Biosynthetic human insulin: effect in healthy men on plasma glucose and non-esterified fatty acids in comparison with highly purified pork insulin.
Biosynthetic human insulin (BHI) produced by recombinant DNA technology was administered subcutaneously and intravenously at two dose levels to two groups, each consisting of six normal men. Responses were compared with those for purified pork insulin (PPI) given by the same routes at the same dose levels to the same two groups. The glycemic response to the insulins was similar with a suggestion (seen both with intravenous and subcutaneous administration) that the glycemic depression with BHI was slightly greater at low dose and less at high dose. No significant difference between insulin types was found in the depression of non-esterified fatty acid (NEFA) concentrations, although significant differences between types with low-dose subcutaneous injection emerged during the later phases of the experiment. After termination of high-rate infusion with both insulins, NEFA concentrations rose more rapidly with some overshoot, suggesting that the rate and depth of blood glucose fall in these experiments might have triggered a brisker counterregulatory response. The small differences found between human and pork insulins, although in some cases significant, are unlikely to be of clinical importance.


Direct fabrication of homogeneous microfluidic channels embedded in fused silica using a femtosecond laser.
We demonstrate direct fabrication of homogeneous microfluidic channels embedded in fused silica by femtosecond laser direct writing, followed by wet chemical etching and glass drawing. In addition, the glass drawing process significantly reduces the inner surface roughness of the fabricated channels, and centimeter-level microfluidic channels with an aspect ratio above 1000 can be realized.


Alterations in NMDAR-mediated signaling within the laterodorsal tegmental nucleus are associated with prenatal nicotine exposure.
Cigarette smoking during pregnancy has been clinically associated with a variety of poorbehavioral outcomes for the exposed individuals, including higher risks for drug abuse and development of attention/deficit-hyperactive disorder (ADHD). Experimental studies support the hypothesis that nicotine might contribute to these risks, since prenatal nicotine exposure (PNE) in rodents was associated with greater addiction liability, hyperactivity, social impairments and a wide range of emotional and cognitive deficits. Alterations of glutamate signaling within brain regions involved in behavioral circuits could contribute to these outcomes. The pontine laterodorsal tegmental nucleus (LDT) exerts cholinergic modulation within the ventral tegmental area, nucleus accumbens, and cortical-projecting thalamic centers and PNE-associated alterations in LDT glutamate signaling could impact cholinergic output to these LDT targets. We have previously demonstrated that PNE alters AMPA-mediated signaling within LDT neurons, and in the present investigation, we focused on changes of NMDA receptors (NMDARs) and presence of silent synapses as an indicator of metaplastic processes in LDT cells associated with PNE treatment. PNE was associated with a decreased functional presence of GluN2B NMDAR subunits in synapses of large, putatively cholinergic neurons, whereas an increased function of this subunit was detected in small, likely GABAergic cells. In addition, PNE was associated with functional alterations of extrasynaptic NMDARs in putative cholinergic neurons, suggestive of an increased presence of GluN3A-containing NMDARs. An increased number of silent synapses was exclusively seen in the small cells. When taken together, we hypothesize that NMDA-mediated signaling changes within LDT neurons following PNE treatment would result in reductions of excitatory cholinergic modulatory tone in target brain regions, which would be expected to contribute to the behavioral deficits found among these individuals.


Relationship between histology and aetiological factors in primary liver cancer.
A review of 205 primary hepatic cancers from different geographic areas reveals that HCC which forms the vast majority (86%) of these, commonly presents as the trabecular variety (76%). The compact and pseudoglandular forms are rare (18% and 6%). Relatively fewer cases of undifferentiated cancer, hepatoblastoma and cholangiocarcinoma are encountered. HCC is often associated with the presence of hepatitis B virus surface antigen (HBsAg) in the liver. This is particularly true of the trabecular variety (81%). A proportion of the compact variety as well as undifferentiated cancers do not appear to be related to HBV infection. Cholangio carcinomas are considered to be related to infection by liver flukes. Hepatoblastomas occur in infancy and childhood and show no known aetiologic association. Aflatoxin may be aetiologically related to same cases of HCC. Continued use of oral contraceptives can occasionally induce HCC.


Unveiling the stability of Sn/Si/graphite composites for Li-ion storage by physical, electrochemical and computational tools.
Complex materials composed of two and three elements with high Li-ion storage capacity are investigated and tested as lithium-ion battery (LiB) negative electrodes. Namely, anodes containing tin, silicon, and graphite show very good performance because of the large gravimetric and volumetric capacity of silicon and structural support provided by tin and graphite. The performance of the composites during the first cycles was studied using ex situ magic angle spinning (MAS) 7Li Nuclear Magnetic Resonance (NMR), density functional theory (DFT) calculations, and electrochemical techniques. The best performance was obtained for Sn/Si/graphite in a 1 : 1 : 1 proportion, due to an emergent effect of the interaction between Sn and Si. The results suggest a stabilization effect of Sn over Si, providing a physical constraint that prevents Si pulverization. This mechanism ensures good cyclability over more than one hundred cycles, low capacity fading and high specific capacity.


Cardiac Toxicity After Radiotherapy for Stage III Non-Small-Cell Lung Cancer: Pooled Analysis of Dose-Escalation Trials Delivering 70 to 90 Gy.
Purpose The significance of radiotherapy (RT) -associated cardiac injury for stage III non-small-cell lung cancer (NSCLC) is unclear, but higher heart doses were associated with worse overall survival in the Radiation Therapy Oncology Group (RTOG) 0617 study. We assessed the impact of heart dose in patients treated at our institution on several prospective dose-escalation trials. Patients and Methods From 1996 to 2009, 127 patients with stage III NSCLC (Eastern Cooperative Oncology Group performance status, 0 to 1) received dose-escalated RT to 70 to 90 Gy (median, 74 Gy) in six trials. RT plans and cardiac doses were reviewed. Records were reviewed for the primary end point: symptomatic cardiac events (symptomatic pericardial effusion, acute coronary syndrome, pericarditis, significant arrhythmia, and heart failure). Cardiac risk was assessed by noting baseline coronary artery disease and calculating the WHO/International Society of Hypertension score. Competing risks analysis was used. Results In all, 112 patients were analyzed. Median follow-up for surviving patients was 8.8 years. Twenty-six patients (23%) had one or more events at a median of 26 months to first event (effusion [n = 7], myocardial infarction [n = 5], unstable angina [n = 3], pericarditis [n = 2], arrhythmia [n = 12], and heart failure [n = 1]). Heart doses (eg, heart mean dose; hazard ratio, 1.03/Gy; P = .002,), coronary artery disease ( P < .001), and WHO/International Society of Hypertension score ( P = .04) were associated with events on univariable analysis. Heart doses remained significant on multivariable analysis that accounted for baseline risk. Two-year competing risk-adjusted event rates for patients with heart mean dose < 10 Gy, 10 to 20 Gy, or ≥ 20 Gy were 4%, 7%, and 21%, respectively. Heart doses were not associated with overall survival. Conclusion Cardiac events were relatively common after high-dose thoracic RT and were independently associated with both heart dose and baseline cardiac risk. RT-associated cardiac toxicity after treatment of stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized.


The effects of antiepileptic drugs on cognitive functional magnetic resonance imaging.
The cognitive dysfunction caused by antiepileptic drugs (AEDs) has been extensively described, although the mechanisms underlying such collateral effects are still poorly understood. The combination of functional magnetic resonance imaging (fMRI) studies with pharmacological intervention (pharmaco-MRI or ph-MRI) offers the opportunity to investigate the effect of drugs such as AEDs on brain activity, including cognitive tasks. Here we review the studies that investigated the effects of AEDs [topiramate (TPM), lamotrigine (LMT), carbamazepine (CBZ), pregabalin (PGB), valproate (VPA) and levetiracetam (LEV)] on cognitive fMRI tasks. Despite the scarcity of fMRI studies focusing on the impact of AEDs on cognitive task, the results of recent work have provided important information about specific drug-related changes of brain function.


Retrospective survival analysis in patients with metastatic pancreatic ductal adenocarcinoma with insulin-treated type 2 diabetes mellitus.
The association between pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus (DM2) has long been evaluated and the role of antidiabetic medications such as metformin has also been investigated. The objective of this study was to examine the association between insulin use and overall survival (OS) in patients with advanced PDAC and DM2. We retrospectively collected data from 164 patients, including an exploratory cohort of 96 patients from Medical Oncology Unit, University Hospital and University of Cagliari, Italy, and a validation cohort of 68 patients from Medical Oncology of Modena University Hospital. Patients had metastatic disease and received a first-line gemcitabine-based chemotherapy and, subsequently, a second-line fluoropyrimidines-based chemotherapy. We performed univariate analysis to evaluate correlation between long-term diabetes and overall survival. Then we performed multivariate analysis, adjusting for sex, metastatic sites, Eastern Cooperative Oncology Group Performance Status, Ca19.9 levels, N/L ratio, and lactate dehydrogenase levels at diagnosis, to confirm the independence of the variable. In the exploratory cohort, DM2 was significantly associated with higher median OS at univariate analysis (16 vs 10 months; p = 0.004). This result was confirmed by validation cohort (11 months vs 6 months; p = 0.01). In multivariate analysis, insulin-treated patients compared with non diabetic patients showed a significantly increased survival of 4.6 months (p = 0.03). Patients with insulin-treated metastatic PDAC showed better OS than non diabetic patients, as demonstrated by both cohorts. The correlation between OS and insulin-treated DM2 should be investigated further through a prospective clinical trial.


Herpes simplex virus infection of the neonatal respiratory tract.
Three patients with neonatal herpes simplex virus (HSV) infection with upper or lower respiratory tract involvement are described. In all three patients, fever and respiratory tract symptoms were the presenting features and occurred in the absence of mucocutaneous lesions or maternal history of HSV Infection. In none of the children was HSV Infection considered likely at the time viral cultures were obtained. These patients demonstrate the need for consideration of HSV in the evaluation of neonatal respiratory tract disease, particularly if it is accompanied by fever and presents after the first several days of life.


