Diagnostic performance of CareStart™ malaria HRP2/pLDH test in comparison with standard microscopy for detection of uncomplicated malaria infection among symptomatic patients, Eastern Coast of Tanzania.
CareStart™ malaria HRP2/pLDH (Pf/pan) combo test is one of the several rapid diagnostic tests (RDT) approved for diagnosis of malaria at the point of care in Tanzania. However, there are limited studies on the diagnostic performance of RDT after wide scale use in primary health care facilities in Tanzania. Therefore, this study was carried out to determine the diagnostic performance of RDT when compared with blood smear (BS) microscopy as a reference standard. A cross-sectional study was conducted between March and August 2019 at Kibiti Health Centre, Pwani region, Tanzania. Blood samples for malaria tests were collected from patients with malaria symptoms. Diagnostic performance parameters of RDT, i.e. sensitivity, specificity, positive and negative likelihood ratios (LR+/-), diagnostic accuracy and predictive values were determined using contingency table. An agreement between RDT and microscopy was statistically determined by Cohen's kappa test. Of 980 patients screened, 567 (57.9%) were found to be malaria positive by RDT, whereas 510 patients (52%) were positive by microscopy. Of the 510 microscopy-positive patients, 487 (95.5%) were infected with Plasmodium falciparum. The geometric mean parasite density was 2921parasites/µl, whereas majority (68.6%) of patients had parasite density greater than 10,000/µl. The sensitivity, specificity, positive and negative predictive values of CareStart™ were 99.8%, 87.6%, 89.8%, and 99.8%, respectively. The LR+ and LR- were 8.0 and 0.002, respectively. The diagnostic accuracy was 0.5. There was a strong agreement between the results obtained using CareStart™ and BS microscopy (kappa = 0.863, P < 0.0001). CareStart™ malaria HRP2/pLDH (Pf/pan) had high sensitivity and strong agreement with microscopy results. However, moderate specificity of RDT resulted in a substantial number of patients with false positive malaria test. Wherever available, microscopy should be used to confirm RDT test results.


Synthesis and crystal structure of a new copper(II) complex based on 5-ethyl-3-(pyridin-2-yl)-1,2,4-triazole.
The title compound, bis-[μ-3-ethyl-5-(pyridin-2-yl)-1H-1,2,4-triazol-1-ido]bis[acetato-(di-methyl-formamide)-copper(II)], [Cu2(C9H9N4)2(C2H3O2)2(C3H7NO)2] or [Cu2(L Et)2(OAc)2(dmf)2], is a triazolate complex, which contains two 3-(2-pyrid-yl)-5-ethyl-triazolates (L Et)- in bidentate-bridged coordination modes. Both copper atoms are involved in the formation of a planar six-membered metallocycle Cu-[N-N]2-Cu. The inversion center of the complex is located at the mid-point of the Cu⋯Cu vector. Each CuII atom has a distorted trigonal-bipyramidal environment formed by the three nitro-gen atoms of the deprotonated bridging 3-(2-pyrid-yl)-5-ethyl-triazolate unit, oxygen atoms of the OAc- group and dmf mol-ecule. In the crystal, C-H⋯O hydrogen bonds link the mol-ecules into chains running along the c-axis direction.


A quantitative collagen fibers orientation assessment using birefringence measurements: calibration and application to human osteons.
Even though mechanical properties depend strongly on the arrangement of collagen fibers in mineralized tissues, it is not yet well resolved. Only a few semi-quantitative evaluations of the fiber arrangement in bone, like spectroscopic techniques or circularly polarized light microscopy methods are available. In this study the out-of-plane collagen arrangement angle was calibrated to the linear birefringence of a longitudinally fibered mineralized turkey leg tendon cut at variety of angles to the main axis. The calibration curve was applied to human cortical bone osteons to quantify the out-of-plane collagen fibers arrangement. The proposed calibration curve is normalized to sample thickness and wavelength of the probing light to enable a universally applicable quantitative assessment. This approach may improve our understanding of the fibrillar structure of bone and its implications on mechanical properties.


Yellow fever cases in French Guiana, evidence of an active circulation in the Guiana Shield, 2017 and 2018.
French Guiana (FG) is a French overseas region bordering Brazil and Suriname that is considered endemic for yellow fever (YF); vaccination is compulsory for residents and travellers. In August 2017 and 2018, two sporadic YF cases were notified 1 year apart, confirming that sylvatic YF virus circulation is active in the region. YF vaccination coverage should be closely monitored and improved in FG and neighbouring territories and clinicians should be aware of the risk.


Outcomes of OSA in surgically naïve young children with and without DISE identified laryngomalacia.
Obstructive sleep apnea (OSA) in young children is caused by upper airway obstruction and is associated with changes in cognitive development, temperament and behavior. Adenotonsillectomy (AT) is often utilized as first line therapy for pediatric OSA. Children with laryngomalacia (LM) have a high chance of residual OSA after AT. There is paucity of literature regarding surgically naïve young children with OSA and laryngomalacia. Our study aimed to compare demographics, comorbidities and outcomes associated with OSA in surgically naïve young children with and without laryngomalacia. Retrospective chart review of surgically naïve young children (<2-year-old) with polysomnogram (PSG) diagnosed OSA. All young children underwent pre-operative PSG followed by drug-induced sleep endoscopy (DISE) directed intervention. Variables documented included demographics, comorbidities, history of adenotonsillectomy, DISE directed surgical interventions and pre and post PSG findings. Laryngomalacia was defined as presence of obstruction (Chan Parikh score ≥ 2) at the supraglottic level on DISE evaluation. Demographics and prevalence of comorbidities of those with and without LM were compared using t-test (continuous) and Chi Square (categorical). P value is significant for <0.05. 79 surgically naïve young children with PSG diagnosed OSA performed between 2015 and 2019 were included in the study. Children with LM were younger in age (11 months) and had a higher OSA-18 score (35) compared to children without LM (17 months) (OSA-18 score: 5). No significant difference was noted in the pre-DISE PSG parameters in the 2 groups. 56.1% of children with OSA and laryngomalacia did not need AT. Both children with and without laryngomalacia showed improvement in AHI on post-DISE PSG. Higher baseline AHI was associated with greater improvement in AHI. Surgically naïve young children with OSA and LM present earlier than those without LM and report a significantly worse quality of life Young children with a higher baseline AHI were found to have greater improvement in severity of OSA post-DISE and surgical intervention. Majority of children with OSA and laryngomalacia did not need adenotonsillectomy after a preprocedural DISE assessment yet showed similar improvement in AHI. More studies are needed to determine which patients with OSA and laryngomalacia will need multilevel interventions.


Defective generation of tetanus-specific antibody-producing B cells after in vivo immunization of Crohn's disease and ulcerative colitis patients.
In vivo booster immunization with tetanus toxoid normally results in the temporal development of circulating populations of B cells that secrete antibody after in vitro culture. In assessing the humoral immunoregulatory status in patients with inflammatory bowel disease, we found that the antibody production by the B cells that spontaneously secrete tetanus-specific immunoglobulin G in vitro, and which occur in the circulation 7 days postimmunization, was highly variable and below normal in the majority of Crohn's disease and ulcerative colitis patients. The decreased in vitro antibody responses correlated with the lack of an increase in the serum antitetanus immunoglobulin G titers, but did not correlate with disease activity, location, or steroid therapy. The majority of patients who did not produce an immunoglobulin G-antitetanus toxoid antibody response similarly failed to produce an immunoglobulin G-antidiphtheria antibody response after immunization. Lymphocytes from the patients who failed to produce normal levels of antitetanus toxoid antibody did, however, proliferate normally when stimulated by tetanus toxoid in vitro. These results suggest there are in vivo humoral immune defects in inflammatory bowel disease.


Assessment of the organization and operation of vaccine rooms in primary health care in Montes Claros, Minas Gerais, Brazil, 2015.
to assess the quality of the organization and operation of vaccine rooms in Montes Claros, Minas Gerais, Brazil, in 2015. descriptive evaluation study on the quality of vaccine rooms, based on the technical guidelines and standards recommended by the National Immunization Program, using a questionnaire adapted from the Evaluation Program of the Vaccine Room Supervision Tool (PAISSV 2.0). all 18 vaccine rooms in the municipality were assessed; regarding the quality concept of the vaccine rooms, six of them were considered ideal, five good, four regular, and three as insufficient. most vaccine rooms were classified as good/ideal; however, there is a need to organize continuous education programs for professionals and structural improvements, in order to meet the standards recommended by the National Immunization Program.


Determination of furosemide and its glucuronide metabolite in plasma, plasma ultrafiltrate and urine by HPLC-MS/MS with application to secretion and metabolite formation clearances in non-pregnant and pregnant women.
Furosemide (FUR) has been used in probe drugs cocktails for in vivo evaluation of the renal transporters OAT1 and OAT3 activities in studies of drug-drug interactions (generally using probenecid as an inhibitor) and drug-disease interactions. The objective of this study was to develop and validate methods for FUR and its glucuronide metabolite (FUR-GLU) analysis in plasma, plasma ultrafiltrate and urine for application in pharmacokinetics studies: a pilot drug-drug interaction study in pregnant women (n = 2), who received a single oral dose of FUR (40 mg) and in another occasion a single oral dose of probenecid (750 mg) before a single oral dose of FUR (40 mg), and in non-pregnant women participants (n = 12), who only received a single oral dose of FUR (40 mg). The samples preparation for FUR in 50 µL of plasma and plasma lysate were carried by acidified liquid-liquid extraction, while 50 µL of urine and 200 µL of plasma ultrafiltrate were simply diluted with the mobile phase. The methods presented linearities in the range of 0.50 - 2500 ng/mL of plasma and plasma lysate, 0.125 - 250 ng/mL of plasma ultrafiltrate, and 50 - 20,000 ng/mL of urine. FUR-GLU methods presented linearities in the range of 0.125 - 250 ng/mL of plasma ultrafiltrate and 50 - 20,000 ng/mL of urine. Precision and accuracy evaluations showed coefficients of variation and relative errors < 15%. In the pregnant women participants, the mean values of FUR CLrenal, CLsecretion, CLformation. FUR-GLU and CLnon-renal were all reduced when probenecid was administered with FUR (8.24 vs 2.89 L/h, 8.15 vs 2.80 L/h, 3.86 vs 1.75 L/h, 48.26 vs 22.10 L/h, respectively). Non-pregnant women presented similar values of FUR CLrenal, CLsecretion, CLformation. FUR-GLU to the pregnant women who received FUR only. Finally, FUR fraction unbound (fu) resulted in values of approximately 1% in pregnant women and to 0.22% in non-pregnant women. These developed and validated methods for FUR and FUR-GLU quantification in multiple matrices can allow the further investigation of UGT1A9/1A1 and the fu when FUR is administered as an OAT 1 and 3 in vivo probe.


