Multi-task dispatch of shared autonomous electric vehicles for Mobility-on-Demand services - combination of deep reinforcement learning and combinatorial optimization method.
The Autonomous Mobility-on-Demand system is an emerging green and sustainable transportation system providing on-demand mobility services for urban residents. To achieve the best recharging, delivering, and repositioning task assignment decision-making process for shared autonomous electric vehicles, this paper formulates the fleet dynamic operating process into a multi-agent multi-task dynamic dispatching problem based on Markov Decision Process. Specifically, the decision-making process at each time step is divided into 3 sub-processes, among which recharging and delivery task assignment processes are transformed into a maximum weight matching problem of bipartite graph respectively, and the repositioning task assignment process is quantified as a maximum flow problem. Kuhn-Munkres Algorithm and Edmond-Karp Algorithm are adopted to solve the above two mathematical problems to achieve the optimal task allocation policy. To further improve the dispatching performance, a new instant reward function balancing order income with trip satisfaction is designed, and a state-value function estimated by Back Propagation-Deep Neural Network is defined as a matching degree between each shared autonomous electric vehicle and each delivery task. The numerical results show that: (i) a reward function focusing on income and satisfaction can increase total revenue by 33.2%, (ii) the introduction of task allocation repositioning increases total revenue by 50.0%, (iii) a re-estimated state value function leads to a 2.8% increase in total revenue, (iv) the combination of charging and task repositioning can reduce user waiting time and significantly improve user satisfaction with the trip.


Transcriptomic analysis of bell pepper (Capsicum annuum L.) revealing key mechanisms in response to low temperature stress.
Bell pepper (Capsicum annuum L.) is one of the most economically and nutritionally important vegetables worldwide. However, its production can be affected by various abiotic stresses, such as low temperature. This causes various biochemical, morphological and molecular changes affecting membrane lipid composition, photosynthetic pigments, accumulation of free sugars and proline, secondary metabolism, as well as a change in gene expression. However, the mechanism of molecular response to this type of stress has not yet been elucidated. To further investigate the response mechanism to this abiotic stress, we performed an RNA-Seq transcriptomic analysis to obtain the transcriptomic profile of Capsicum annuum exposed to low temperature stress, where libraries were constructed from reads of control and low temperature stress samples, varying on average per treatment from 22,952,190.5-27,305,327 paired reads ranging in size from 30 to 150 bp. The number of differentially expressed genes (DEGs) for each treatment was 388, 417 and 664 at T-17 h, T-22 h and T-41 h, respectively, identifying 58 up-regulated genes and 169 down-regulated genes shared among the three exposure times. Likewise, 23 DEGs encoding TFs were identified at T-17 h, 30 DEGs at T-22 h and 47 DEGs at T-42 h, respectively. GO analysis revealed that DEGs were involved in catalytic activity, response to temperature stimulus, oxidoreductase activity, stress response, phosphate ion transport and response to abscisic acid. KEGG pathway analysis identified that DEGs were related to flavonoid biosynthesis, alkaloid biosynthesis and plant circadian rhythm pathways in the case of up-regulated genes, while in the case of down-regulated genes, they pertained to MAPK signaling and plant hormone signal transduction pathways, present at all the three time points of low temperature exposure. Validation of the transcriptomic method was performed by evaluation of five DEGs by quantitative polymerase chain reaction (q-PCR). The data obtained in the present study provide new insights into the transcriptome profiles of Capsicum annuum stem in response to low temperature stress. The data generated may be useful for the identification of key candidate genes and molecular mechanisms involved in response to this type of stress.


Cannibalism and early instar survival in a larval damselfly.
Cannibalism by larval damselflies late in larval development on larvae a few instars smaller has been widely documented. I examine here the survival of eggs oviposited near the end of the flight season of adult Enallagma boreale in the presence and absence of potential cannibals, individuals that hatched from eggs earlier in the season, over an extended part of the life-cycle. The role of competition as a modifier of cannibalism was examined by manipulating egg density, environmental productivity, and habitat complexity. Survival in the absence of potential cannibals ranged from 5% to nearly 50% but was only 0-3% in the presence of cannibals. Survival of small larvae was related to manipulations of habitat complexity but not initial density or resources. There were no significant interactions of the presence of large larvae with other experimental treatments on the survival of small larvae. The mean size of small larvae was greater in the presence of cannibals. This may be because the cannibalism treatment reduced the density of small larvae and reduced competition for resources, or that the cannibals preferentially fed on small larvae and only relatively large individuals remained. Fertilization of the habitat or manipulating the initial density of small larvae did not affect mass of small larvae at the end of the experiment, which would be expected if small larvae were affected by competition for resources. Potential cannibals, however, emerged at higher mass when small larvae were present at low density and when productivity of the habitat was increased. This suggests that the negative effect of competition by small larvae outweighs the positive effect of being potential prey for large larvae.


Comparison of Drug-Coated Balloon Angioplasty Alone and Directional Atherectomy Combined with Drug-Coated Balloon Angioplasty in Patients with Lower Extremity Peripheral Arterial Disease with Claudication.
The objective of the study was to compare drug-coated balloon (DCB) angioplasty alone and directional atherectomy (DA) combined with DCB angioplasty in patients with lower extremity peripheral arterial disease (LE-PAD). Subjects treated with DCB angioplasty alone (group A) and DA combined with DCB angioplasty (group B) were enrolled in the study. A retrospective chart review was performed between the 4 years. Subjects with severe and occluded LE-PAD were included. Demographic data, atherosclerotic vessel properties, and procedural data were recorded. For both groups, success rates (technical, procedural, and clinical) were presented. In total, 226 patients were evaluated. For baseline characteristics, only tobacco use and hyperlipidemia were higher in group B (P = 0.001 and P = 0.010, respectively). For the ankle-brachial index, no significant difference existed at the first, third, sixth, 12th or 24th month follow-ups. No significant difference existed for the Rutherford class at the first, third, sixth, or 12th months according to the groups. A significant difference was found at 24-month Rutherford levels. The incidence of severe claudication in group A was significantly higher than that in group B (13 [12.4%] for group A and 3 [2.8%] for group B, P = 0.035). The stenosis rate after predilatation in group B was significantly higher than that in group A (54.56 ± 5.36 for group A and 59.20 ± 6.21 for group B, P = 0.012). The distribution of full patency in the 12th month in group B was significantly higher than that in group A. The rate of 70-100% stenosis in the 12th month was significantly higher in group A than in group B. According to the groups, the distribution of the patients who were lost to follow-up and died during the follow-up and secondary results, primary patency rates, and 2-year disease-free survival rates were also similar. Atherectomy combined with DCB is superior for the long-term treatment of LE-PAD.


B cell sub-types following acute malaria and associations with clinical immunity.
Repeated exposure to Plasmodium falciparum is associated with perturbations in B cell sub-set homeostasis, including expansion atypical memory B cells. However, B cell perturbations immediately following acute malaria infection have been poorly characterized, especially with regard to their relationship with immunity to malaria. To better understand the kinetics of B cell sub-sets following malaria, the proportions of six B cell sub-sets were assessed at five time points following acute malaria in four to 5 years old children living in a high transmission region of Uganda. B cell sub-set kinetics were compared with measures of clinical immunity to malaria-lower parasite density at the time of malaria diagnosis and recent asymptomatic parasitaemia. Atypical memory B cell and transitional B cell proportions increased following malaria. In contrast, plasmablast proportions were highest at the time of malaria diagnosis and rapidly declined following treatment. Increased proportions of atypical memory B cells were associated with greater immunity to malaria, whereas increased proportions of transitional B cells were associated with evidence of less immunity to malaria. These findings highlight the dynamic changes in multiple B cell sub-sets following acute, uncomplicated malaria, and how these sub-sets are associated with developing immunity to malaria.


Stereopsis following surgery in children with congenital and developmental cataracts: A systematic review and meta-analysis.
We estimated the proportion of children with stereopsis following surgery in congenital and developmental cataracts by systematic review and meta-analysis and also considered the factors influencing stereopsis, such as intervention age and presence of strabismus. Stereopsis is directly related to quality of life, and investigating its levels following cataract surgery in children may help decide the right time to intervene, particularly in the context of brain plasticity. We conducted a systematic literature search using Scopus, PubMed, and Web of Science and found 25 case series, 3 cohorts, and 3 clinical trial studies from 1/1/1995 to 31/12/2020. Study-specific proportions of stereopsis from 923 children were pooled using a random-effects model, and stratified analyses were conducted based on intervention age and pre-existing strabismus as a confounder. We appraised the risk of bias using tools published by National Institutes of Health and evaluated publication bias with funnel plots and the Egger test. The pooled proportions of stereopsis based on 8 unilateral and 6 bilateral congenital cataract studies were 0.37 (95% CIs: [0.24, 0.53]) and 0.45 (95% CIs: [0.24,0.68]) when patients with preexisting strabismus were excluded as a confounder. When the intervention age was ≤6 months, proportions in unilateral congenital cataract group significantly increased to 0.52 (95% CIs: [0.37, 0.66]; P = 0.49) compared to 0.26 (95% CIs: [0.14, 0.44]; P = 0.16) otherwise. A similar increase in proportions was found when intervention age ≤4 months. In both unilateral and bilateral congenital cataract groups, proportions increased significantly when the confounder was excluded. Overall, proportions in bilateral congenital cataracts were significantly greater than unilateral cases (irrespective of confounder). Eight unilateral and 5 bilateral developmental cataract studies resulted in pooled proportions of 0.62 (95% CIs: [0.27, 0.88] and 0.82 (95% CIs: [0.4, 0.97]), respectively. Although proportions for bilateral developmental cataracts were greater than unilateral cataracts (irrespective of confounder), results were not statistically significant. Finally, proportions in unilateral developmental cataracts were significantly greater than unilateral congenital cataracts (Z = 7.413, P = 6.173694e-14). We conclude that surgical intervention within first 4-6 months can significantly affect postoperative outcomes in unilateral congenital cataracts. Analysis of existing data does not show a significant effect of intervention age on stereopsis outcomes for developmental cataracts.


