflammatory arthropathies. Although each of these potential causes have been well-studied, their contributions to the development of glenohumeral arthritis in the young person has not been described extensively.


Genital Tract Infections in Women, Pregnancy and Neonates.
Treatable genital tract infections in women are common and most are transmitted via sexual contact with the potential for vertical transmission during pregnancy. Adverse infection outcomes include pelvic inflammatory disease, infertility, ectopic pregnancy, preterm delivery, and congenital or neonatal infection. Highly sensitive molecular diagnostic testing for genital tract infections is now recommended in many countries. Unfortunately, this testing is not yet widely available in low- and middle-income countries because of cost. Improved access to early diagnosis and treatment for curable genital tract infections is critical to improving women's health and reaching global STI elimination targets by 2030.


Update on the treatment of juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases of childhood. Although the pathophysiology behind this disease is poorly understood, there are effective treatments for JIA based on the subtype of disease. Treatment options include non-steroidal anti-inflammatory drugs, intra-articular glucocorticoid injections, and traditional disease modifying anti-rheumatic drugs such as methotrexate. In the past decade, the use of biologic therapy in JIA, including tumor necrosis factor inhibitors, interleukin-1 inhibitors, and interleukin-6 inhibitors, has dramatically increased with promising outcomes.


Comparison of radiologist performance with photon-counting full-field digital mammography to conventional full-field digital mammography.
The purpose of this study was to assess the performance of a MicroDose photon-counting full-field digital mammography (PCM) system in comparison to full-field digital mammography (FFDM) for area under the receiver-operating characteristic (ROC) curve (AUC), sensitivity, specificity, and feature analysis of standard-view mammography for women presenting for screening mammography, diagnostic mammography, or breast biopsy. A total of 133 women were enrolled in this study at two European medical centers, with 67 women who had a pre-existing 10-36 months FFDM enrolled prospectively into the study and 66 women who underwent breast biopsy and had screening PCM and diagnostic FFDM, including standard craniocaudal and mediolateral oblique views of the breast with the lesion, enrolled retrospectively. The case mix consisted of 49 cancers, 17 biopsy-benign cases, and 67 normal cases. Sixteen radiologists participated in the reader study and interpreted all 133 cases in both conditions, separated by washout period of ≥4 weeks. ROC curve and free-response ROC curve analyses were performed for noninferiority of PCM compared to FFDM using a noninferiority margin Δ value of 0.10. Feature analysis of the 66 cases with lesions was conducted with all 16 readers at the conclusion of the blinded reads. Mean glandular dose was recorded for all cases. The AUC for PCM was 0.947 (95% confidence interval [CI], 0.920-0.974) and for FFDM was 0.931 (95% CI, 0.898-0.964). Sensitivity per case for PCM was 0.936 (95% CI, 0.897-0.976) and for FFDM was 0.908 (95% CI, 0.856-0.960). Specificity per case for PCM was 0.764 (95% CI, 0.688-0.841) and for FFDM was 0.749 (95% CI, 0.668-0.830). Free-response ROC curve figures of merit were 0.920 (95% CI, 0.881-0.959) and 0.903 (95% CI, 0.858-0.948) for PCM and FFDM, respectively. Sensitivity per lesion was 0.903 (95% CI, 0.846-0.960) and 0.883 (95% CI, 0.823-0.944) for PCM and FFDM, respectively. The average false-positive marks per image of noncancer cases were 0.265 (95% CI, 0.171-0.359) and 0.281 (95% CI, 0.188-0.374) for PCM and FFDM, respectively. Noninferiority P values for AUC, sensitivity (per case and per lesion), specificity, and average false-positive marks per image were all statistically significant (P < .001). The noninferiority P value for free-response ROC was <.025, from the 95% CI for the difference. Feature analysis resulted in PCM being preferred to FFDM by the readers for ≥70% of the cases. The average mean glandular dose for PCM was 0.74 mGy (95% CI, 0.722-0.759 mGy) and for FFDM was 1.23 mGy (95% CI, 1.199-1.262 mGy). In this study, radiologist performance with PCM was not inferior to that with conventional FFDM at an average 40% lower mean glandular dose.


Is There a Benefit to Head Size Greater Than 36 mm in Total Hip Arthroplasty?
This study compares the rate of dislocation and revision for instability between 36-mm and anatomic femoral heads (large diameter metal-on-metal THA, dual-mobility bearings, and hip resurfacing arthroplasty) in patients at high risk for dislocation. A total of 501 high-risk patients, over a 10-year period, were identified (282 36-mm THA, 24 dual-mobility bearings, 83 metal-on-metal arthroplasty, and 112 hip resurfacing arthroplasty). There were 13 dislocations in the 36-mm group compared to 1 in the anatomic group (4.6% vs 0.5%; P = .005). Four patients dislocated more than once in the 36-mm group (1.4% vs 0%; P = .04), and 2 patients in the 36-mm group required a revision for instability (0.7% vs 0%; P = .11). These results suggest that anatomic head sizes significantly lower the risk of dislocation in high-risk patients.


First report of a Chinese patient carrying Hb Ty Gard: A case report.
More than 1300 mutations which lead to abnormal hemoglobin (Hb) have been recorded in the HbVar database. Hb Ty Gard has rarely been reported and has not been reported in China. A 2-year-old Chinese girl was healthy with normal physical development and hematological parameters. Capillary electrophoresis suggested that Hb F increased slightly, while Hb A2 levels were normal. Flow cytometry, fluorescence hybridization, and Sanger sequencing were used to characterize the genotypes. Sanger sequencing detected a heterozygous mutation at codon 124 of the β-globin gene (HBB: c.374 C > A), which was previously reported as Hb Ty Gard in the HbVar database. We report the first case of HbTy Gard in a Chinese population. In areas with a high incidence of Hb diseases, sensitive detection of Hb components and accurate diagnosis of Hb variation are very important, and the combined application of capillary electrophoresis and gene sequencing can diagnose more Hb variants.


Procalcitonin for discrimination between activity of systemic autoimmune disease and systemic bacterial infection.
To investigate whether serum procalcitonin (PCT) levels could be useful to differentiate between systemic infection and the activity of the underlying disease in autoimmune disease. In 18 patients with systemic lupus erythematodes (SLE) and 35 patients with systemic antineutrophil cytoplasmic antibody-associated vasculitis (AAV) clinical disease activity was assessed by score systems. Infection was defined by clinical and microbiological means. PCT was determined in parallel with concentrations of neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP) in 397 serum samples. Only in 3 of the 324 samples taken from patients with autoimmune disease but without concomitant infection, serum PCT levels were above the normal range (>0.5 ng/ml), whereas neopterin, CRP and IL-6 were elevated in patients with active underlying disease. All systemic infections (N=16 in AAV-patients) were associated with markedly elevated PCT-levels (mean+/-SD:1.93+/-1.19 ng/ml). PCT may serve as a useful marker for the detection of systemic bacterial infection in patients with autoimmune disease.


Reusable fluorescent sensor for captopril based on energy transfer from photoluminescent graphene oxide self-assembly multilayers to silver nanoparticles.
In this work we designed a self-assembly multilayers, in which photoluminescent graphene oxide was employed as a fluorescence probe. This multilayers film can effectively recognize captopril by resonance energy transfer from graphite oxide to silver nanoparticles. A new interfacial sensing method for captopril with high signal to noise ratio was established, by means of that multilayers was quenched by silver nanoparticles and subsequently recovered by adding captopril. The linear relation between intensity and captopril concentration was good, and the detection limit was found to be 0.1578 μM. Also, this novel detection platform demonstrated intriguing reusable properties, and the sensor could be repeated more than ten times without obviously losing its sensing performance.