[Biological mechanisms involved in the spread of traumatic brain damage].
Traumatic brain injury (TBI) is a worldwide health problem that is especially prevalent in young adults. It is characterized by one or more primary injury foci, with secondary spread to initially not compromised areas via cascades of inflammatory response, excitotoxicity, energy failure conditions, and amplification of the original tissue injury by glia. In theory, such progression of injury should be amenable to management. However, all neuroprotective drug trials have failed, and specific treatments remain lacking. These negative results can be explained by a neuron centered approach, excluding the participation of other cell types and pathogenic mechanisms. To change this situation, it is necessary to secure a better understanding of the biological mechanisms determining damage progression or spread. We discuss the biological mechanisms involved in the progression of post-trauma tissue damage, including the general physiopathology of TBI and cellular mechanisms of secondary damage such as inflammation, apoptosis, cell tumefaction, excitotoxicity, and the role of glia in damage propagation. We highlight the role of glia in each cellular mechanism discussed. Therapeutic approaches related to the described mechanisms have been included. The discussion is completed with a working model showing the convergence of the main topics.


Recombinant human IgG antibodies recognizing distinct extracellular domains of EGF receptor exhibit different degrees of growth inhibitory effects on human A431 cancer cells.
Recently, we isolated 4 distinct kinds of single chain antibody against human EGF receptor (EGFR) after screening the Keio phage display scFv library by using two methods of target-guided proximity labeling. In the current study, these monovalent scFv antibodies were converted to bivalent IgGs of humanized forms (hIgGs) by recombinant technology using the specially designed expression vectors followed by protein production in CHO cells. The resulting recombinant hIgGs were examined for their binding specificity using several different transformed human BJ cell lines that express deletion mutants of EGFR, each lacking one of 4 distinct extracellular domains (L1, L2, C1 and C2). Immuno-fluorescent microscopy and immuno-precipitation assay on these cells indicated that 4 distinct kinds of hIgGs bind to one of 3 different domains (L1, C1 and C2). Then, these hIgGs were further examined for biological effects on human A431 cancer cells, which overexpress EGFR. The results indicated that hIgG38 binding to L1 and hIgG45 binding to C2 substantially suppressed the EGF-induced phosphorylation of EGFR, resulting in the growth inhibition of A431 cancer cells. On the contrary, hIgG40 binding to C1 and hIgG42 binding to another site (epitope) of C2 exhibited no such inhibitory effects. Thus, the newly produced four recombinant hIgG antibodies recognize 4 different sites (epitopes) in 3 different extracellular domains of EGFR and exhibit different biological effects on cancer cells. These characteristics are somewhat different from the currently utilized therapeutic anti-EGFR antibodies. Hence, these hIgG antibodies will be invaluable as a research tool for the detailed molecular analysis of the EGFR-mediated signal transduction mechanism and more importantly a possible application as new therapeutic agents to treat certain types of cancers.


Empagliflozin alleviates endoplasmic reticulum stress and augments autophagy in rotenone-induced Parkinson's disease in rats: Targeting the GRP78/PERK/eIF2α/CHOP pathway and miR-211-5p.
Empagliflozin, a selective sodium-glucose co-transporter-2 inhibitor, has been demonstrated to provide additional non-glycemic benefits, including neuroprotection. Endoplasmic reticulum (ER) stress is a key player in neurodegeneration and occurs at the crossroads of other pathologic mechanisms; however, its role in the pathogenesis of Parkinson's disease (PD) is still elusive. miR-211-5p regulates neuronal differentiation and viability and was predicted to target CHOP, a downstream effector in the ER stress pathway. For the first time, this study investigated the possible neuroprotective effect of empagliflozin in a rotenone-induced rat model of PD from the perspective of ER stress. Rotenone (1.5 mg/kg) was administered subcutaneously every other day for 3 weeks. Meanwhile, the treated group received empagliflozin 10 mg/kg/day orally for 15 consecutive days post-PD induction. On the molecular level, the ER stress pathway components; GRP78, total and phosphorylated PERK, eIF2α and CHOP, along with miR-211-5p expression were upregulated in the striatum of rotenone-injected rats. Concurrently, the untreated rats showed elevated striatal α-synuclein levels along with diminished autophagy and the proteasome system as evidenced by reduced beclin-1 protein and ELF2/NERF mRNA expression levels. The rotenone-induced striatal oxidative stress and neuroinflammation were expressed by reduced catalase activity and elevated interleukin (IL)-1β levels. miR-211-5p was positively correlated with PERK/eIF2α/CHOP, IL-1β and α-synuclein, while negatively correlated with ELF2/NERF, beclin-1 and catalase activity. Empagliflozin treatment showed a restorative effect on all biochemical alterations and improved the motor function of rats tested by open field, grip strength and footprint gait analysis. In the histopathological examination, empagliflozin increased the intact neuron count and attenuated astrogliosis and microgliosis by reducing the glial fibrillary acidic protein and ionized calcium-binding adaptor protein 1 immunostaining. Conclusively, these results emphasize the neurotherapeutic impact of empagliflozin in PD by moderating the GRP78/PERK/eIF2α/CHOP ER stress pathway, downregulating miR-211-5p, resolving oxidative stress, lessening astrocyte/microglial activation and neuroinflammation, along with augmenting autophagy.


[Magnetic resonance imaging of hypertrophic cardiomyopathy : evaluation of diastolic function].
Hypertrophic cardiomyopathy (HCM) has a prevalence of approximately 0.2% and is clinically asymptomatic in many patients or presents with unspecific symptoms. This explains the importance of imaging for the diagnosis of HCM as well as for the assessment of the clinical course. The definitive finding in HCM is myocardial hypertrophy with thickening of the ventricular wall ≥ 15 mm. While echocardiography is an excellent screening tool magnetic resonance imaging (MRI) allows a comprehensive analysis of the heart in HCM. This includes a detailed analysis of the distribution and extent of myocardial hypertrophy, a thorough evaluation of systolic and diastolic cardiac function, the assessment of the presence and extent of dynamic outflow tract obstruction as well as the description of the systolic anterior motion (SAM) phenomenon of the mitral valve with secondary mitral insufficiency. When contrast material is administered, additional information about myocardial perfusion as well as the presence and extent of myocardial fibrosis can be obtained. This study compared systolic functional parameters as well as end systolic and end diastolic wall thickness of patients with and without diastolic dysfunction.


Effect of fiber-matrix adhesion on the creep behavior of CF/PPS composites: temperature and physical aging characterization.
The influence of fiber-matrix adhesion on the linear viscoelastic creep behavior of 'as received' and 'surface modified' carbon fibers (AR-CF and SM-CF, respectively) reinforced polyphenylene sulfide (PPS) composite materials was investigated. Short-term tensile creep tests were performed on ±45° specimens under six different isothermal conditions, 40, 50, 60, 65, 70 and 75 °C. Physical aging effects were evaluated on both systems using the short-term test method established by Struik. The results showed that the shapes of the curves were affected neither by physical aging nor by the test temperature, allowing then superposition to be made. A unified model was proposed with a single physical aging and temperature-dependent shift factor, aT,te . It was suggested that the surface treatment carried out in SM-CF/PPS had two major effects on the creep response of CF/PPS composites at a reference temperature of 40 °C: a lowering of the initial compliance of about 25 % and a slowing down of the creep response of about 1.1 decade.


Synthesis and possible role of proteoglycans during Volvox development.
During the embryonic development of Volvox the cells synthesize proteoglycans of relatively small molecular size up to 14 h after inversion. In the following stages there is a gradual transition towards larger forms, due to an increase in sulfated sugar moieties. The presence of sulfate in the medium was obligatory for this transition. None of these molecules could be dissociated in 4.0 M GuHCl, neither could they be digested by glycosidases. Of all proteases examined subtilisin, a bacterial protease, digested the proteoglycans. The possible role of proteoglycans during Volvox morphogenesis has been examined. Somatic proteoglycans caused spheroids to start their swimming earlier, although they inhibited their expansion. Spheroids cultured in sulfate-free medium start their swimming 24 h later than controls, but the addition of somatic proteoglycans to the sulfate-free medium could induce motility almost as well as in the normal forms. Embryonic weight proteoglycans caused aggregation of the spheroids, an effect that also appeared in the sulfate-free medium.


Optimizing extinguishing angle of 6MF-30 pneumatic extinguisher for wildland fire-fighting based on CFD and experiments.
The 6MF-30 pneumatic extinguisher is a widely utilized and efficient tool for combating wildland fires. However, using incorrect extinguishing angles can diminish its effectiveness. This study aimed to determine the optimal extinguishing angle for the 6MF-30 pneumatic extinguisher by conducting computational fluid dynamics simulations and experimental verification. The findings revealed that ground roughness did not significantly affect the optimal extinguishing angle or the attenuation of jet velocity near the fan outlet region. The study determined that an optimal extinguishing angle of 37° applies to lossless ground, natural grassland, grassland with artificial disturbance, and enclosed grassland. Furthermore, among the selected angles, the highest rate of jet velocity reduction was observed at 45°, whereas the slowest reduction occurred at 20° and 25°. These findings offer valuable insights and recommendations for enhancing the efficacy of wildland fire-fighting when employing the 6MF-30 pneumatic extinguisher.


Prevalence of vancomycin-resistant enterococcus in Africa in one health approach: a systematic review and meta-analysis.
Vancomycin-resistant enterococci are a global challenge currently as reported by the World Health Organization. It is also important to recognize that combating antimicrobial resistance needs to recognize the interconnections between people, animals, plants and their shared environment in creating public health, the so-called One Health approach. Although the presence of VRE has been described in many regions of the world, there is a lack of comprehensive data indicating their prevalence of in Africa. Therefore, this study aimed to aggregate the result of studies describing VRE reported across multiple regions in Africa. A literature search was conducted on PubMed, Google scholar, and Hinari with the term "Vancomycin resistance enterococcus in Africa" on August 1-3, 2019. All available articles were downloaded to "Endnote version 7.1" then to Microsoft Word 2013. Articles determined to meet our criteria for the review was extracted to Microsoft Excel 2013. Those articles that reported the prevalence of vancomycin resistance Enterococcus obtained from all sample types and published from 2010 to 2019 in the English language were included for the review. A meta-analysis was conducted with OpenMetaAnalyst version R.3.1.0 software. The effect size was determined using a binary random effect model and statically significant considered when p < 0.05. Heterogeneity determined with the inconsistency index. A leave one out analysis used to perform the sensitivity analysis. There were 151 articles identified from the database searches; of this, 36 articles included after extensive review with two independent authors. Out of 4073 samples collected, 1488 isolates identified with an overall pooled prevalence of VRE 26.8% (95% CI; 10.7-43.0%) in Africa with a one-health perspective. The analysis showed that considerable heterogeneity among the studies (I2 = 99.97%; p < 0.001). Subgroup analysis in-country, African region, laboratory method, year of publication, and sample source showed that a high prevalence was identified from South Africa (74.8%), South African regions (74.8%), PCR (959.2%), 2010-2015 years (30.3%) and environmental (52.2%), respectively. This meta-analysis indicates that there was a high-pooled prevalence of vancomycin-resistant enterococci in African. A lot should be done to prevent and control the transmission of vancomycin resistance enterococci to a human being from the environment in the continent.


