Use of pseudosubstrate affinity to measure active protein kinase A.
Traditional cAMP-dependent protein kinase (also known as protein kinase A [PKA]) assays, which are based on substrate phosphorylation, often have high background activity from other kinases, thereby limiting sensitivity and making it difficult to detect low levels of active PKA in cell lysates. Therefore, a better technique that measures active PKA in crude cell lysates undoubtedly is necessary. We developed an efficient and sensitive assay to compare active PKA levels based on binding of the active PKA catalytic subunit to its pseudosubstrate domain inhibitor (PKI) fused with glutathione S-transferase (GST-PKI). This pseudosubstrate affinity assay can detect variations in the active PKA levels in the presence of common inducers of PKA activity such as forskolin and prostaglandins. It has resolution to detect a concentration-dependent curve of active PKA in a linear range, and it also has sensitivity to detect up to 2.5 ng of active enzyme. An observed change in the binding affinity between PKA and PKI in the presence of the PKA inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89) shows that this assay can be successfully used to measure how active PKA is affected by specific inhibitors. We conclude that this method is a simple, inexpensive, and nonhazardous method to compare active PKA levels with high sensitivity and specificity with negligible background.


Immunization against dental caries.
Dental caries is one of the most common infectious diseases. Of the oral bacteria, mutans streptococci, such as Streptococcus mutans and S. sobrinus, are considered to be causative agents of dental caries in humans. There have been numerous studies of the immunology of mutans streptococci. To control dental caries, dental caries vaccines have been produced using various cell-surface antigens of these organisms. Progress in recombinant DNA technology and peptide synthesis has been applied to the development of recombinant and synthetic peptide vaccines to control dental caries. Significant protective effects against dental caries have been shown in experimental animals, such as mice, rats and monkeys, which have been subcutaneously, orally, or intranasally immunized with these antigens. Only a few studies, however, have examined the efficacy of dental caries vaccines in humans. Recently, local passive immunization using murine monoclonal antibodies, transgenic plant antibodies, egg-yolk antibodies, and bovine milk antibodies to antigens of mutans streptococci have been used to control the colonization of the organisms and the induction of dental caries in human. Such immunization procedures may be a safer approach for controlling human dental caries than active immunization.


Vasospasm after arteriovenous malformation rupture.
Vasospasm and resultant clinical deterioration caused by delayed cerebral ischemia (CD-CDI) are a considerable source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). Although they are a relatively common cause of spontaneous SAH, AVM rupture and ensuing vasospasm are rarely reported. We reviewed our own series of 122 patients with AVMs. Seventy-three patients sustaining 84 hemorrhages were analyzed. In addition, we performed a review of the literature of vasospasm after AVM rupture. Seventy of 84 hemorrhages (83%) had an intraparenchymal component, 27 (32%) a subarachnoid component, and 51 (61%) had an intraventricular component. No patients experienced CD-DCI, and of the 84 hemorrhages reported, only one patient experienced mild angiographic vasospasm (1.1%). Alternatively, this finding represents 1 in 34 cases (2.9%) who underwent definitive angiography between the fourth and fifteenth day after the hemorrhage. Nineteen additional cases of angiographic vasospasm after AVM rupture are reported in the literature. The mean age of these patients was 33 years; there was a 1.25:1 female to male predominance in this group. One-half of these patients had an intraparenchymal hemorrhage, and only 56% of them had SAH. All patients had intraventricular hemorrhage when assessed. The median time to onset of vasospasm was nine days. Across four series, the rate of angiographic spasm after SAH from an AVM was 6.3% (9/142 cases). Even in cases of SAH from AVMs, angiographic vasospasm after AVM rupture is relatively rare. We thus do not recommend empiric delayed angiography to assess for vasospasm in these patients. Nevertheless, it does remain a rare possibility and should be considered in those with CD-DCI.


Decapitation in the long-necked Triassic marine reptile Tanystropheus.
Extreme neck elongation was a common evolutionary strategy among Mesozoic marine reptiles, occurring independently in several lineages1,2. Despite its evolutionary success, such an elongate neck might have been particularly susceptible to predation1, but direct evidence for this possibility has been lacking. Composed of only 13 hyperelongate vertebrae and associated strut-like ribs, the configuration of the long neck of the Triassic archosauromorph Tanystropheus is unique among tetrapods. It was probably stiffened and used to catch prey through an ambush-strategy2. Here, we show that the neck was completely severed in two Tanystropheus specimens (Figure 1), most likely due to a predatory attack, providing vivid evidence of predator-prey interactions among Mesozoic marine reptiles that are rarely preserved in the fossil record. The recurring incidence of decapitation suggests that the elongate neck was a functional weak spot in Tanystropheus, and possibly the long-necked marine reptile bauplan more generally.