Promoter 7 of the Escherichia coli pfl operon is a major determinant in the anaerobic regulation of expression by ArcA.
The anaerobically inducible pfl operon of Escherichia coli has a regulatory sequence comprising 494 bp, which includes two anaerobically regulated promoters, termed P6 and P7. In this study, we show that in its normal context the activity of P7 is constrained and that one important function of the promoter is to mediate controlled ArcA-dependent regulation of the operon.


Augmenter of liver regeneration promotes drug resistance of acute lymphoblastic leukemia through the alteration of mitochondrial functions and the inhibition of the mitochondrial apoptosis pathway.
Acute T lymphoblastic leukemia (T-ALL) occurs in 25% of adults diagnosed with Acute lymphocytic leukemia (ALL), and drug resistance is still a clinical obstacle. Augmenter of liver regeneration (ALR) is important to ALL drug resistance and is involved in the regulation of mitochondrial function; we speculated that the high expression of ALR in T-ALL promotes drug resistance through the alteration of mitochondrial function and the inhibition of the mitochondrial apoptosis pathway. We silenced and overexpressed ALR in the T-ALL cell lines that were untreated or treated with dexamethasone (DXM) or methotrexate (MTX). Apoptosis, proliferation, reactive oxygen species and ATP productions, mitochondrial membrane potential, and mitochondrial respiratory chain complex expression in cells were examined. The data were collated to comprehensively evaluate the effects of ALR expression change on mitochondrial function and drug resistance in T-ALL cells. ALR knockdown led to the inhibition of proliferation, an increase in apoptosis, and the promotion of the cells' sensitivity to drugs. It also showed mitochondrial dysfunction. ALR knockdown actived the mitochondrial apoptosis pathway. The treatment of ALR knockdown T-ALL cells with MTX or DXM further altered the mitochondrial function of T-ALL cells and actived the mitochondrial apoptosis pathway. Overexpression of ALR promoted cell proliferation and drug resistance, reduced apoptosis, protected mitochondrial function, and inhibited the mitochondrial apoptosis pathway. T-ALL resistance caused by ALR through the alteration of mitochondrial function is associated with the inhibition of the mitochondrial apoptosis pathway.


An ICT based "turn on/off" quinoline armed calix[4]arene fluoroionophore: its sensing efficiency towards fluoride from waste water and Zn2+ from blood serum.
A novel structurally simple calix[4]arene appended 8-amidoquinoline linked conjugate was synthesized and has been used as a turn-on fluorescence probe for Zn(2+) and turn off fluorescence probe for F(-). Moreover, this probe has been applied for Zn(2+) detection in blood serum upto 8.7 μM and fluoride detection upto 22 nM in waste water samples, using emission spectra.


Evaluating patient experiences in decentralised acute care using the Picker Patient Experience Questionnaire; methodological and clinical findings.
Decentralised acute care services have, through the establishment of municipality acute wards (MAWs), been launched in Norway. The aim is to provide treatment for patients who otherwise would need hospitalisation. Currently there is a lack of studies investigating patient experiences in such services. The aims of this study were therefore to a) translate and validate the Picker Patient Experience Questionnaire (PPE-15) in Norwegian, and b) assess patient experiences in decentralised acute care, and potential factors associated with these experiences. Patients were recruited from five municipal acute wards in southeastern Norway during the period from June 2014 to June 2015. Data on socio-demographics, length of stay and comorbidity (Charlson comorbidity index (CCI)) were collected. Patients completed the Picker Patient Experience Questionnaire (PPE-15) and the EuroQOL 5-dimension, 3-level version. Convergent validity of the PPE-15 was assessed by correlation of items in PPE-15 and the Nordic Patient Experience Questionnaire (NORPEQ). A retest of the PPE-15 was performed in a subgroup of patients approximately 3 weeks after baseline assessment. Test-retest agreement was assessed with Cohens' unweighted Kappa. A total of 479 patients responded, median age 78.0 years and 41.8% men. A total of 68 patients participated in the retest. Testing of convergent validity revealed an overall weak to moderate correlation. Kappa statistics showed from fair to good test-retest agreement. Most problems were related to continuity and transition, while fewest problems were related to respect for patient preferences. A higher Charlson comorbidity score was the only variable that was negatively associated with patient experience. Patients reported problems in several items of the PPE-15 after discharge from decentralised acute wards. The findings from the current study may be helpful for planning ways to improve quality of care, e.g., by providing feedback to healthcare personnel or by using patient experience as a quality indicator.


Synthesis and in vitro antitumoral activity of new hydrazinopyrimidine-5-carbonitrile derivatives.
A new series of 2-amino-6-(2-alkyl or arylidenehydrazinyl)-4-(dialkylamino)pyrimidine-5-carbonitriles, 5-24, were synthesized in satisfactory overall yield, using 2-amino-4-(dialkylamino)-6-hydrazino-5-pyrimidinecarbonitriles 3, 4, as key intermediates, by applying classical synthetic methods to construct the hydrazone moiety at C-6 of the pyrimidine ring. Hydrazinopyrimidine derivatives 5-24 were evaluated for their in vitro anticancer activity toward cell lines of nine different types of human cancers. Some of the newly prepared compounds demonstrated inhibitory effects on the growth of a wide range of cancer cell lines generally at 10(-5)M level and in some cases at 10(-7)M concentrations.


Molecular Phenotype, Multigene Assays, and the Locoregional Management of Breast Cancer.
Molecular profiling has revealed that breast cancer is not a single disease entity, but rather a class of heterogeneous subtypes, each with its own inherent biology and natural history. As a result, different treatment approaches have been optimized for the various subtypes and, in turn, the ability to identify subtypes has become a critical element in the management of breast cancer. Comprehensive transcriptional profiling studies have revealed at least 4 principal subtypes that, in practice, are often distinguished by immunohistochemical staining of the estrogen receptor (ER), progesterone receptor (PR), and HER2, along with a determination of histologic grade or Ki-67 staining: luminal A (ER+/HER2-/grade 1 or 2), luminal B (ER+/HER2-/grade 3), HER2 enriched (any HER2+ tumor), and basal like (ER-/PR-/HER2-). Although these immunohistochemically derived subtypes show robust prognostic and predictive ability, there remain many cases that demand profiling that more closely approximates the original transcriptionally derived definitions of the intrinsic subtypes. The need for improved prognostication and risk stratification has led to the development of several multigene assays in breast cancer. Although there is little molecular overlap between current assays, they all rely heavily on quantifying the transcriptional output of ER signaling and proliferation-related genes. These data are typically then used in multivariate prediction models that incorporate other canonical risk factors such as the tumor size, lymph node involvement, and patient demographic parameters, among others. Indeed, the advent of scalable molecular profiling technologies has brought a number of assays into routine clinical use for optimizing risk prediction and treatment assignment. The landscape of these assays and the clinical utility of contemporary molecular profiles are the main focus of this overview. In addition to the clinical advances in transcriptional subtyping, recent reports have characterized the most common genomic and epigenomic alterations that are likely to drive certain breast cancers. The identification of these "driver" lesions has heralded an era of precision medicine in which vulnerable oncogenic pathways may be targeted to disrupt the etiologic lesion(s) of a specific tumor. A number of such early targeted approaches have yielded success in treating breast cancer, demonstrating the critical need for molecular diagnostics in this disease.


An algebraic interpretation of PSP composition.
The introduction of time in artificial neurons is a delicate problem on which many groups are working. Our approach combines some properties of biological models and the algebraic properties of McCulloch and Pitts artificial neuron (AN) (McCulloch and Pitts, 1943) to produce a new model which links both characteristics. In this extended artificial neuron, postsynaptic potentials (PSPs) are considered as numerical elements, having two degrees of freedom, on which the neuron computes operations. Modelled in this manner, a group of neurons can be seen as a computer with an asynchronous architecture. To formalize the functioning of this computer, we propose an algebra of impulses. This approach might also be interesting in the modelling of the passive electrical properties in some biological neurons.