Post-pacing T loop abnormalities.
Vectorcardiograms of paced and unpaced beats were recorded from 18 patients with implanted pacemakers to investigate the characteristics of post-pacing T inversions. The intraventricular conduction during sinus rhythm of unpaced beats was normal in 13 of 18 patients and abnormal in the other 5 (RBBB in 3, LBBB in 2). The directions of the maximum QRS vector in paced beats (max QRSp.V) and maximum T vector in unpaced beats (max T unp.V) were studied. In 8 of 13 patients with normal intraventricular conduction (group A) and in 3 patients with right bundle branch block (RBBB), the differences between the directions of max QRSp.V and max T unp.V in both frontal and horizontal planes were less than 30 degrees, and in 5 of 13 patients with normal intraventricular conduction (group B) and 2 patients with left bundle branch block (LBBB), differences exceeded 30 degrees. The direction of max T unp.V tended to be superiorly, posteriorly and to the right regardless of max QRSp.V direction. The similarity in direction of max QRSp.V and max T unp.V supports the hypothesis by Rosenbaum et al that post-pacing T inversions may be, in part, explained on the basis of 'cardiac memory'. However the absence of correlation between the max QRSp.V and max T unp.V suggests that the post-pacing T inversions may be caused by other unknown mechanisms.


Comprehensive management of haemophilia.
Haemophilia is a congenital, life-long disorder that may cause major disabilities. The goal of comprehensive care is to prevent problems when possible, to treat early in order to minimize morbidity, and to restore function to disabled patients. The co-ordinated efforts of many experts are needed for success.


Etest versus vitek 2 vancomycin minimum inhibitory concentration testing methods for methicillin-resistant staphylococcus aureus: an antimicrobial stewardship initiative to evaluate the degree of discordance among methods at a rural tertiary hospital.
To evaluate the discordance between Vitek 2 and Etest vancomycin minimum inhibitory concentration (MIC) testing methods in methicillin-resistant Staphylococcus aureus (MRSA) isolates. Inclusion criteria consisted of MRSA isolates with blood, respiratory, or wound origin of culture, inpatient or emergency department location at time of culture and isolates with a Vitek 2 MIC reported. Isolates were subjected to Etest and the resulting MICs were compared to the corresponding Vitek 2 MICs, and both the rate and degree of discordance were evaluated. Seventy-five MRSA isolates met the inclusion criteria. Etest resulted in an MIC value greater than that of Vitek 2 in 64 isolates (85.3%). Furthermore, of the 35 isolates with an MIC of ≤ 0.5 mcg/mL via Vitek 2, Etest reported 27 isolates with an MIC >1 mcg/mL. Of the 39 isolates with a Vitek 2 MIC of 1 mcg/mL, Etest reported 30 isolates with an MIC >1 mcg/mL. We have demonstrated that Etest commonly reports MICs greater than 1 mcg/mL, even among isolates with MICs as low as ≤ 0.5 mcg/mL, according to Vitek 2. The clinical significance of these findings is unknown and would be an area of further study.


Antigenic specificity of gingival crevicular fluid antibody to Actinobacillus actinomycetemcomitans.
Elevated antibody levels to periodontopathogens in GCF have been identified and used as support for local antibody synthesis in periodontitis. This study examined both cross-sectional and longitudinal GCF samples for the antigenic specificity of antibody in the fluid. GCF samples were collected from each tooth of 27 periodontitis patients infected with A. actinomycetemcomitans. Levels of IgG antibody in the GCF were assessed by means of an ELISA and compared with serum for determination of local elevations. A proportion of those GCF samples that exhibited significantly elevated antibody were examined by Western immunoblotting to outer membrane antigens from A. actinomycetemcomitans. Homologous sera were also examined for comparison of antibody specificities. Of the sites with elevated IgG antibody, 87% were colonized by A. actinomycetemcomitans; however, 46% of sites with A. actinomycetemcomitans infection did not have elevated antibody. Cross-sectional studies identified a 78 to 100% agreement between the antibody specificities in GCF and those in serum. Additionally, patterns of antibody reactivity in both GCF and serum in the subjects were often very distinctive. Longitudinal alterations in GCF antibody were examined in 15 patients through a monitoring interval of up to 2 years and showed a general conservation of specificities. However, 7/15 patients exhibited a definite acquisition of different antibody specificities during the monitoring. These results describe a relationship between elevated local antibody and A. actinomycetemcomitans infection. Furthermore, the antibody specificities in serum appear to reflect generally the local response to this pathogen.


Immunosuppression induced in vitro by mastocytoma tumor cells and cell-free extracts.
Suppressed anti-sheep RBC responses occurred when spleen cells from mastocytoma-bearing mice were incubated in vitro and immunized with red blood cells. Marked immunosuppression also occurred when mastocytoma cells were added to spleen cell cultures from normal mice immunized in vitro with the sheep RBC. Suppressed immune responses also occurred when the mastocytoma cells were separated from the normal cells by 0.4-mu nucleopore membranes, but not by dialysis membranes in double chambered culture vessels. Cell-free homogenates prepared from mastocytoma cells, as well as ascitic fluid from tumor-bearing mice, also impaired the responsiveness of normal splenocytes to the SRBC. The suppressive activity of the cell-free homogenates was abolished by heating at 56 degrees C for 30 min. The immunosuppressive activity, however, was retained in supernatant ultracentrifugates of the cell-free homogenate after 100,000 times G for 90 min. Immunosuppression was most evident when mastocytoma extracts were added to cultures of normal splenocytes at the time of in vitro immunization and culture initiation. Suppression was not reversed by washing of the cultured cells and addition of fresh medium. Immunosuppression also occurred when mastocytoma extracts were incubated with spleen cells from allogeneic tumor resistant C57BL/6 mice. Additional physicochemical analyses should provide information as to the nature and specificty of the inhibitory factor(s) and its role as an immunoregulatory substance important in the host-tumor relationship.


Sensitization of intracellular Salmonella enterica serovar Typhimurium to aminoglycosides in vitro and in vivo by a host-targeted antimicrobial agent.
Aminoglycosides exhibit relatively poor activity against intracellular Salmonella enterica serovar Typhimurium due to their low permeativity across eukaryotic cell membranes. Previously, we identified the unique ability of AR-12, a celecoxib-derived small-molecule agent, to eradicate intracellular Salmonella Typhimurium in macrophages by facilitating autophagosome formation and suppressing Akt kinase signaling. In light of this unique mode of antibacterial action, we investigated the ability of AR-12 to sensitize intracellular Salmonella to aminoglycosides in macrophages and in an animal model. The antibacterial activities of AR-12 combined with various aminoglycosides, including streptomycin, kanamycin, gentamicin, and amikacin, against intracellular S. Typhimurium in murine RAW264.7 macrophages were assessed. Cells were infected with S. Typhimurium followed by treatment with AR-12 or individual aminoglycosides or with combinations for 24 h. The in vivo efficacies of AR-12, alone or in combination with gentamicin or amikacin, were also assessed by treating S. Typhimurium-infected BALB/c mice daily for 14 consecutive days. Exposure of S. Typhimurium-infected RAW264.7 cells to a combination of AR-12 with individual aminoglycosides led to a reduction in bacterial survival (P < 0.05), both intracellular and extracellular, that was greater than that seen with the aminoglycosides alone. This sensitizing effect, however, was not associated with increased aminoglycoside penetration into bacteria or macrophages. Moreover, daily intraperitoneal injection of AR-12 at 0.1 mg/kg of body weight significantly increased the in vivo efficacy of gentamicin and amikacin in prolonging the survival of S. Typhimurium-infected mice. These findings indicate that the unique ability of AR-12 to enhance the in vivo efficacy of aminoglycosides might have translational potential for efforts to develop novel strategies for the treatment of salmonellosis.


Thorough chemical modification of wood-based lignocellulosic materials in ionic liquids.
Homogenous acylation and carbanilation reactions of wood-based lignocellulosic materials have been investigated in ionic liquids. We have found that highly substituted lignocellulosic esters can be obtained under mild conditions (2 h, 70 degrees C) by reacting wood dissolved in ionic liquids with acetyl chloride, benzoyl chloride, and acetic anhydride in the presence of pyridine. In the absence of pyridine, extensive degradation of the wood components was found to occur. Highly substituted carbanilated lignocellulosic material was also obtained in the absence of base in ionic liquid. These chemical modifications were confirmed by infrared spectroscopy, (1)H NMR, and quantitative (31)P NMR of the resulting derivatives. The latter technique permitted the degrees of substitution to be determined, which were found to vary between 81% and 95% for acetylation, benzoylation, and carbanilation, accompanied by similarly high gains in weight percent values. Thermogravimetric measurements showed that the resulting materials exhibit different thermal stabilities from those of the starting wood, while differential scanning calorimetry showed discrete new thermal transitions for these derivatives. Scanning electron microscopy showed the complete absence of fibrous characteristics for these derivatives, but instead, a homogeneous porous, powdery appearance was apparent. A number of our reactions were also carried out in completely recycled ionic liquids, verifying their utility for potential applications beyond the laboratory bench.


[3-dimensional documentation of wound-healing].
The objective evaluation of the course of wound-healing represents a substantial parameter for the quality assurance of a modern wound management in chronic wounds. Established procedures exclusively based on a two-dimensional measurement of the wound surface with planimetry or digital photo documentation in combination with a metric statement of size. Thus so far an objective method is missing for the evaluation of the volumes of chronic wounds. By the linkage of digital photography, optical grid by means of digital scanner and an image processing software in co-operation with the company RSI we were able to do an accurate 3-dimensional documentation of chronic wounds (DigiSkin). The generated scatter-plots allow a visual, computer-assisted 3-dimensional measurement and documentation of chronic wounds. In comparison with available systems it is now possible for the first time to objectify the volume changes of a chronic wound. On the basis of a case report of a female patient with an venous leg ulcer, which has been treated with a vacuum closure therapy before and after performing a mesh-graft transplantation, we would like to describe the advantages and the resulting scientific use of this new, objective wound documentation system in the clinical employment.


Structure and molecular packing in smectic BCr and Ad phases of Schiff base liquid crystal compounds through the analyses of layer spacing, entropy and crystal structure.
Single-crystal structural analyses and heat capacity measurements were performed on two Schiff base liquid crystal compounds, 5CBAA (4-chlorobenzylidene-4'-pentyloxyaniline) and 5ABCA (4-pentyloxybenzylidene-4'-chloroaniline). The alkyloxy-chain of a 5CBAA molecule was conformationally ordered in the crystal at room temperature. While that of 5ABCA was partially disordered in the room temperature phase but ordered in a low-temperature phase at 100 K. The structural phase transition involving the disordering of the conformation was observed at 107 K in the heat capacity of 5ABCA. Both compounds showed two liquid crystalline phases, SmBCr and SmAd. The net entropy change associated with the chain disordering was essentially the same in them despite the difference in the orientation of their central -CH[double bond, length as m-dash]N- moiety. The layer-spacings of SmBCr and SmAd phases were analyzed for their chain-length dependence in both series of mesogens (nCBAA and nABCA), as well as in the case of nBBAA (4-bromobenzylidene-4'-alkyloxyaniline). The results reveal that these smectic structures are composed of alternately stacked core- and chain-layers with an antiparallel arrangement of cores and a bent-form of molecules.