Intratumoral injection of hydrogel-embedded nanoparticles enhances retention in glioblastoma.
Intratumoral drug delivery is a promising approach for the treatment of glioblastoma multiforme (GBM). However, drug washout remains a major challenge in GBM therapy. Our strategy, aimed at reducing drug clearance and enhancing site-specific residence time, involves the local administration of a multi-component system comprised of nanoparticles (NPs) embedded within a thermosensitive hydrogel (HG). Herein, our objective was to examine the distribution of NPs and their cargo following intratumoral administration of this system in GBM. We hypothesized that the HG matrix, which undergoes rapid gelation upon increases in temperature, would contribute towards heightened site-specific retention and permanence of NPs in tumors. BODIPY-containing, infrared dye-labeled polymeric NPs embedded in a thermosensitive HG (HG-NPs) were fabricated and characterized. Retention and distribution dynamics were subsequently examined over time in orthotopic GBM-bearing mice. Results demonstrate that the HG-NPs system significantly improved site-specific, long-term retention of both NPs and BODIPY, with co-localization analyses showing that HG-NPs covered larger areas of the tumor and the peri-tumor region at later time points. Moreover, NPs released from the HG were shown to undergo uptake by surrounding GBM cells. Findings suggest that intratumoral delivery with HG-NPs has immense potential for GBM treatment, as well as other strategies where site-specific, long-term retention of therapeutic agents is warranted.


Antecedents of graduates' competence in the agro-food processing technical and vocational training system of Ethiopia as perceived by graduates and their trainers.
The purpose of this study was to scrutinize the interdependence among training quality, graduate demographic characteristics, and graduate competence and employability in the agro-food processing sub-sector of the TVET system in Ethiopia. To that effect, the commitment and competence of graduates and trainers, the quantitative and qualitative aspects of resource supplies, training and assessment practices including industry involvement or cooperative training, and the relationships with and influence of the human and material resources on graduate competence were examined. The descriptive survey design of the quantitative approach that involved 637 participants was employed. Data analyses through descriptive and inferential statistics revealed that colleges were challenged with trainer skill gaps, poor material resource supply, and poor cooperative training. It was also found that the human inputs (trainer competence, trainer commitment, and trainee characteristics) significantly predicted the core competence of graduates whereas material resources had a very weak predictive power. In addition, an inverse relationship between employment status and all forms of graduates' competence was found. Accordingly, it is plausible to conclude that poor institutional capacity that denied to pay necessary attention for the input and process of the training delivery has obstructed the competence of graduates.


A study of the Huntington's disease associated trinucleotide repeat in the Scottish population.
Accurate measurements of a specific CAG repeat sequence in the Huntington's disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish population showed a range from 35 to 62 repeats in affected subjects and eight to 33 in normal subjects. A link between early onset of symptoms and very high repeat number was seen. For HD patients with the most common affected allele sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at onset of symptoms. There was variability in the transmitted repeat size for both sexes in the HD size range. We observed a significant increase of repeat size for paternal transmission of the disease and greater instability for paternally transmitted CAG repeats in the HD size range.


[The importance of the radiological angle between talus and calcaneus in patients with congenital clubfoot (author's transl)].
A reduction of the angle between the longitudinal axes of talus and calcaneus in the lateral X-ray view of a clubfoot is a sign of persistent supination of the subtalar joint and not due to anatomical changes of the bone. Correction of this deformity by closed manipulation produces a normal angle between talus and calcaneus. The angle between talus and calcaneus can thus be used as a guide for adequate correction of the subtalar deformity.