Effect of single-liquid acidic primers on bonding of a composite luting agent joined to a prefabricated alumina coping material.
The aim of this study was to assess the effect of acidic primers on adhesive bonding to prefabricated alumina material designed for fixed restorations. High-purity alumina disks (Procera AllCeram) were primed with one of the following materials: Acryl Bond, All Bond II Primer B, Alloy Primer, Estenia Opaque Primer, M.L. Primer, MR. Bond, and Super- Bond Liquid. The specimens were bonded with a dualpolymerizing luting composite (Variolink II). Unprimed specimen was prepared as the control. Bond strengths were determined both before and after thermocycling. Average bond strength before thermocycling ranged from 12.0 to 39.1 MPa, whereas average bond strength after thermocycling varied from 0.0 to 26.9 MPa. The statistically highest post-thermocycling bond strength was obtained with the use of the Alloy Primer, Estenia Opaque Primer, and M.L. Primer agents. It can be concluded that the use of either the Estenia or Alloy Primer material, which contain 10- methacryloyloxydecyl dihydrogen phosphate (MDP), or the M.L. Primer, which contains 6-methacryloyloxyhexyl phosphonoacetate (6-MHPA), is recommended for bonding the Procera alumina copings with the Variolink II composite.


Predator effects on prey population dynamics in open systems.
Animal population dynamics in open systems are affected not only by agents of mortality and the influence of species interactions on behavior and life histories, but also by dispersal and recruitment. We used an extensive data set to compare natural loss rates of two mayfly species that co-occur in high-elevation streams varying in predation risk, and experience different abiotic conditions during larval development. Our goals were to generate hypotheses relating predation to variation in prey population dynamics and to evaluate alternative mechanisms to explain such variation. While neither loss rates nor abundance of the species that develops during snowmelt (Baetis bicaudatus) varied systematically with fish, loss rates of the species that develops during baseflow (Baetis B) were higher in streams containing brook trout than streams without fish; and surprisingly, larvae of this species were most abundant in trout streams. This counter-intuitive pattern could not be explained by a trophic cascade, because densities of intermediate predators (stoneflies) did not differ between fish and fishless streams and predation by trout on stoneflies was negligible. A statistical model estimated that higher recruitment and accelerated development enables Baetis B to maintain larger populations in trout streams despite higher mortality from predation. Experimental estimates suggested that predation by trout potentially accounts for natural losses of Baetis B, but not Baetis bicaudatus. Predation by stoneflies on Baetis is negligible in fish streams, but could make an important contribution to observed losses of both species in fishless streams. Non-predatory sources of loss were higher for B. bicaudatus in trout streams, and for Baetis B in fishless streams. We conclude that predation alone cannot explain variation in population dynamics of either species; and the relative importance of predation is species- and environment-specific compared to non-predatory losses, such as other agents of mortality and non-consumptive effects of predators.


Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract.
Sutherlandia frutescens is a medicinal plant, traditionally used to treat various types of human diseases, including cancer. Previous studies of several botanicals link suppression of prostate cancer growth with inhibition of the Gli/hedgehog (Gli/Hh) signaling pathway. Here we hypothesized the anti-cancer effect of S. frutescens was linked to its inhibition of the Gli/Hh signaling in prostate cancer. We found a dose- and time-dependent growth inhibition in human prostate cancer cells, PC3 and LNCaP, and mouse prostate cancer cell, TRAMP-C2, treated with S. frutescens methanol extract (SLE). We also observed a dose-dependent inhibition of the Gli-reporter activity in Shh Light II and TRAMP-C2QGli cells treated with SLE. In addition, SLE can inhibit Gli/Hh signaling by blocking Gli1 and Ptched1 gene expression in the presence of a Gli/Hh signaling agonist (SAG). A diet supplemented with S. frutescens suppressed the formation of poorly differentiated carcinoma in prostates of TRAMP mice. Finally, we found Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli-reporter in Shh Light II cells. Together, this suggests that the S. frutescens extract may exert anti-cancer effect by targeting Gli/Hh signaling, and Sutherlandioside D is one of the active compounds.


The necessity of sewers to carry sediment has been recognized for many years. Typically, old sewage systems were designated based on self-cleansing concept where there is no deposition in sewer. These codes were applicable to non-cohesive sediments (typically storm sewers). This study presents adaptive neuro-fuzzy inference system (ANFIS), which is a combination of neural network and fuzzy logic, as an alternative approach to predict the functional relationships of sediment transport in sewer pipe systems. The proposed relationship can be applied to different boundaries with partially full flow. The present ANFIS approach gives satisfactory results (r(2) = 0.98 and RMSE = 0.002431) compared to the existing predictor.


Experimental pathophysiology of panic.
In this article, we review how the knowledge of the pathophysiology of panic disorder has expanded, with special emphasis on laboratory models using lactate and carbon dioxide challenges. Experiments in the late 1960s revealed that lactate infusion can induce panic attacks. A prominent feature of these attacks is hyperventilation. Because lactate infusion induces a metabolic alkalosis, one would rather expect a compensatory hypoventilation. For years hyperventilation was thought to be causally linked to panic, but it has since been proven to be a symptom rather than a cause of panic attacks. Similarly, it is not hypocapnia but hypercapnia that has proven to be capable of provoking panic attacks. Carbon dioxide challenges are comparable to lactate infusion in the degree to which they meet the criteria for an ideal model of panic disorder. Experiments with carbon dioxide in first-degree relatives of panic disorder patients and in monozygotic twins support the idea of a constitutional predisposition to panic disorder. Of the various other agents that have been used to trigger panic attacks, cholecystokinin seems particularly promising as a valid laboratory model of panic disorder and may provide valuable data regarding the mechanism of panic attacks. The false suffocation alarm theory, proposed by Klein, is an integrative hypothesis that may account for a large number of the laboratory as well as clinical observations.


T-cell subsets in lesions of systemic and discoid lupus erythematosus.
In 6 patients with untreated systemic lupus erythematosus (SLE) in the progressive stage, and in 6 with discoid lupus erythematosus (DLE), an analysis of inflammatory infiltrates was performed in situ using the avidin-biotin-peroxidase complex (ABC) method with monoclonal antibodies. In all patients, over 75% of the infiltrates reacted with the pan T-cell antibody OKT3, but only sporadically with that of B-cell OKB7. In addition, a large number of the infiltrates were OKIal-positive, indicating that they were in an activated state. Many OKT8-positive cells were seen infiltrating the epidermis especially in the vicinity of basal keratinocytes. Staining for T-cell subsets revealed that the proportion of OKT8-positive cells (suppressor/cytotoxic) was from 2 to 3 fold higher than that of OKT4-positive cells (helper/inducer) in lesions of SLE. On the contrary, in DLE, a predominance of OKT4-positive cells (the OKT4/OKT8 ratio was from 1:1 to 3:1) was observed. Thus, our results provide further evidence that these 2 main types of LE show quite contrary findings on immunohistochemical analysis of T-cell subsets, and that besides the humoral immune mechanism, the cell-mediated immune mechanism may be involved in the pathogenesis of these disorders.


Influence of various purified interferons on effects of drugs in mice.
Direct determinations indicate that some types of interferon increase the duration of hexobarbital-induced sleep time and decrease acetaminophen toxicity. Pretreatment of mice with cloned human leukocyte interferon subtype A, IFN-alpha A, did not increase hexobarbital sleep time but pretreatment with mouse interferon or a hybrid human leukocyte interferon, IFN-alpha AD (Bgl), increased the duration of the effect of the barbiturate. Hybrid IFN-alpha AD (Bgl) also decreased the lethality of acetaminophen. These findings are predictable based on reports of hepatic cytochrome P450 depression resulting from treatment with some interferons.