Experiences of women receiving childbirth care from public health facilities in Kumasi, Ghana.
to explore women's experiences with childbirth care in Kumasi, Ghana. exploratory, qualitative research design using in-depth interviews and content analysis. four public health facilities in Kumasi, Ghana. fifty-six women attending either antenatal or postnatal care at the four public health facilities. individual in-depth interviews were used to explore women's experiences with childbirth care. Mothers had both encouraging and discouraging experiences during care, which influenced their willingness to seek assisted health care during childbirth in the future. Participants who had experiences of empathetic support and continuous labour support and attention reported these to be encouraging. Other participants reported discouraging experiences such as disrespectful care and inadequate communication and involvement in care decisions. Women in our study wanted to be seen as partners in the care process and not subordinate to care providers. Midwives and student midwives must be given the tools and support to deliver patient-centred childbirth care.


4-hydroxynonenal and transforming growth factor-beta1 expression in colon cancer.
In vivo studies on human colon adenocarcinoma showed decreased transforming growth factor-beta1 (TGF-beta1) antiproliferative cytokine content in tumour tissue related to malignancy progression, with a corresponding decrease in lipid peroxidation aldehydic end-product, 4-hydroxynonenal (HNE). The tumour mechanism to escape TGF-beta1-mediated growth inhibition may be due to an altered TGF-beta1 receptor system. Subsequent in vitro analyses showed a differential distribution of TGF-beta1 receptors depending on the human colon cancer cell line considered (CaCo-2 or HT-29): compared to HT-29 cells, CaCo-2 cells showed a decrease of the two main TGF-beta1 receptors, RI and RII. Notwithstanding their partial TGF-beta1 RI and RII deficiency, treatment of CaCo-2 cells with adequate doses of the cytokine (10 ng/ml) was able to induce apoptosis. Of note, co-treatment of these cells with 1 microM HNE increased the apoptotic effect. The constant low concentration of TGF-beta1 in the tumour mass may be related to the low content of antiproliferative HNE observed in colon cancer: the latter phenomenon, which reduces TGF-beta1 production in the tumour area, may represent a favourable condition for neoplastic progression. The enhancement of TGF-beta1-induced apoptosis by HNE in CaCo-2 cells supports this hypothesis. The different transcriptional components regulated by the distinct signaling pathways of these two molecules might be proposed; in particular, crosstalk between the MAPK and the Smad pathway could modulate and co-operate in the transcription of target genes involved in regulation of cell proliferation.


Changing referral pattern of biliary injuries sustained during laparoscopic cholecystectomy.
More patients with less severe type biliary injury are being referred earlier to a specialist hepatobiliary unit. Most patients still have ineffective corrective surgery before transfer. Presented in part to the European Congress of the International Hepato-Pancreatico-Biliary Association in Budapest, Hungary, May 1999 and published in abstract form as Digestive Surgery 1999; 16(Suppl 1): 32.


ERK is involved in the regulation of CpG ODN 2395 on the expression levels of anti-lipopolysaccharide factors in Chinese mitten crab, Eriocheir sinensis.
CpG oligodeoxynucleotides (ODN), as an effective adjuvant or immunopotentiator, activate the immune system and induce various immune responses. Recently, it has also been reported that high dose of CpG ODN can lead to immunosuppression. However, the underlying mechanism of CpG ODN-mediated immune response remains largely unknown in invertebrates. In the present study, the role of ERK in regulating expression levels of anti-lipopolysaccharide factors (ALFs) induced by different doses of CpG ODN 2395 was analyzed in Chinese mitten crab, Eriocheir sinensis. The mRNA expression levels of EsALFs (EsALF1, EsALF2 and EsALF3) and EsERK in haemocytes were observed to increase from 6 h to 48 h post low doses of CpG ODN 2395 (0.5 μg and 2.5 μg) stimulation, while they were suppressed after high dose of CpG ODN 2395 (12.5 μg) injection. Meanwhile, the phosphorylation levels of ERK in haemocytes were significantly promoted after low doses of CpG ODN 2395 injection, and a reduce level of ERK phosphorylation was observed after high dose of CpG ODN 2395 injection. Further investigation showed that the expression levels of EsALFs induced by CpG ODN 2395 were markedly down-regulated after knocking down the expression of EsERK. Similarly, the EsALFs mRNA expression were also inhibited post different doses of CpG ODN 2395 stimulation in PD98059 (ERK inhibitor) injection crabs. These results collectively suggest that ERK is involved in regulating the expression level of EsALFs induced by different dose of CpG ODN 2395 in Chinese mitten crab, which contribute to the understanding of the regulation of CpG ODN involving in immune response in crustaceans.


The double-plate fixation technique prevents varus collapse in AO type C3 supra-intercondylar fracture of the distal femur.
Varus collapse followed by osteosynthesis for distal femoral fractures with conventional implants has been well documented but is seldom mentioned in fractures managed with locking plates. The purpose of this study was to assess the incidence of varus collapse after treating complex supra-intercondylar fractures of the distal femur (AO type C3) using a Single Plate (SP) or Double Plate (DP) fixation technique. We retrospectively reviewed 357 patients with distal femoral fractures who were treated at our hospital between 2006 and 2017. After excluding cases of infection, malignancy, periprosthetic fracture, revision surgery, pediatric fracture, and extra-articular fracture, 54 patients were included in the study. All demographic data and radiological and clinical outcomes were reviewed and analyzed. There were 54 patients enrolled into this study with age from 15 to 85 years old (mean 41.6, SD = 19.9), and 32 of them were open fractures (59%). The patients were further divided into either an SP (n = 15) or a DP group (n = 39). Demographics, including age, sex, injury severity score, and open fracture type, were all compatible between the two groups. The overall nonunion rate was 25.9% (n = 14; 6 from the SP and 8 from the DP group; p = 0.175). The varus collapse rate was 9.3% (n = 5; 4 from the SP and 1 from the DP group (p = 0.018). The varus collapse rate after osteosynthesis with a single lateral locking plate could be as high as 26.7% in AO type C3 fractures of the distal femur, which would be decreased to 2.6% by adding a medial buttress plate. Surgeons should consider DP fixation to avoid varus collapse in severely comminuted complete intra-articular fractures of the distal femur.


Nonalcoholic Steatohepatitis is the Most Rapidly Increasing Indication for Liver Transplantation in Young Adults in the United States.
To analyze the frequency and trend of liver transplantation (LT) for nonalcoholic steatohepatitis (NASH) cirrhosis in young adults aged 18 to 40 years and to assess post-LT outcomes in this age group. NASH is currently the fastest-growing indication for LT in US adults. It is believed that NASH is a rare indication for LT among young adults. Using the United Network for Organ Sharing database, we performed a retrospective cohort analysis of all LTs in young adults between 2002 and 2012. Incidence rate ratio was calculated for each indication. A total of 5157 young adults underwent LT over the study period-54% were male, 23% obese. Mean (±SD) age and body mass index were 31.6±6.7 years and 26.3±6.1 kg/m, respectively. The incidence of LTs performed for NASH cirrhosis increased from 0.53% in 2002 to 4.46% in 2012. NASH was the most rapidly growing indication for LT among all other etiologies with a 14% increment per year (incidence rate ratio, 1.14; 95% confidence interval, 1.09-1.20, P<0.001). The 5-year post-LT outcomes were comparable between NASH and non-NASH recipients, but graft survival was lower and retransplantation cumulative rates were higher in NASH recipients compared with those with other metabolic liver diseases (63.5% vs. 81.4%, P=0.003 and 12.7% vs. 4.2%, P=0.046, respectively). NASH is the fastest-growing indication for LT among young US adults aged 18 to 40 years and now accounts for almost 5% of all LTs in this age group.


Studies on the replication of a bovine parvovirus.
Optimal replication of a bovine parvovirus type 1 was found to occur when parasynchronous bovine embryonic lung cells were infected during the S phase of the cell cycle, just prior to maximum DNA synthesis. Viral antigen was first detected in the cytoplasm by immunofluorescence at 8 h post-infection, reaching a maximum at this location by 16 h and then disappearing. In the nucleus, antigen was first detected at 12 h, concurrent with early inclusion body formation and first detection of intracellular virus production. Intranuclear antigen then increased rapidly to a maximum at 20 h, as the inclusions progressively matured, large amounts of virus were produced within the cell, with some release to the environment. From 24 h, the nuclear inclusions became increasingly shrunken and basophilic as virus migrated to the cytoplasm and was progressively released to the exterior concurrent with cell degeneration and fragmentation. The majority of virus remained cell associated, even at 28 h post-inoculation. Two morphological types of early and late stage intranuclear inclusions were produced by the virus, these appearing to be a distinct feature of bovine strains. In other aspects, the replication of bovine parvovirus appeared similar to that of other members of the genus.


[Treatment of stable coronary artery disease in type II diabetes mellitus: drugs, coronary intervention and bypass surgery].
The prognosis of patients with type 2 diabetes is reduced by coronary artery disease. The aim of treatment is therefore not only to treat angina symptoms but also improve the prognosis by medical and interventional treatment. LDL-lowering and coronary revascularisation have the largest beneficial impact on prognosis.


An initiation factor causing dissociation of E. coli ribosomes.
Purification of crude initiation factors, essential for polypeptide synthesis in cell-free systems of E. coli, yielded a fraction DF which causes dissociation of 70 S ribosomes. Its stoichiometric action on 70 S ribosomes is antagonized by increasing Mg(2+) concentrations but not by the addition of 30 S and 50 S subunits washed with high salt concentration. GTP did not stimulate this dissociating action. 2 &mgr;g of our most purified preparation caused 100% dissociation of 100 &mgr;g of 70 S ribosomes without added GTP. DF-induced dissociation is a very rapid process at 37 degrees C and is temperature-dependent in the range of 0 degrees -37 degrees C. DF, which is thermolabile factor, is much less or not effective with complexed 70 S ribosomes bearing peptidyl-tRNA and mRNA.


Do pain specialists meet the needs of the referring physician? A survey of primary care providers.
To study the factors that influence the use of opioids in the management of chronic noncancer pain (CNCP) by primary care providers (PCPs) for patients returning from a pain specialist. A survey of PCPs. Two physician groups in the Minneapolis-St. Paul metropolitan area. Two seventy-six PCPs surveyed and 80 surveys returned. Participants rated the importance of specific concerns regarding the role of pain specialists and the use of opioids in the management of CNCP. Past experience with pain specialists, comfort using opioids, and opinions regarding a trilateral opioid agreement were also examined. The top concerns for PCPs were as follows: the use of opioids in patients with chemical dependency or psychological issues, the escalation of opioid dosing, and the use of opioids in pain states without objective findings. They also ranked highly the importance of coordinating the return of patients from a pain specialist with explicit opioid instructions and the availability of consultation by phone or a timely follow-up visit. PCPs were supportive of the concept of a trilateral opioid agreement. PCPs have significant concerns regarding the prescribing of opioids in CNCP. They desire closer collaboration with pain specialists, including more explicit plans of care when patients are transferred back to them. The trilateral agreement may provide one framework for better collaboration.