A Dicyanoisoflurone-based Near-infrared Fluorescence Probe for Highly Sensitive Detection of Hg2.
Due to its high toxicity, long durability, easy absorption by aquatic organisms, and significant bioaccumulation, Hg2+ has caused substantial environmental damage and posed serious threats to human health. Therefore, effective detection of Hg2+ is of utmost importance. In this study, a turn-on fluorescent probe based on dicyanoisoflurone was developed for the detection of Hg2+. The probe exhibited near-infrared fluorescence signal at 660 nm upon excitation by 440 nm UV light in a mixture of CH3CN and HEPES buffer (4:1, v/v, 10 mM, pH = 7.5), with selective binding to Hg2+ in a molar ratio of 1:1. This binding event was accompanied by a visible color change from light yellow to orange. By utilizing the enhanced fluorescence signal change, this probe enables highly sensitive analysis and detection of Hg2+ with excellent selectivity (association constant = 1.63 × 104 M- 1), large Stokes shift (220 nm), high sensitivity (detection limit as low as 5.6 nM), short reaction time (30 s), and a physiological pH range of 7.5-9.5. The probe was successfully employed for detecting of Hg2+ in real water and living cells.


Improved separation of perch liver metallothionein by fast protein liquid chromatography.
The separation of metallothionein isoforms by Mono-Q column chromatography by fast protein liquid chromatography is described and compared to separation on a DEAE-Sephadex A-25 ion-exchange column. The separation of two isoforms of rainbow trout (Salmo gairdneri) metallothionein was possible by DEAE-Sephadex A-25 chromatography, while only one form of perch (Perca fluviatilis) metallothionein was obtained with this method. However, by applying FPLC on a Mono-Q column it was possible to separate two isoforms of perch metallothionein. When comparing the chromatographic behaviour of rainbow trout and perch metallothioneins it was found that the two isoforms of perch metallothionein were eluted closer together than the two rainbow trout metallothioneins. Both forms of perch and rainbow trout metallothioneins lacked aromatic amino acids and histidine, and had a high cystein content (30 mol%). The molecular weight was estimated to be 6000 for the apothioneins. The results from this study demonstrate the usefulness of FPLC to improve the resolution of metallothionein separations.


An analysis of velopharyngeal timing in normal adult speakers using a microcomputer based photodetector system.
Using a microcomputer interface and dedicated software, a photodetector was employed to collect data on the timing of velopharnygeal movements during the production of speech by 10 normally speaking adult subjects. The duration of velopharnygeal closing gestures varied consistently across productions of /m/, /n/ and /n/ in both normal and fast speech. Velopharyngeal opening movements also appeared to be affected by the nasal consonant that was produced. These phenomena are explained in terms of biomechanical constraints known to act upon the velopharyngeal mechanism.


Prospects for population screening and diagnosis of lung cancer.
Deaths from lung cancer exceed those from any other type of malignancy, with 1·5 million deaths in 2010. Prevention and smoking cessation are still the main methods to reduce the death toll. The US National Lung Screening Trial, which compared CT screening with chest radiograph, yielded a mortality advantage of 20% to participants in the CT group. International debate is ongoing about whether sufficient evidence exists to implement CT screening programmes. When questions about effectiveness and cost-effectiveness have been answered, which will await publication of the largest European trial, NELSON, and pooled analysis of European CT screening trials, we discuss the main topics that will need consideration. These unresolved issues are risk prediction models to identify patients for CT screening; radiological protocols that use volumetric analysis for indeterminate nodules; options for surgical resection of CT-identified nodules; screening interval; and duration of screening. We suggest that a demonstration project of biennial screening over a 4-year period should be undertaken.


In Vivo Myoblasts Tracking Using the Sodium Iodide Symporter Gene Expression in Dogs.
Stem cell-based therapies are a promising approach for the treatment of degenerative muscular diseases; however, clinical trials have shown inconclusive and even disappointing results so far. Noninvasive cell monitoring by medicine imaging could improve the understanding of the survival and biodistribution of cells following injection. In this study, we assessed the canine sodium iodide symporter (cNIS) reporter gene as an imaging tool to track by single-photon emission computed tomography (SPECT/CT) transduced canine myoblasts after intramuscular (IM) administrations in dogs. cNIS-expressing cells kept their myogenic capacities and showed strong 99 mTc-pertechnetate (99 mTcO4 -) uptake efficiency both in vitro and in vivo. cNIS expression allowed visualization of cells by SPECT/CT along time: 4 h, 48 h, 7 days, and 30 days after IM injection; biopsies collected 30 days post administration showed myofiber's membranes expressing cNIS. This study demonstrates that NIS can be used as a reporter to track cells in vivo in the skeletal muscle of large animals. Our results set a proof of concept of the benefits NIS-tracking tool may bring to the already challenging cell-based therapies arena in myopathies and pave the way to a more efficient translation to the clinical setting from more accurate pre-clinical results.