Inflammatory bowel disease in Turkish children.
This study was undertaken to evaluate demographics, clinical manifestations, laboratory findings and outcomes of children with inflammatory bowel disease (IBD) in Turkey. We analyzed the medical records of 127 children diagnosed with IBD (under 18 years old) between January 2004 and January 2012 in 8 pediatric gastroenterology centers. Of the 127 patients, 90 (70.9%) suffered from ulcerative colitis (UC), 29 (22.8%) from Crohn's disease (CD), and 8 (6.3%) from IBD unclassified. The mean age of the 127 patients was 11.6 ± 4.1 years, and 11.8% of the patients were below 5 years old. Of the patients, 49.6% were male, and males were more predominant in patients with CD than in those with UC (72.4% vs. 42.2%, P = 0.008; a male/female ratio of 2.62 in CD, P = 0.0016). Approximately one fifth of the patients had extra-intestinal manifestations and 13.3% of the patients had associated diseases. Extraintestinal manifestations and associated diseases were more common in early onset disease [P = 0.017, odds ratio (OR) = 4.02; P = 0.03, OR = 4.1]. Of the patients, 15% had normal laboratory parameters including anemia, high platelet count, hypoalbuminemia, hypoferritinemia, and high sedimentation rate. Area under receiver operation characteristics was used to predict pancolitis in patients with UC. The values of C-reactive protein, sedimentation rate and pediatric ulcerative colitis activity were 0.61 (P = 0.06), 0.66 (P = 0.01) and 0.76 (P = 0.0001), respectively. Four (4.4%) patients with UC underwent colectomy, and finally two (1.5%, 95% confidence interval: 0-3.7%) patients died from primary disease or complications. IBD is an increasing clinical entity in Turkey. Features of IBD are similar to those in other populations, but prospective multicenter studies are needed to analyze the true incidence of IBD in Turkish children.


Intensive perioperative rehabilitation improves surgical outcomes after pancreaticoduodenectomy.
Although the mortality rate for pancreaticoduodenectomy (PD) has decreased to around 2.8-5% in high-volume centers, postoperative complications are still common in 30-50% of cases. Preoperative exercise, called "prehabilitation," has been recently reported to reduce the frequency of complications after surgery. This study aims to evaluate the impact of the intensive perioperative rehabilitation on improvement of surgical outcomes for patients undergoing PD. Between 2003 and 2014, 576 consecutive patients underwent PD in Wakayama Medical University Hospital. Of these, 331 patients received perioperative rehabilitation combined with prehabilitation and postoperative rehabilitation between 2009 and 2014. Previously, 245 patients underwent PD without perioperative rehabilitation between 2003 and 2008. We compared surgical outcomes between the patients undergoing PD with and without perioperative rehabilitation to evaluate the efficacy of our rehabilitation program. The frequency of pulmonary complications was significantly lower in patients undergoing PD with perioperative rehabilitation than those without (0.9% vs. 4.3%, P = 0.011). There were no significant differences in other complication or mortality rates. Length of hospital stay was also shorter in patients receiving perioperative rehabilitation than that of those not receiving it (16 vs. 24 days, P < 0.001). Intensive perioperative rehabilitation might reduce postoperative pulmonary complications and shorten postoperative hospital stay after PD. Therefore, we suggest that perioperative rehabilitation should be included as part of enhanced recovery after surgery for patients undergoing PD, although further large-scale studies are necessary to confirm our results.


Interleukin-35 suppresses pyroptosis and protects against neuronal death in retinal ischaemia/reperfusion injury.
Retinal ischaemia-reperfusion (I/R) is a pathological process in many eye disorders. Neuroinflammation and cell pyroptosis have been recognized as important in the pathogenesis of tissue damage in retinal I/R. Interleukin (IL)-35 is a novel heterodimeric cytokine that exhibits anti-inflammatory activity in various autoimmune diseases, but its role in retinal I/R and the underlying molecular mechanisms remain unexplored. This research investigated the effect of IL-35 on retinal I/R and the inhibition of pyroptosis and neuronal death. In our study, a murine retinal I/R model was used to explore the neuroprotective effect of recombinant IL-35 protein in vivo. Primary murine microglial cells in pyroptosis and retinal ganglion cells (RGCs) in oxygen and glucose deprivation/reoxygenation (OGD/R) models were employed to assess the antipyroptotic and antiapoptotic effects of IL-35 in vitro. The data showed that IL-35 decreases retinal damage, RGC death, and inner plexiform layer (IPL) thinning in mice with retinal I/R injury, with significant attenuation of pyroptosis in the retina. The study also demonstrated the anti-pyroptotic action of IL-35 in primary microglia stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Furthermore, primary RGC apoptosis induced by OGD/R was directly suppressed by IL-35, and IL-35-mediated neuroprotection was abrogated when miR-21 was blocked. In conclusion, our results suggest the mechanisms of RGC apoptosis and a new therapeutic target, IL-35, that exerts a robust neuroprotective effect against retinal I/R.


Partitioning of inorganic nitrogen assimilation between the roots and shoots of cerrado and forest trees of contrasting plant communities of South East Brasil.
Woody plants growing in cerrado and forest communities of south-east Brasil were found to have low levels of nitrate reductase activity in their leaves suggesting that nitrate ions are not an important nitrogen source in these communities. Only in the leaves of species growing in areas of disturbance, such as gaps and forest margins, were high levels of nitrate reductase present. When pot-grown plants were supplied with nitrate, leaves and roots of almost all species responded by inducing increased levels of nitrate reductase. Pioneer or colonizing species exhibited highest levels of nitrate reductase and high shoot: root nitrate reductase activities. Glutamine synthetase, glutamate synthase and glutamate dehydrogenase were present in leaves and roots of the species examined.15N-labelled nitrate and ammonium were used to compare the assimilatory characteristics of two species:Enterolobium contortisiliquum, with a high capacity to reduce nitrate, andCalophyllum brasiliense, of low capacity. The rate of nitrate assimilation in the former was five times that of the latter. Both species had similar rates of ammonium assimilation. Results for eight species of contrasting habitats showed that leaf nitrogen content increased in parallel with xylem sap nitrogen concentrations, suggesting that the ability of the root system to acquire, assimilate or export nitrate determines shoot nitrogen status. These results emphasise the importance of nitrogen transport and metabolism in roots as determinants of whole plant nitrogen status.


Synthesizing evidence from clinical trials with dynamic interactive argument trees.
Evidence-based medicine propagates that medical/clinical decisions are made by taking into account high-quality evidence, most notably in the form of randomized clinical trials. Evidence-based decision-making requires aggregating the evidence available in multiple trials to reach -by means of systematic reviews- a conclusive recommendation on which treatment is best suited for a given patient population. However, it is challenging to produce systematic reviews to keep up with the ever-growing number of published clinical trials. Therefore, new computational approaches are necessary to support the creation of systematic reviews that include the most up-to-date evidence.We propose a method to synthesize the evidence available in clinical trials in an ad-hoc and on-demand manner by automatically arranging such evidence in the form of a hierarchical argument that recommends a therapy as being superior to some other therapy along a number of key dimensions corresponding to the clinical endpoints of interest. The method has also been implemented as a web tool that allows users to explore the effects of excluding different points of evidence, and indicating relative preferences on the endpoints. Through two use cases, our method was shown to be able to generate conclusions similar to the ones of published systematic reviews. To evaluate our method implemented as a web tool, we carried out a survey and usability analysis with medical professionals. The results show that the tool was perceived as being valuable, acknowledging its potential to inform clinical decision-making and to complement the information from existing medical guidelines. The method presented is a simple but yet effective argumentation-based method that contributes to support the synthesis of clinical trial evidence. A current limitation of the method is that it relies on a manually populated knowledge base. This problem could be alleviated by deploying natural language processing methods to extract the relevant information from publications.


Inter-device agreement between spectral domain optical coherence tomography, ultrasound biomicroscopy, and gonioscopy in evaluating the iridocorneal angle in normotensive dogs.
There has not been a thoroughly reported study of the comparison between spectral domain-optical coherence tomography (SD-OCT) with both ultrasound biomicroscopy (UBM) and gonioscopy on the evaluation of the iridocorneal angle (ICA) in dogs. To investigate the diagnostic value of SD-OCT for the early detection of narrowing ICA by comparing and assessing inter-device agreement in anterior chamber angle (ACA) measurements obtained by SD-OCT and UBM, and ICA evaluations by gonioscopy. A total of 28 eyes from 28 client-owned dogs with normal intraocular pressure were included for examination. The ACA and angle opening distance (AOD) were measured from the SD-OCT and UBM images, and gonioscopy images were analyzed using the ICA grade and ZibWest angle index. The mean ACA and AOD for SD-OCT were 28.31° ± 5.37° and 658.42 ± 219.90 µm, and for UBM, 28.34° ± 5.82° and 859.29 ± 221.80 µm, respectively. The mean difference in ACA between the average values of SD-OCT and UBM measurements was 0.03° with a 95% limit of agreement (LoA) span of 16.2°, indicating positive agreement; that in AOD was 200.85 µm with a 95% LoA span of 1,110.95 µm, indicating poor agreement. The Pearson correlation coefficient of the ACA of SD-OCT and ZibWest indices of gonioscopy was 0.624, indicating strong agreement; that of UBM and gonioscopy was 0.43, indicating moderate agreement. SD-OCT is well tolerated by canine patients due to its non-contact method and might be an alternative option for early screening of ICA narrowing in clinical settings.


Price and consumption of tobacco in Italy over the last three decades.
Changes in cigarette price have had an appreciable impact on smoking consumption in several countries. We analysed the price elasticity of demand for cigarettes in Italy over the period 1970-2001. A 1% increase in price of cigarettes led to a 0.30% decline in smoking prevalence and to a 0.43% decline in cigarette consumption. The present analyses confirm the existence of an inverse association between price and prevalence/consumption of cigarettes in Italy, and indicate that economic aspects may have important public health implications in tobacco control.