Transfer of cobalamin from the cobalamin-binding protein of egg yolk to R binder of human saliva and gastric juice.
Patients may fail to absorb cobalamin (vitamin B12) bound to food even when they have adequate intrinsic factor to absorb free cobalamin normally. We studied cobalamin transfer from egg yolk cobalamin-binding protein to human saliva and gastric juice as a model of this important first step in cobalamin assimilation. The cobalamin-binding protein of egg yolk eluted with human R binder on Sephadex gel chromatography and bound cobalamin with a comparable affinity, but it did not cross-react with R binder immunologically. Transfer of cobalamin from egg yolk to saliva or gastric juice R binder did not occur at neutral pH. Slight transfer (8%-12% of the 57Co-cobalamin bound to egg yolk) occurred when the saliva was acidified to pH 1.5. This minor transfer by acid was not inhibited by pepstatin A, a pepsin inhibitor. Acidification caused variable transfer to gastric juice R binder (12%-40%) that appeared to be partially due to residual gastric pepsin activity. Adding 1200 U of pepsin per milliliter enhanced cobalamin transfer to saliva or gastric juice R binders (39%-58% transfer). At no time was cobalamin transferred directly to intrinsic factor; R binder-deficient gastric juice failed to accept cobalamin from egg yolk. The transfer of cobalamin from egg yolk to human R binder requires both an acid pH and pepsin activity. While as little as 30 U of pepsin added per milliliter of saliva promoted transfer of cobalamin, the requirement for an acid pH was very strict. Virtually no transfer occurred when pH exceeded 2.0, regardless of the amount of pepsin present. Acid provided an optimal pH for pepsin activity and, to a lesser extent, affected transfer by a mechanism unrelated to pepsin. Our data suggest that compromised pepsin secretion and, probably even more importantly, compromised acid secretion interfere with transfer of food cobalamin to R binder.


Ultrastructural studies on erythropoiesis in the avian thymus. II. A stereological analysis of the lymphoid and erythroid cells.
The cortex of enlarging thymic lobes from adult haemorrhaged Quelea quelea were found to be similar to those of wild birds where the thymic enlargement was occurring naturally. A detailed stereological analysis of cells broadly designated as lymphoid, and the construction of models to account for the results, indicates that the enlarging thymic lobe contains both large and small blast cells, a heterogenous group of medium lymphocytes, erythroid cells, and two types of very small lymphocytes. The distinction between early erythroid cells and some lymphocytes, despite this detailed analysis is very difficult, but it is possible in enlarging thymic lobes that up to 42% of the lymphoid cells may have erythroid characteristics.


Capsaicin-induced depletion of substance P-like immunoreactivity in guinea pig sympathetic ganglia.
The distribution of substance P immunoreactive nerve fibers in guinea pig sympathetic ganglia was studied in normal and capsaicin-treated animals. A marked depletion of substance P-like immunoreactivity was observed in both pre- and paravertebral ganglia after capsaicin treatment. In the inferior mesenteric and pelvic ganglia, however, intensely fluorescent fibers surrounding some of the principal ganglion cells remain after capsaicin treatment. Ligation experiments on the inferior mesenteric ganglion indicate that the capsaicin-insensitive substance P immunoreactive fibers in this ganglion are of lumbar splanchnic origin. Whether or not they represent capsaicin-resistant primary afferent neurons is not known. The enkephalin, vasoactive intestinal polypeptide, cholecystokinin and bombesin immunoreactive fiber networks in the inferior mesenteric ganglion were also studied, and no differences were observed between normal and capsaicin-treated animals.


Essential type II mixed cryoglobulinemia causing pyoderma gangrenosum-like ulcers.
A 47-year-old, otherwise healthy woman presented with multiple deep ulcers located primarily on her lower extremities that presented 6 days ago as blisters. A biopsy revealed livedoid vasculopathy, without any evidence of vasculitis. Extensive laboratory workup was positive only for type II cryoglobulins.


The alignment of protein structures in three dimensions.
This article extends the use of dynamic programming algorithms in molecular sequence comparison to the alignment of the alpha-carbon (C alpha-) coordinates of two protein structures in three dimensions. The algorithm is described in detail and is applied to the comparison of alpha-lactalbumin with both hen egg white lysozyme and T4 lysozyme. In the first case, the structures are similar, while the second comparison is between two distantly related molecules. References are made to the usual sequence alignments. A variety of complementary methods are introduced to display the results.


An audit of children referred with suspected epilepsy.
Members of the British Paediatric Neurology Association were invited to participate in a national audit of children presenting with a possible diagnosis of epilepsy. The audit was based on a 'standard' or set of pre-determined questions drawn up by an advisory audit group. The audit form comprised a total of 30 questions divided into four sections addressing history, examination, investigation, treatment and communication. Information for the audit was obtained retrospectively from the child's case notes. Each participating centre or consultant was asked to audit the case notes of 20 children. At the end of the 12-month recruitment period three centres responded, contributing audit forms on 50 children. The required information was provided for the majority of the questions in each of the four sections, thereby meeting the audit 'standard'. Within the history section, only 32 of the 50 (64%) case notes had recorded whether or not there was 'any obvious provoking factor or circumstance to the episodes'. Communication was the least satisfactorily completed section with between none and 48% of the case notes documenting that the child's family had been informed of the existence of a voluntary epilepsy organization. Despite the simplicity of the audit form, the response for this national audit was considerably lower than anticipated.


Surface and swelling properties of mucoadhesive blends and their ability to release fluconazole in a mucin environment.
The aim of this study is to characterize the matrices for the controlled release of fluconazole and to expand the knowledge of their physicochemical properties that influence the process of mucoadhesion. Polymeric carriers of fluconazole were prepared using the following mucoadhesive polymers: Carbopol 974 P NF, Noveon AA-1, HPMC, HEC, chitosan and film-forming polymer Kollidon VA 64. The potential mucoadhesive properties of the polymers and their blends were evaluated by measuring the wettability and then calculating the surface free energy defined by OWRK and vOCG models, determining the polar and dispersion forces, spreading coefficients and work of adhesion of polymers and their blends with fluconazole in the form of tablets. Prepared tablets were characterized by swelling capacity and in vitro drug release to estimate the amount of fluconazole release from selected polymer blends. The study of drug release from selected blends both in simulated saliva fluid (pH = 6.8) and in simulated vaginal fluid (pH = 4.2) containing mucin confirmed the ability of polymeric carriers to continuously deliver drug over a period of about 8 h.


Correlation between auditory thalamic area evoked responses and species-specific call characteristics. II. H. Hyla cinerea (Anura: Hylidae).
Evoked potentials were recorded from the posterior dorsal thalamus of green treefrogs (Hyla cinerea) in response to single tones and combinations of two and three tones. 1. The responses to two tones were largest when one of the component tones was 500 Hz and when the second component was between 2000 and 4000 Hz (Fig.3). 2. The response to 500 + 3000 Hz showed nonlinear facilitation; i.e., the amplitude of the response was greater than the sum of the responses to the component tones alone (Figs. 4, 5). This result provides evidence that cells functioning as 'AND' gates will be found in this center. 3. When a third tone around 1200 Hz was added to a stimulus of 500 + 3000 Hz a 65% decrease in the evoked response amplitude occurred (Fig. 6). 4. The largest evoked response amplitude to a two-tone stimulus (500 + 3000 Hz) occurred when the rise-time was less than 50 ms (Fig. 7). 5. The two-tone tuning was found to be temperature dependent. The optimal lower frequency tone shifted downward with decreasing temperatures (Fig. 8). 6. When the temperatures of the neurophysiological and the behavioral experiments are matched, the optimal stimuli for evoking a large response are closely correlated to the parameters of the acoustic stimuli preferred by gravid H. cinerea females in discrimination tests. This center therefore appears to be very important for the processing of complex species-specific sounds.