Politicization during the 2012 U.S. Presidential Elections: bridging the personal and the political through an identity content approach.
We investigated U.S. citizens' politicization (i.e., switching from not self-defining to self-defining as an active political party supporter) during the 2012 U.S. Presidential Elections. We used a novel identity content approach to explore qualitative changes in overlap between personal and politicized identity traits. We collected longitudinal data from a community sample of U.S. citizens (N = 760), tracking whether and how personal and politicized identity content developed: two months before (T1), immediately before (T2), and 2 months after (T3) the election. We explored a subsample of participants who met inclusion criteria (n = 115), comparing 87 participants who did not politicize with 28 participants who self-labeled as unpoliticized at T1, but politicized at T2/T3. Results confirmed hypotheses: Only politicizers showed greater integration between their personal and politicized identity content over time; moreover, identity content was a significant positive predictor of politicization and action engagement. We discuss the value of identity content for politicization research.


Residual disease activity in psoriatic arthritis: discordance between the rheumatologist's opinion and minimal disease activity measurement.
To assess how many PsA patients with an acceptable disease state according to the treating rheumatologist have quiescent disease defined as minimal disease activity (MDA). This cross-sectional study included 250 PsA patients. To assess current clinical practice as closely as possible, acceptable disease state was not determined by predefined activity measures, but instead was defined by asking rheumatologists to refer those patients whom they considered sufficiently treated. Patients were evaluated for current disease activity including clinical assessments and patient reported outcomes (PROs). One-third (88/250) of the patients with acceptable disease state according to the rheumatologist did not fulfil MDA (MDA-). The presence of tender joints and patient pain and global disease activity scores most frequently contributed to not fulfilling MDA (not achieved in 83, 82 and 80%, respectively). However, also objective signs of disease activity were higher in the MDA- than MDA+ patient group: a swollen joint count >1 occurred in 35% vs 7% (P < 0.001), enthesitis >1 in 14% vs 3% (P = 0.002) and Psoriasis Area and Severity Index >1 in 43% vs 26% (P = 0.002). Residual disease was more frequent in females, elder patients and those with a raised BMI, independent of the treatment schedule, and negatively influenced PROs of function and quality of life. One-third of the PsA patients with acceptable disease state according to the treating rheumatologist did not fulfil the MDA criteria and had residual disease activity on both subjective and objective disease activity measurements. As residual disease activity was associated with worse PROs, future strategy trials should evaluate if treatment adjustments are beneficial for this patient group.


Neddylation, an Emerging Mechanism Regulating Cardiac Development and Function.
Defects in protein quality control have been increasingly recognized as pathogenic factors in the development of heart failure, a persistent devastating disease lacking efficacious therapies. Ubiquitin and ubiquitin-like proteins, a family of post-translational modifying polypeptides, play important roles in controlling protein quality by maintaining the stability and functional diversity of the proteome. NEDD8 (neural precursor cell expressed, developmentally downregulated 8), a small ubiquitin-like protein, was discovered two decades ago but until recently the biological significance of NEDD8 modifications (neddylation) in the heart has not been appreciated. In this review, we summarize the current knowledge of the biology of neddylation, highlighting several mechanisms by which neddylation regulates the function of its downstream targets, and discuss the expanding roles for neddylation in cardiac physiology and disease, with an emphasis on cardiac protein quality control. Finally, we outline challenges linked to the study of neddylation in health and disease.


Modular bimetallic complexes with a sulfonamido-based ligand.
A series of bimetallic complexes prepared with the ligands N,N,N',N'-tetramethylethane-1,2-diamine (TMEDA) and N,N',N''-[2,2',2''-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido) ([MST]3-) is described. Four diiron compounds of the formulation (TMEDA)FeII(X)-(μ-OH)-FeIIIMST were prepared, in which the X- ligands are the anions OTf-, Br-, SCN-, or N3-. Additionally, two heterobimetallic compounds of the formulation (TMEDA)MII(OTf)-(μ-OH)-FeIIIMST (MII = CoII or NiII) were synthesized. All these compounds have similar spectroscopic and structural properties. The diiron compounds exhibit perpendicular-mode electron paramagnetic resonance spectra consistent with S = 1/2 spin ground states, which is expected for high-spin FeII and FeIII centres that are antiferromagnetically coupled. The heterobimetallic (TMEDA)NiII(OTf)-(μ-OH)-FeIIIMST complex had a spin state of S = 3/2 that also resulted from antiferromagnetic coupling between the high-spin NiII and FeIII centres. The modularity of this system is further demonstrated by the substitution of the TMEDA ligand with ethylenediamine (en); for this species two equivalents of en coordinate to the FeII centre to form [(en)2FeII-(μ-OH)-FeIIIMST]OTf. These results demonstrate that a modular bimetallic system has been developed in which the key components can be modified.


[Behaviour and HIV seroprevalence investigation in sex workers of Dirkou, Niger, 2002].
In the framework of the Human Immunodeficiency Virus (HIV) surveillance, seroprevalence and behavioural survey was conducted in 2002 in Dirkou, a place of concentration of female sex workers (FSW) in Niger The global HIV seroprevalence found was 50% (CI at 95%: 40.6-59.36%). The behavioural survey revealed that 98% of FSW had heard about HIV whereas 78.7% know at least one HIV transmission way and 76.9% know at least one HIV prevention means. Only 33.3% declared using condom, what show that sensitisation efforts are needed to induce a behaviour change in FSW and their clients.


Reduced mitochondrial function in obesity-associated fatty liver: SIRT3 takes on the fat.
Aging is associated with various metabolic disorders that may have their origin in the liver, including non-alcoholic fatty liver disease, obesity, type 2 diabetes mellitus, and atherosclerosis. Although well-characterized in models of caloric restriction, relatively little is known about the role of sirtuins and acetylation under conditions of caloric excess. Sirtuins are NAD (+)-dependent protein deacetylases that mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized within the mitochondrial matrix, where it regulates acetylation levels of a diverse set of metabolic enzymes. When normal mice are fed a high fat diet they demonstrate reduced SIRT3 activity, impaired mitochondrial function, and hyperacetylation of a diverse set of proteins in their livers. Furthermore, SIRT3 knockout mice have signs of accelerated aging and cancer. Understanding SIRT3?s biochemical function and regulation in the liver under conditions of caloric excess may potentially increase our understanding of the normal aging process and diseases associated with aging, such as diabetes, fatty liver disease, or cancer.


[Five year dynamics of the characteristics of left ventricular diastolic function in patients with arterial hypertension in the Far North].
The work was aimed to study five-year dynamics of characteristics of left ventricular diastolic function in patients with arterial hypertension (AH) under conditions of continuous shiftwork in the Far North. The first stage of the study (2003-2005) involved 95 patients including 53 day-shift ones and 42 subjects working alternately on day and night shifts. At the second stage (2007-2011), prospective observation of both groups using Doppler echocardiography was organized. The patients were divided into 2 subgroups (with treated and untreated AH). It was shown that AH patients in the Far North frequently suffer disturbances of left ventricular diastolic function manifest as increased contribution of left atrial systole to left ventricular filling. This phenomenon was more pronounced in nightshift workers.


Infratemporal fossa approach to lesions in the temporal bone and base of the skull.
An infratemporal fossa approach for extensive tumors of the temporal bone, clivus, and parasellar and parasphenoid regions features permanent anterior transposition of the facial nerve, resection of the mandibular condyle, and mobilization of the zygoma and lateral orbital rim. Obliteration of the pneumatic spaces of the temporal bone with permanent occlusion of the Eustachian tube and blindsack closure of the external auditory canal avoids the danger of postoperative infection and leads to primary wound healing in the shortest time. Three cases demonstrate selective utilization of the infratemporal fossa approach. Short-term results and complications were observed in 51 patients.


Clinical types of tinea capitis and species identification in children: an experience from tertiary care centres of Karachi, Pakistan.
To study the clinical types of Tinea Capitis and identify species in children reporting to two tertiary care centres of Karachi, Pakistan. The descriptive, cross-sectional study was conducted at the Dermatology Outpatients' Department, PNS Shifa Hospital and the Institute of Skin Diseases, Karachi, from January 1, 2008 to December 31, 2009. It comprised 202 children with clinical diagnosis of tinea capitis, confirmed by skin scrapings, showing fungal hyphae and spores in 10% potassium hydroxide on direct microscopy. Wood's lamp examination was carried out and the scrapings were cultured on Sabouraud's agar. A detailed dermatological examination was performed for evidence of fungal infection elsewhere in the body. SPSS 19 was used for data analysis. Male-to-female ratio was 1.1:1 and age ranged from 1 to 14 years.The commonest clinical type gray patch was observed in 71 (35.1%) of the patients, black dot in 63 (31.2%), kerion in 50 (24.8%), favus in 10 (5.0%), diffuse pustular in 6 (3.0%), and diffuse scale in 2 (1.0%) patients. The most frequent species grown on culture was Trichophyton (T). Soudanense, followed by T. Tonsurans, T. Schoenleinii, and T. Mentagrophytes respectively. Most of the patients of Tinea capitis presented with gray patch and black dot variety. The most common species identified by culture was Trichophyton Soudanense. Disease was equal in both gender and predominantly affected the population belonging to low and middle socioeconomic class.