Stat6-deficient mice develop airway hyperresponsiveness and peribronchial fibrosis during chronic fungal asthma.
Signal transducer and activator of transcription 6 (Stat6) is critical for Th2-mediated responses during allergic airway disease. To investigate the role of Stat6 in fungus-induced airway hyperresponsiveness and remodeling, Stat6-deficient (Stat6-/-) and Stat6-wildtype (Stat6+/+) mice were sensitized to Aspergillus fumigatus and airway disease was subsequently assessed in both groups at days 21, 30, 38, and 44 after an intratracheal challenge with live A. fumigatus conidia. At all times after conidia, histological analysis revealed an absence of goblet cell hyperplasia and markedly diminished peribronchial inflammation in Stat6-/- mice in contrast to Stat6+/+ mice. Airway hyperresponsiveness and peribronchial fibrosis in Stat6-/- mice were significantly reduced at day 21 after conidia compared with Stat6+/+ mice, but both groups exhibited significant, similar increases in these parameters at all subsequent times after conidia. In separate experiments, IL-13-responsive cells in Stat6-/- mice were targeted via the daily intranasal administration of 200 ng of IL-13-PE38QQR (IL13-PE), comprised of human IL-13 and a derivative of Pseudomonas exotoxin, from days 38 to 44 after the conidia challenge. IL13-PE treatment abolished airway hyperresponsiveness, but not peribronchial fibrosis in Stat6-/- mice. Taken together, these data demonstrate that the chronic development of airway hyperresponsiveness during fungal asthma is IL-13-dependent but Stat6-independent.


Trochanteric locking nail versus arthroplasty in unstable intertrochanteric fracture in patients aged over 75 years.
In trochanteric fracture, whatever its anatomic type, internal fixation is currently the standard attitude, with arthroplasty as a relatively unusual option. Hip implants are an excellent alternative to osteosynthesis in unstable trochanteric fracture in patients aged over 75 years. A non-randomised prospective multicenter study compared osteosynthesis by trochanteric nailing (n=113) to hip arthroplasty (n=134) in unstable trochanteric fracture (AO types 31 A2.2 and 3 and A3.3) in 247 patients over the age of 75 years. The series was recruited during 2007 in seven centres, four of which included only arthroplasties, two only osteosyntheses and one both. The two groups were comparable in age, sex, preoperative Parker score, pre-fracture place of residence, fracture type, time to surgery and preoperative comorbidity. The sole difference was in operators, with more senior surgeons in arthroplasty (62% versus 27%). Three-month mortality was identical in the two groups (21.2% versus 21%). General complications did not differ, although mechanical complications were more frequent in the nailing group (12.5% versus 2.8%). Functional results (Parker and PMA scores) were better in the implant than in the nail group. The present study validated hip arthroplasty in these indications. Cemented stems associated to a dual-mobility acetabular component gave the best results. Prospective, level of evidence III.


Retrograde (ventriculoatrial) conduction.
Interest in retrograde VA conduction has been renewed with the advent of tachycardias induced by physiologic pacemakers with atrial sensing capabilities. Accurate representation of ventriculoatrial conduction requires detailed electrophysiologic analysis during sinus rhythm, during tachycardias whether or not associated with accessory pathways, and during ventricular pacing studies. Retrograde conduction should be assessed in patients considered for implantation of atrial sensing and tracking pacemakers (VAT, VDD, DDD), until technologic advances overcome the problems of endless loop tachycardias.


Comparison of dietary intake patterns in hemodialysis patients by nutritional status: A cross-sectional analysis.
Although appropriate dietary adjustments in hemodialysis (HD) patients are important, most HD patients have difficulty adhering to dietary therapy due to the stress of a restricted-food diet or loss of appetite, which eventually leads to malnutrition and other complications. The dietary intake of HD patients stratified by nutritional status has not yet been studied. In total, 111 HD patients from five dialysis centers were stratified into 2 groups based on the Subjective Global Assessment: the well-nourished group and the poorly nourished group. The 7-day dietary intake and food behaviors of the two groups were compared. Logistic regression analysis was performed to reveal the factors associated with poorly nourished status. The 7-day dietary survey showed a lower intake of total calories and protein and a higher intake of sodium and potassium than in the standard recommendations, but there were no differences between groups. The poorly nourished group ate fried food significantly more frequently than the well-nourished group. Moreover, higher hip and waist circumferences were significantly associated with poorly nourished status.


Models of communication for polygenic scores and associated psychosocial and behavioral effects on recipients: A systematic review.
This study aimed to systematically review current models for communicating polygenic scores (PGS) and psycho-behavioral outcomes of receiving PGSs. Original research on communicating PGSs and reporting on psycho-behavioral outcomes was included. Search terms were applied to 5 databases and were limited by date (2009-2021). In total, 28 articles, representing 17 studies in several disease settings were identified. There was limited consistency in PGS communication and evaluation/reporting of outcomes. Most studies (n = 14) presented risk in multiple ways (ie, numerically, verbally, and/or visually). Three studies provided personalized lifestyle advice and additional resources. Only 1 of 17 studies reported using behavior change theory to inform their PGS intervention. A total of 8 studies found no evidence of long-term negative psychosocial effects up to 12 months post result. Of 14 studies reporting on behavior, 9 found at least 1 favorable change after PGS receipt. When stratified by risk, 7 out of 9 studies found high PGS was associated with favorable changes including lifestyle, medication, and screening. Low-risk PGS was not associated with maladaptive behaviors (n = 4). PGS has the potential to benefit health behavior. High variability among studies emphasizes the need for developing standardized guidelines for communicating PGSs and evaluating psycho-behavioral outcomes. Our findings call for development of best communication practices and evidence-based interventions informed by behavior change theories.


APC and CTNNB1 mutations are rare in sporadic ependymomas.
The ependymoma is the second most common malignant brain tumor of childhood; however, its molecular basis is poorly understood. The formation of multiple ependymomas has been reported as an occasional feature of Turcot syndrome type 2 (TS2), a familial cancer syndrome caused by inherited mutations of the APC tumor suppressor gene, and characterised by the concurrence of a primary CNS tumor (predominantly medulloblastoma) and multiple colorectal adenomas. APC is a critical component of the Wnt/Wingless signaling pathway, which is disrupted in sporadic cancers (e.g., colorectal adenomas, hepatocellular carcinomas, and medulloblastomas) by somatic mutations affecting multiple genes encoding alternative pathway components, including APC and CTNNB1 (encoding beta-catenin). To investigate any role for genetic disruption of the Wnt/Wingless pathway in sporadic ependymomas, we performed mutation analysis of APC and CTNNB1 in 77 primary tumors. Two synonymous APC polymorphisms (PRO1442PRO; THR1493THR) were identified, which were detected at equivalent rates in ependymomas and control nonneoplastic DNA samples (n =50); however, no further APC or CTNNB1 sequence variations were found. In summary, although inherited APC mutations may be associated with ependymoma development in certain TS2 cases, these data indicate that somatic mutations affecting APC and CTNNB1 do not play a major role in the pathogenesis of sporadic ependymomas.


Factors Associated with 90-Day Outcomes of Patients with Acute Posterior Circulation Stroke Treated By Mechanical Thrombectomy.
Early recanalization of acute posterior circulation stroke caused by large intracranial vessel occlusion by mechanical thrombectomy with stent retrievers may improve the outcome of patients. However, evidence of patient selection is still lacking. This study investigated the prognostic factors of acute posterior circulation stroke caused by large intracranial arterial occlusion when treated with stent-retriever thrombectomy. A total of 69 patients from March 2012 to November 2016 were included in the study. These patients presented with acute posterior circulation stroke caused by large intracranial vessel occlusion and underwent mechanical thrombectomy with Solitaire AB or combined with additional balloon and/or stenting angioplasty. Baseline characteristics, clinical course, and imaging data of the patients were analyzed. Good clinical outcome (defined as a modified Rankin Scale score of 0-2 at 90 days) and safety outcome (defined as death within 90 days after thrombectomy) were considered as end points. The association between factors with good clinical outcome and safety outcome was evaluated with both logistic regression and receiver operating characteristic curve analyses. Of the 69 patients, mean age was 59 years (standard deviation, 8 years) and men comprised 82.6% (57/69). The median onset-to-treatment time was 360 minutes (interquartile range, 250-537 minutes). The median National Institutes of Health Stroke Scale (NIHSS) score was 25 (interquartile range, 17-30) on admission. Successful recanalization was achieved in 62 of the 69 cases (89.9%) and 36.2% (25/69) were independent at 90 days. Regression analysis showed that stroke subtype (intracranial atherosclerotic disease vs. embolism; odds ratio [OR], 0.101; 95% confidence interval [CI], 0.020-0.501; P = 0.005), baseline NIHSS score (≥22 vs. <22; OR, 0.157; 95% CI, 0.040-0.614; P = 0.008) and posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) on diffusion-weighted imaging [DWI] (weighted magnetic resonance imaging) before thrombectomy (≥6 vs. <6; OR, 7.335; 95% CI, 1.495-36.191; P = 0.014) were independent predictive factors of good clinical outcome, respectively at 90 days, whereas high NIHSS score (≥30 vs. <30; OR, 5.569; 95% CI, 1.573-19.716; P = 0.008) and collateral status (≥2 vs. <2; OR, 0.210; 95% CI, 0.059-0.752; P = 0.016) before treatment were associated with mortality at 90 days. Based on receiver operating characteristic curves, baseline NIHSS score (area under the curve [AUC] = 0.779; cutoff, ≥22; P < 0.001; sensitivity, 72%; specificity, 77.3%), pc-ASPECTS on DWI (AUC = 0.820; cutoff, ≥6; P < 0.001; sensitivity, 72%; specificity, 77.3%) before treatment were independent indicators predicting good clinical outcome at 90 days. Increased risk of death by 90 days was associated with baseline NIHSS score (AUC = 0.719; cutoff, ≥30; P = 0.007; sensitivity, 64.7%; specificity, 78.9%) and worse collateral status (AUC = 0.820; cutoff, ≥2; P < 0.001; sensitivity, 58.8%; specificity, 80.8%) before treatment. Stroke subtype, initial stroke severity, and pc-ASPECTS on DWI as well as collateral status before thrombectomy are independent factors affecting the clinical outcome in patients treated with Solitaire AB thrombectomy for acute posterior circulation stroke caused by large intracranial vessel occlusion.