Inhibition of monoamine oxidase modulates the behaviour of semicarbazide-sensitive amine oxidase (SSAO).
The specific activity and kinetic behaviour of semicarbazide-sensitive amine oxidase (EC 188.8.131.52; SSAO) towards benzylamine, in the rat heart, is affected by in vivo treatment with the non-selective monoamine oxidase (MAO) inhibitor tranylcypromine, but not by the selective MAO-A and -B inhibitors, clorgyline and lazabemide. SSAO activity was increased to 178% of control activity after 7 days of treatment with tranylcypromine. This increase appears to represent an increase in the limiting velocity (V(max)) for benzylamine oxidation with no significant change in the K(m) at that time-point. However, the K(m) for benzylamine oxidation was found to decrease in both controls and treated groups, in a time-dependent manner, during the treatment regime. These findings suggest a link between SSAO and cellular stress and may have importance in the context of the recent finding that tissue-SSAO is identical to a vascular adhesion protein (VAP1), involved in the process of inflammation.


Virtual Reality Educational Tool for Human Anatomy.
Virtual Reality is becoming widespread in our society within very different areas, from industry to entertainment. It has many advantages in education as well, since it allows visualizing almost any object or going anywhere in a unique way. We will be focusing on medical education, and more specifically anatomy, where its use is especially interesting because it allows studying any structure of the human body by placing the user inside each one. By allowing virtual immersion in a body structure such as the interior of the cranium, stereoscopic vision goggles make these innovative teaching technologies a powerful tool for training in all areas of health sciences. The aim of this study is to illustrate the teaching potential of applying Virtual Reality in the field of human anatomy, where it can be used as a tool for education in medicine. A Virtual Reality Software was developed as an educational tool. This technological procedure is based entirely on software which will run in stereoscopic goggles to give users the sensation of being in a virtual environment, clearly showing the different bones and foramina which make up the cranium, and accompanied by audio explanations. Throughout the results the structure of the cranium is described in detailed from both inside and out. Importance of an exhaustive morphological knowledge of cranial fossae is further discussed. Application for the design of microsurgery is also commented.


The effect of cimetidine and 15(S) 15-methyl prostaglandin E2 on the healing of laser-induced gastric mucosal damage.
Delayed perforation, a complication of laser photocoagulation, could be reduced by accelerating healing and inhibiting gastric secretion. With the use of the Nd:YAG laser, a beam was passed through a single glass fiber (400 micrometer) with 10 degrees divergence at a constant power of 80 W for 1 sec at a 1-cm distance from the gastric mucosa. Rats were then randomly allocated to receive cimetidine (50 mg/kg), 15(S)15-methyl prostaglandin E2 (50 micrograms/kg), or saline intraperitoneally twice daily for 4 or 7 days. The surface area of ulceration at 4 days for the control rats and the cimetidine- and prostaglandin-treated rats was 29, 34, and 28 mm2, respectively, and was much larger than the initial lesion of 15 mm2. Histologically, all lesions showed the typical appearances of peptic ulceration with perforation in half the prostaglandin-treated rats. By 7 days, the surface area in the cimetidine-treated rats appeared to decrease, but the light microscopic changes were similar to the saline- and prostaglandin-treated rats. Neither cimetidine nor prostaglandin enhanced healing in this study.


Abuse liability assessment of atomoxetine in a drug-abusing population.
Atomoxetine is a non-amphetamine medication approved to treat ADHD in children, adolescents, and adults. Previous studies demonstrated low abuse potential for atomoxetine in recreational drug users. This study assessed the abuse potential of atomoxetine in stimulant-preferring drug abusers compared to methylphenidate and phentermine as positive controls and desipramine and placebo as negative controls. Forty male and female, 32-53 years old stimulant-preferring drug abusers completed this balanced Latin-square designed study. Subjects received acute, double-blind doses of placebo, desipramine (100 and 200 mg), methylphenidate (90 mg), phentermine (60 mg), and atomoxetine (45, 90, and 180 mg). Subjective and physiological effects were collected for 24 h following each drug treatment. Methylphenidate and phentermine were liked significantly more than placebo, atomoxetine, or desipramine. No atomoxetine dose was liked significantly more than placebo and liking scores for atomoxetine were similar to, or significantly lower than, desipramine, as assessed by the Drug Rating Questionnaire-Subject. While atomoxetine 45 and 180 mg did not significantly change any Addiction Research Center Inventory (ARCI) scores, atomoxetine 90 mg significantly increased A and BG stimulant scores of the ARCI and both methylphenidate and phentermine produced greater A and BG increases than any atomoxetine dose and also increased MBG (euphoria) scores relative to placebo. Atomoxetine has significantly less abuse liability than methylphenidate or phentermine and no greater abuse liability than desipramine.


Alternative methods of selecting rat hepatocellular nodules resistant to 2-acetylaminofluorene.
Dietary 2-acetylaminofluorene (2-AAF) coupled with a stimulus for cell proliferation such as a 2/3 partial hepatectomy (PH) or a necrotizing dose of carbon tetrachloride is frequently employed to generate nodules of resistant ("initiated") rat hepatocytes. This regimen is a useful model for experimental analysis of alterations in hepatocytes during carcinogenesis, and also as an assay for initiation by various carcinogens. Because of the decreasing availability of carcinogen-containing diets from commercial sources, we have developed alternative methods of 2-AAF administration to generate nodules in rats initiated with N-nitrosodiethylamine. This study compared the nodule-selecting and cancer-promoting efficacy of 2-AAF administered by the Solt-Farber procedure (0.02% in diet for 2 weeks) with 2-AAF administered by gavage, as a suspension in 1% aqueous carboxymethyl-cellulose (CMC). Three or 4 daily administrations of 2-AAF by gavage (20 mg/kg/day) followed by PH on day 4 were equivalent to the dietary regimen in generating early resistant nodules, late persistent nodules and hepatocellular carcinomas. These regimens were similar to the dietary regimen of 2-AAF in inhibiting virtually all normal hepatocyte proliferation. These regimens permit control over the duration and level of 2-AAF exposure and the resulting size of selected nodules.


[Monkeypox to Mpox or the re-emergence of an old zoonosis].
Monkeypox is a zoonotic disease caused by the Monkeypox virus (MPXV) of the Orthopoxvirus genus. The first human cases occurred in Africa in the 1970s and remained confined to the African continent for a long time until 2003, when several dozen cases occurred in the United States, following contamination by prairie dogs. Unprecedented transmission events have led to more than 80,000 reported cases worldwide between May 2022 and February 2023, primarily affecting men who have sex with men. The changing epidemiology of Mpox has raised concerns about its ability to become endemic beyond its traditional geographic areas. Confirmatory diagnosis is based on direct detection by molecular biology. Pre- or post-exposure smallpox vaccination was widely deployed in early summer 2022 to limit the spread of the disease. In case of severe forms, the use of antivirals can be considered, only tecovirimat being recommended in this indication. The current epidemic has had the merit of showing that a disease that was previously confined to regions of initial virus circulation can spread very rapidly in Western countries and of the need to reinforce the implementation of tools for the surveillance and control of communicable diseases.


Prospective multiparametric CMR characterization and MicroRNA profiling of anthracycline cardiotoxicity: A pilot translational study.
Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required. The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery. Twenty-four patients (age 56 range 18-75 years; 42 % female) with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272 mg/m2 doxorubicin equivalent) were recruited and evaluated at three timepoints (baseline, completion of chemotherapy, and 6 months after completion of chemotherapy) with multiparametric 1.5 T CMR, echocardiography and circulating miRNAs sequencing. Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy (61 ± 3 vs 53 ± 3 %, p < 0.001), before recovering significantly at 6-month follow-up (55 ± 3 %, p = 0.018). Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery (poor recovery, partial recovery, good recovery). CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7 ± 1.5 mm) in comparison to partial recovery (13.7 ± 2.7 mm), and good recovery (15.7 ± 3.1 mm; p = 0.028). Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline (54.0 ± 4.6 to 57.8 ± 4.9 ms, p = 0.001), but was not predictive of LVEF recovery. No changes to LV mass, extracellular volume fraction, T1 mapping or late gadolinium enhancement were observed. Baseline CMR-derived MAPSE, circulating miRNA-181-5p, and miRNA-221-3p were associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy, suggesting their potential predictive role in this context. T2 mapping increased significantly on completion of chemotherapy but was not predictive of LVEF recovery.


Osimertinib for lung cancer cells harboring low-frequency EGFR T790M mutation.
Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, shows significant benefit among patients with EGFR T790M mutation at disease progression. We analyzed the whole exome sequence of 48 samples obtained from 16 lung cancer patients with a longitudinal follow-up: treatment-naïve-baseline primary tumors positive for EGFR activating-mutations, paired re-biopsies upon disease progression but negative for EGFR T790M mutation based on qPCR, and their matched normal blood samples. Our Next generation sequencing (NGS) analysis identified an additional set of 25% re-biopsy samples to harbor EGFR T790M mutation occurring at a low-allele frequency of 5% or less, undetectable by conventional qPCR-based assays. Notably, the clinical utility of osimertinib among patients harboring low-allele frequency of EGFR T790M in tissue biopsy upon disease progression remains less explored. We established erlotinib-resistant PC-9R cells and twenty single-cell sub-clones from erlotinib-sensitive lung cancer PC-9 cells using in vitro drug-escalation protocol. NGS and allele-specific PCR confirmed the low-allele frequency of EGFR T790M present at 5% with a 100-fold higher resistance to erlotinib in the PC-9R cells and its sub-clones. Additionally, luciferase tagged PC-9, and PC-9R cells were orthotopically injected through the intercostal muscle into NOD-SCID mice. The orthotopic lung tumors formed were observed by non-invasive bioluminescence imaging. Consistent with in vitro data, osimertinib, but not erlotinib, caused tumor regression in mice injected with PC-9R cells, while both osimertinib and erlotinib inhibited tumors in mice injected with PC-9 cells. Taken together, our findings could extend the benefit of osimertinib treatment to patients with low EGFR T790M mutation allele frequency on disease progression.