Kangiella geojedonensis sp. nov., isolated from seawater.
A Gram-stain-negative, non-motile, non-spore-forming bacterial strain, YCS-5(T), was isolated from seawater off the southern coast of Korea. Strain YCS-5(T) grew optimally at 30 °C and in the presence of 2% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain YCS-5(T) fell within the clade comprising Kangiella species. Strain YCS-5(T) exhibited 16S rRNA gene sequence similarity values of 96.6, 95.7 and 97.9% to the type strains of Kangiella koreensis, Kangiella aquimarina and Kangiella japonica, respectively, and less than 89.8% to strains of other species used in the phylogenetic analysis. Strain YCS-5(T) contained Q-8 as the predominant ubiquinone and iso-C(17:0), iso-C(15:0), iso-C(11:0) 3-OH and iso-C(17:1)ω9c as the major fatty acids. The polar lipid profile of strain YCS-5(T) was similar to that of K. koreensis SW-125(T), with phosphatidylglycerol and an unidentified aminolipid as major polar lipids. The DNA G+C content was 47 mol%. The mean DNA-DNA relatedness value between strain YCS-5(T) and K. japonica JCM 16211(T) was 12%. Differential phenotypic properties and the phylogenetic and genetic distinctiveness of strain YCS-5(T) demonstrated that this strain is distinguishable from other Kangiella species. On the basis of the data presented, strain YCS-5(T) is considered to represent a novel species of the genus Kangiella, for which the name Kangiella geojedonensis sp. nov. is proposed; the type strain is YCS-5(T) (=KCTC 23420(T)=CCUG 60526(T)).


P2Y2R deficiency attenuates experimental autoimmune uveitis development.
We aimed to study the role of the nucleotide receptor P2Y2R in the development of experimental autoimmune uveitis (EAU). EAU was induced in P2Y2+/+ and P2Y2-/- mice by immunization with IRBP peptide or by adoptive transfer of in vitro restimulated semi-purified IRBP-specific enriched T lymphocytes from spleens and lymph nodes isolated from native C57Bl/6 or P2Y2+/+ and P2Y2-/- immunized mice. Clinical and histological scores were used to grade disease severity. Splenocytes and lymph node cell phenotypes were analyzed using flow cytometry. Semi-purified lymphocytes and MACS-purified CD4+ T lymphocytes from P2Y2+/+ and P2Y2-/- immunized mice were tested for proliferation and cytokine secretion. Our data show that clinical and histological scores were significantly decreased in IRBP-immunized P2Y2-/- mice as in P2Y2-/- mice adoptively transfered with enriched T lymphocytes from C57Bl/6 IRBP-immunized mice. In parallel, naïve C57Bl/6 mice adoptively transferred with T lymphocytes from P2Y2-/- IRBP-immunized mice also showed significantly less disease. No differences in term of spleen and lymph node cell recruitment or phenotype appeared between P2Y2-/- and P2Y2+/+ immunized mice. However, once restimulated in vitro with IRBP, P2Y2-/- T cells proliferate less and secrete less cytokines than the P2Y2+/+ one. We further found that antigen-presenting cells of P2Y2-/- immunized mice were responsible for this proliferation defect. Together our data show that P2Y2-/- mice are less susceptible to mount an autoimmune response against IRBP. Those results are in accordance with the danger model, which makes a link between autoreactive lymphocyte activation, cell migration and the release of danger signals such as extracellular nucleotides.


On Visually-Grounded Reference Production: Testing the Effects of Perceptual Grouping and 2D/3D Presentation Mode.
When referring to a target object in a visual scene, speakers are assumed to consider certain distractor objects to be more relevant than others. The current research predicts that the way in which speakers come to a set of relevant distractors depends on how they perceive the distance between the objects in the scene. It reports on the results of two language production experiments, in which participants referred to target objects in photo-realistic visual scenes. Experiment 1 manipulated three factors that were expected to affect perceived distractor distance: two manipulations of perceptual grouping (region of space and type similarity), and one of presentation mode (2D vs. 3D). In line with most previous research on visually-grounded reference production, an offline measure of visual attention was taken here: the occurrence of overspecification with color. The results showed effects of region of space and type similarity on overspecification, suggesting that distractors that are perceived as being in the same group as the target are more often considered relevant distractors than distractors in a different group. Experiment 2 verified this suggestion with a direct measure of visual attention, eye tracking, and added a third manipulation of grouping: color similarity. For region of space in particular, the eye movements data indeed showed patterns in the expected direction: distractors within the same region as the target were fixated more often, and longer, than distractors in a different region. Color similarity was found to affect overspecification with color, but not gaze duration or the number of distractor fixations. Also the expected effects of presentation mode (2D vs. 3D) were not convincingly borne out by the data. Taken together, these results provide direct evidence for the close link between scene perception and language production, and indicate that perceptual grouping principles can guide speakers in determining the distractor set during reference production.


Determination and Assessment of the Toxic Heavy Metal Elements Abstracted from the Traditional Plant Cosmetics and Medical Remedies: Case Study of Libya.
Henna and walnut tree bark are widely used by Libyan women as cosmetics. They may contain lead (Pb), cadmium (Cd) and arsenic (As), which, in turn, pose a high risk to their health. This study aims to determine the levels of Pb, Cd and As in henna and walnut tree bark products sold in Libyan markets. The products were analyzed for their Pb, Cd and As content by using inductively coupled plasma mass spectrometry (ICP-MS) after a microwave acid digestion. The results showed a significant difference between the henna and walnut tree bark samples in terms of their heavy metals content (p < 0.05). The highest heavy metal concentrations were observed in the walnut tree bark samples whereas the lowest was observed in the henna samples. In addition, 60% of the henna and 90% of the walnut tree bark samples contained Pb levels and approximately 80% of the henna and 90% the walnut tree bark samples contained Cd levels, which are much higher than the tolerance limit. However, As concentrations in all the samples were lower. The results indicated that such cosmetics expose consumers to high levels of Pb and Cd and hence, to potential health risks. Thus, studying the sources and effects of heavy metals in such cosmetics is strongly recommended.


Effect of pancreas transplantation on the prevention of nephropathy in alloxan-induced diabetic rats.
We studied the effects of pancreas transplantation on kidney lesions of rats with alloxan-induced diabetes. Ninety inbred male Lewis rats were randomly assigned to 3 experimental groups: group NC included 30 non-diabetic control rats, group DC included 30 alloxan-induced diabetic control rats, and group PT included 30 alloxan-induced diabetic rats that received pancreas transplants from normal donor Lewis rats. Each group was further divided into 3 subgroups of 10 rats which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical and laboratory parameters during these periods were documented. The kidneys of 5 rats in each subgroup were studied and 50 glomeruli and tubules from each kidney were analyzed by light microscopy by two different investigators in a double-blind study. There was progressive glomerular basement membrane thickening (GBMT), mesangial enlargement (ME), and Bowman's capsule thickening (BCT) in kidneys of rats in the 3 experimental groups during follow-up. These alterations were significantly higher in DC rats (GBMT: 1.99 +/- 0.31; ME: 2.00 +/- 0.33; BCT: 1.88 +/- 0.27) when compared to NC (GBMT: 1.54 +/- 0.30; ME: 1.56 +/- 0.47; BCT: 1.36 +/- 0.35) and PT rats (GBMT: 1.49 +/- 0.29; ME: 1.57 +/- 0.36; BCT: 1.35 +/- 0.28) at 6 months (P < 0.01). The extent of GBMT, ME, and BCT observed in DC rats at 1 and 3 months was not significantly different from NC and PT rats. The amount of kidney lesions in PT rats was similar to that of NC rats and lower than those of DC rats at 6 months (P < 0.01). In addition, Armanni-Ebstein lesions of the tubules (AE) and tubular lumen protein (PRO) observed in DC rats were not present in NC or PT rats. We conclude that pancreas transplantation in alloxan-induced diabetic rats prevents the development of kidney lesions beginning at 6 months after transplantation.


The effect of modified citrus pectin on urinary excretion of toxic elements.
This study was undertaken to evaluate the effect of modified citrus pectin (MCP) on the urinary excretion of toxic elements in healthy individuals. MCP is a reduced molecular weight pectin (weight-average molar mass = 15,400) that is mostly linear homogalacturonan with a 3.8% degree of esterification and approximately 10% rhamnogalacturonan II based on the presence of 2-keto-3-deoxy-octonic acid. Subjects ingested 15 g of MCP (PectaSol, EcoNugenics Inc., Santa Rosa, California 95407) each day for 5 days and 20 g on day 6. Twenty-four hour urine samples were collected on day 1 and day 6 for comparison with baseline. The urine samples were analysed for toxic and essential elements. In the first 24 h of MCP administration the urinary excretion of arsenic increased significantly (130%, p < 0.05). On day 6, urinary excretion was increased significantly for cadmium (150%, p < 0.05). In addition, lead showed a dramatic increase in excretion (560%, p < 0.08). This pilot trial provides the first evidence that oral administration of MCP increases significantly the urinary excretion of toxic metals in subjects with a 'normal' body load of metals. It is suggested that systemic chelation of toxic metals by MCP may in part be attributable to the presence of rhamnogalacturonan II, which has been shown previously to chelate metals.


Bioprospective of Sorbus aucuparia leaf extract in development of silver and gold nanocolloids.
At the present time the bioprospective field is a dynamic area of research. The rapid biosynthesis of silver and gold nanoparticles without using toxic chemicals is reported here. Sorbus aucuparia is omnipresent in Europe. The aqueous leaves extract of the plant were used as reducing agent for the synthesis of silver and gold nanoparticles from their salt solutions. The synthesized nanoparticles were spherical, triangular and hexagonal in shape with an average size of 16 and 18nm for silver and gold, respectively. Different extract quantities, metal concentrations, temperatures and contact times were investigated to find their effect on nanoparticles synthesis. The resulting silver and gold nanoparticles were characterized by transmission electron microscopy (TEM), UV-vis spectroscopy, X-ray diffraction (XRD), energy dispersive X-ray (EDX) and Fourier transform infrared spectroscopy (FTIR). The concentration of residual silver and gold ions was measured by Inductively Coupled Plasma (ICP) spectroscopy. Silver and gold nanoparticle suspensions gave maximum UV-vis absorbance at 446 and 560nm, respectively. The XRD data illustrated characteristic diffraction patterns of the elemental silver and gold phases and the average size of the crystallites were estimated from the peak profiles by Scherrer method. FTIR spectra of the leaf extract before and after the development of nanoparticles were determined to allow identification of possible functional groups responsible for the conversion of metal ions to metal nanoparticles.