Clinical and pharmacokinetic study evaluating the effect of food on the disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in patients with solid tumors.
9-Nitrocamptothecin (9NC) is an orally administered camptothecin analogue that has completed phase III trials for pancreatic cancer. In biological matrices, camptothecin analogues exist in equilibrium between the active-lactone (LAC) and inactive-hydroxy acid (HA) forms. 9NC has been administered on an empty stomach; however, it is unclear if food alters the absorption and disposition of 9NC and its 9-aminocamptothecin (9AC) active-metabolite. Thus, we evaluated the disposition of 9NC and 9AC after administration of 9NC under fasting conditions and after a standard meal. Patients were randomized to receive 9NC as a single oral dose at 1.5 mg/m(2) with 8 ounces (oz) of an acidic beverage under fasting conditions, or after a meal consisting of two eggs, 8 oz of orange juice, buttered toast, 8 oz of milk, and 4 oz of hash brown potatoes. Following a 72 h washout period, 9NC was administered with the alternative condition (i.e., with food or fasting). 9NC was then continued for 5 days of every week. Serial blood samples were obtained prior to and from 0.25 to 24 h after administration of 9NC. The total (sum of LAC + HA) of 9NC and 9AC were measured by an LC-MS/MS assay. Area under the plasma concentration versus time curve (AUC) for 9NC and 9AC total were calculated. After the pharmacokinetic section of the study, patients received 9NC 1.5 mg/m(2) orally under fasting conditions daily for 5 days per week for 8 weeks. Sixteen patients with median (range) age 62 (47-83) years, diagnoses of colorectal (six patients), lung (two patients), and other (eight patients) malignancies, received 83 [median (range) 4 (2-9)] weeks of therapy. Patients with toxicities greater than grade 2: were diarrhea (1), nausea (2), vomiting (2), fatigue (2), anemia (3), neutropenia (3), and febrile neutropenia (2). Three patients (lung, unknown primary, and colon) had stable disease for eight weeks. The mean+/-SD of 9NC AUC(food) and 9NC AUC(fast) (n=9) were 330+/-182 and 558+/-379 ng/ml.h, respectively (P<0.05). The mean+/-SD of 9AC AUC(food) and 9AC AUC(fast) (n=9) were 244+/-60 and 256+/-101 ng/ml.h, respectively (P>0.05). The mean +/- SD ratio of 9NC AUC(food) to AUC(fasting) in individual patients (n=9) was 0.67+/-0.22. The mean +/- SD ratio of 9AC AUC(food) to AUC(fasting) in individual patients (n=9) was 1.14+/-0.61. Co-administration of 9NC with food reduces the oral absorption of 9NC; however, there was no difference in the exposure of 9AC. The is high interpatient variability in the effect of food on the absorption of 9NC and the interpatient variability in the effect of food on the disposition of 9AC is even greater when compared to 9NC.


Cost and cost drivers associated with setting-up a prime vendor system to complement the national medicines supply chain in Tanzania.
Economic analysis of supply chain management interventions to improve the availability of healthcare commodities at healthcare facilities is important in generating evidence for decision-makers. The current study assesses the cost and cost drivers for setting-up a public-private partnership programme in Tanzania in which all public healthcare facility orders for complementary medicines are pooled at the district level, and then purchased from one contracted supplier, the prime vendor (referred to as 'Jazia Prime Vendor System' (Jazia PVS)). Financial and economic costs of Jazia PVS were collected retrospectively and using the ingredients approach. The financial costs were spread over the implementation period of January 2014-July 2019. In addition, we estimated the financial rollout costs of Jazia PVS to the other 23 regions in the country over 2 years (2018-2019). A multivariate sensitivity analysis was conducted on the estimates. Jazia PVS start-up and recurrent financial costs amounted to US$2 170 989.74 and US$709 302.32, respectively. The main cost drivers were costs for short-term experts, training of staff and healthcare workers and the Jazia PVS technical and board management activities. The start-up financial cost per facility was US$2819.47 and cost per capita was US$0.37. In conclusion, the study provides useful information on the cost and cost drivers for setting-up a complementary pharmaceutical supply system to complement an existing system in low-income settings. Despite the substantial costs incurred in the initial investment and operations of the Jazia PVS, the new framework is effective in achieving the desired purpose of improving availability of healthcare commodities.


The phosphatidylinositol (4,5)-bisphosphate-Rab35 axis regulates migrasome formation.
Migrasomes are recently discovered organelles, which are formed on the ends or branch points of retraction fibers at the trailing edge of migrating cells. Previously, we showed that recruitment of integrins to the site of migrasome formation is essential for migrasome biogenesis. In this study, we found that prior to migrasome formation, PIP5K1A, a PI4P kinase which converts PI4P into PI(4,5)P2, is recruited to migrasome formation sites. The recruitment of PIP5K1A results in generation of PI(4,5)P2 at the migrasome formation site. Once accumulated, PI(4,5)P2 recruits Rab35 to the migrasome formation site by interacting with the C-terminal polybasic cluster of Rab35. We further demonstrated that active Rab35 promotes migrasome formation by recruiting and concentrating integrin α5 at migrasome formation sites, which is likely mediated by the interaction between integrin α5 and Rab35. Our study identifies the upstream signaling events orchestrating migrasome biogenesis.


Small-Scale Isolation of Bacterial Artificial Chromosome (BAC) DNA and Verification by Polymerase Chain Reaction (PCR).
In this protocol, small amounts of selected bacterial artificial chromosome (BAC) DNAs are prepared from 5-mL cultures of the Escherichia coli host transformed with the BAC clone. DNA is isolated by an adaptation of the alkaline lysis method. The yield is 0.1-0.4 µg, and the BAC DNA is suitable for analysis by polymerase chain reaction (PCR). Considerations for clone selection are also addressed.


Association analysis of KIR/HLA genotype with liver cirrhosis, hepatocellular carcinoma, and NUC freedom in chronic hepatitis B patients.
Natural killer cells are modulated through the binding of killer cell immunoglobulin-like receptors (KIRs) with human leukocyte antigen (HLA) class I ligands. This study investigated the association of KIR/HLA pairs with progression to liver cirrhosis, hepatocellular carcinoma (HCC) development, and nucleot(s)ide (NUC) treatment freedom in hepatitis B virus (HBV) infection. KIR, HLA-Bw, and HLA-C were genotyped in 280 Japanese HBV patients for clinical comparisons. No significant associations of KIR/HLA pairs were detected in terms of liver cirrhosis development. The KIR2DS3 positive rate was significantly higher in patients with HCC (n = 39) than in those without (n = 241) [30.8% vs. 14.9%, odds ratio (OR) 2.53, P = 0.015]. The KIR3DL1/HLA-Bw4 pair rate was significantly lower in the NUC freedom group (n = 20) than in the NUC continue group (n = 114) (25.0% vs. 52.6%, OR 0.30, P = 0.042). In conclusion, this study indicated remarkable associations of KIR/HLA with HCC development (KIR2DS3) and freedom from NUC therapy (KIR3DL1/HLA-Bw4) in HBV patients, although the number of cases was insufficient for statistical purposes. Additional multi-center analyses of larger groups are needed to clarify whether KIR/HLA pairs play a role in HBV patient status.


The language of the protein universe.
Proteins, the main cell machinery which play a major role in nearly every cellular process, have always been a central focus in biology. We live in the post-genomic era, and inferring information from massive data sets is a steadily growing universal challenge. The increasing availability of fully sequenced genomes can be regarded as the 'Rosetta Stone' of the protein universe, allowing the understanding of genomes and their evolution, just as the original Rosetta Stone allowed Champollion to decipher the ancient Egyptian hieroglyphics. In this review, we consider aspects of the protein domain architectures repertoire that are closely related to those of human languages and aim to provide some insights about the language of proteins.


Does education modify motor compensation in Parkinson's disease?
In Alzheimer's disease, higher educational attainment is associated with fewer cognitive deficits despite similar pathological lesions. In animal models of Parkinson's disease (PD), enhanced levels of cognitive and physical stimulation can reduce motor deficits due to dopaminergic neuronal loss. Therefore, in this study, we tested whether higher educational attainment has a beneficial influence on PD motor symptoms. We included data from 182 patients with de novo PD without dementia, who underwent dopamine transporter (DAT) scans for an initial diagnostic work-up. Patients were divided into 2 groups according to their educational attainment; high education (HE-PD; ≥12years of education) and low education (LE-PD; <12years of education). The HE-PD group exhibited significantly higher mini-mental state exam scores, fewer motor deficits, and lower DAT binding to the posterior putamen than the LE-PD group, despite a similar duration of PD symptoms. A general linear model revealed that this difference in motor deficits remained statistically significant after controlling for potential confounding factors (p=0.032). These results suggest that higher educational attainment can lead to reduced motor deficits in PD despite greater reductions in dopamine levels.


Synthesis, characterization and antitumor evaluation of CMCS-DTX conjugates as novel delivery platform for docetaxel.
The purpose of this study is to synthesis and evaluate the antitumor efficacy of a novel carboxymethyl chitosan-docetaxel (CMCS-DTX) conjugates and the availability of CMCS as the polymer material in polymer-drug conjugates development. Docetaxel (DTX) was attached to carboxymethyl chitosan (CMCS) via biodegradable linker for the first time and the weight percentage of DTX in the CMCS-DTX conjugates was up to 20%. The resulting CMCS-DTX conjugates could spontaneously self-assemble into nanoparticles in aqueous buffer, with uniform size of 127.2±3.58 nm and zeta potential of -25.65 mV. The stability test result showed that only 12.46% of DTX was released after incubation in plasma for 48 h, indicating good stability of CMCS-DTX conjugates in plasma. The results of in vitro cytotoxicity and Hoechst staining indicated that CMCS-DTX conjugates exhibited significant cytotoxicity against B16 and HepG2 cells. CMCS-DTX conjugates also displayed better antitumor effect than Duopafei® by inhibiting tumor growth and prolonging the survival time of B16 melanoma bearing mice more effectively (the median survival time was >30 days for CMCS-DTX conjugates versus 24 days for the Duopafei®). Besides, CMCS-DTX conjugates demonstrated an excellent safety profile with a maximum tolerated dose (MTD) of >250 mg/kg in mice, which was more than 4 fold higher than that of Duopafei® (50 mg/kg). CMCS-DTX conjugates could be exploited as a promising platform for the effective delivery of DTX and CMCS was a favorable choice as the polymer material in polymer-drug conjugates development.