Evaluation of a pharmacist vs. Haematologist-managed anticoagulation clinic: A retrospective cohort study.
Warfarin is the core component in the management of various thromboembolic disorders, which requires specialized expertise to optimize outcomes. There is limited data comparing a pharmacist vs. a haematologist-managed anticoagulation clinic in our setting, and in the Middle East. We aimed to evaluate the effectiveness and safety of a pharmacist vs. a haematologist-managed anticoagulation clinic in the Ambulatory Care Center at King Abdulaziz Medical City, Jeddah, Saudi Arabia. A retrospective cohort study was conducted from 2016 to 2018, which included adult patients who have been followed-up for at least six months and who received warfarin for an extended period. The primary outcome was the proportion of time the patients in the two arms were in the therapeutic range. The secondary outcomes were the differences in expanded time in the therapeutic range, as well as the frequency of bleeding and thromboembolic events between the two arms. We enrolled 104 and 124 patients in the pharmacist and haematologist arms respectively. The median time in the therapeutic range for the pharmacist arm was 71.4%, IQR (60.8-83.8) vs. 65%, IQR (43.5-79.1), in the haematologist arm (p = 0.0049). The median expanded time in the therapeutic range was 86.4%, IQR (77.5-95.3) vs. 81.21%, IQR (67.1-93.3) in the pharmacist vs. haematologist arm (p = 0.015) respectively. Major bleeding events occurred in 5.7 % vs. 3.2 %, and thromboembolic events in 5.7% vs. 4%, in the pharmacist vs. haematologist arm respectively. Our results demonstrated that the time in the therapeutic range was significantly higher in the pharmacist arm, with no significant difference in bleeding and thromboembolic events compared to the haematologist arm.


Membranes as metabolic pacemakers.
1. In the present review, we suggest that a few common processes linked to membranes consume the majority of energy used by most organisms. 2. Membranes may act as metabolic pacemakers through changes in lipid composition, altering membrane characteristics and the working environment of membrane proteins. 3. Experiments involving membrane exchanges show predictable changes in protein activities (sodium pump) that are dependent upon the type of membrane used. 4. Potential mechanisms discussed include fluidity, electrical fields, surface area requirements of lipids and peptide-lipid interactions.


Descriptive epidemiology of Moraxella bovis, Moraxella bovoculi and Moraxella ovis in beef calves with naturally occurring infectious bovine keratoconjunctivitis (Pinkeye).
Infectious bovine keratoconjunctivitis (IBK) is an ocular disease that causes substantial weight loss in beef calves. The objective of this study was to evaluate the association between Moraxella bovoculi, Moraxella bovis and Moraxella ovis and IBK incidence. A cohort design was used. From 239 calves and 478 eyes, 77 randomly chosen eyes were monitored for M. bovoculi, M. bovis, M. ovis and IBK incidence over 4 months. One hypothesis tested was that IBK hazard in eyes was not associated with detection of M. bovoculi, M. bovis and M. ovis. A secondary hypothesis tested that IBK cases were not associated with increased prevalence of M. bovoculi, M. bovis and M. ovis. 23% of 77 eyes developed IBK. M. ovis was identified in one IBK-negative eye. The adjusted hazard ratio (HR) for IBK incidence from eyes where M. bovoculi or M. bovis were recovered prior to disease occurrence were not statistically significant (M. bovoculi HR=1.38, 95% CI: 0.54-3.53, p=0.49, M. bovis HR=1.60, 95% CI: 0.48-5.53, p=0.44). The adjusted hazard ratio for M. bovoculi in IBK lesions was 6.45 (95% CI: 3.35-12.44, p<0.001). The adjusted hazard ratio for M. bovis in IBK lesions was 2.33 (95% CI: 1.22-4.45, p=0.01). A temporal association between prior exposure to M. bovoculi or M. bovis and subsequent IBK incidence was not demonstrated. However, M. bovoculi and M. bovis are more frequently recovered from eyes with IBK lesions than unaffected eyes and this provides weak evidence for a causal role.