Uncinaria sanguinis sp. n. (Nematoda: Ancylostomatidae) from the endangered Australian sea lion, Neophoca cinerea (Carnivora: Otariidae).
This study investigates the identity of hookworms parasitising the Australian sea lion, Neophoca cinerea (Péron), from three colonies in South Australia, Australia. The Australian sea lion is at risk of extinction because its population is small and genetically fragmented. Using morphological and molecular techniques, we describe a single novel species, Uncinaria sanguinis sp. n. (Nematoda: Ancylostomatidae). The new species is most similar to hookworms also parasitic in otariid hosts, Uncinaria lucasi Stiles, 1901 and Uncinaria hamiltoni Baylis, 1933. Comparative morphometrics offered limited utility for distinguishing between species within this genus whilst morphological features and differences in nuclear ribosomal DNA sequences delineated U. sanguinis sp. n. from named congeners. Male specimens of U. sanguinis sp. n. differ from U. lucasi and U. hamiltoni by relatively shorter anterolateral and externodorsal rays, respectively, and from other congeners by the relative lengths and angulations of bursal rays, and in the shape of the spicules. Female specimens of U. sanguinis sp. n. are differentiated from Uncinaria spp. parasitic in terrestrial mammals by differences in vulval anatomy and the larger size of their eggs, although are morphologically indistinguishable from U. lucasi and U. hamiltoni. Molecular techniques clearly delimited U. sanguinis sp. n. as a distinct novel species. Obtaining baseline data on the parasites of wildlife hosts is important for the investigation of disease and the effective implementation and monitoring of conservation management.


Standardization of monoclonal antibodies for use in autologous bone marrow transplantation for common acute lymphoblastic leukemia.
Two monoclonal antibodies suitable for leukemia cell purging of remission bone marrow from patients with common acute lymphoblastic leukemia (common-ALL) are described. WM-21, reacting with the gp 100 common-ALL associated antigen (CALLA), and FMC-8, reactive with a p24 surface antigen, both bind to the majority of leukemic blast cells from cases of common ALL, and promote complement-mediated lysis of CALLA+ leukemias and cell lines. After initial dye exclusion studies to standardize antibody and rabbit complement concentrations and incubation times, an in vitro plating assay using CALLA+ p24+ cell lines was used to investigate the lytic ability of monoclonal antibody treatment. Incubation with WM-21, FMC-8, and complement produced up to 5 logs inhibition of growth in this system. Under similar conditions, no inhibition of in vitro growth of normal bone marrow myeloid progenitor cells was seen. These antibodies therefore appear to be useful therapeutic reagents for removing residual common ALL blast cells from bone marrow prior to autologous marrow transplantation.


Orthogonal Reversed-Phase C18 and Pentafluorophenyl HPLC Separation for Phytochemical Profiling of Serrulatanes in Eremophila denticulata.
Serrulatanes constitute a class of unique diterpenoids derived from all-Z nerylneryl diphosphate rather than the conventional all-E diterpenoid precursor geranylgeranyl diphosphate and thus provide an intriguing expansion of the chemical space of plant specialized metabolites. Plants of the Australian Eremophila genus are rich sources of structurally diverse serrulatanes. Here, we report the identification of 15 hitherto undescribed serrulatanes (eremoculatanes A-N), together with 16 previously reported compounds, from the EtOAc extract of Eremophila denticulata leaves. Isolation was performed by a combined use of systematic HPLC-PDA-HRMS-based phytochemical profiling and orthogonal reversed-phase C18 and pentafluorophenyl separations. Among the new compounds isolated, eremoculatane A contains a C12 backbone, for which the configuration was established by comparison of experimentally measured and theoretically calculated ECD spectra. The antihyperglycemic and antibacterial activities of the E. denticulata extract were investigated by high-resolution inhibition profiling, and they indicated that major constituents, mainly serrulatanes and flavonoids, contributed to the observed activity of the extract. One flavonoid, eupafolin (4), displayed moderate α-glucosidase inhibitory activity with an IC50 value of 41.3 μM, and four serrulatanes (8, 9, 19g, and 19j) showed more than 50% PTP1B inhibition at 200 μM.


Determination of some trace elements in food and soil samples by atomic absorption spectrometry after coprecipitation with holmium hydroxide.
The determination of trace elements in food and soil samples by atomic absorption spectrometry was investigated. A coprecipitation procedure with holmium hydroxide was used for separation-preconcentration of trace elements. Trace amounts of copper(II), manganese(II), cobalt(II), nickel(ll), chromium(lll), iron(Ill), cadmium(ll), and lead(ll) ions were coprecipitated with holmium hydroxide in 2.0 M NaOH medium. The optimum conditions for the coprecipitation process were investigated for several commonly tested experimental parameters, such as amount of coprecipitant, effect of standing time, centrifugation rate and time, and sample volume. The precision, based on replicate analysis, was lower than 10% for the analytes. In order to verify the accuracy of the method, the certified reference materials BCR 141 R calcareous loam soil and CRM 025-050 soil were analyzed. The procedure was successfully applied for separation and preconcentration of the investigated ions in various food and soil samples. An amount of the solid samples was decomposed with 15 mL concentrated hydrochloric acid-concentrated nitric acid (3 + 1). The preconcentration procedure was then applied to the final solutions. The concentration of trace elements in samples was determined by atomic absorption spectrometry.


Modified pectin with anticancer activity in breast cancer: A systematic review.
Breast cancer is the most commonly diagnosed cancer among women worldwide. The current pharmacological treatments for breast cancer have numerous adverse effects and are not always effective. Recently, the anticancer activity of modified pectins (MPs) against various types of cancers, including breast cancer, has been investigated. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, including scientific articles from the last 22 years that measured the anticancer activity of MPs on breast cancer. The articles were searched in four databases with the terms: "modified pectin" and "breast cancer". Nine articles were included, five in vitro and four mixed (in vitro and in vivo). Different models and methods by which anticancer activity was measured were analyzed. All the studies reported positive results in both cell lines and in vivo murine models of breast cancer. The extracted data suggest a positive effect and provide mechanistic evidence of MPs in the treatment of breast cancer. However, as limited number of studies were included, further in vivo studies are required to obtain more conclusive preclinical evidence.


Effect of Intravenous Thrombolysis on Clot Survival during Mechanical Thrombectomy in Acute Large Vessel Occlusion Strokes.
The benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke is uncertain. Conventional metrics of final modified thrombolysis in cerebral ischemia (mTICI) score and 90-d modified Rankin Scale may be insensitive to IVT effects on procedural complexity and duration. To study the effect of IVT prior to MT on clot survival. We performed a single-center retrospective analysis of 257 acute stroke patients with LVO undergoing MT and analyzed the effect of IVT prior to MT using a novel, pass-by-pass clot survival methodology. The use of IVT was associated with a significantly lower number of passes to attain mTICI 2B or greater (P = .002) or mTICI 3 (P = .039) reperfusion. The number of patients who achieved mTICI 2B or greater after the first pass was significantly higher in the IVT group (P = .003). This increased rate of reperfusion persisted into subsequent passes. IVT prior to MT reduces the number of thrombectomy passes required to achieve mTICI 2B or mTICI 3 reperfusion. This information should be considered as the merits of IVT prior to MT are debated.


Relativistic Real-Time Time-Dependent Equation-of-Motion Coupled-Cluster.
We present a relativistic time-dependent equation-of-motion coupled-cluster with single and double excitations (TD-EOM-CCSD) formalism. Unlike other explicitly time-dependent quantum chemical methods, the present approach considers the time correlation function of the dipole operator, as opposed to the expectation value of the time-dependent dipole moment. We include both scalar relativistic effects and spin-orbit coupling variationally in this scheme via the use of the exact two-component (X2C) wave function as the reference that enters the coupled-cluster formalism. In order to evaluate the accuracy of X2C-TD-EOM-CCSD, we compare zero-field splitting in atomic absorption spectra of open-shell systems (Na, K, Mg+, and Ca+) with values obtained from experiment. In closed-shell species (Na+, K+, Mg2+, and Ca2+), we observe singlet-triplet mixing in the X2C-TD-EOM-CC calculations, which results from the use of the X2C reference. The effects of the X2C reference are evaluated by comparing spectra derived from X2C-TD-EOM-CC calculations to those from TD-EOM-CC calculations using a complex generalized Hartree-Fock ([Formula: see text]-GHF) reference.


Etiological spectrum of persistent fever in the tropics and predictors of ubiquitous infections: a prospective four-country study with pooled analysis.
Persistent fever, defined as fever lasting for 7 days or more at first medical evaluation, has been hardly investigated as a separate clinical entity in the tropics. This study aimed at exploring the frequencies and diagnostic predictors of the ubiquitous priority (i.e., severe and treatable) infections causing persistent fever in the tropics. In six different health settings across four countries in Africa and Asia (Sudan, Democratic Republic of Congo [DRC], Nepal, and Cambodia), consecutive patients aged 5 years or older with persistent fever were prospectively recruited from January 2013 to October 2014. Participants underwent a reference diagnostic workup targeting a pre-established list of 12 epidemiologically relevant priority infections (i.e., malaria, tuberculosis, HIV, enteric fever, leptospirosis, rickettsiosis, brucellosis, melioidosis, relapsing fever, visceral leishmaniasis, human African trypanosomiasis, amebic liver abscess). The likelihood ratios (LRs) of clinical and basic laboratory features were determined by pooling all cases of each identified ubiquitous infection (i.e., found in all countries). In addition, we assessed the diagnostic accuracy of five antibody-based rapid diagnostic tests (RDTs): Typhidot Rapid IgM, Test-itTM Typhoid IgM Lateral Flow Assay, and SD Bioline Salmonella typhi IgG/IgM for Salmonella Typhi infection, and Test-itTM Leptospira IgM Lateral Flow Assay and SD Bioline Leptospira IgG/IgM for leptospirosis. A total of 1922 patients (median age: 35 years; female: 51%) were enrolled (Sudan, n = 667; DRC, n = 300; Nepal, n = 577; Cambodia, n = 378). Ubiquitous priority infections were diagnosed in 452 (23.5%) participants and included malaria 8.0% (n = 154), tuberculosis 6.7% (n = 129), leptospirosis 4.0% (n = 77), rickettsiosis 2.3% (n = 44), enteric fever 1.8% (n = 34), and new HIV diagnosis 0.7% (n = 14). The other priority infections were limited to one or two countries. The only features with a positive LR ≥ 3 were diarrhea for enteric fever and elevated alanine aminotransferase level for enteric fever and rickettsiosis. Sensitivities ranged from 29 to 67% for the three RDTs targeting S. Typhi and were 9% and 16% for the two RDTs targeting leptospirosis. Specificities ranged from 86 to 99% for S. Typhi detecting RDTs and were 96% and 97% for leptospirosis RDTs. Leptospirosis, rickettsiosis, and enteric fever accounted each for a substantial proportion of the persistent fever caseload across all tropical areas, in addition to malaria, tuberculosis, and HIV. Very few discriminative features were however identified, and RDTs for leptospirosis and Salmonella Typhi infection performed poorly. Improved field diagnostics are urgently needed for these challenging infections. NCT01766830 at ClinicalTrials.gov.


Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid.
Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.


[Clinical and pathological analysis of chronic rejection following orthotopic liver transplantation].
To investigate the clinical manifestation and pathological features of chronic rejection (CR) and the management of CR after orthotopic liver transplantation (OLT). From January 2004 to December 2006, there were 516 patients who had undergone OLT. All the clinical and pathological data were collected and retrospectively studied. Clinical manifestation, histopathological feature, diagnosis and anti-rejection treatment of CR were summarized and analyzed. The incidence of CR was 2.3% (12/516), including 7 cases with early phases of CR and 5 cases with late phases of CR. The main pathological changes of CR were the vanishing bile duct syndrome and obliterative arteriopathy;and the early stage of CR were the damage of inter lobular bile duct, necrotic inflammation in central lobule, and inflammatory cells infiltration in portal area. Among 12 patients with CR, 7 cases with early CR were reversed by methylprednisolone (MP) pulse treatment and adjusting immunosuppressant dose, including 2 cases of whom were prescribed OKT3 treatment and 2 cases treated by ATG, and 5 cases with late CR underwent liver retransplantation (re-LT). Two patients died from infection, 1 case died from multiple organ failure in perioperative period after re-LT, another 2 cases were cured by re-LT, and the CR related mortality was 25.0% (3/12). Chronic rejection following OLT is lack of typical clinical manifestation and pathological features, and the pathological changes can overlap and coexist. Post-transplant liver biopsy and graft specimen after re-LT is still "gold standard" to CR diagnosis. Some of early CRs can be reversed by early diagnosis and early treatment; for late CR recipient, re-LT should be considered.


Identifying Escherichia coli genes involved in intrinsic multidrug resistance.
Multidrug resistance is a major cause of clinical failure in treating bacterial infections. Increasing evidence suggests that bacteria can resist multiple antibiotics through intrinsic mechanisms that rely on gene products such as efflux pumps that expel antibiotics and special membrane proteins that block the penetration of drug molecules. In this study, Escherichia coli was used as a model system to explore the genetic basis of intrinsic multidrug resistance. A random mutant library was constructed in E. coli EC100 using transposon mutagenesis. The library was screened by growth measurement to identify the mutants with enhanced or reduced resistance to chloramphenicol (Cm). Out of the 4,000 mutants screened, six mutants were found to be more sensitive to Cm and seven were more resistant compared to the wild-type EC100. Mutations in 12 out of the 13 mutants were identified by inverse polymerase chain reaction. Mutants of the genes rob, garP, bipA, insK, and yhhX were more sensitive to Cm compared to the wild-type EC100, while the mutation of rhaB, yejM, dsdX, nagA, yccE, atpF, or htrB led to higher resistance. Overexpression of rob was found to increase the resistance of E. coli biofilms to tobramycin (Tob) by 2.7-fold, while overexpression of nagA, rhaB, and yccE significantly enhanced the susceptibility of biofilms by 2.2-, 2.5-, and 2.1-fold respectively.


Non-tuberculous mycobacterial keratitis: a study of 22 cases.
To investigate causes and clinical findings of non-tuberculous mycobacterial keratitis, and to study its response to topical antibiotic therapy and surgical extirpative keratectomy. A single centre, retrospective review of 22 patients with non-tuberculous mycobacterial keratitis seen in a 3 year period. Laboratory diagnoses were established with Ziehl-Nielsen acid fast staining and Löwenstein-Jensen cultures. In 20 patients (91%), there was an antecedent history of foreign body eye trauma (18 patients) or elective surgery (two patients). There were 19 cases of Mycobacterium chelonei, and three of M fortuitum. Clinical signs included epithelial defects, satellite or ring stromal infiltrates, crystalline keratopathy, and hypopyon. For topical antibiotic therapy, 20 patients received amikacin, while one patient received rifampin and another received ciprofloxacin, each in accordance with the results of the in vitro drug sensitivities. An extirpative keratectomy was performed in 15 cases; four of these cases additionally required a temporary conjunctival flap in order to finally eradicate the infection. At the end of the follow up period (median 18 months; range 3 months to 3 years) all eyes were stable and free of infection, with 19 (86%) having final visual acuities of 20/200 or better. Early clinical recognition and prompt laboratory diagnosis, together with aggressive topical antibiotic therapy and early keratectomy, may shorten morbidity and improve the clinical outcome of non-tuberculous mycobacterial keratitis.


Reduced-Beclin1-Expressing Mice Infected with Zika-R103451 and Viral-Associated Pathology during Pregnancy.
Here, we used a mouse model with defective autophagy to further decipher the role of Beclin1 in the infection and disease of Zika virus (ZIKV)-R103451. Hemizygous (Becn1+/-) and wild-type (Becn1+/+) pregnant mice were transiently immunocompromised using the anti-interferon alpha/beta receptor subunit 1 monoclonal antibody MAR1-5A3. Despite a low mortality rate among the infected dams, 25% of Becn1+/- offspring were smaller in size and had smaller, underdeveloped brains. This phenotype became apparent after 2-to 3-weeks post-birth. Furthermore, the smaller-sized pups showed a decrease in the mRNA expression levels of insulin-like growth factor (IGF)-1 and the expression levels of several microcephaly associated genes, when compared to their typical-sized siblings. Neuronal loss was also noticeable in brain tissues that were removed postmortem. Further analysis with murine mixed glia, derived from ZIKV-infected Becn1+/- and Becn1+/+ pups, showed greater infectivity in glia derived from the Becn1+/- genotype, along with a significant increase in pro-inflammatory molecules. In the present study, we identified a link by which defective autophagy is causally related to increased inflammatory molecules, reduced growth factor, decreased expression of microcephaly-associated genes, and increased neuronal loss. Specifically, we showed that a reduced expression of Beclin1 aggravated the consequences of ZIKV infection on brain development and qualifies Becn1 as a susceptibility gene of ZIKV congenital syndrome.


Study of the Addition Mechanism of 1H-Indazole and Its 4-, 5-, 6-, and 7-Nitro Derivatives to Formaldehyde in Aqueous Hydrochloric Acid Solutions.
The reaction of NH-indazoles with formaldehyde in aqueous hydrochloric acid has been experimentally studied by solution and solid-state nuclear magnetic resonance (NMR) and crystallography. The mechanism of the formation of N1-CH2OH derivatives was determined. For the first time, 2-substituted derivatives have been characterized by multinuclear NMR. Theoretically, calculations with gauge-invariant atomic orbitals (GIAOs) at the Becke three-parameter (exchange) Lee-Yang-Parr B3LYP/6-311++G(d,p) level have provided a sound basis for the experimental observations. The first X-ray structures of four (1H-indazol-1-yl)methanol derivatives are reported.


Indian contribution toward biomedical research and development in COVID-19: A systematic review.
COVID-19 pandemic led to an unprecedented collaborative effort among industry, academia, regulatory bodies, and governments with huge financial investments. Scientists and researchers from India also left no stone unturned to find therapeutic and preventive measures against COVID-19. Indian pharmaceutical companies are one of the leading manufacturers of vaccine in the world, are utilizing its capacity to its maximum, and are one among the forerunners in vaccine research against COVID-19 across the globe. In this systematic review, the information regarding contribution of Indian scientists toward COVID-19 research has been gathered from various news articles across Google platform apart from searching PubMed, WHO site, COVID-19 vaccine tracker, CTRI, clinicaltrials.gov, and websites of pharmaceutical companies. The article summarizes and highlights the various therapeutic and vaccine candidates, diagnostic kits, treatment agents, and technology being developed and tested by Indian researcher community against COVID-19.


Amyloids of α-Synuclein Promote Chemical Transformations of Neuronal Cell Metabolites.
The assembly of α-synuclein into cross-β structured amyloid fibers results in Lewy body deposits and neuronal degeneration in Parkinson's disease patients. As the cell environment is highly crowded, interactions between the formed amyloid fibers and a range of biomolecules can occur in cells. Although amyloid fibers are considered chemically inert species, recent in vitro work using model substrates has shown α-synuclein amyloids, but not monomers, to catalyze the hydrolysis of ester and phosphoester bonds. To search for putative catalytic activity of α-synuclein amyloids on biologically relevant metabolites, we here incubated α-synuclein amyloids with neuronal SH-SY5Y cell lysates devoid of proteins. LC-MS-based metabolomic (principal component and univariate) analysis unraveled distinct changes in several metabolite levels upon amyloid (but not monomer) incubation. Of 63 metabolites identified, the amounts of four increased (3-hydroxycapric acid, 2-pyrocatechuic acid, adenosine, and NAD), and the amounts of seventeen decreased (including aromatic and apolar amino acids, metabolites in the TCA cycle, keto acids) in the presence of α-synuclein amyloids. Many of these metabolite changes match what has been reported previously in Parkinson's disease patients and animal-model metabolomics studies. Chemical reactivity of α-synuclein amyloids may be a new gain-of-function that alters the metabolite composition in cells and, thereby, modulates disease progression.


Histological examination of vascular lesions caused by stent implantation in humans and in comparative experimental animal model.
A comparative analysis of human and experimental animal (canine) tissues was performed to characterize and describe cellular and histological responses during the processes of newly forming intravascular tissues after stent implantation. Routine histological and immunohistochemical evaluation of 20 human samples and 9 samples from animal models were used one day, one week and one month after the stent implantation. After one day of implantation, there was no difference between the human and canine peripheral arteries, suggesting a similar cellular and histological response in the early phase. In contrast, after one week of implantation, during the proliferative phase the repairing human tissue showed less intensive production of inflammatory cells and more intensive increase in number of vascular cells than did the canine model. In addition, cellular changes normally restituted by the end of one month in canine peripheral arteries, but vascular cells persisted in human atherosclerotic arteries. In conclusion, results of this study suggest differences in both phases of vascular repair in the post-stented period, because both proliferative and regressive phases showed histological differences in canine and human samples. In canine, the restitution of vascular wall was completed by the end of first month but persistent vascular cell proliferation was visible in the human peripheral arteries. It can be suggested that delayed cellular response might indicate restenosis but also can be considered considered as a progression of the original arterial disease.


Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role.
Uncontrolled proliferation is a hallmark of malignant tumour growth. Its prognostic role in non-small cell lung cancer (NSCLC) has been investigated in numerous studies with controversial results. We aimed to resolve these controversies by assessing the Ki-67 proliferation index (PI) in three large, independent NSCLC cohorts. Proliferation index was retrospectively analysed by immunohistochemistry in a cohort of 1065 NSCLC and correlated with clinicopathological data including outcome and therapy. RESULTS were validated in two independent cohorts of 233 squamous cell carcinomas (SQCC) and 184 adenocarcinomas (ADC). Proliferation index (overall mean: 40.7%) differed significantly according to histologic subtypes with SQCC showing a mean PI (52.8%) twice as high as ADC (25.8%). In ADC PI was tightly linked to growth patterns. In SQCC and ADC opposing effects of PI on overall (OS), disease-specific and disease-free survival were evident, in ADC high PI (optimised validated cut-off: 25%) was a stage-independent negative prognosticator (hazard ratio, HR OS: 1.56, P=0.004). This prognostic effect was largely attenuated by adjuvant radio-/chemotherapy. In SQCC high PI (optimised validated cut-off: 50%) was associated with better survival (HR OS: 0.65, P=0.007). Our data demonstrate that PI is a clinically meaningful biomarker in NSCLC with entity-dependent cut-off values that allow reliable estimation of prognosis and may potentially stratify ADC patients for the need of adjuvant therapy.


In vivo/in vitro correlations for four differently dissolving ketorolac tablets.
This study assesses whether in vitro immediate release ketorolac tablet dissolution profiles (utilizing the recently proposed USP dissolution test for ketorolac tablets) can be correlated with in vivo plasma pharmacokinetic parameters. Four batches of ketorolac tablets were utilized: a ketorolac tablet batch that demonstrated a rapid dissolution rate during USP in vitro dissolution testing, two tablet batches that were manufactured such that they dissolved at moderate rates, and a tablet batch that was manufactured such that it dissolved at a distinctly slow rate. The single-dose mean pharmacokinetic characteristics and relative bioavailability of the four different 10 mg ketorolac tromethamine tablets were evaluated in 12 healthy volunteers in a randomized study of Latin square design. The amount dissolved of the various tablets at 10, 20, and 30 min was in the order of fast-dissolving tablets > medium-1-dissolving tablets = medium-2-dissolving tablets > slow-dissolving tablets. In general, the profiles of the average plasma concentrations for ketorolac were similar for the fast- and the two medium-dissolving tablet batches (even though a statistically significant difference was found between the tmax of the fast-dissolving tablet and one of the medium-dissolving tablet batches). The mean plasma concentrations for the slow-dissolving tablet, however, reached peak levels much later, with the peak also being significantly smaller. There were no statistically significant differences in the total AUC or in the mean plasma half-lives among the four formulations. Good correlations were obtained for mean tmax versus the percentage dissolved at 20, 30, and 45 min. Correlations were generally weaker for percentage dissolved versus Cmax or percentage bioavailability. This indicates that in vitro dissolution testing for immediate release ketorolac tablets can be a useful indicator of in vivo time to maximum plasma concentration when comparing similarly formulated tablets. Further, the proposed USP dissolution test and specification would have appropriately failed the slow-dissolving tablet batch, which demonstrated a significantly slower rate of absorption as per tmax and Cmax.


Analysis of [FeFe]-hydrogenase genes for the elucidation of a hydrogen-producing bacterial community in paddy field soil.
Hydrogen (H2) is one of the most important intermediates in the anaerobic decomposition of organic matter. Although the microorganisms consuming H2 in anaerobic environments have been well documented, those producing H2 are not well known. In this study, we elucidated potential members of H2 -producing bacteria in a paddy field soil using clone library analysis of [FeFe]-hydrogenase genes. The [FeFe]-hydrogenase is an enzyme involved in H2 metabolism, especially in H2 production. A suitable primer set was selected based on the preliminary clone library analysis performed using three primer sets designed for the [FeFe]-hydrogenase genes. Soil collected in flooded and drained periods was used to examine the dominant [FeFe]-hydrogenase genes in the paddy soil bacteria. In total, 115 and 108 clones were analyzed from the flooded and drained paddy field soils, respectively. Homology and phylogenetic analysis of the clones showed the presence of diverse [FeFe]-hydrogenase genes mainly related to Firmicutes, Deltaproteobacteria, and Chloroflexi. Predominance of Deltaproteobacteria and Chloroflexi suggests that the distinct bacterial community possessed [FeFe]-hydrogenase genes in the paddy field soil. Our study revealed the potential members of H2 -producing bacteria in the paddy field soil based on their genetic diversity and the distinctiveness of the [FeFe]-hydrogenase genes.


Iodine content of commercially-prepared cat foods.
Twenty-eight varieties of commercially-available cat food (23 canned, 5 dried) were analysed for iodine. The iodine concentration varied from less than 0.37 micromol/kg to 41.8 pmol/kg, wet weight (less than 1.48 micromol/kg to 167 micromol/kg, dry weight). Excessive or insufficient iodine intake or wide swings in iodine intake over prolonged periods may contribute to thyroid disorders in cats.


MicroRNAs as Biomarkers for Animal Health and Welfare in Livestock.
MicroRNAs (miRNAs) are small and highly conserved non-coding RNA molecules that orchestrate a wide range of biological processes through the post-transcriptional regulation of gene expression. An intriguing aspect in identifying these molecules as biomarkers is derived from their role in cell-to-cell communication, their active secretion from cells into the extracellular environment, their high stability in body fluids, and their ease of collection. All these features confer on miRNAs the potential to become a non-invasive tool to score animal welfare. There is growing interest in the importance of miRNAs as biomarkers for assessing the welfare of livestock during metabolic, environmental, and management stress, particularly in ruminants, pigs, and poultry. This review provides an overview of the current knowledge regarding the potential use of tissue and/or circulating miRNAs as biomarkers for the assessment of the health and welfare status in these livestock species.


Metabotropic glutamate receptors in the rat nucleus accumbens contribute to amphetamine-induced locomotion.
This study examined the role played by metabotropic glutamate receptors in the nucleus accumbens in dopamine agonist-induced locomotion. Rats received microinjections into this nucleus of the selective metabotropic glutamate receptor antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine, alone or with amphetamine and their locomotor activity was subsequently measured for 2 hr. None of the doses of (RS)-alpha-methyl-4-carboxyphenylglycine tested (0.025, 0.25, 2.5, or 25 nmol/0.5 microliter/side) when administered alone produced effects on locomotion that differed significantly from those observed after saline. However, when co-injected with amphetamine (6.8 nmol [2.5 micrograms]/side) into the nucleus accumbens, a moderately high dose of (RS)-alpha-methyl-4-carboxyphenylglycine (25 nmol/side) completely blocked, whereas a lower dose (0.25 nmol/side) potentiated the locomotor effects of amphetamine. (RS)-alpha-Methyl-4-carboxyphenylglycine (25 nmol/side) also blocked the locomotor-activating effects of apomorphine (32.9 nmol [10 micrograms]/side), when co-injected with this direct dopamine receptor agonist into the nucleus accumbens. These results suggest that metabotropic glutamate receptors in the nucleus accumbens contribute to amphetamine-induced locomotion and that this contribution may be mediated, at least in part, by metabotropic glutamate receptors expressed by intrinsic nucleus accumbens cells located postsynaptic to dopamine neuron terminals.


Fragility of the Fractional Josephson Effect in Time-Reversal-Invariant Topological Superconductors.
Time-reversal-invariant topological superconductor (TRITOPS) wires host Majorana Kramers pairs that have been predicted to mediate a fractional Josephson effect with 4π periodicity in the superconducting phase difference. We explore the TRITOPS fractional Josephson effect in the presence of time-dependent "local mixing" perturbations that instantaneously preserve time-reversal symmetry. Specifically, we show that just as such couplings render braiding of Majorana Kramers pairs nonuniversal, the Josephson current becomes either aperiodic or 2π periodic (depending on conditions that we quantify) unless the phase difference is swept sufficiently quickly. We further analyze topological superconductors with T^{2}=+1 time-reversal symmetry and reveal a rich interplay between interactions and local mixing that can be experimentally probed in nanowire arrays.


Sex related biases for attending to object color versus object position are reflected in reaction time and accuracy.
Processing of visual features related to objects and space relations occurs within separate cortical streams that interact with selective attention. Such separation has implications for cognitive development because the perception of 'what' and 'where' provide a neural foundation for the development of aspects of higher cognition. Thus, a small attentional bias in early development for attending to one aspect over the other might influence subsequent higher cognitive processing in tasks involving object recognition and space relations. We examined 134 men and women for evidence of an inherent sex-related bias for attending to basic perceptual features related to object discrimination versus object position. Each stimulus consisted of a circle located in one of 9 positions within a surrounding frame. Circles were one of three shades of blue or red. These stimuli were used in a match-to-sample paradigm where participants were required to match circles on the basis of color or spatial position. The first stimulus appeared in the center of the screen for 400 msec and the matching stimulus subsequently appeared for 400 msec oriented 5 degrees to the right or left of center. The same stimuli were used to test the perception of color and position, with order of testing counterbalanced across participants. Results showed significantly longer reaction times in females compared with males, with better accuracy to discriminate color when that color was tested before position. Males showed better accuracy when object position was tested before color discrimination. A second experiment employed the same procedure, but enhanced selective attention by adding an endogenous cue that predicted the right or left location for the appearance of the matching stimulus. This manipulation greatly attenuated the sex differences in reaction time and accuracy compared to Experiment 1, suggesting that the sex-related attentional biases are strongly coupled to bottom-up processing. Overall, the sex related attentional biases toward processing object characteristics versus object position location suggest a differential manifestation of biased competition between the weighted systems of dorsal and ventral stream processing. Results are discussed with how a developmental bias in the processing objects versus space relations may contribute to adult cognitive sex differences in humans and animals.


Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data.
Persistent Pseudomonas aeruginosa (PPA) infection promotes lung function deterioration in children with cystic fibrosis (CF). Although early CF diagnosis through newborn screening (NBS) has been shown to provide nutritional/growth benefit, it is unclear whether NBS lowers the risk of PPA infection and how the effect of NBS vary with age. Modeling the onset age of PPA infection is challenging because 1) the onset age of PPA infection is interval censored in patient registry data; and 2) some risk factors such as NBS may have time-varying effects. This problem fits into the framework of a recently developed Bayesian dynamic Cox model for interval censored data, where each regression coefficient is allowed to be time-varying to an extent determined by the data. Application of the methodology to data from the CF Foundation Patient Registry revealed interesting findings. Compared with patients with meconium ileus or diagnosed through signs or symptoms, patients diagnosed through NBS had significantly lower risks of acquiring PPA infection between age 1 and 2 years, and the benefit in survival rate was found to last up to age 4 years. Two cohorts of five years apart were compared. Patients born in cohort 2003-2004 had significantly lower risks of the PPA infections at any age up to 4 years than those born in 1998-1999. The study supports benefits of NBS on PPA infection in early childhood. In addition, our analyses demonstrate that patients in the more recent cohort had significantly lower risks of acquiring PPA infection up to age 4 years, which suggests improved CF treatment and care over time.


Efficacy of an albendazole feed formulation against bovine gastrointestinal nematodes including arrested larvae of Ostertagia ostertagi.
The efficacy of an albendazole feed premix formulation was compared with that of an albendazole drench suspension for control of gastrointestinal nematodes in 31 beef cattle. The premix (11 cattle) and drench suspension (9 cattle) were found to have similar efficacies at a dosage of 7.5 mg/kg of body weight. When compared with controls (11 cattle), both formulations caused significant (P less than 0.05) reductions in worm counts with an efficacy of 98% or greater against adult Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia punctata, and C pectinata. There was no significant effect against arrested 4th-stage larvae of O ostertagi. Adverse effects of albendazole treatment were not observed, and the premix formulation was readily consumed by cattle.


Endoscopic thyroidectomy using a new bilateral axillo-breast approach.
Endoscopic techniques have recently been applied in thyroid surgery using cervical, axillary, and breast approaches. We modified the axillo-bilateral breast approach (ABBA) and developed the bilateral axillo-breast approach (BABA) to obtain optimal visualization for total thyroidectomy. We used two 12-mm ports through bilateral circumareolar incisions for flexible videoscopy and Harmonic scalpel and two 5-mm ports through both axillae for graspers and dissectors. Thyroidectomy was performed under full visualization of the superior and inferior thyroidal arteries, parathyroid glands, and recurrent laryngeal nerves. After performing 25 ABBA endoscopic thyroid surgeries, we developed BABA and performed 110 operations using this method. The BABA operations included 52 total thyroidectomies, 2 near-total thyroidectomies, 8 subtotal thyroidectomies, 43 lobectomies, and 3 subtotal lobectomies. Pathology revealed 41 benign lesions and 69 cancers. Mean operation time was 165.3 +/- 43.5 minutes. There were 2 cases of conversion to open surgery, 1 due to cancer with capsular invasion and the other due to tracheal injury. Nine postoperative complications developed: transient unilateral vocal cord palsy in 4 cases, transient hypocalcemia in 4 cases, and postoperative infection in 1 case. The 2-month postoperative thyroglobulin level was less than 1 ng/ml in all examined cases of total thyroidectomy. Cosmetic results were excellent. The BABA technique for endoscopic thyroid surgery is a feasible method of total thyroidectomy with a low rate of postoperative complications and, additionally, excellent cosmetic results. Therefore, in selected cases of thyroid cancer, the BABA endoscopic total thyroidectomy should be considered as a valid surgical option.


Swedish snuff (snus) and its effects on oral health: an update
Swedish snus (smokeless moist tobacco) is becoming increasingly popular in Switzerland. Consumption and import of snus are permitted in Switzerland, however, sales were prohibited in 2004 by the European Court. Snus is an addictive nicotine containing product, which additionally contains carcinogenic nitrosamines. Both consumers and oral health professionals are lacking important information on the health consequences. The present paper therefore reviews the impact of snus consumption on oral health. For all snus consumers and particularly for adolescents, more detailed information should be provided by oral health professionals. Specifically with heavy snus users, more frequent follow-up is recommended to detect potential precancerous lesions or neoplasias in early stages.


Predicting adverse outcomes of cardiac surgery with the application of artificial neural networks.
Risk-stratification models based on pre-operative patient and disease characteristics are useful for providing individual patients with an insight into the potential risk of complications and mortality, for aiding the clinical decision for surgery vs non-surgical therapy, and for comparing the quality of care between different surgeons or hospitals. Our study aimed to apply artificial neural networks (ANN) models to predict mortality and morbidity after cardiac surgery, and also to compare the efficacy of this model to that of the logistic regression model and Parsonnet score. The accuracy of the ANN, logistic regression and Parsonnet score in predicting mortality was 83.8%, 87.9% and 78.4%. The accuracy of the ANN, logistic regression and Parsonnet score in predicting major morbidity was 79.0%, 74.3% and 68.6%. The area under the receiver operating characteristic curves (AUC) of the ANN, logistic regression and Parsonnet score in predicting in-hospital mortality were 0.873, 0.852 and 0.829. The AUCs of the ANN, logistic regression and Parsonnet score in predicting major morbidity were 0.852, 0.789 and 0.727. The results showed the ANN models have the best discriminating power in predicting in-hospital mortality and morbidity among these models.


An Interactive Java Statistical Image Segmentation System: GemIdent.
Supervised learning can be used to segment/identify regions of interest in images using both color and morphological information. A novel object identification algorithm was developed in Java to locate immune and cancer cells in images of immunohistochemically-stained lymph node tissue from a recent study published by Kohrt et al. (2005). The algorithms are also showing promise in other domains. The success of the method depends heavily on the use of color, the relative homogeneity of object appearance and on interactivity. As is often the case in segmentation, an algorithm specifically tailored to the application works better than using broader methods that work passably well on any problem. Our main innovation is the interactive feature extraction from color images. We also enable the user to improve the classification with an interactive visualization system. This is then coupled with the statistical learning algorithms and intensive feedback from the user over many classification-correction iterations, resulting in a highly accurate and user-friendly solution. The system ultimately provides the locations of every cell recognized in the entire tissue in a text file tailored to be easily imported into R (Ihaka and Gentleman 1996; R Development Core Team 2009) for further statistical analyses. This data is invaluable in the study of spatial and multidimensional relationships between cell populations and tumor structure. This system is available at http://www.GemIdent.com/ together with three demonstration videos and a manual.


Comparison of different internal fixation models in ankle arthrodesis using 3D finite-element analysis.
The purpose of this study is to use three-dimensional finite-element analysis to better understand the biomechanical features of various internal fixators for ankle arthrodesis. We used finite-element analysis to compare four different types of internal fixations in ankle arthrodesis: Group A had three crossed screws (Ø6.5 mm); Group B had two crossed screws (Ø6.5 mm) and an anterior plate (Ø2.7 mm); Group C only had an anterior anatomical plate (Ø3.5 mm); Group D had one anterior anatomical plate (Ø3.5 mm) and one posterior-lateral screw (Ø6.5 mm). We adopted Ansys 21.0 software to analyze and compare the four types in terms of the displacement of the arthrodesis surface and the stress peak and stress distribution of these models under intorsion, extorsion, dorsiflexion torque, and neutral vertical load. ① Displacement of the arthrodesis surface: In Group A, the maximum displacement was larger than Group D under neutral vertical load and dorsiflexion torque but less than it under intorsion and extorsion torque. In Group B, the maximum displacement against dorsiflexion, neutral vertical load, intorsion, and extorsion was less than that in the other three fixation models. In Group C, the maximum displacement against the above four loading patterns were significantly higher than that in another three fixation models. ② Stress peak and stress distribution: based on the stress distribution of the four models, the peak von Mises stress was concentrated in the central sections of the compression screws, plate joints, and bending parts of the plates. The fixation model consisting of two crossed screws and an anterior outperformed the other three fixation models in terms of biomedical advantages; thus, this model can be deemed a safe and reliable internal fixation approach for ankle arthrodesis.


Migration and dementia: a meta-analysis of epidemiological studies in Europe.
To provide an overview of epidemiological studies of dementia among migrant groups in Europe and to estimate their pooled odds ratio (OR) v. the reference population. Search for articles reporting on incidence or prevalence of dementia among ethnic minorities and migrants in Europe, published before 21 December 2018. We performed several meta-analyses, using a random-effects model, and, when there was no evidence of heterogeneity, a fixed-effects model. We distinguished between all migrants, African-Europeans and Asian-Europeans. We retrieved five population-based surveys and two health care record studies. The latter included one incidence study, the remainder were prevalence studies. The meta-analysis of all studies yielded a pooled OR, adjusted for age and sex, of 1.73 (95% CI 1.42-2.11) for dementia in all migrant groups. However, the pooled OR of population surveys (3.10; 95% CI 2.12-4.51) was significantly higher than that for the health care record studies (OR 0.94; 95% CI 0.80-1.11). The pooled ORs for African-Europeans and Asian-Europeans, based on population surveys, were 2.54 (95% CI 1.70-3.80) and 5.36 (95% CI 2.78-10.31), respectively. The discrepancy between health care record studies and population surveys suggests that many migrants remain undiagnosed. Migrants from Asia and Africa seem to be at significantly increased risk of dementia in Europe. Since the prevalence rates in their countries of origin are generally not higher than those for natives in Europe, there may be a parallel with the epidemiology of schizophrenia.


An architecture for genomics analysis in a clinical setting using Galaxy and Docker.
Next-generation sequencing is used on a daily basis to perform molecular analysis to determine subtypes of disease (e.g., in cancer) and to assist in the selection of the optimal treatment. Clinical bioinformatics handles the manipulation of the data generated by the sequencer, from the generation to the analysis and interpretation. Reproducibility and traceability are crucial issues in a clinical setting. We have designed an approach based on Docker container technology and Galaxy, the popular bioinformatics analysis support open-source software. Our solution simplifies the deployment of a small-size analytical platform and simplifies the process for the clinician. From the technical point of view, the tools embedded in the platform are isolated and versioned through Docker images. Along the Galaxy platform, we also introduce the AnalysisManager, a solution that allows single-click analysis for biologists and leverages standardized bioinformatics application programming interfaces. We added a Shiny/R interactive environment to ease the visualization of the outputs. The platform relies on containers and ensures the data traceability by recording analytical actions and by associating inputs and outputs of the tools to EDAM ontology through ReGaTe. The source code is freely available on Github at https://github.com/CARPEM/GalaxyDocker.