Completing the research process: presentations and publications.
In neuroscience nursing there are many opportunities to present scientific research and scholarly inquiry. Once the effort has been made to share information with colleagues in the settings of conferences, meetings and workshops, the investigator should make the additional effort to prepare the information for publication. The publishable manuscript has many similarities to the oral presentation, however, there are also specific changes that must occur to render the paper appropriate for publication.


Bilateral vocal cord paralysis in Williams syndrome.
Williams syndrome was first described in 1961 (Williams et al. 1961) and is a well-recognised clinical syndrome characterised by growth deficiency, learning difficulties and a typical facies. We describe a 9-year-old girl with classical features of Williams syndrome who presented with acute vocal cord paralysis for which no other cause was found.


Other viral infections in solid organ transplantation.
Viral infections are a major cause of morbidity and even mortality in solid organ transplant recipients. This article reviews key aspects of infections in solid organ transplant recipients from respiratory viruses, such as influenza, polyomavirus, erythrovirus B19 and measles.


[Bacterial osteitis. Special considerations in immunocompromised patients].
With increasing life expectancy and better medical competence, the number of older patients with multimorbidity is growing. Patients with a deficient immune system need more attention during diagnosis and treatment of osteomyelitis.


C-reactive protein and white blood cell count do not improve clinical decision-making in acute appendicitis.
Acute appendicitis (AA) remains a diagnostic challenge as indicated by the high rate of unnecessary surgery. Blood samples, primarily C-reactive protein (CRP) and leucocyte counts, are used as a diagnostic supplement despite their relatively low sensitivities and specificities. However, their influence on diagnostic decision-making has not previously been investigated. The aim of the present study was to investigate if the results of CRP and leucocytes had any positive or negative influence on the decision-making of surgeons handling patients with suspected AA. This was a prospective, observational cohort study including patients (≥ 15 years of age) admitted on suspicion of AA. The surgeons were instructed to perform their physical examination and to register whether they found the patient more or less than 50% likely to have AA. Thereafter, the surgeons had to assess the blood results and re-evaluate their diagnosis. The surgeon's diagnosis before and after was compared with the final diagnosis defined by surgical findings or follow-up. The gold standard was any degree of appendicitis on histology. A total of 226 patients were included of whom 91 (40.3%) had appendicitis on histology. The surgeons changed their diagnosis in nine cases after assessing blood samples. The changes in the proportion of correct diagnoses, sensitivity, specificity and predictive values after assessing blood samples were not significant. The results of CRP and leucocyte counts did not influence clinical decision-making. Financial support was obtained from the Danish Council for Independent Research (Ref. no. 12-132020). Clinicaltrials.gov: NCT02304653.


Evaluation of three automated Treponema pallidum antibody assays for syphilis screening.
The accuracy of the test is critical for the syphilis serology diagnosis. This study aims to evaluate the values of the Elecsys syphilis assay, the Architect syphilis assay, and the Mindray syphilis assay, as syphilis screening tests for pregnant women and patients with syphilis or other diseases. A reverse algorithm was used for the syphilis serology diagnosis. Serum samples (n = 584) were tested with three automated screening assays. All reactive sera by one, two, or three screening assays were further analyzed with the tolulized red unheated serum test (TRUST). Inconsistent results were confirmed by the Treponema pallidum particle agglutination assay (TPPA). The final patient diagnosis was made according to the results of syphilis serology, clinical evidence, and past medical history. The sensitivity, specificity, accuracy, and kappa value of each assay were as follows: for the Elecsys syphilis assay, 100.0%, 98.5%, 98.6%, and 0.927, respectively; for the Architect syphilis assay: 100.0%, 94.5%, 95.0%, and 0.770; and for the Mindray syphilis assay: 100.0%, 97.0%, 97.3%, and 0.862. The McNemar test showed that there were significant differences in the performance between the Elecsys syphilis assay and the Architect syphilis assay (P < 0.001), and between the Mindray syphilis assay and the Architect syphilis assay (P = 0.001). Our study demonstrated that three automated Treponema pallidum antibody assays generally showed high sensitivities and specificities, and so, they are suitable for use in screening for syphilis. The performances of the Elecsys syphilis assay and the Mindray syphilis assay are superior to Architect syphilis assay.


A novel method based on 220Rn (thoron) exhalation rate of indoor surfaces for robust estimates of 220Rn concentration and equilibrium factor to compute inhalation dose.
The research into 220Rn (thoron) has generated an increasing interest in recent times due to the realisation of its radiological importance in many indoor environments. Though it is assumed that the contribution of 220Rn, per se, to the inhalation dose is negligible in comparison with that of its decay products, this may not be always true. Correct estimation of inhalation dose due to thoron requires a reliable method to measure the concentration of both 220Rn and its decay products in indoor air. However, due to its very short half-life (55.6 s) 220Rn shows large variation in its indoor activity concentration. This makes it difficult to have a robust value of 220Rn concentration which can be considered representative of a house, thus making the dose estimation unreliable. This issue has been addressed in the present study by developing a novel method that utilises the 220Rn exhalation rate from indoor surfaces as the basis for estimation of average 220Rn concentration in indoor air. The 220Rn concentration estimated in this manner can be converted to decay products concentration using a suitable equilibrium factor and finally the inhalation dose using appropriate dose conversion factors. A wall mounting accumulator setup has been developed for easy in-situ measurement of 220Rn exhalation from room surfaces. The method has been validated through comprehensive measurements in 25 dwellings in two different regions of India. The developed method is very good for large scale field surveys because of fast and easy applicability.


The role of structural water in the formation of nucleotide mispairs.
The results of NMR investigation of the double-helical nucleic acid fragments containing A.C, C.U, m6G.U and m6G.G mispairs can be explained on the assumption that the bases in such pairs being in usual tautomeric forms are linked via water bridges. A computer analysis of intermolecular interactions in the systems containing two bases and one or two water molecules shows that these pairs correspond to the energy minima. The formation of pairs with water bridges can be considered an intermediate step in mutagenesis caused by some spontaneous errors arising during nucleic acid biosynthesis as well in mutagenesis induced by alkylating agents.


Independent risk factors for cardiac operations in adults with congenital heart disease: a retrospective study of 543 operations for 500 patients.
Adults with congenital heart disease (CHD) are an increasing population requiring cardiac operations. To date, the perioperative risk factors for this group have not been identified. This study aimed to identify clinical, morphologic, and hemodynamic risk factors for an adverse outcome. This study retrospectively analyzed a cohort of 500 patients (ages >16 years) who underwent 543 operations between January 2004 and December 2008 at a single center. The composite end point of an adverse outcome was in-hospital death, a prolonged intensive care exceeding 4 days, or both. The composite end point was reached by 253 of the patients (50.6%). Of the 500 patients, 13 (2.6%) died within 30 days after the operation. After logistic regression analysis, the following eight items remained significant: male gender (P = 0.003; odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2-2.6), cyanosis (P > 0.006; OR 3.7; 95% CI 1.5-9.4), functional class exceeding 2 (P = 0.004; OR 2.2; 95% CI 1.3-3.7), chromosomal abnormalities (P = 0.004; OR 3.3; 95% CI 1.4-7.7), impaired renal function (P = 0.019; OR 3.8; 95% CI 1.2-11.5), systemic right ventricle (RV) in a biventricular circulation (P = 0.027; OR 3.3; 95% CI 1.1-9.5), enlargement of the systemic ventricle (P = 0.011; OR 1.7; 95% CI 1.1-2.6), and operation with extracorporeal circulation (P = 0.002; OR 4.3; 95% CI 1.7-11.4). Early mortality in the current adult CHD population is low. Morbidity, however, is significant and influenced by the patients' conditions (male gender, chromosomal abnormalities), history (cyanosis, New York Hospital Association [NYHA] class), and underlying morphology (systemic RV). This information for a large cohort of patients could help progress toward more adequate counseling for adults with a congenital heart defect.


Mediterranean spotted fever in Algeria--new trends.
Mediterranean spotted fever (MSF) due to Rickettsia conorii is the most important tick-borne disease occurring in North Africa. However, there are only a few fragmentary reports on the epidemiology and clinical aspects of rickettsioses in North Africa, and cases are still rarely documented. We report herein a prospective study conducted in Oran, the second largest city in Algeria. This disease has not been properly described in Oran or in other Algerian cities. A total of 167 cases of Mediterranean spotted fever were documented for the first time by the use of reference methods including immunofluorescence serology and Western blot and absorption studies, including isolation in culture by the shell-vial techniques, and molecular tools. Although some aspects of MSF were found to be in accordance with the general epidemiology of the disease, uncommon aspects were found, including increased incidence and the presence of multiple inoculation eschars in 12% of patients. The role of climatic changes in alterations of host-seeking and feeding behaviors of the vectors, including the brown dog tick Rhipicephalus sanguineus, is discussed. Also, 49% of patients were hospitalized with a severe form. The global death rate was 3.6%, but it was 54.5% in patients hospitalized with major neurological manifestations and multiorgan involvement. The present report gives a unique panel of clinical aspects of MSF as well as new trends in this disease. Entomological, climatic, and molecular studies are needed to better understand both epidemiological and clinical aspects of MSF.


Previous intra-amniotic infection as a risk factor for subsequent peripartal uterine infections.
The risk of recurrent intra-amniotic infection was assessed in 76 women with a previous pregnancy complicated by intra-amniotic infection. Recurrent intra-amniotic infection occurred in five (6.6%), not significantly different from the incidence of 4.4% in a comparison population. When controlled by logistic regression for the increased cesarean section rate in the group with previous intra-amniotic infection, the incidence of endometritis was not significantly different between the groups. After eliminating nulliparas and patients who did not undergo labor, the incidence of intra-amniotic infection in patients with previous infections was not significantly increased over the comparison group. Those patients who did develop recurrent intra-amniotic infection had significantly longer labors (P less than .001), duration of ruptured membranes (P = .002), and duration of internal monitoring (P less than .001), and an increased number of vaginal examinations (P less than .001).