Highly specific and sensitive non-enzymatic determination of uric acid in serum and urine by extended gate field effect transistor sensors.
A potentiometric non-enzymatic sensor using off-chip extended-gate field effect transistor (EGFET) with a ferrocenyl-alkanethiol modified gold electrode is demonstrated for determining the uric acid concentration in human serum and urine. Hexacyanoferrate (II) and (III) ions are used as redox reagent. This potentiometric sensor measures the interface potential on the ferrocene immobilized gold electrode, which is modulated by the redox reaction between uric acid and hexacyanoferrate ions. The device shows a near Nernstian response to uric acid and is highly specific. The interference that comes from glucose, bilirubin, ascorbic acid and hemoglobin is negligible in normal concentration range of these interferents. The sensor also exhibits excellent long term reliability. This extended gate field effect transistor based sensors can be used as a point of care UA testing tool, due to the small size, low cost, and low sample volume consumption.


Morphometric evaluation of the hypothalamic-ovarian axis of the ketonuric, diabetic Chinese hamster: relationship to the reproductive cycle.
The relationship between diabetes and the morphological alterations which occur in hypothalamic and ovarian tissue was examined in the long-term, ketonuric-diabetic Chinese hamster. Matched diabetic and non-diabetic control hamsters were inspected daily for changes in the reproductive cycle by vaginal lavage. On dioestrus, animals were perfused, the hypothalamus and ovaries collected, prepared for microscopy and morphometrically analyzed. The nuclei in the medial basal hypothalamus of diabetic hamsters exhibited a decreased area (p less than 0.01) and neuronal population (p less than 0.05-0.01) compared with controls. The ovaries of the diabetic animals had a reduced follicular population (p less than or equal to 0.05) and an increased atresia rate (p less than or equal to 0.05) compared with controls. In addition, all diabetic hamsters were acyclic. In diabetic animals, the corpora luteal cells contained a reduced lipid content (p less than or equal to 0.001) which was possibly functionally related to a significant decline in serum progesterone levels (p less than or equal to 0.01). Based on these results it is suggested that the hypothalamic-ovarian axis is both morphologically and functionally impaired in the diabetic hamster.


Migraine and ischemic stroke: a debated question.
Numerous epidemiologic observations reporting high prevalence of migraine among young individuals with stroke as well as dysfunction of cerebral arteries during migraine attacks prompt speculation on the existence of a comorbidity between the two disorders. The recent finding of silent infarct-like brain lesions in migraineurs reinforced this hypothesis and raised questions on whether migraine may be a progressive disorder rather than simply an episodic disorder. Stroke can occur during the course of migraine attacks with aura, supporting the assumption of a causal relation between the two diseases. Migraine may accentuate other existing risk factors for stroke, and both jointly increase the risk of cerebral ischemia outside of migraine attacks. In this regard, the role of migraine might be that of predisposing condition for cerebral ischemia. Migraine and ischemic stroke may be the end phenotype of common pathogenic mechanisms. Evidence of a migraine-stroke relation in cases of specific disorders, such as CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), strongly supports this concept. Finally, acute focal cerebral ischemia can trigger migraine attacks, and, thus, migraine may be the consequence of stroke. In this paper, we will review contemporary epidemiologic studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.


Symmetry-breaking induced magnetic Fano resonances in densely packed arrays of symmetric nanotrimers.
Due to unique properties and great design flexibilities, Fano resonances represent one of the most promising optical features mediated by metallic nanostructures, while the excitation of some Fano modes is impossible due to symmetry reasons. The aim of this work is to show that dense lattice arrangements can have a profound impact on the optical properties of nanostructures and, in particular, can enable the excitation of otherwise dark modes. Here, we demonstrate this concept using the example of rectangular arrays of symmetric trimers packed so densely that the coupling between neighbouring unit cells imposes a symmetry break, enabling the excitation of magnetic Fano resonances. We found that in experiments as well as in simulations, electric and magnetic Fano resonances can be simultaneously formed in cases where the inter-trimer distances are sufficiently small. By analysing the transition from an isolated trimer mode into a regime of strong near-field coupling, we show that by modifying the rectangular unit cell lengths due to the symmetry mismatch between lattice and trimer, two types of Fano resonances can be found, especially magnetic Fano resonances with loop-type magnetic field distributions within the centre of each trimer, which can be either enhanced or suppressed. In addition, the influence of the refractive index environment was measured, showing sensitivity values of approximately 300 nm/RIU. Our work provides fundamental insights into the interaction of the lattice and nanostructure response and paves the way towards the observation of novel optical excitations.


The incidence and factors of inappropriate rapid antigen test usage for group A streptococcus.
Although rapid antigen tests (RADTs) for group A streptococcus (GAS) can help diagnose group A streptococcal pharyngitis, little is known about the inappropriate use of these RADTs. This retrospective observational study compared the appropriate vs. inappropriate use of RADTs in patients who had a RADT between January 2019 and August 2022. RADTs for patients with a low Centor score of 0-1 point were deemed inappropriate. Of the 1015 patients, 380 (37.4%) had inappropriate RADTs. Patients with asthma were associated with an increased risk of inappropriate testing. In contrast, during the coronavirus 2019 pandemic, outpatients and residents were associated with a reduced risk of inappropriate testing. Consequent to the inappropriate use of RADTs, 162 (16.0%) patients received potentially inappropriate antibiotics. Our results suggest that diagnostic stewardship for pharyngitis, including education for healthcare workers, is needed to reduce inappropriate test ordering and prevent unnecessary care.


Gene therapy: challenges in cell culture scale-up.
Gene therapy is designed to cure various diseases resulting from genetic defects. Currently, recombinant adeno-associated viral vectors (rAAV) are the vehicles of choice for therapeutic gene delivery in vivo. To date, manufacturing sufficient rAAV product to meet rapidly expanding clinical demand remains a bottleneck in the industry. In the past decade, multiple production platforms have been rapidly implemented with encouraging improvements in productivity and scalability. In this review, we discuss the advantages and limitations of the most popular production platforms in the industry with a focus on the cell culture process scale-up.


Technological transfers from the European space programs: a dynamic view and comparison with other R&D projects.
This article presents the results and lessons learned from a series of studies carried out by the BETA research team (University Louis Pasteur of Strasbourg, France) to measure the spin-offs and technological transfers that resulted from European space programs. Beyond the quantitative results that are analyzed in detail, the article examines some of the main qualitative characteristics that shape the technology transfer process generated by these programs. In particular, it is demonstrated that three main characteristics have a significant impact on the technology transfer process: the nature of the technologies at stake (their degree of maturity, their degree of diversity, the extent to which they are generic or specific), the nature of the network of participants to the programs (the degree of mutual trust, the existence of absorptive capabilities) and the nature of the organizational structure of those firms which participated in the projects (their degree of decentralization, their degree of vertical integration). The article concludes by discussing how these lessons learned could be used to shape the procurement policies to be followed by space agencies in order to favor a high potential for technological transfers arising from future space projects.


Evaluating Equity in Health Financing Using Benefit Incidence Analysis: A Framework for Accounting for Quality of Care.
Equity in health care financing has gained increased attention in low- and middle-income countries (LMICs) following the renewed global interest in universal health coverage (UHC), a key component of the sustainable development goals (SDGs). UHC requires that people have access to the health services they need without risking financial hardship. Health financing is central to UHC and many LMICs have initiated reforms to align their health financing systems with the goals of UHC. Evaluation of the equity impact of these reforms has become a growing area of research, especially in countries with large health inequalities where the pressure to move towards UHC is most intense and the need for evidence to inform policy most critical. However, current analytical tools for evaluating equity in health financing conspicuously exclude indicators of quality, an important dimension of UHC. The aim of this paper was to address this critical methodological gap by introducing quality scores into benefit incidence analysis (BIA), one of the key techniques for assessing equity in health financing. BIA measures the extent to which different socioeconomic groups benefit from public spending on health care through their use of health services. The benefit (public subsidy) is captured in monetary terms by multiplying the quantity of a particular health service consumed by the unit cost of that service and subtracting any out-of-pocket costs incurred while using the service. It does not account for variations in the quality of health services in the computation of the public subsidy.