Easy performance of 6-color confocal immunofluorescence with 4-laser line microscopes.
Confocal laser scanning microscopy is an advanced technique for imaging tissue samples in vitro and in vivo at high optical resolution. The development of new fluorochrome variants do not only make it possible to perform multicolor flow cytometry of single cells, but in combination with high resolution laser scanning systems also to investigate the distribution of cells in lymphoid tissues by confocal immunofluorescence analyses, thus allowing the distinction of various cell populations directly in the tissue. Here, we provide a protocol for the visualization of at least six differently fluorochrome-labeled antibodies at the same time using a conventional confocal laser scanning microscope with four laser lines (405 nm, 488 nm, 555 nm, and 639 nm laser wavelength) in both murine and human tissue samples. We further demonstrate that compensation correction algorithms are not necessary to reduce spillover of fluorochromes into other channels when the used fluorochromes are combined according to their specific emission bands and the varying Stokes shift for co-excited fluorochromes with the same laser line.


What should we teach the teachers? Identifying the learning priorities of clinical supervisors.
Clinicians who teach are essential for the health workforce but require faculty development to improve their educational skills. Curricula for faculty development programs are often based on expert frameworks without consideration of the learning priorities as defined by clinical supervisors themselves. We sought to inform these curricula by highlighting clinical supervisors own requirements through answering the research question: what do clinical supervisors identify as relative strengths and areas for improvement in their teaching practice? This mixed methods study employed a modified version of the Maastricht Clinical Teaching Questionnaire (mMCTQ) which included free-text reflections. Descriptive statistics were calculated and content analysis was conducted on textual comments. 481 (49%) of 978 clinical supervisors submitted their mMCTQs and associated reflections for the research study. Clinical supervisors self-identified relatively strong capability with interpersonal skills or attributes and indicated least capability with assisting learners to explore strengths, weaknesses and learning goals. The qualitative category 'establishing relationships' was the most reported strength with 224 responses. The qualitative category 'feedback' was the most reported area for improvement, with 151 responses. Key areas for curricular focus include: improving feedback practices; stimulating reflective and agentic learning; and managing the logistics of a clinical education environment. Clinical supervisors' self-identified needs provide a foundation for designing engaging and relevant faculty development programs.


[Phylogenetic relationships of the Far Eastern Araliaceae inferred from ITS sequences of nuclear rDNA].
In eight species of the family Araliaceae, inhabiting the territory of the Russian Far East, the sequences of ITS regions of nuclear rDNA were determined. A comparison of these sequences enabled establishment of phylogenetic relationships between the Far Eastern and other members of the family. It was demonstrated that Aralia sensu populations from Primorye and Sakhalin were genetically different and, hereby, could be classified as interspecific taxa. Aralia continentalis along with A. cordata were attributed to the section Aralia sensu. Oplopanax elaus and O. horridus were found to be very close to each other, possibly being the subspecies of one species or relatively young species. Legitimacy of the isolation of two sections within the genus Eleutherococcus was confirmed.


[Metabolism of immunoglobulin receptors by lymphocytes maintained in mouse spleen at the peak of the primary response].
Splenocytes obtained from mice on the 5th day after the injection of sheep red blood cells (SRBC) lost irreversibly approximately 50% of their surface immunoglobulins in the course of four-hour in vitro incubation. On the contrary, there were no changes in the total amount of surface immunoglobulins following in vitro incubation of splenocytes obtained on the 9th day after the antigen injection. Metabolism of antigen-binding receptors of immune splenocytes was studied by the method of rosette-formation. Incubation for 20 hours of splenocytes obtained on the 5th day after the SRBC injection demonstrated a loss of 70% of rosette-forming (RFC). The remaining RFC belonged to the theta-positive lymphocytes with the half-life of their antigen-binding receptors of approximately 4 hrs. Similar half-life was found for the RFC receptors of mouse spleen on the 9th day after the antigenic stimulation. No reduction of the RFC count occurred during their in vitro incubation for 20 hrs. It is supposed that a reduction in the number of the RFC obtained at the peak of the primary immune response could result from the inability of immune lymphocytes to synthesize new receptors or from blocking the newly-formed receptors by a soluble factor produced by immune lymphocytes following their in vitro incubation.


Modeling uncertainty in the measurement of low-level analytes in environmental analysis.
The use of analytical chemistry measurements in environmental monitoring is dependent on an assessment of measurement error. Models for variation in measurements are needed to quantify uncertainty in measurements, set limits of detection, and preprocess data for more sophisticated analysis in prediction, classification, and clustering. This article explains how a two-component error model can be used to accomplish all of these objectives. In addition, we present applications to quantitating biomarkers of exposure to toxic substances using gene expression microarrays.


Bacteremia, endocarditis, and the Hancock valve.
Among 373 patients with porcine xenografts, there were 27 instances of exposure of the xenograft to bloodstream or endocardial infection in 22 patients. Nine patients underwent 10 separate insertions of xenografts for active infective endocarditis. There were no early infections or valve failures. Three patients returned with a late prosthetic valve endocarditis (PVE) due to a new infection. There were 6 instances of bacteremia early after xenograft valve insertion with no early infection, no valve dysfunction, and 1 instance of late PVE. Eleven patients had PVE on a porcine xenograft. Blood cultures in the 10 patients treated with antibiotics promptly became negative. There were 3 valve-related deaths: 2 from valve incompetence and 1 from mitral and aortic xenograft stenosis. Our experience suggests that the Hancock porcine xenograft is: (1) as resistant to infection as are rigid prostheses in active infective endocarditis; (2) resistant to early postoperative bacteremias; and (3) easier to sterilize than rigid prostheses and more durable than other tissue valves in the face of PVE.


Differences in the Biodiversity of the Fecal Microbiota of Infants With Rotaviral Diarrhea and Healthy Infants.
Rotaviral diarrhea (RD) has been associated with the biodiversity of the fecal microbiota in infants; however, the differences in the biodiversity of the fecal microbiota between infants with RD and healthy (H) infants have not been clearly elucidated. This study aimed to reveal the changes in the biodiversity of the fecal microbiota of infants with RD. For this study, 30 fecal samples from 15 RD infants and 15 H infants were collected. The biodiversity of the fecal microbiota from the two groups was compared via polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and gene sequencing. The Shannon-Weaver index showed that the biodiversity of the fecal microbiota from the RD infants was significantly lower (P < 0.05) than that from the H infants. All fifteen RD infants were grouped into one cluster and were separated from the H infants by the un weighted-pair group method, with the arithmetic average (UPGMA) clustering algorithm. In addition, when compared with the healthy infants, the communities of the dominant microbes, Lactobacillus and Bifidobacterium, in the fecal microbiota from the RD infants have obviously changed. With regard to improving the understanding of the differences in the biodiversity of the fecal microbiota between RD infants and H infants, the findings of this study can provide a possible basis to reveal the relationship between RD and intestinal microbiota.


Occurrence and phenotypic characterization of Yersinia ruckeri strains with biofilm-forming capacity in a rainbow trout farm.
The presence of Yersinia ruckeri in a French fish farm was investigated. Y. ruckeri was isolated mainly from algae and sediment samples rather than from water. Twenty-two Y. ruckeri isolates were obtained, and three strains were distinguished by enterobacterial repetitive intergenic consensus PCR amplification. These strains were able to adhere to solid supports. This characteristic was correlated with flagellum-mediated motility. Killing experiments showed that sessile cells were more resistant to oxolinic acid than their planktonic counterparts. Our results demonstrate that surface colonization of fish farm tanks by Y. ruckeri biofilms is a potential source of recurrent infection for extended periods of time.


Characteristic responses of a phospholipid molecular layer to polyols.
Polyols (sugar alcohols) are widely used in foods, pharmaceutical formulations and cosmetics, and therefore it is important to understand their effects on cell membranes and skin. To address this issue, we examined the effect of polyols (1,2-ethanediol (ethylene glycol), 1,3-butanediol, 1,2,3-propanetriol (glycerol), and 1,2,3,4-butanetetraol) on artificial membrane systems (liposomes, monolayers, or dry films) prepared from phospholipid (1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)). 1,2-Ethanediol and 1,3-butanediol had little effect on the size of the DMPC liposomes or the surface pressure (π)-surface area (A) isotherm of DMPC monolayers at an air-water interface, whereas 1,2,3-propanetriol or 1,2,3,4-butanetetraol increased both liposome size and surface pressure. Attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) and differential scanning calorimetry (DSC) were used to evaluate the interaction between DMPC and polyols. These experimental results suggest that the chemical structure of polyol plays an important role in the characteristic interaction between polyol and DMPC.


Cause-specific mortality in Scottish patients with colorectal cancer with and without type 2 diabetes (2000-2007).
The objective of this study was to use Scottish national data to assess the influence of type 2 diabetes on (1) survival (overall and cause-specific) in multiple time intervals after diagnosis of colorectal cancer and (2) cause of death. Data from the Scottish Cancer Registry were linked to data from a population-based national diabetes register. All people in Scotland diagnosed with non-metastatic cancer of the colon or rectum in 2000-2007 were included. The effect of pre-existing type 2 diabetes on survival over four discrete time intervals (<1, 1-2, 3-5 and >5 years) after cancer diagnosis was assessed by Cox regression. Cumulative incidence functions were calculated representing the respective probabilities of death from the competing causes of colorectal cancer, cardiovascular disease, other cancers and any other cause. Data were available for 19,505 people with colon or rectal cancer (1,957 with pre-existing diabetes). Cause-specific mortality analyses identified a stronger association between diabetes and cardiovascular disease mortality than that between diabetes and cancer mortality. Beyond 5 years after colon cancer diagnosis, diabetes was associated with a detrimental effect on all-cause mortality after adjustment for age, socioeconomic status and cancer stage (HR [95% CI]: 1.57 [1.19, 2.06] in men; 1.84 [1.36, 2.50] in women). For patients with rectal cancer, diabetes was not associated with differential survival in any time interval. Poorer survival observed for colon cancer associated with type 2 diabetes in Scotland may be explained by higher mortality from causes other than cancer.


[A differential peptidomics analysis of hippocampal tissue in a rat model of premature white matter injury].
To observe differential peptidomics in the hippocampal tissue in a rat model of premature white matter injury, and to investigate the mechanism of premature white matter injury. Twenty neonatal Sprague-Dawley rats were randomly and equally divided into a control group and a model group. Rats in the model group underwent permanent ligation of the right common carotid artery 2 days after birth, followed by 2 hours of hypoxia. For rats in the control group, the right common carotid artery was isolated, but without ligation and hypoxia. Brain tissue samples were collected from the two groups, and hippocampal tissue was isolated. Liquid chromatography-tandem mass spectrometry combined with tandem mass spectrometry was used for peptidomic profiling of hippocampal tissue, and the differentially expressed peptides between the two groups were subjected to bioinformatics analysis to assess their possible roles in neural development and function. A total of 4164 peptides were identified and quantified, and 262 of them were differentially expressed (absolute fold change ≥2.5), including 164 upregulated peptides and 98 downregulated peptides. The numbers of differentially expressed peptides of the precursor proteins ELN, PCLO, MYO15a, MAP4, and MAP1b were the most, and may play significant roles in the pathogenesis of premature white matter injury. CDK5 signaling pathway in the hippocampus was activated in the rat model of premature white matter injury. The differentially expressed peptides related to precursor proteins such as MAP1b may be key bioactive peptides involved in neural development and function in premature white matter injury, and activation of the CDK5 signaling pathway may be associated with premature white matter injury.