Evaluation of electroactive denitrifiers at different potentials, temperatures and buffers based on microcalorimetry.
Electroactive denitrifiers contribute to the nitrate removal in a bioelectrochemical system, but their metabolism and growth parameters remain vague. In this study, microcalorimetry as a suitable method was used to evaluate the metabolism and growth parameters of electroactive denitrifiers at different cathode potentials, temperatures and buffer solutions. The suitable cathode potential and temperature for electroactive denitrifiers were deemed as -100 mV and 30 °C, respectively. The suitable buffer was found to be phosphate buffer solution but can be replaced by bicarbonate buffer solution. When cultivated with bicarbonate buffer solution at -100 mV and 30 °C, electroactive denitrifiers achieved a specific nitrate removal rate of 2.20 ± 0.08 × 10-10 mg NO3--N·(min·cell)-1 and two growth rate constants (k1 = 0.0051 ± 0.0004 min-1, k2 = 0.0030 ± 0.0004 min-1), with gaseous nitrogen as the end product. The bioelectrochemical denitrification behaved as a two-step process, in which the nitrite reduction to gaseous nitrogen was the rate-limiting step.


Male-female conflict and genitalia: failure to confirm predictions in insects and spiders.
Some recent models suggest a new role for evolutionary arms races between males and females in sexual selection. Female resistance to males is proposed to be driven by the direct advantage to the female of avoiding male-imposed reductions in the number of offspring she can produce, rather than by the indirect advantage of selecting among possible sires for her offspring, as in some traditional models of sexual selection by female choice. This article uses the massive but hitherto under-utilized taxonomic literature on genitalic evolution to test, in a two-step process, whether such new models of arms races between males and females have been responsible for rapid divergent evolution of male genitalia. The test revolves around the prediction that 'new arms races' are less likely to occur in species in which females are largely or completely protected from unwanted sexual attentions from males (e.g. species which mate in leks or in male swarms, in which males attract females from a distance, or in which females initiate contact by attracting males from a distance). The multiple possible mechanical functions of male genitalia are summarized, and functions of male genitalic structures in 43 species in 21 families of Diptera are compiled. Functions associated with intromission and insemination (e.g. seizing and positioning the female appropriately, pushing past possible barriers within the female, orienting within the female to achieve sperm transfer), which are unlikely to be involved in new arms races when females are protected, are shown to be common (> 50 % of documented cases). This information is then used to generate the new arms race prediction: differences in genitalic form among congeneric species in which females are protected should be less common than differences among congeneric species in which females are vulnerable to harassment by males. This prediction was tested using a sample of 361 genera of insects and spiders. The prediction clearly failed, even when the data were adjusted to take into account several possible biases. Comparative analyses within particular taxonomic groups also failed to show the predicted trends, as did less extensive data on other non-genitalic male display traits. Arms races, as defined in some recent models, seem to have been less important in male-female coevolution of genitalic structures than has been suggested. By elimination, alternative interpretations, such as traditional female choice, which do not predict associations between female protection from harassment and rapid divergent evolution, are strengthened.


Effects of Synbiotic-Containing Bacillus coagulans (GBI-30) on the Cardiovascular Status of Patients With Polycystic Ovary Syndrome: A Triple-blinded, Randomized, Placebo-controlled Study.
Despite the high risk of cardiovascular diseases in women with polycystic ovary syndrome, fewer studies have addressed the improvement of cardiometabolic status of these patients. This study was conducted with the aim of investigating the effects of synbiotic-containing, spore-forming Bacillus coagulans on cardiometabolic indicators, including lipid profile, C-reactive protein, and atherogenic indexes in patients with polycystic ovary syndrome. In the present 12-week, triple-blinded, randomized, placebo-controlled clinical trial, 72 women with polycystic ovaries were randomized to receive either 2 g of synbiotic sachet (n = 36) or placebo (n = 36) plus lifestyle modification. Fasting blood samples were taken before and after the intervention. Statistical analysis was performed in 60 participants with a mean (SD) age of 28.25 (5.98) years who completed the intervention (synbiotic group [n = 34] and placebo group [n = 26]). A significant mean (SD) decrease in C-reactive protein level was observed in the synbiotic group compared with the placebo group (-0.12 [9.57] v. -0.008 [4.69], P = 0.03). No significant differences in mean changes of lipid profile and atherogenic indexes were seen between the 2 groups. Although the estimated mean changes in atherogenic indexes in the synbiotic group indicates a greater reduction than the placebo group, no significant difference was detected. Our 12-week synbiotic intervention improved the inflammatory status in women with polycystic ovaries without affecting lipid profile or atherogenic indexes.


A graphene oxide-molybdenum disulfide composite used as stationary phase for determination of sulfonamides in open-tubular capillary electrochromatography.
A graphene oxide-molybdenum disulfide (GO-MoS2) composite was synthesized and utilized as the highly efficient stationary phase of open-tubular capillary electrochromatography (OT-CEC). The characterization results indicated that GO-MoS2 composite was successfully synthesized. The GO-MoS2-coated capillary column was prepared by covalent immobilization method for the determination of seven sulfonamides. The baseline separation of seven sulfonamides was achieved by GO-MoS2-coated capillary column. The linear range was 0.05-100 μg/mL for sulfisomidine, sulfathiazole, sulfamerazine, phthalylsulfathiazole and sulfacetamide, 0.1-100 μg/mL for sulfamonomethoxine and sulfachloropyridazine with a satisfactory correlation coefficients (R2) > 0.9994. This developed OT-CEC method was successfully applied to determinate of seven sulfonamides in environmental water and milk samples with good recoveries of 85.77% - 109.10% and 80.03% - 109.97%, respectively. These results indicated that GO-MoS2-coated capillary column possessed good stability and repeatability.


An allelic variant of the sperm-specific lactate dehydrogenase C4 (LDH-X) isozyme in humans.
An unusual pattern of LDH isozymes was observed by gel electrophoresis of an extract of a human testis. This isozyme composition is consistent with an allelic variant of Ldh-c.


Rapid, in situ synthesis of bidentate ligands: chromatography-free generation of catalyst libraries.
The parallel synthesis of chiral bidentate ligands and their subsequent use in situ for a catalytic process is described. The ligands thus prepared gave comparable results to those obtained when the ligands were synthesized and purified by conventional means. This includes oxazolines and other compounds of similar complexity, meaning that for the first time these valuable compounds have been brought into the field of combinatorial catalysis.


Leveraging mathematical models of disease dynamics and machine learning to improve development of novel malaria interventions.
Substantial research is underway to develop next-generation interventions that address current malaria control challenges. As there is limited testing in their early development, it is difficult to predefine intervention properties such as efficacy that achieve target health goals, and therefore challenging to prioritize selection of novel candidate interventions. Here, we present a quantitative approach to guide intervention development using mathematical models of malaria dynamics coupled with machine learning. Our analysis identifies requirements of efficacy, coverage, and duration of effect for five novel malaria interventions to achieve targeted reductions in malaria prevalence. A mathematical model of malaria transmission dynamics is used to simulate deployment and predict potential impact of new malaria interventions by considering operational, health-system, population, and disease characteristics. Our method relies on consultation with product development stakeholders to define the putative space of novel intervention specifications. We couple the disease model with machine learning to search this multi-dimensional space and efficiently identify optimal intervention properties that achieve specified health goals. We apply our approach to five malaria interventions under development. Aiming for malaria prevalence reduction, we identify and quantify key determinants of intervention impact along with their minimal properties required to achieve the desired health goals. While coverage is generally identified as the largest driver of impact, higher efficacy, longer protection duration or multiple deployments per year are needed to increase prevalence reduction. We show that interventions on multiple parasite or vector targets, as well as combinations the new interventions with drug treatment, lead to significant burden reductions and lower efficacy or duration requirements. Our approach uses disease dynamic models and machine learning to support decision-making and resource investment, facilitating development of new malaria interventions. By evaluating the intervention capabilities in relation to the targeted health goal, our analysis allows prioritization of interventions and of their specifications from an early stage in development, and subsequent investments to be channeled cost-effectively towards impact maximization. This study highlights the role of mathematical models to support intervention development. Although we focus on five malaria interventions, the analysis is generalizable to other new malaria interventions.


Complications from radiotherapy.
Radiotherapy (RT) of the brain is associated with significant stigma in the neuro-oncology community. This is primarily because of the potentially severe complications with which it may be associated. These complications, especially in subacute and latent settings, are often unpredictable, potentially progressive, and irreversible. The onset of complications may start from the first fraction of 2 Gy, continuing over several months after end of RT with persistent drowsiness and apathy. It may also extend over many years with progressive onset of neurocognitive impairments such as memory decline, and diminished focus/attention. For long-term survivors, such as young patients irradiated for a favorable low-grade glioma, quality of life can be seriously impacted by RT. It is essential, as in the pediatric field, to propose patient-specific regimens from the very outset of therapy. The use of molecular biomarkers to better predict survival, control of comorbidities along with judicious use of medications such as steroids and antiepileptics, improved targeting with the help of modern imaging and RT techniques, modulation of the dose, and fractionation aimed at limiting integral dose to the healthy brain all have the potential to minimize treatment-related complications while maintaining the therapeutic efficacy for which RT is known. Sparing "radiosensitive" areas such as hippocampi could have a modest but measurable impact with regard to cognitive preservation, an effect that can possibly be enhanced when used in conjunction with memantine and/or donepezil.


[Telemetry in the clinical setting].
Telemetric cardiac monitoring was invented in 1949 by Norman J Holter. Its clinical use started in the early 1960s. In the hospital, biotelemetry allows early mobilization of patients with cardiovascular risk and addresses the need for arrhythmia or oxygen saturation monitoring. Nowadays telemetry either uses vendor-specific UHF band broadcasting or the digital ISM band (Industrial, Scientific, and Medical Band) standardized Wi-Fi network technology. Modern telemetry radio transmitters can measure and send multiple physiological parameters like multi-channel ECG, NIPB and oxygen saturation. The continuous measurement of oxygen saturation is mandatory for the remote monitoring of patients with cardiac pacemakers. Real 12-lead ECG systems with diagnostic quality are an advantage for monitoring patients with chest pain syndromes or in drug testing wards. Modern systems are light-weight and deliver a maximum of carrying comfort due to optimized cable design. Important for the system selection is a sophisticated detection algorithm with a maximum reduction of artifacts. Home-monitoring of implantable cardiac devices with telemetric functionalities are becoming popular because it allows remote diagnosis of proper device functionality and also optimization of the device settings. Continuous real-time monitoring at home for patients with chronic disease may be possible in the future using Digital Video Broadcasting Terrestrial (DVB-T) technology in Europe, but is currently not yet available.