A weight-of-evidence approach to identify nanomaterials in consumer products: a case study of nanoparticles in commercial sunscreens.
Nanoscale ingredients in commercial products represent a point of emerging environmental concern due to recent findings that correlate toxicity with small particle size. A weight-of-evidence (WOE) approach based upon multiple lines of evidence (LOE) is developed here to assess nanomaterials as they exist in consumer product formulations, providing a qualitative assessment regarding the presence of nanomaterials, along with a baseline estimate of nanoparticle concentration if nanomaterials do exist. Electron microscopy, analytical separations, and X-ray detection methods were used to identify and characterize nanomaterials in sunscreen formulations. The WOE/LOE approach as applied to four commercial sunscreen products indicated that all four contained at least 10% dispersed primary particles having at least one dimension <100 nm in size. Analytical analyses confirmed that these constituents were comprised of zinc oxide (ZnO) or titanium dioxide (TiO2). The screening approaches developed herein offer a streamlined, facile means to identify potentially hazardous nanomaterial constituents with minimal abrasive processing of the raw material.


CyTOF mass cytometry analysis of human memory CD4+ T cells and memory B cells.
High-dimensional mass cytometry provides unparalleled insight into the cellular composition of the immune system. Here, we describe a mass-cytometry-based protocol to examine memory CD4+ T cell and memory B cell (MBC) responses in human peripheral blood. This approach allows for the identification of >50 distinct memory CD4+ T cell and MBC populations from a single clinical sample. This highly reproducible protocol has been successfully applied to multiple infectious disease settings to identify correlates of susceptibility or protection from infection. For complete details on the use and execution of this protocol, please refer to Ioannidis et al. (2021).


Extreme sports performance for more than a week with severely fractured sleep.
Severely fractured sleep is mostly portrayed negatively, but investigations in extreme sports show that humans can maintain performance with a minimum of sleep. With two cases of long-lasting extreme sports performances, we demonstrate that severely fragmented sleep does not necessarily lead to a deterioration of physical and cognitive performance. We performed continuous polysomnography on a 34 year-old skier for 11 days and nights during a world record attempt in long-term downhill skiing and monitored a 32 year-old cyclist during the Race Across America for 8.5 days via sleep and activity logs. The skier slept fractured fashion in 15-16 naps with a daily average of 6 h consisting of 77% in sleep stage 1 and 2, 11% in stage 3, and 13% in stage REM. The cyclist slept a total of 7 h and 52 min in 8.5 days, split up into 11 short naps and 6 sleep periods. The average duration of napping was 8.8 min and of sleep 64.2 min. These two cases demonstrate that outstanding performances are possible with severely fractured sleep and/or sleep deprivation. In well-trained athletes, breaking new recordsis possible despite extreme sleep habits.


Common congenital brain anomalies.
Craniocerebral malformations remain enigmas to many radiologists because their pathogeneses are obscure, noninvasive imaging modalities could not display them in detail until recently, and concise classifications have been lacking. In this article the MRI findings of the most common congenital brain malformations are presented with an emphasis on the characteristic features of each malformation and the clinical symptoms and course.


Animal models of the non-motor features of Parkinson's disease.
The non-motor symptoms (NMS) of Parkinson's disease (PD) occur in roughly 90% of patients, have a profound negative impact on their quality of life, and often go undiagnosed. NMS typically involve many functional systems, and include sleep disturbances, neuropsychiatric and cognitive deficits, and autonomic and sensory dysfunction. The development and use of animal models have provided valuable insight into the classical motor symptoms of PD over the past few decades. Toxin-induced models provide a suitable approach to study aspects of the disease that derive from the loss of nigrostriatal dopaminergic neurons, a cardinal feature of PD. This also includes some NMS, primarily cognitive dysfunction. However, several NMS poorly respond to dopaminergic treatments, suggesting that they may be due to other pathologies. Recently developed genetic models of PD are providing new ways to model these NMS and identify their mechanisms. This review summarizes the current available literature on the ability of both toxin-induced and genetically-based animal models to reproduce the NMS of PD.


Assessment of MRI issues for the Argus II retinal prosthesis.
The objective was to evaluate magnetic resonance imaging (MRI) issues (magnetic field interactions, heating, artifacts and functional alterations) at 1.5 T and 3 T for the Argus II Retinal Prosthesis (Second Sight Medical Products, Sylmar, CA, USA). Standardized protocols were used to assess magnetic field interactions (translational attraction and torque; 3 T, worst case), MRI-related heating (1.5 and 3 T), artifacts (3 T; worst case) and functional changes (1.5 and 3 T) associated with MRI. The magnetic field interactions were acceptable. MRI-related heating, which was studied at a relatively high, MR system-reported whole body averaged specific absorption rates, will not pose a hazard to the patient under the conditions used for testing. While artifacts were "moderate" in relation to the dimensions of the Argus II Retinal Prosthesis, optimization of MRI parameters can reduce the size of the artifacts. Exposures to MRI conditions at 1.5 and 3 T did not damage or alter the functional aspects of the Argus II Retinal Prosthesis. In consideration of the test results, a patient with the Argus II Retinal Prosthesis may undergo MRI at 1.5 T or 3 T when specific guidelines and MRI conditions are followed, including those advised by the manufacturer.


Pathology reporting of breast cancer: trends in 1989-1999, following the introduction of mammographic screening in Western Australia.
A survey of pathology reporting of breast cancer in Western Australia in 1989 highlighted the need for improvement. The current study documents (1) changes in pathology reporting from 1989 to 1999 and (2) changes in patterns of histopathological prognostic indicators for breast cancer following introduction of mammographic screening in 1989. Data concerning all breast cancer cases reported in Western Australia in 1989, 1994 and 1999 were retrieved using the State Cancer Registry, Hospital Morbidity data system, and pathology laboratory records. Pathology reports improved in quality during the decade surveyed. For invasive carcinoma, tumour size was not recorded in 1.2% of pathology reports in 1999 compared with 16.1% in 1989 (p<0.001). Corresponding figures for other prognostic factors were: tumour grade 3.3% and 51.6% (p<0.001), tumour type 0.2% and 4.1% (p<0.001), vascular invasion 3.7% and 70.9% (p<0.001), and lymph node status 1.9% and 4.5% (p = 0.023). In 1999, 5.9% of reports were not in a synoptic/checklist format, whereas all reports were descriptive in 1989 (p<0.001). For the population as a whole, the proportion of invasive carcinomas <1 cm was 20.9% in 1999 compared with 14.5% in 1989 (p<0.001); for tumours <2 cm the corresponding figures were 65.4% and 59.7% (p = 0.013). In 1999, 30.5% of tumours were histologically well-differentiated compared with 10.6% in 1989 (p<0.001), and 61.7% were lymph node negative in 1999 compared with 57.1% in 1989 (p = 0.006). Pure ductal carcinoma in situ (DCIS) constituted 10.9% and 7.9% of total cases of breast carcinoma in 1999 and 1989, respectively (p = 0.01). Quality of pathology reporting improved markedly over the period, in parallel with adoption of standardised synoptic pathology reports. By 1999, recording of important prognostic information was almost complete. Frequency of favourable prognostic factors generally increased over time, reflecting expected effects of mammographic screening.