A colorful, charismatic, community-oriented campaign.
You might think that the draw of blue skies, palm trees, and warm climates would be enough to lure workers to NCH Healthcare Systems, centered in Naples, FL. With a unique benefits plan, NCH launched a unique campaign to organize the many elements that make working for the facility like a day at the beach.


Dietary quality differences between women with and without weight loss in nutritional treatment.
The obesity nutritional treatment is structured to weight loss and diet is considered an important indicator of treatment effectiveness. The purpose of this study is to compare the diet quality among women who lost weight to women who maintained or gained weight during the nutritional treatment. This is a retrospective study that included 66 obese women in nutritional treatment for weight loss, over six months, divided in tercile according to their weight loss. The diet quality was evaluated by score, which was obtained with a food frequency questionnaire. The diet quality comparison was made among the group with weight loss (GL; n = 22) and the group that maintained or gained weight during the nutritional treatment (GG; n = 22) showed that both groups had improvement in their diet quality scores from pre-treatment to post-treatment. Nevertheless, the GG had higher sugar consumption than the GL in the pre-treatment (p = 0.02) and in the post-treatment (p 0.01) periods. In the post-treatment, GL increased their scores for leafy vegetables (0.013), fruit (0.004), sweets (p 0.03), and soft drinks (p 0.02). GL improved their scores for fried food (p 0.01) and sweets (p 0.008). This indicates that in the weight loss treatment special attention should be given to the incentive to the fruit and leafy vegetables consumption and, to reduce the consumption of sweets.


Catalog of insect type specimens preserved at the Kunming Institute of Zoology, Chinese Academy of Science with corrections of some specimens.
This article presents a list of insect types preserved in Kunming Natural History Museum of Zoology (KNHMZ). As of March, 2015, 3 412 type specimens belonging to 266 species/subspecies of 37 families in 9 orders (Odonata, Isoptera, Mantodea, Orthoptera, Hemiptera, Coleoptera, Diptera, Hymenoptera and Lepidoptera) are included. Information corrections of some specimens are provided in this article.


Staining of proteoglycans in mouse lung alveoli. II. Characterization of the Cuprolinic blue-positive, anionic sites.
The nature of Cuprolinic Blue-positive anionic filaments in mouse lung alveoli has been characterized. The contrast of filaments in the alveolar basement membrane of type I epithelial cells was lost on treatment with nitrous acid and pronase (without prefixation). In contrast, neither neuraminidase, chondroitinase ABC or AC, nor Streptomyces hyaluronidase had any effect. Treatment with pronase (after prefixation) and 2.0 M MgCl2 (after prefixation) also had no effect, indicating that the filaments are heparan sulphate proteoglycans. The filaments in the alveolar basement membrane of type II epithelial cells and in the capillary basement membrane of the endothelial cells were also nitrous acid sensitive, but chondroitinase ABC-insensitive. A model in which the whole alveolus contains a single layer of heparan sulphate-containing proteoglycan monomers is proposed. Furthermore, the collagen fibril associated filaments remained unaffected after treatment with nitrous acid, neuraminidase or Streptomyces hyaluronidase, or after digestion with pronase (after prefixation) and treatment with 2.0 M MgCl2 (after prefixation). These filaments, however, could no longer be detected when digestion with chondroitinase ABC or pronase (without prefixation) was applied; chondroitinase AC treatment clearly affected the filaments, although they still were visible. These results indicate that the filaments are dermatan sulphate-containing proteoglycans. Some functional aspects of the proteoglycans are discussed.


Histopathological observation of the heart with diffuse and abnormal proliferation of mitochondria in myocardial cells (mitochondrial cardiomyopathy): report of an adult case.
An autopsy case of idiopathic dilated cardiomyopathy with abnormal proliferation of mitochondria in the myocardial cells is reported. The case is that of a 39-year-old male with congestive heart failure. The heart was 700 g and showed marked dilatation of all cardiac chambers with myocardial fibrosis of the left ventricular myocardium and interventricular septum, especially in the basal portion of the left ventricular posterior wall. Myocardial cells were hypertrophied with a marked increase of fine-granular sarcoplasm, containing numerous mitochondria, seen by electron microscopy. The mitochondria were usually round or oval and ranged in size from 0.3 to 1.2 micron in diameter. The cristae of these mitochondria frequently showed a concentric lamellar or reticular configuration. Myofibrils were unusually scarce, but the sarcomere structure and arrangement of myofilaments were well-preserved. Epicardial and intramural coronary vessels were almost normal. From these findings, we consider this to be an adult case of mitochondrial cardiomyopathy.


Levofloxacin- versus metronidazole-based rescue therapy for H. pylori infection in Japan.
The ideal second-line treatment regimens for Helicobacter pylori infection may differ between the areas, countries and races. The aim was to confirm which was the better regimen for second-line therapy after treatment failure with a standard triple therapy in Japan, a high dosage of levofloxacin- or metronidazole-based therapy. Sixty outpatients with persistent H. pylori infection after a standard triple therapy were enrolled in this prospective, open-label and randomised trial. The subjects were randomly administered levofloxacin (300 mg b.d.)- or metronidazole (500 mg b.d.)-based therapy with lansoprazole (30 mg b.d.) and amoxicillin (1000 mg b.d.) for 7 days, and the cure rates and side effects were analysed. Antimicrobial susceptibility was also examined before second-line therapy using the E-test. Good compliance was obtained without severe side effects in both the groups except for two patients. The cure rates, expressed as intention-to-treat and per-protocol analyses, respectively, were 70.0 and 72.4% in the levofloxacin group, and 96.7 and 100% in the metronidazole group. Each regimen often overcame even clarithromycin-resistant strains. Metronidazole-based triple therapy is recommended as second-line therapy in Japan, and levofloxacin-based therapy can be an alternative treatment option.


Chitosan modified multi-walled carbon nanotubes and arginine aerogel for enhanced carbon capture.
Global warming is emerging as a significant issue because of increasing CO2 levels in the atmosphere due to urbanization, industrialization, and fossil-fuel usage. Therefore, reducing atmospheric CO2 levels using new materials with high carbon capture capacity and efficient CO2 capture technologies is essential. Herein, we propose a hybrid chitosan (CS) aerogel containing multi-walled carbon nanotubes (MWCNTs) and an arginine (Arg) aerogel (CSCNTArg aerogel) for efficient carbon capture. This aerogel was successfully synthesized using a cross-linker reagent via step-freeze drying method. Fourier-transform infrared spectroscopy and X-ray diffraction analyses confirmed the successful grafting of CS, MWCNTs, and Arg onto the CSCNTArg aerogel. The thermogravimetric analysis (TGA) confirmed good thermal stability up to 500 °C of the as-developed aerogel. Field-emission scanning electron microscopy showed that the surface morphology of the CSCNTArg aerogel differed from that of CS, Arg, and MWCNTs with pores on their surfaces. N2 and CO2 adsorption-desorption studies on the CSCNTArg aerogel were performed using the Brunauer-Emmett-Teller method and TGA, respectively. The CSCNTArg aerogel showed a high adsorption capacity of approximately 5.00 mmol g-1 at 35 °C. Therefore, this new material may be useful for facilitating high-efficiency CO2 adsorption to reduce atmospheric carbon footprint.


Leptomeningeal carcinomatosis: prognostic value of clinical, cerebrospinal fluid, and neuroimaging features.
Leptomeningeal carcinomatosis (LC) is a devastating complication occurring in 5% of all patients with cancer. To date there are no well-established prognostic markers in patients with LC, except for the presence of cerebrospinal fluid (CSF) blocks and the Karnofsky performance status scale (KPS). We aimed to identify clinical, neuroradiologic and CSF prognostic factors related to LC survival and to develop an easy-to-use Prognostic Scoring Scale (PSS) to identify patients who are more likely to benefit from receiving treatment. Single-center retrospective study evaluating patients who had a diagnosis of LC during a 10-year period. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LC were also included. Fifty patients with LC were analyzed (58% women). Median age was 54.4 years, and KPS was 60%. The most common types of tumor were breast (35%), lung (24%), and hematologic malignancies (16%). Thirty-two percent of patients were diagnosed by imaging, 22% by cytology, and 40% by both. Median overall survival (OS) was 10 weeks (95% confidence interval 5.1-14.9). Median OS for patients who received specific treatment was 21.2 weeks vs. 6.38 weeks for patients receiving supportive care only (p<0.001). In multivariate analysis, initial KPS, initial CSF protein level (<112 mg/dL) and time from diagnosis of primary tumor to diagnosis of LC (>67 weeks) were significant and independent predictors of increased survival. Prognosis remains poor in LC. The predictive factors for patients with LC here identified could help to improve the selection of patients who are more likely to benefit from receiving treatment.


Action of lysosomotropic amines on spontaneous and interferon enhanced NK and CTL cytolysis.
Cell-mediated cytotoxicities, such as natural killer (NK) and T-dependent cytotoxic (CTL) activities, are inhibited to the same extent by lysosomotropic amines, even when interferon is added to cultures to enhance lysis. It is postulated that the amines block steps common to spontaneous and IFN-enhanced NK and CTL lytic mechanisms.


Acylation of 1-palmitoyl-lysophosphatidylglycerol in a alveolar type II cells from rat lung.
1. Alveolar type II cells from adult rat lung have the enzymic capability to acylate 1-palmitoyl-lysophosphatidyl-glycerol, using palmitoyl-CoA to form dipalmitoylphosphatidylglycerol. 2. On a protein basis the acylation of 1-palmitoyl-lysophosphatidylglycerol is at least 2-fold more active in sonicated type II cells than in whole lung homogenates. 3. Both type II cells and whole lung homogenates show higher activity towards palmitoyl-CoA than towards oleoyl-CoA for acylation of 1-palmitoyl-lysophosphatidylglycerol. 4. Both in type II cells and in whole lung homogenates the rates of acylation of 1-palmitoyl-lysophosphatidylglycerol and 1-palmitoyl-lysophosphatidylcholine with palmitate are of the same order of magnitude, while the rate of acylation of 1-palmitoyl-lysophosphatidylethanolamine is much lower.