Increased blood--brain barrier transport of protein-bound anticonvulsant drugs in the newborn.
The extraction of heroin, caffeine, diphenylhydantoin, and phenobarbital has been measured in the newborn, suckling, and adult brain. Anticonvulsant drugs such as diphenylhydantoin and phenobarbital are bound by plasma protein, and it is generally believed that only the fraction of drug that is free (dialyzable) in vitro is available for transport through the blood-brain barrier in vivo. In both the adult and neonatal rat or rabbit, lipid-mediated transport of free phenytoin occurs. In addition, a fraction of the drug that enters the capillary bound to plasma protein also gains access to the brain. A greater amount of protein-bound drug permeates the newborn brain, and this is ascribed to a longer capillary transit time in the neonate. With regard to phenobarbital, the total (i.e., both free and protein-bound) plasma drug enters the newborn brain. In contrast, no protein-bound phenobarbital permeates the adult brain, and it is only the free drug fraction that gains access to the brain. Since the blood-brain barrier permeability-surface area product for the two anticonvulsants is unchanged in newborn and older animals, the age-related differences in brain uptake of protein-bound drugs can be attributed to developmental changes in cerebral blood flow and capillary transit time. The increased transport of protein-bound drugs in the newborn may cause increased concentrations (i.e., brain:plasma ratios) of these anticonvulsants in the neonatal brain.


Anti-hepatitis C virus antibody prevails in fulminant hepatic failure.
Serial serum samples obtained from 27 patients with fulminant hepatic failure (FHF) in a variety of etiology were tested for anti-hepatitis C virus antibody (anti-HCV). Seven out of 10 patients (70%) with FHF due to hepatitis B virus (HBV) infection were positive for anti-HCV, showing a significantly higher rate than that in acute HBV hepatitis (0/17, 0%): In particular, all 3 post-transfusion HBV-FHF cases were found to be positive for the antibody. The incidence of anti-HCV in sporadic non-A non-B (NANB)-FHF patients (7/11, 64%) tended to be greater than that in acute sporadic NANB hepatitis as recently surveyed in this country. In addition, anti-HCV was also detected in a patient with hepatitis A virus (HAV)-FHF and in 2 out of 4 drug-induced FHF patients. Moreover, anti-HCV appeared earlier in FHF (median; 27.5 days, n = 9) regardless of etiology, when compared to acute NANB hepatitis (3 to 6 months). Hence, co-infection and/or superinfection of HCV with enhanced antibody response may play an important role in the development of this fatal disease.


The effect of functional calibration methods on gait kinematics in adolescents with idiopathic rotational deformity of the femur.
Due to anatomical deviations, assumptions of the conventional calibration method for gait analysis may be violated in individuals with rotational deformities of the femur. Functional calibration methods were compared with conventional methods in this group for 1) localization of the hip joint center and orientation of the knee axis, and 2) gait kinematics. Twenty-four adolescents with idiopathic rotational deformity of the femur underwent gait analysis and a CT scan. During standing, distance between hip joint centers and knee axis orientation were compared between calibration methods, with CT serving as reference for hip joint center estimation. Gait kinematics were compared using statistical parametric mapping. The conventional calibration method estimated the hip joint center closer to the CT reference (4±12 mm more lateral) than the functional calibration method (26 ± 20 mm more lateral). Orientation of the knee joint axis was 2.6° less internal in the functional calibration method. During gait, statistical parametric mapping revealed significantly more hip flexion, less external hip rotation during the swing phase, less knee varus-valgus motion, and larger knee flexion angles when applying the functional method. Functional calibration methods were less accurate in determining the hip joint center location than the conventional calibration method and resulted in a knee joint axis that was less internally rotated. Importantly, there was less knee joint angle crosstalk during gait when using the functional method. Although differences between methods on gait kinematics were within clinically acceptable limits for the sagittal plane, relatively larger differences on transversal hip kinematics may hold clinical importance.


Assessment of reduced glutathione: comparison of an optimized fluorometric assay with enzymatic recycling method.
Glutathione is an important tripeptide involved in a variety of cellular processes. Thus, precise knowledge of its levels is essential. Glutathione exists in two free forms-reduced and oxidized-and a number of methods exist to measure its levels. The aim of our work was to optimize a spectrofluorometric assay for reduced glutathione based on the reaction between glutathione and o-phthalaldehyde. We found that a change of excitation wavelength to 340 nm and modification of pH to 6.0 enhance sensitivity and specificity of the method (intraassay coefficient of variation CV < 3%, interassay CV = 5.1%, recovery = 98-102%, linearity = 0-1000 μM GSH, calibration R2 = 1.00). We also anticipated possible effect of various amino acids on the fluorescence signal, but no interference was found. We compared the optimized fluorometric method with a popular enzymatic recycling glutathione assay and found very strong correlation of results (r = 0.99, n = 45). We introduce here an optimized fluorometric method possessing sufficient sensitivity and specificity that is comparable to the enzymatic glutathione assay. Because the fluorometric assay procedure is faster and lower in cost, it could be ideal for routine analysis of reduced glutathione levels in a large number of samples.


For an Ethnomethodology of healthcare ethics.
This paper considers the utility of Ethnomethodology (EM) for the study of healthcare ethics as part of the empirical turn in Bioethics. I give a brief introduction to EM through its respecification of sociology, the specific view on the social world this generates and EM's posture of 'indifference'. I then take a number of EM concepts and articulate each in the context of an EM study of healthcare ethics in professional practice. Having given an overview of the relationship and perspective EM might bring to the professional practice of healthcare ethics I consider whether and how such an approach could be deployed. Whilst an ethnographic study might be problematic I suggest a number of alternative methods through which such EM research could be accomplished. I conclude with the suggestion that, as a particular approach to sociological research, EM offers good deal of potential for the empirical study of healthcare ethics in practice which could result in an improved reflexive understanding of professional ethical practices in bioethics.


Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models.
Nature has revealed to be a key source of innovative anticancer drugs. This study evaluated the antitumour potential of the marine bromoditerpene sphaerococcenol A on different cancer cellular models. Dose-response analyses (0.1-100 µM; 24 h) were accomplished in eight different tumour cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-MEL-28). Deeper studies were conducted on MFC-7 cells, namely, determination of hydrogen peroxide (H2O2) levels and evaluation of apoptosis biomarkers (phosphatidylserine membrane translocation, mitochondrial dysfunction, Caspase-9 activity, and DNA changes). The ability of the compound to induce genotoxicity was verified in L929 fibroblasts. Sphaerococcenol A capacity to impact colorectal-cancer stem cells (CSCs) tumourspheres (HT29, HCT116, SW620) was evaluated by determining tumourspheres viability, number, and area, as well as the proteasome inhibitory activity. Sphaerococcenol A hepatoxicity was studied in AML12 hepatocytes. The compound exhibited cytotoxicity in all malignant cell lines (IC50 ranging from 4.5 to 16.6 µM). MCF-7 cells viability loss was accompanied by H2O2 generation, mitochondrial dysfunction, Caspase-9 activation and DNA nuclear morphology changes. Furthermore, the compound displayed the lowest IC50 on HT29-derived tumourspheres (0.70 µM), followed by HCT116 (1.77 µM) and SW620 (2.74 µM), impacting the HT29 tumoursphere formation by reducing their number and area. Finally, the compound displayed low cytotoxicity on AML12 hepatocytes without genotoxicity. Overall, sphaerococcenol A exhibits broad cytotoxic effects on different tumour cells, increasing H2O2 production and apoptosis. It also affects colorectal CSCs-enriched tumoursphere development. These data highlight the relevance to include sphaerococcenol A in further pharmacological studies aiming cancer treatments.


Oral Motor Abilities Are Task Dependent: A Factor Analytic Approach to Performance Rate.
Measures of performance rates in speech-like or volitional nonspeech oral motor tasks are frequently used to draw inferences about articulation rate abnormalities in patients with neurologic movement disorders. The study objective was to investigate the structural relationship between rate measures of speech and of oral motor behaviors different from speech. A total of 130 patients with neurologic movement disorders and 130 healthy subjects participated in the study. Rate data was collected for oral reading (speech), rapid syllable repetition (speech-like), and rapid single articulator movements (nonspeech). The authors used factor analysis to determine whether the different rate variables reflect the same or distinct constructs. The behavioral data were most appropriately captured by a measurement model in which the different task types loaded onto separate latent variables. The data on oral motor performance rates show that speech tasks and oral motor tasks such as rapid syllable repetition or repetitive single articulator movements measure separate traits.


FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight.
Fragile X mental retardation protein (FMRP), strongly associated with fragile X syndrome, plays important roles by regulating gene expression via interacting with other RNA binding proteins in the brain. However, the role of FMRP in hypothalamus, a central part responsible for metabolic control, is poorly known. Our study shows that FMRP is primarily located in the hypothalamic arcuate nucleus (ARC). Using proteomic analysis, we identified 56 up-regulated and 22 down-regulated proteins in the hypothalamus of Map1b KO mice, with microtubule-associated protein 1 B (MAP1B) being the most outstanding increased protein (more than 10 folds). Immunofluorescent assays showed that MAP1B significantly increased in the Map1b-KO ARC, in which the number of agouti-related peptide (AgRP)-staining neurons significantly reduced, but not altered for pro-opiomelanocortin (POMC) neurons. We further showed an age-dependent reduces in food intake and body weight of the KO mice, along with the decreases of MAP1B and AgRP at the same time points. In hypothalamic GT1-7 cells, the AgRP expression decreased upon knockdown of FMRP or overexpression of MAP1B, and increased in response to overexpression of FMRP or knockdown of MAP1B. Co-knockdown or co-overexpression of FMRP and MAP1B led to a reverse expression of AgRP compared to overexpression of knockdown of FMRP alone, demonstrating that MAP1B is essential for the regulatory effect of FMRP on AgRP expression. Taken together, these data suggest that FMRP-deficiency-induced increase of hypothalamic MAP1B and decrease of AgRP might be associated with reduces in food intake and body weight.