Dissociable brain structural asymmetry patterns reveal unique phenome-wide profiles.
Broca reported ~150 years ago that particular lesions of the left hemisphere impair speech. Since then, other brain regions have been reported to show lateralized structure and function. Yet, studies of brain asymmetry have limited their focus to pairwise comparisons between homologous regions. Here, we characterized separable whole-brain asymmetry patterns in grey and white matter structure from n = 37,441 UK Biobank participants. By pooling information on left-right shifts underlying whole-brain structure, we deconvolved signatures of brain asymmetry that are spatially distributed rather than locally constrained. Classically asymmetric regions turned out to belong to more than one asymmetry pattern. Instead of a single dominant signature, we discovered complementary asymmetry patterns that contributed similarly to whole-brain asymmetry at the population level. These asymmetry patterns were associated with unique collections of phenotypes, ranging from early lifestyle factors to demographic status to mental health indicators.


The impacts of algae biological pump effect on the occurrence, source apportionment and toxicity of SPM-bound PAHs in lake environment.
The algae biological pump (ABP) effect for hydrophobic organic contaminants in deep oligotrophic lakes and oceans has been well studied. Suspended particulate matter (SPM) plays a connective role in ABP processes. However, little is known about the impacts of ABP effect on the occurrence, source apportionment and toxicity of SPM-bound polycyclic aromatic hydrocarbons (PAHs) in a typically shallow eutrophic lake under strong anthropogenic emissions of PAHs. In this study, we study this gap knowledge on the eutrophic Lake Chaohu, China. SPM-bound PAHs in Lake Chaohu were controlled by anthropogenic emissions in all seasons. Apparent ABP effect only occurred in spring and summer in lake area. Algae blooms in spring and summer significantly increased 46.5% ± 7.9% (mean ± standard deviation) and 19.8% ± 2.4% of Σ21 SPM-bound PAHs, and greatly enhanced their toxicity (1.98 ± 0.46 times in spring and 32.9% ± 4.2% in summer). Therefore, there need more attentions focusing on the coupling effect of persistent toxic substances such as PAHs and harmful algae blooms in aquatic environment for sustainable development. The apparent ABP effect had little influence on their source apportionment. However, it may cause a regime shift for the source apportionment on a short-term scale. Further study could pay more attentions on in-depth and short-term studies on ABP effect.


Surgery of persistent hyperinsulinaemic hypoglycaemia.
Hyperinsulinism (HI) is the commonest cause of persistent or recurrent hypoglycaemia in childhood. HI is genetically and phenotypically diverse. Key management issues involve early diagnosis by insuring that appropriate investigations are undertaken at the point of hypoglycaemia, prevention of recurrent hypoglycaemia and clinical, biochemical and genetic characterisation of the HI syndrome. Children with persistent diazoxide resistant HI require investigation at specialist centres to differentiate those with a generalised disorder of the pancreas (diffuse HI; di-HI) from those with localised abnormalities within the pancreas (focal HI; fo-HI). Fo-HI may be managed by selective pancreatic resection of the focal abnormality. Di-HI is only managed by surgery if combination drug therapies are unable to prevent hypoglycaemia. Pancreatic beta-cell dysfunction persists following subtotal pancreatectomy of di-HI.


Connective tissue growth factor (CTGF/CCN2) in serum is an indicator of fibrogenic progression and malignant transformation in patients with chronic hepatitis B infection.
Still a challenging medical problem is the non-invasive monitoring of patients with a variety of chronic liver diseases being on risk to develop fibrosis, cirrhosis, and, finally, primary liver cell carcinoma. Previously, we have shown that CTGF/CCN2, a down-stream mediator of TGF-β, in serum might be a promising non-invasive biomarker of fibrosis, which is extended in the following study to cirrhosis and liver cell carcinoma. Healthy individuals (n=56), as well as fibrotic (n=77), cirrhotic (n=17), and HCC-patients (n=72) with chronic hepatitis B (HBV) infection, clinically, biochemically and histopathologically well characterized and classified, were included for the measurements of CTGF-concentrations in serum using a newly developed CTGF-enzyme immunoassay. A statistical significant increase of the mean serum CTGF-concentrations was associated with different stages of fibrosis, ranging from 15.9 μg/L (S0), 20.3 μg/L (S1/2) to 36.9 μg/L (S3/4). The highest CTGF-concentrations were measured in cirrhotic patients (43.6 μg/L), compared to healthy subjects (17.7 μg/L), followed by a decrease in cirrhotic HCC-patients (38.5 μg/L; p=0.001). Of note, HCC patients without underlying cirrhosis (n=8) had CTGF levels (13.5±13.2 μg/L) comparable to those in healthy controls. No statistical relation between CTGF levels and parameters of liver injury (e.g. AST, ALT) was noticed, but CTGF levels are correlated negatively with serum albumin levels (p=0.007) and platelet counts (p=0.0032), respectively. The latter was negatively correlated with the stage of fibrosis (p=0.025). In HCC patients, CTGF concentrations decreased with tumor progression and size, with lower levels in TNM stage II (30.5 μg/L) and stage III (33.6 μg/L) compared to TNM stage I (41.6 μg/L). Our data suggest a valuable diagnostic impact of CTGF in serum for the follow-up of patients suffering from chronic liver diseases developing fibrosis, cirrhosis and finally HCC. CTGF serum levels in HCC are most likely due to underlying fibrosis/cirrhosis but not due to malignancy per se.


Production and characterization of virus-like particles of grapevine fanleaf virus presenting L2 epitope of human papillomavirus minor capsid protein.
Virus-like particle (VLP) platform represents a promising approach for the generation of efficient and immunogenic subunit vaccines. Here, the feasibility of using grapevine fanleaf virus (GFLV) VLPs as a new carrier for the presentation of human papillomavirus (HPV) L2 epitope was studied. To achieve this goal, a model of the HPV L2 epitope secondary structure was predicted and its insertion within 5 external loops in the GFLV capsid protein (CP) was evaluated. The epitope sequence was genetically inserted in the αB-αB" domain C of the GFLV CP, which was then over-expressed in Pichia pastoris and Escherichia coli. The highest expression yield was obtained in E. coli. Using this system, VLP formation requires a denaturation-refolding step, whereas VLPs with lower production yield were directly formed using P. pastoris, as confirmed by electron microscopy and immunostaining electron microscopy. Since the GFLV L2 VLPs were found to interact with the HPV L2 antibody under native conditions in capillary electrophoresis and in ELISA, it can be assumed that the inserted epitope is located at the VLP surface with its proper ternary structure. The results demonstrate that GFLV VLPs constitute a potential scaffold for surface display of the epitope of interest.


Monte Carlo simulation of diffusion and ionic conductivity in a simple cubic random alloy via the interstitialcy mechanism.
This Monte Carlo study deals with mass and charge transport in binary ionic alloys governed by interstitialcy defects acting as diffusion vehicles. In particular, we calculate tracer correlation factors f(A) and f(B) in a simple cubic random alloy AB for diffusion via the collinear interstitialcy mechanism as a function of composition and jump frequency ratio wA/wB. [corrected]. Interstitialcy correlation factors f(I), which play a crucial role in the interpretation of ion-conductivity data, are also determined. The evaluation of partial correlation factors provides insight into the types of jumps that mostly contribute to the different transport processes under consideration. Examination of the percolation behaviour yields the site-percolation threshold of the mobile component B for w(A) = 0. Surprisingly, a unique second-order threshold composition is found, which relates to the abundance of different interstitialcy jump types when wA << wB [corrected]. Both numerically obtained threshold values are accurately reproduced by estimated analytical expressions based on simple arguments. Practical implications of the simulation results are explored by calculating tracer diffusivity ratios D*(A)/D*(B) and by comparing self-diffusion with ionic conductivity using the Nernst-Einstein equation.