Shear bond strength vs interfacial fracture toughness - Adherence to CAD/CAM blocks.
To compare shear bond strength (SBS) and interfacial fracture toughness (IKIC) results when assessing the effect of surface roughness and thermocycling on the adherence of a resin composite luting agent (RCLA) to a CAD/CAM resin composite block (RCB). Tetric CAD HT along with the recommended bonding system, Adhese Universal and Variolink Esthetic LC, were used. Surface roughness was achieved with 600/320/60 grit SiC papers. Samples were stored 24h in 37°C water or thermocycled 10000× (5°C-55°C) prior to testing. Results were analyzed by univariate ANOVA and Scheffé modified t-tests (α=0.05). Fractured specimens were viewed with a stereo microscope and selected specimens with a scanning electron microscope. SBS results showed a significant difference between the 60 grit group and the other groups, both after 24h and thermocycling. A large number of SBS samples showed cohesive fracture or subsurface damage in RCB. Thermocycling led to a significant decrease in SBS in all groups. IKIC results showed no significant differences due to surface preparation after 24h storage in 37°C. After thermocycling, there was a significant difference between the 60 and the 600 grit groups. All KIC samples fractured adhesively at the RCB surface. KIC of the RCLA was significantly higher than IKIC of all groups. The results endorse the use of fracture mechanics methodology for the assessment and characterization of adherence, while identifying difficulties in its implementation. The results suggest also that adherence to CAD/CAM RCB may be limited by the strength of the resin composite block - adhesive interface.


Recognition of different DNA sequences by a DNA-binding protein alters protein dynamics differentially.
λ-Repressor-operator sites interaction, particularly O(R)1 and O(R)2, is a key component of the λ-genetic switch. FRET from the dansyl bound to the C-terminal domain of the protein, to the intercalated EtBr in the operator DNA indicates that the structure of the protein is more compact in the O(R)2 complex than in the O(R)1 complex. Fluorescence anisotropy reveals enhanced flexibility of the C-terminal domain of the repressor at fast timescales after complex formation with O(R)1. In contrast, O(R)2 bound repressor shows no significant enhancement of protein dynamics at these timescales. These differences are shown to be important for correct protein-protein interactions. Altered protein dynamics upon specific DNA sequence recognition may play important roles in assembly of regulatory proteins at the correct positions.


A report of Epstein-Barr virus-positive primary cutaneous natural killer-/T-cell lymphoma.
We describe a patient who presented with Epstein-Barr virus-positive tumor-stage primary cutaneous lymphoma. Our patient had previously been treated with oral methotrexate for long-standing rheumatoid arthritis. Tissue analysis revealed large tumor cells that were surface CD2- and CD3-positive; T-cell-restricted intracellular antigen-positive; CD56-, CD20-, and CD30-negative; and stained positively for Epstein-Barr virus. Our case is noteworthy for several reasons. Although the presence of rheumatoid arthritis and therapy with methotrexate are putative risk factors for the development of immune suppression-related and Epstein-Barr virus-related lymphomas, the vast majority of lymphomas in this setting are of B-cell origin, and rarely are these primary cutaneous in nature. In addition, our patient's tumor displayed an unusual phenotype, with immunophenotypic features suggestive of an atypical natural killer-/T-cell lymphoma. Methotrexate was withdrawn, and our patient was successfully treated with local radiotherapy. She has remained in complete remission 28 months since diagnosis.


Case studies in neuroscience: cortical contributions to the frequency-following response depend on subcortical synchrony.
Frequency-following responses to musical notes spanning the octave 65-130 Hz were elicited in a person with auditory neuropathy, a disorder of subcortical neural synchrony, and a control subject. No phaselocked responses were observed in the person with auditory neuropathy. The control subject had robust responses synchronized to the fundamental frequency and its harmonics. Cortical onset responses to each note in the series were present in both subjects. These results support the hypothesis that subcortical neural synchrony is necessary to generate the frequency-following response-including for stimulus frequencies at which a cortical contribution has been noted. Although auditory cortex ensembles may synchronize to fundamental frequency cues in speech and music, subcortical neural synchrony appears to be a necessary antecedent.NEW & NOTEWORTHY A listener with auditory neuropathy, an absence of subcortical neural synchrony, did not have electrophysiological frequency-following responses synchronized to an octave of musical notes, with fundamental frequencies ranging from 65 to 130 Hz. A control subject had robust responses that phaselocked to each note. Although auditory cortex may contribute to the scalp-recorded frequency-following response in healthy listeners, our results suggest this phenomenon depends on subcortical neural synchrony.


Gas-phase sugar formation using hydroxymethylene as the reactive formaldehyde isomer.
Carbohydrates (CH2O)n are the formal adducts of carbon (atoms) to water with a repeating unit that structurally resembles H-C̈-OH (hydroxymethylene). Although hydroxymethylene has been suggested as a building block for sugar formation, it is a reactive species that had escaped detection until recently. Here we demonstrate that formaldehyde reacts with its isomer hydroxymethylene to give glycolaldehyde in a nearly barrierless reaction. This carbonyl-ene-type transformation operates in the absence of base and solvent at cryogenic temperatures similar to those found in extraterrestrial environments or interstellar clouds. Hydroxymethylene acts as a building block for an iterative sugar synthesis, as we demonstrate through the formation of the triose glyceraldehyde. The thermodynamically preferred ketose dihydroxyacetone does not form, and the formation of further branched sugars in the iterative synthesis presented here is unlikely. The results therefore provide a link between the well-known formose (Butlerow) reaction and sugar formation under non-aqueous conditions.


Mesoporous α-Al2O3-supported PdCu bimetallic nanoparticle catalyst for the selective semi-hydrogenation of alkynes.
The selective hydrogenation of alkynes to alkenes is widely applied in the chemical industry; nevertheless, achieving highly selective hydrogenation with high catalytic activity is considerably challenging. Herein, ultrafine PdCu bimetallic nanoparticles encapsulated by high-surface-area mesoporous α-Al2O3 were prepared by high-temperature calcination-reduction using a porous organic framework (POF) as the template. As-obtained PdCu@α-Al2O3 exhibited a high selectivity of 95% for the semi-hydrogenation of phenylacetylene as a probe reaction under mild reaction conditions. The separation of continuous Pd atoms and modification of the Pd electronic state by Cu atoms suppressed β-hydride formation and alkene adsorption, contributing to high selectivity for the catalytic hydrogenation of alkynes. The catalytic activity was maintained after 7 cycles due to the strong interaction between the PdCu bimetallic nanoparticles and α-Al2O3 as well as the encapsulation effect of mesoporous α-Al2O3. Thus, the current work provides a facile strategy for fabricating high-surface-area mesoporous α-Al2O3-supported catalysts for industrial catalysis applications.


NK cells stimulated with IL-15 or CpG ODN enhance rituximab-dependent cellular cytotoxicity against B-cell lymphoma.
Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism in the clinical activity of rituximab for treatment of B-cell malignancies. Natural killer (NK) cells, through the activating receptor FcgammaRIIIa (CD16), play a major role in rituximab-mediated ADCC. We have studied the in vitro effect of NK stimulators, such as interleukin-15 (IL-15) and CpG oligodeoxynucleotides A-Class (CpG ODN A), in the enhancement of rituximab-mediated ADCC against B-cell lymphoma. Peripheral blood mononuclear cells (PBMC), purified NK cells, or NK-depleted PBMC from healthy donors, were activated with IL-15 or CpG ODN A, and cocultured with B-lymphoma cells in the presence of rituximab to evaluate the enhancement of the cytotoxicity. The rituximab-mediated ADCC of IL-15-activated PBMC was twofold compared to unstimulated PBMC (73% +/- 7% vs 37% +/- 5% respectively, p < 0.001). Similarly, rituximab-mediated ADCC was enhanced when PBMC were activated with CpG ODN A as compared to CpG ODN control (61% +/- 11% vs 36% +/- 8%, respectively, p = 0.02). Nevertheless, the ADCC of purified NK cells was increased only with IL-15. NK-depleted PBMC activated with either IL-15 or CpG ODN A showed no ADCC, suggesting that NK are the major effector cells. Furthermore, IL-15 or CpG ODN A-activated PBMC, but not activated purified NK cells, secreted large amounts of interferon-gamma in the presence of rituximab-coated lymphoma cells. IL-15 and CpG ODN A enhance rituximab-mediated ADCC against B-cell lymphoma. Under these conditions, NK cells seem to be the main effector cells mediating ADCC. These findings suggest that these agents could be used as adjuvants in combination with rituximab for patients with B-cell lymphoma.


Sol-gel encapsulation of lactate dehydrogenase for optical sensing of L-lactate.
Sol-gel encapsulation of lactate dehydrogenase and its cofactor can be employed as a disposable sensor for L-lactate. The sensor utilized the changes in absorbance or fluorescence from the reduced cofactor nicotinamide adenine dinucleotide (NADH) upon exposure to L-lactate. Although, problems such as diminished enzymatic activity and/or leaching of enzyme from the sol-gel matrix occurred, the sol-gel process is sufficiently mild to permit retention of enzymatic activity. The apparent activity of LDH in the sensor is at least 10% of that of the dissolved enzyme. The sensor has a linear dynamic range over the normal physiological L-lactate level and has a long-term storage stability of at least 3 weeks.


Minimally invasive versus sternotomy approach for double-patch repair of partial anomalous pulmonary venous connection and sinus venosus defect in pediatric and adult patients: Mid to long-term outcomes.
Several surgical techniques have been proposed to repair right partial anomalous pulmonary venous connection (PAPVC) along with sinus venosus defect (SVD). This study aimed to compare the perioperative data and outcomes of double-patch repair using a minimally invasive approach versus conventional sternotomy in pediatric and adult patients. This retrospective study was conducted on 48 minimally invasive cases and 35 sternotomy cases, undergoing surgery by a single surgeon between July 2002 and August 2020. For all patients, repair was performed using the double-patch technique. In the minimally invasive approach, right mini-thoracotomy was performed with central cannulation for children and with peripheral cannulation for adults. The patients were classified into two pediatric and adult groups, and each group was categorized into minimally invasive and sternotomy approaches. They were followed-up by transthoracic echocardiography and electrocardiography before and early after surgery, 3 and 6 months after surgery, and then annually. The relative data were compared between the two approaches in terms of perioperative findings, postoperative pulmonary vein or superior vena cava (SVC) stenosis, and sinus node dysfunction. This study included 25 minimally invasive cases and 19 sternotomy cases in the pediatric group (mean age, 4.99 ± 4.28 and 6.10 ± 4.39 years, respectively) and 23 minimally invasive cases and 16 sternotomy cases in the adult group (mean age, 35.73 ± 8.06 and 32.62 ± 9.80 years, respectively). The mean and median follow-ups were 6.31 ± 4.92 years and 6 years (range: 6 month-18 year) in the pediatric group and 6.15 ± 4.53 years and 5 years (range: 6 month-18 year) in the adult group, respectively. The mean chest tube drainage was significantly lower in the minimally invasive pediatric group (p = .03), and the mean blood transfusion volume was significantly lower in the minimally invasive adult group compared to the other groups (p = .03). No stenosis occurred in the pulmonary veins. Mild SVC stenosis occurred in one patient in the minimally invasive pediatric group, with no need for reintervention. All patients had a normal sinus rhythm, except for the mentioned case with a transient, first-degree atrioventricular block, which spontaneously reverted to the normal sinus rhythm. The minimally invasive approach can be a safe and practical alternative for the double-patch repair of PAPVC and SVD. It ensures a repair with comparable quality to sternotomy, but with better cosmetic and psychological outcomes.