Equilibrium and kinetic studies of ferricyanide adsorption from aqueous solution by activated red mud.
In this study, activated red mud (ARM) was used as a new adsorbent for the removal of ferricyanide anions from aqueous solution. Based on the percentage of ferricyanide removal and ferricyanide adsorption capacity, optimum conditions were evaluated using the response surface method (RSM) and central composite design (CCD). In optimum conditions (pH = 5.6, adsorbent dosage of 2.59 g, ferricyanide concentration of 60 ppm and contact time of 60 min), the percentage of ferricyanide removal and ferricyanide adsorption capacity were obtained as 79.6% and 1.8 mg/g, respectively. The kinetics and equilibrium studies were evaluated by considering the effective parameters including pH and ferricyanide concentration. Kinetic studies were evaluated by kinetic models of pseudo first-order, pseudo-second-order (four different linearized forms), Elovich and intraparticle diffusion. The results of the kinetic study indicated that the mechanism of ferricyanide adsorption onto the ARM adsorbent is a chemisorption interaction by a fast ferricyanide adsorption onto ARM and subsequently the slow diffusion of ferricyanide ions into the ARM inner adsorption sites. The equilibrium studies showed that the adsorption process followed the Langmuir model in which ferricyanide adsorption onto ARM was homogeneous with monolayer adsorption. The results indicated that the activation process of red mud improved adsorbent efficiency and increased the adsorption capacity.


Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma.
Both mesotheliomas and renal cell carcinomas can present a wide variety of cytomorphologic features and histologic patterns. Because of this, renal cell carcinomas metastatic to the pleura and lung can be confused with mesotheliomas. Recently, a variety of positive carcinoma markers, including kidney-associated markers, have become available. The aim of this study is to investigate the value of some of these markers, specifically PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4, for assisting in distinguishing pleural epithelioid mesotheliomas from metastatic renal cell carcinomas. To do so, a total of 40 pleural epithelioid mesotheliomas and 55 renal cell carcinomas (33 clear cell, 10 papillary, and 12 chromophobe) were investigated. In all, 91% of the renal cell carcinomas expressed claudin-4, 89% PAX8, 60% PAX2, 71% carbonic anhydrase IX, and 29% napsin A. All of the mesotheliomas were positive for carbonic anhydrase IX and were negative for all of the other markers. On the basis of these results, it is concluded that claudin-4 and PAX8 have a higher sensitivity and specificity for assisting in discriminating between pleural epithelioid mesotheliomas and renal cell carcinomas when compared with all of the other positive carcinoma markers that are, at present, recommended to be included in the immunohistochemical panels used in this differential diagnosis. Even though PAX2 and napsin A are highly specific, because of their low sensitivity, they have only a limited value. Carbonic anhydrase IX is not useful.


Further advancements in predicting adsorption equilibria using excess formalism: calculation of adsorption excesses at the liquid/solid interface.
Prediction of adsorption equilibria for ternary liquid mixtures on solid surfaces by means of adsorption data for the corresponding three binary liquid mixtures can be improved by combining the thermodynamic excess formalism with geometrical models. This new strategy for the prediction of excess adsorption isotherms is examined for four ternary adsorption systems ranging from ideal to highly non-ideal ternary mixtures. The predicted isotherms are discussed and compared with experimental ones as well as with those obtained for a model based on the absolute quantities. The results confirm: (i) superiority of predicting adsorption in terms of excess quantities, and (ii) utility of geometrical models for constructing ternary molar compositions on the basis of binary ones to predict equilibria not only for liquid mixtures alone but also for adsorption of liquid mixtures on solid surfaces.


Influence of hyperglycemia on the satiating effect of CCK in humans.
In the present study the effects of intraduodenal (i.d.) fat (endogenous CCK) and of CCK infusion on satiety were studied during normo-and hyperglycemic conditions. Eight healthy subjects participated in two protocols consisting of two experiments each. First protocol: (a) normoglycemia (control) with i.d. emulsified fat (i.d. fat) infusion, (b) acute hyperglycemia (HG) with plasma glucose levels stabilized at 15 mmol/L and i.d. fat infusion. In the second protocol the effect of exogenous cholecystokinin (CCK) on satiety was studied during normo- and hyperglycemia. Intraduodenal fat (Intralipid 10%) was infused at a dose of 1 g/h via a nasoduodenal tube in the first protocol, whereas in the second protocol CCK-33 was infused intravenously at a dose of 0.5 IDU/kg x h. Satiety was scored using visual analog scales (VAS). Plasma CCK levels were determined at regular intervals. During infusion of i.d. fat and i.v. CCK the VAS scores of wish to eat, hunger, and prospective feeding decreased significantly (p<0.05) in the normoglycemic experiments. During hyperglycemia satiety did not significantly change in the basal period; however, the scores of wish to eat, hunger, and prospective feeding increased significantly (p<0.05) when i.d. fat or i.v. CCK was administered. Plasma CCK levels in the basal and the stimulated period were not significantly different between normo- and hyperglycemia. In summary, the present study shows that in healthy humans volunteers 1) during normoglycemic conditions satiety can be induced by very low dose of i.d. fat and by CCK infusion, 2) during hyperglycemia the effect of i.d. fat and CCK on satiety are reversed, resulting in increased appetite.


Device to measure intra-operatively the primary stability of cementless hip stems.
The primary stability of cementless prostheses is critical for the long-term outcome of the operation. Surgeons are currently driven only by their experience in evaluating the extent of stem stability achieved. The aim of the present work was to develop a new device that enables the stability of a cementless stem to be quantitatively assessed intraoperatively. The angle of the stem/femur rotation under torsion and the torque are acquired and compared in real-time to a pre-set threshold inferred from the literature. The device indicates whether the stem is stable or not. It was extensively tested and finally validated in vitro on cadaveric and composite femurs hosting different sizes of the same kind of prostheses, implanted with different levels of press-fitting. The overall accuracy (23%) takes into account not only the overall measurement error but also the variability due to differences in bone quality and stem press-fitting. This error was deemed sufficient to discriminate between stable and unstable implants.


A transient rise in cyclic AMP levels following chemotactic stimulation of neutrophil granulocytes.
A short transient rise of cyclic AMP is observed within 1 minute after primary stimulation of neutrophils with chemotactic serum peptides containing classical anaphylatoxin (CAT). A second administration of these peptides after two minutes failed to produce a second peak of cAMP. Human serum albumin (HSA) which has chemokinetic but no chemotactic activities did not change cAMP levels. There was no significant change in cGMP levels within 1 minute following stimulation of rabbit neutrophils with chemotactic peptides or HSA.


Copublication improved the dissemination of Cochrane reviews and benefited copublishing journals: a retrospective cohort study.
To evaluate the impact of copublication on the citation of Cochrane evidence. This was a retrospective cohort study including Cochrane reviews published up to 31 December 2015 and their citing up to 11 July 2021, identified from the Web of Science Core Collection database. A total of 101 copublished and 202 noncopublished Cochrane reviews were included. The median for the total number of citations and the medians for the numbers of citations to the Cochrane review in the first, second, third, and fifth years after publication in the copublished group were higher than those in the noncopublished group [71 (interquartile range {IQR}: 37.5, 118.5) vs. 32.5 (13, 67); 1 (0, 3) vs. 0 (0, 1); 6 (3, 11.5) vs. 2 (1, 5); 8 (4, 15) vs. 3.5 (1, 8); 8 (4, 15) vs. 3 (1, 9), respectively, all P < 0.001]. Copublication of Cochrane reviews meant that 4 of 21 journals and 6 of 22 journals had a higher impact factor in the first and the second year after the copublication than they would have had without the copublication. Copublication is associated with a higher citation frequency of Cochrane reviews and may increase the impact factor of the journal in which it is copublished. This facilitates broader application of Cochrane evidence and promotes its dissemination.


Genomic Testing for Diagnosis of Genetic Disorders in Children: Chromosomal Microarray and Next-Generation Sequencing.
Chromosomal microarray and Next-generation sequencing are two widely used genomic tests that have improved the diagnosis of children with a genetic condition. Chromosomal microarray has become a first-tier test in evaluating children with intellectual disability, multiple malformations and autism due to its higher yield and resolution. Next generation sequencing, that includes targeted panel testing, exome sequencing and whole genome sequencing ends diagnostic odyssey in 25-30% of unselected children with rare monogenic syndromes, especially when the condition is genetically heterogeneous. This article provides a review of these genomic tests for pediatricians.


[Atmocausis vaporization. Most severe internal burns following intrauterine use of steam].
The article gives a brief historical review of the now obsolete method of atmocausis and reports on two cases of very deep internal burns after direct intrauterine application of superheated steam; one of the patients died as a result of this procedure. In the thirties this method was used especially to arrest intrauterine perimenopausal bleeding, but has since been abandoned.


Beige fat is dispensable for the metabolic benefits associated with myostatin deletion.
Increasing muscle mass and activating beige fat both have great potential for ameliorating obesity and its comorbidities. Myostatin null mice have increased skeletal muscle mass and are protected from obesity and its sequelae. Deletion of myostatin has also been suggested to result in the activation of beige adipocytes, thermogenic fat cells with anti-obesity and anti-diabetes properties. It is not known whether beige fat activation contributes to the protection from obesity in myostatin null mice. To investigate the role of beige fat activation in the metabolic benefits associated with myostatin deletion, we crossed myostatin null mice to adipocyte-specific PRDM16 knockout mice. We analyzed this new mouse model using molecular profiling, whole mount three-dimensional tissue imaging, tissue respiration, and glucose and insulin tolerance tests in models of diet-induced obesity. Here, we report that PRDM16 is required for the activation of beige fat in the absence of myostatin. However, we show in both male and female mice that beige fat activation is dispensable for the protection from obesity, glucose intolerance, insulin resistance, and hepatic steatosis mediated by myostatin deletion. These findings demonstrate that increasing muscle mass can compensate for the inactivation of beige fat and raise the possibility of targeting muscle mass as a therapeutic approach to offset the deleterious effects of adipose tissue dysfunction in obesity and metabolic syndrome.