Agreement among sources of adult influenza vaccination in the age of immunization information systems.
Many vaccination studies rely on self-reported vaccination status, with its inherent biases. Accuracy of influenza vaccination self-report has been evaluated periodically, typically using the medical record as the gold standard. The burgeoning of electronic medical records (EMRs) and immunization information systems (IISs) and the rise of adult vaccine administration in community pharmacies suggest the need for a reevaluation of self-reported vaccination status. Vaccination data from self-report, the state IIS, the health system EMR and other sources were compared for participants in outpatient and inpatient influenza vaccine effectiveness studies for four seasons (2016-2017 to 2019-2020). Agreement among the sources was calculated along with sensitivity and specificity. Tests for trend assessed changes in completeness of the Pennsylvania - Statewide IIS (PA-SIIS) data over time. With self-report as the gold standard, agreement with the local EMR, PA-SIIS, and all sources was 62%, 77% and 85%, respectively. Sensitivity of the EMR was 42% (95% CI = 41, 43) and specificity was 91% (90, 92). With PA-SIIS-as the gold standard, agreement with the local EMR and all sources was 77% and 78%, respectively. Sensitivity of all sources combined was 96% (95, 97) and specificity was (63% (62, 64). Capture of influenza vaccinations in the IIS has not consistently improved over time, with a significant increase among children (P = 0.001), no change among working-age adults and a decrease among older adults (P = 0.004). However, PA-SIIS provided the largest percentage of verified vaccines (69.3%) compared with EMR (43.3%) and other sources (12.4%). Both self-report and PA-SIIS are good estimates of actual vaccine uptake. When high accuracy data are required, such as for vaccine effectiveness studies, triangulation using multiple sources should be conducted.


Regulation of protein synthesis in mitogen-activated bovine lymphocytes. Analysis of actin-specific and total mRNA accumulation and utilization.
In response to the mitogenic lectin concanavalin A, the rate of protein synthesis in bovine small lymphocytes increased about 3-fold in 10 h and about 6-fold in 24 h. The rate of synthesis of the cytoskeletal protein actin, which comprises about 10% of total protein synthesis, increased in parallel with total protein synthesis. The cellular levels of actin mRNA were determined at various times after mitogen addition using a cDNA probe derived from a recombinant plasmid carrying a fragment coding for bovine actin. Actin mRNA sequences were found to increase significantly within 3 h and to increase 3.6 +/- 1.2-fold within 10 h after mitogen addition. Therefore, the increase in actin synthesis after mitogenic activation seems to be accounted for by accumulation of actin mRNA sequences. Total translatable mRNA and poly(A) sequences also accumulated in parallel with total protein synthesis, suggesting that regulation of actin synthesis was not unique. Two direct studies of mRNA utilization indicated that there is little, if any, translational regulation of actin synthesis. A detailed examination of actin mRNA-containing polysomes and total polysomes revealed no significant change in the average size of polysomes after cell activation. Therefore, given that the rates of polypeptide elongation and termination are constant after mitogen addition (Kay, J.E., Ahern, T., Lindsay V.J., and Sampson, J. (1975) Biochim. Biophys. Acta 378, 241-250), the rate of translational initiation per active mRNA must be unchanged. In addition, no significant amount of unutilized, nonpolysomal actin mRNA was detected in total cell extracts from either unstimulated or activated cells. Together these data suggest that elevated protein synthesis in activated lymphocytes is regulated by mRNA level.


Emerging polymeric electrospun fibers: From structural diversity to application in flexible bioelectronics and tissue engineering.
Electrospinning (e-spin) technique has emerged as a versatile and feasible pathway for constructing diverse polymeric fabric structures, which show potential applications in many biological and biomedical fields. Owing to the advantages of adjustable mechanics, designable structures, versatile surface multi-functionalization, and biomimetic capability to natural tissue, remarkable progress has been made in flexible bioelectronics and tissue engineering for the sensing and therapeutic purposes. In this perspective, we review recent works on design of the hierarchically structured e-spin fibers, as well as, the fabrication strategies from one-dimensional individual fiber (1D) to three-dimensional (3D) fiber arrangements adaptive to specific applications. Then, we focus on the most cutting-edge progress of their applications in flexible bioelectronics and tissue engineering. Finally, we propose future challenges and perspectives for promoting electrospun fiber-based products toward industrialized, intelligent, multifunctional, and safe applications.