Resonant Andreev Spectroscopy in normal-Metal/thin-Ferromagnet/Superconductor Device: Theory and Application.
We develop a theoretical model to describe the transport properties of normal-metal/thin-ferromagnet/superconductor device. We perform experimental test of the model using a gold tip on PdNi/Nb bilayer. The resonant proximity effect causes conductance features very sensitive to the local ferromagnetic properties, enabling accurate measurement of polarization and thickness of the ferromagnet by point contact spectroscopy.


Nanoscale regulation of L-type calcium channels differentiates between ischemic and dilated cardiomyopathies.
Subcellular localization and function of L-type calcium channels (LTCCs) play an important role in regulating contraction of cardiomyocytes. Understanding how this is affected by the disruption of transverse tubules during heart failure could lead to new insights into the disease. Cardiomyocytes were isolated from healthy donor hearts, as well as from patients with cardiomyopathies and with left ventricular assist devices. Scanning ion conductance and confocal microscopy was used to study membrane structures in the cells. Super-resolution scanning patch-clamp was used to examine LTCC function in different microdomains. Computational modeling predicted the impact of these changes to arrhythmogenesis at the whole-heart level. We showed that loss of structural organization in failing myocytes leads to re-distribution of functional LTCCs from the T-tubules to the sarcolemma. In ischemic cardiomyopathy, the increased LTCC open probability in the T-tubules depends on the phosphorylation by protein kinase A, whereas in dilated cardiomyopathy, the increased LTCC opening probability in the sarcolemma results from enhanced phosphorylation by calcium-calmodulin kinase II. LVAD implantation corrected LTCCs pathophysiological activity, although it did not improve their distribution. Using computational modeling in a 3D anatomically-realistic human ventricular model, we showed how LTCC location and activity can trigger heart rhythm disorders of different severity. Our findings demonstrate that LTCC redistribution and function differentiate between disease aetiologies. The subcellular changes observed in specific microdomains could be the consequence of the action of distinct protein kinases. This work was supported by NIH grant (ROI-HL 126802 to NT-JG) and British Heart Foundation (grant RG/17/13/33173 to JG, project grant PG/16/17/32069 to RAC). Funders had no role in study design, data collection, data analysis, interpretation, writing of the report.


Sequence complexity of polyadenylate ribonucleic acid in El mouse brain.
To elucidate the sequence complexity of polyadenylate messenger RNA [poly(A+)mRNA] regarding the seizure-susceptible El mouse brain, the proportion of complexity was measured by saturation hybridization using a single-copy DNA (scDNA) with excess RNA. At saturation, 3.81, 3.85 and 4.00% of scDNA hybridized with polysomal poly(A+)mRNAs of El(+), El(O) which had not been convulsed, and ddY (nonsusceptible) mice, respectively. The additive hybridization of a mixture of El(+) and ddY mouse mRNAs was 4.04%. The results suggest that there are considerable overlapping sets within the poly(A+)mRNA sequences between the ddY and El mice, but the complexity of ddY mice mRNA is slightly larger than that of the El mice, whereas poly(A+) heterogeneous nuclear RNA (hnRNA) hybridized with about 18% of scDNA in three strains of mice.


C-index regression for recurrent event data.
Recurrent event data analysis plays an important role in many fields, e.g., medicine, social science, and economics. While the existing approaches under the proportional rates or mean model yield poor performance when the underlying model is misspecified, we propose a novel model-free approach by introducing a lower bound on the concordance index (C-Index). We develop an estimation method through deriving a continuous lower bound on the C-Index based on the log-sigmoid function and also provide a variable selection procedure in high dimensional settings. Under both low and high dimensional settings, simulation results show that the proposed methods outperform the gamma frailty recurrent event model when the proportional mean assumption is violated. Moreover, an application to the hospital readmission dataset shows results in line with previous studies and a higher C-Index value further assures model decency.


Congenital partial pericardial defect discovered incidentally during surgery for lung cancer: a case report and literature review.
Congenital pericardial defects are rare congenital anomalies, often asymptomatic and incidentally detected during thoracic surgery. A 74-year-old man with primary lung cancer (cT1cN0M0, Stage IA3) underwent thoracoscopic radical lobectomy. At the time of thoracotomy, a pericardial defect was found on the ventral side of the hilar region, and the left atrial appendage was exposed. Due to concern that contact between the bronchial stump and the left atrial appendage may lead to postoperative bleeding and heart hernia, the pericardial defect was closed with an expanded polytetrafluoroethylene GoreTex® membrane. Preoperative computed tomography was reanalyzed with a 1 mm slice, congenital pericardial defect was detected as the pericardium had penetrated under the left atrial appendage. In congenital partial pericardial defect, contact between the left atrial appendage and bronchial stump, due to movement of the lung or heart, increases the risk of bleeding after lung resection. Therefore, closure of the defect should be considered. Although it is difficult to diagnose congenital partial pericardial defect preoperatively, computed tomography taken with a slice thickness of 1 mm is useful for diagnosis.


Cell proliferation in EMT6 tumors treated with single doses of x-rays or hydroxyurea. I. Experimental results.
EMT6 mouse mammary tumors were treated in vivo with 5 mg/mouse of hydroxyurea (HU) or 300 rads of X-rays. The proliferation of the tumor cells was followed for 28 hr after treatment. Changes in the 3H-TdR labeling index, the mitotic index, the specific activity of the 3H-TdR-labeled DNA, and the proportion of suspended, clonogenic cells in the S phase of the cell cycle were examined and compared. Evidence was found for reassortment of the surviving cells in treated tumors into partially synchronous cohorts. The partial synchrony in the proliferation of the surviving cells was not accurately predicted by the changes in the labeling index and the mitotic index. The changes in DNA specific activity proved unacceptable as an indicator of cell proliferation in solid EMT6 tumors treated with low doses of radiation or HU.


Cytotoxicity of a factor from normal and abnormal human spleens for allogenic leukemia cells.
A search for an endogenous cytotoxic factor (ECF) was made by analyzing 103 spleens from normal humans and patients suffering from hematopoietic malignancies, solid tumors, inflammatory diseases, and congestive and hyperplastic splenomegalies. A highly purified ECG was obtained by a combination of gel filtration and ion-exchange column chromatography. The factor is a low-molecular-weight (less than 2,000) substance and is probably a peptide or peptide-nucleotide complex. The biologic activity of EC was assayed on myelogenous and lymphatic leukemia cells of human origin. The spleens from normal individuals produced and/or stored the largest quantity of the ECF. The amount of ECF extractable from the pathologic spleen was drastically diminished regardless of the disease or therapeutic regimen. The ECF was significantly more cytotoxic for lymphatic than for myelogenous leukemia cells.


Fringe consciousness in sequence learning: the influence of individual differences.
We first describe how the concept of "fringe consciousness" () can characterise gradations of consciousness between the extremes of implicit and explicit learning. We then show that the NEO-PI-R personality measure of openness to feelings, chosen to reflect the ability to introspect on fringe feelings, influences both learning and awareness in the serial reaction time (SRT) task under conditions that have previously been associated with implicit learning (). This provides empirical evidence for the proposed phenomenology and functional role of fringe consciousness in so-called implicit learning paradigms (). Introducing an individual difference variable also helped to identify possible limitations of the exclusion task as a measure of conscious sequence knowledge. Further exploration of individual differences in fringe awareness may help to avoid polarity in the implicit learning debate, and to resolve apparent inconsistencies between previous SRT studies.


Contributions of Myc to tumorigenesis.
Despite intensive research, the mechanisms by which deregulation of myc gene expression contributes to tumorigenesis are still not fully resolved and many aspects are still enigmatic. Several recent reviews, including one published in this series a few months ago, have summarized recent progress in our understanding of the biochemistry of Myc proteins [Eisenmann, Genes Dev. (2001) in press; Amati et al., Biochim. Biophys. Acta 1471 (2001) 135-145]. Also, the evidence documenting a central role of Myc proteins in human tumorigenesis has been extensively reviewed [Henriksson and Lüscher, Cancer Res. 68 (1996) 109-182]. In this article, we will argue that current progress allows us to present testable hypotheses on how Myc affects specific properties of transformed cells.


Fatigue behaviour of a self-healing dental composite.
Novel self-healing resin-based composites containing microcapsules have been developed to improve the mechanical performance of dental restorations. However, the long-term fatigue behaviour of these self-healing composites has still been hardly investigated. Therefore, this manuscript studied the fatigue behaviour of self-healing composites containing microcapsules by subjecting the specimens to traditional staircase tests and ageing in a custom-designed chewing simulator (Rub&Roll) to simulate oral ageing physiologically relevant conditions. To prepare self-healing composite, poly(urea-formaldehyde) microcapsules containing acrylic self-healing liquids were synthesized. Subsequently, these microcapsules (10 wt%) and initiator (benzoyl peroxide, BPO, 2 wt%) were incorporated into a commercial flowable resin-based composite. Microcapsule-free resin-based composites with and without BPO were also prepared as control specimens. A three-point flexural test was used to measure the initial flexural strength (Sinitial). Subsequently, half of the specimens were used for fatigue testing using a common staircase approach to measure the fatigue strengths (FS). In addition, the other specimens were aged in the Rub&Roll machine for four weeks where after the final flexural strength (Sfinal) was measured. Compared to Sinitial, FS of all tested specimens significantly decreased as measured through staircase testing. After 4 weeks of ageing in the Rub&Roll machine, Sfinal was significantly reduced compared to Sinitial for microcapsule-free resin-based composites, but not for the self-healing composites (p = 0.3658). However, the self-healing composites are still in the experimental phase characterized by a low mechanical strength, which still impedes further clinical translation. Self-healing composites containing microcapsules exhibit improved fatigue resistance compared to microcapsule-free non-self-healing composites.