Gender differences in accessing cardiac surgery across England: a cross-sectional analysis of the health survey for England.
To examine gender differences in access to cardiac surgery in a nationally representative sample. Nationwide cross sectional household based survey (Health Survey for England). Private households in England around 1993 and 1994. 1708 subjects reporting a history of either doctor diagnosed angina or heart attack from a stratified random sample of 32 378 people aged 16 and above. The proportion reporting having had cardiac surgery or on a waiting list. 13.5% reported previous (n = 206) or pending (n = 25) cardiac surgery. Men were more likely than women to have had or to be waiting for cardiac surgery (19.1% of men versus 6.8% of women, chi2 54.7, P<0.001). This finding was consistent regardless of age group and across three regional areas. The unadjusted odds ratio for cardiac surgery for men versus women was 3.3 (95% Cl 2.3, 4.5, P<0.001) and was only slightly attenuated to 2.8 (95% CI 1.9, 4.0. P<0.001), after adjustment for other factors. The gender difference remained even when analysis was restricted to subjects reporting a previous heart attack, and after statistical adjustment for disease severity. Women are less likely than men to receive cardiac surgery across all age groups and regional areas. These results include private operations and adjust for individual behavioural data. Neither disease severity or co-morbidity explains these discrepancies. Further studies are required to determine why this inequality occurs and how it can be addressed.


Retroperitoneal hemorrhage due to bilateral adrenal metastases from lung adenocarcinoma.
A 56-yr-old man was admitted to our university hospital for severe back pain one month after a resection for lung adenocarcinoma (stage IIIA) without evidence of the adrenal mass. Computed tomography (CT) of the abdomen showed bilateral bleeding of adrenal tumors. Endocrinological laboratory studies showed high plasma ACTH and normal serum cortisol levels with the loss of circadian rhythm. Although plasma ACTH levels increased, there was no cortisol response to administration of human corticotropichormone (hCRH). Core-needle biopsy was performed on the right adrenal tumor and revealed adenocarcinoma cells mimicking a primary lung tumor previously examined. We diagnosed retroperitoneal hemorrhage due to bilateral adrenal gland metastasis from lung adenocarcinoma with adrenal insufficiency. Adrenal metastases most commonly originate from a primary lung tumor, followed by stomach, esophagus and liver/bile ducts. Bilateral adrenal metastases were noted in approximately half of all adrenal metastases patients. Clinically significant adrenal hemorrhage by metastasis is exceedingly rare and non-specific symptoms, such as abdominal, chest or back pain, nausea and vomiting, confusion, weakness, hypotension, shock and high fever, are often observed in these patients. We present a case of massive retroperitoneal hemorrhage and adrenal insufficiency due to adrenal gland metastasis from adenocarcinoma of lung.


[Construction of the digital models of masseter and temporal muscles with three-dimensional laser scanning].
To explore a new method for establishing digital models of the masseter and temporal muscles and superficial soft tissue using three-dimensional laser scanning technique. One adult male cadaveric head without malformation was dissected to expose the superficial portion of the masseter and temporalis. Multiple aspects of the sample were scanned with three-dimensional laser scanning system, and the point clouds of the masseter and temporal muscles were generated. The specimen was scanned again after the masseter and temporal muscles had been removed. The digital model of the muscles was reconstructed with the point clouds using Geomagic software, and the morphology of the muscle model was observed and measured. The 3-D digital models of the masseter and temporal muscles with the anatomical characteristics were reconstructed based on the point clouds using Geomagic 8.0 software. The digital model of the muscles can vividly demonstrate the muscle contours, which provides a basis for morphological study and biomechanical analysis of the muscles.


Comparison of effect of an increased dosage of vonoprazan versus vonoprazan plus lafutidine on gastric acid inhibition and serum gastrin.
Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H2RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml. Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.


Quinoline Hydrazone Derivatives as New Antibacterials against Multidrug Resistant Strains.
To develop novel antimicrobial agents a series of 2(4)-hydrazone derivatives of quinoline were designed, synthesized and tested. QSAR models of the antibacterial activity of quinoline derivatives were developed by the OCHEM web platform using different machine learning methods. A virtual set of quinoline derivatives was verified with a previously published classification model of anti-E. coli activity and screened using the regression model of anti-S. aureus activity. Selected and synthesized 2(4)-hydrazone derivatives of quinoline exhibited antibacterial activity against the standard and antibiotic-resistant S. aureus and E. coli strains in the range from 15 to 30 mm by the diameter of growth inhibition zones. Molecular docking showed the complex formation of the studied compounds into the catalytic domain of dihydrofolate reductase with an estimated binding affinity from -8.4 to -9.4 kcal/mol.


Transmural pressure and membrane potential in human saphenous vein.
An increase in transmural pressure reportedly depolarizes myocytes in various arterial blood vessels. We have examined the relationship between transmural pressure and membrane potential (E(m)) in human saphenous veins with a view to determine whether contractile force generation, hence spasmogenesis in vein grafts, involves a similar process of mechanoelectrical excitation. Intracellular recordings were made by sharp glass microelectrodes in human isolated saphenous veins and parallel measurements were performed in ring preparations. E(m) values obtained in pressurized vessels at four different pressure levels were (mean+/-SD): -74.4+/-5.5 mV (0-6 cm H(2)O; n=10), -72.6+/-6.5 mV (11-14 cm H(2)O; n=27), -72.1+/-6.5 mV (26-27 cm H(2)O; n=30), and -72.9+/-4.0 mV (50-54 cm H(2)O; n=38), demonstrating the lack of an overt pressure-dependence. Except at the lowest transmural pressure tested, these values were significantly different from E(m) obtained in ring preparations (-77.8+/-4.0 mV; n=30). Raising extracellular K(+) to 80 mM produced a comparable depolarization in tissues either pressurized to 50-54 cm H(2)O (-64.9+/-4.3 mV; n=27) or set up as ring preparations (-64.06+/-6.9 mV; n=35). Human saphenous veins respond to transmural pressure with a limited depolarization that lacks correlation with pressure. The absence of a pressure-induced graded depolarization suggests that pressure-dependent vasoconstriction does not play a primary role in blood flow regulation in lower limb large veins. Moreover, this raises doubts that mechanical stimuli per se would lead to development of vasospasm in the early stages of saphenous vein grafting into arterial vascular beds.


Treatment of calcified ostial disease by rotational atherectomy and adjunctive cutting balloon angioplasty prior to stent implantation.
Both heavily calcified and ostial lesions are difficult to deal with by percutaneous transluminal coronary angioplasty (PTCA) alone. Acute results are often sub-optimal, complications are more frequent, and long-term results are disappointing. Optimal stent deployment may not be possible unless satisfactory lesion dilatation is achieved and the lesion made more compliant. The use of rotational atherectomy and cutting balloon angioplasty to a calcified ostial lesion in the left circumflex coronary artery prior to stent implantation is reported.


Quantification of postural sway in normals and patients with cerebellar diseases.
Posturography was performed in 41 patients with cerebellar diseases by means of a force measuring platform using an on-line computer program which calculated sway path, sway area, antero-posterior and lateral sway components and the amount of visual stabilization. Postural ataxia was quantitatively studied in 8 patients with spinal ataxia (Friedreich's), 6 patients with vestibulocerebellar lesions, 11 patients with anterior lobe atrophy, 7 patients with hemispheral cerebellar lesions, and 9 patients with a disease affecting all parts of the cerebellum. Patients with lesions of the cerebellar hemispheres could not be separated from normals by means of posturography. Lesions of the spino-cerebellar afferents (Friedreich' ataxia) caused an omnidirectional low frequency sway with preserved visual stabilization. Patients with anterior lobe atrophy showed a predominant antero-posterior sway, often with a spontaneous high frequency body tremor around 3 Hz. Vestibulo-cerebellar lesions exhibited omnidirectional low frequency sway poorly stabilized by vision. Quantitative posturography helps to localize cerebellar lesions and allows for quantitative follow-up studies of cerebellar diseases.