[Specialised treatment of colorectal cancer in certified cancer centres: Do patients really have to travel further?]
In Germany, many cancer patients are treated outside of cancer centres certified by the German Cancer Society (DKG) resulting in underuse of these facilities and inferior oncological treatment. One way to address this issue would be to restructure the healthcare landscape by following the Danish approach that limits cancer treatment to specialized hospitals. Such an approach would have an impact on the travelling times to treatment centers. The present study determines the impact on patient travel times using the example of colorectal cancer. For the present analysis, data from structured quality reports (sQB) and from patients insured with the AOK who underwent resection of the colon or rectum during 2018 were used. In addition, data from the DKG regarding an existing certification of a colorectal cance centre were used. Travel time was defined as the time patients spent in an average car with average traffic from the midpoint of the ZIP code of their residence to the coordinates of the hospital. The coordinates of the hospitals and the midpoints of the ZIP codes were obtained by querying the Google API. Travel times were calculated with a local Open Routing Machine server. The statistical programs R and Stata were used for analyses and cartographic representations. In 2018, nearly half of all patients with colon cancer were treated at the hospital nearest to their place of residence, of whom approximately 40% were treated at a certified colorectal cancer centre. Overall, only about 47% of all treatments took place at a certified colorectal cancer centre. Travel time to the chosen treatment site averaged 20 minutes. It was minimally shorter (18 minutes) if no certified centre was chosen and minimally longer (21 minutes) for those whose treatment took place in a certified colorectal cancer centre. Modeling of redistributions of all patients to certified centres resulted on an average travel time of 29 minutes. Even if treatment were limited to specialized hospitals, treatment close to home would still be guaranteed. Regardless of certification, parallel structures can be identified, especially in metropolitan areas, which indicate a potential for restructuring.


Transport of basic amino acids by the dinitrogen-fixing cyanobacterium Anabaena PCC 7120.
Two transport systems for L-arginine were evident in Anabaena sp. strain PCC 7120: a high-affinity one (Km, 1.7 microM) that accumulated arginine within the cells through an energy-requiring process and another one that exhibited low affinity for L-arginine (Km, 0.75 mM) and was unable to accumulate the substrate. Both systems were inhibited by L-canavanine, L-lysine, and L-ornithine. Two systems were also evident for L-lysine uptake (Km, 1.9 and 110 microM, respectively). After selection for resistance to canavanine or hydroxylysine, independent mutants were isolated which were impaired in the high-affinity uptake of arginine and lysine. A common permease appears, therefore, to be involved in the high-affinity transport of these basic amino acids. Both the high- and the low-affinity systems can contribute to the growth of Anabaena sp. on L-arginine. However, arginine did not effectively repress either nitrogenase or nitrate reductase.


Spin relaxation dynamics of holes in intrinsic GaAs quantum wells studied by transient circular dichromatic absorption spectroscopy at room temperature.
Spin relaxation dynamics of holes in intrinsic GaAs quantum wells is studied using time-resolved circular dichromatic absorption spectroscopy at room temperature. It is found that ultrafast dynamics is dominated by the cooperative contributions of band filling and many-body effects. The relative contribution of the two effects is opposite in strength for electrons and holes. As a result, transient circular dichromatic differential transmission (TCD-DT) with co- and cross-circularly polarized pump and probe presents different strength at several picosecond delay time. Ultrafast spin relaxation dynamics of excited holes is sensitively reflected in TCD-DT with cross-circularly polarized pump and probe. A model, including coherent artifact, thermalization of nonthermal carriers and the cooperative contribution of band filling and many-body effects, is developed, and used to fit TCD-DT with cross-circularly polarized pump and probe. Spin relaxation time of holes is achieved as a function of excited hole density for the first time at room temperature, and increases with hole density, which disagrees with a theoretical prediction based on EY spin relaxation mechanism, implying that EY mechanism may be not dominant hole spin relaxation mechanism at room temperature, but DP mechanism is dominant possibly.


Mechanistic study and kinetic determination of vitamin C.
A simple specific method for the determination of vitamin C has been investigated by elucidating the reaction mechanism of its oxidation with cerium(IV) in sulphuric acid media. The reaction kinetics and rate measurements which form the basis of this method were determined by following the decrease of the intense yellow colour of cerium(IV) at 405 nm. The fixed-time and fixed-concentration methods were investigated. The former was found to be more precise and was consequently used for the determination. Advantages of this method over the B.P. and other methods are discussed.


A short review: Doxorubicin and its effect on cardiac proteins.
Doxorubicin (DOX) is a boon for cancer-suffering patients. However, the undesirable effect on health on vital organs, especially the heart, is a limiting factor, resulting in an increased number of patients with cardiac dysfunction. The present review focuses on the contractile machinery and associated factors, which get affected due to DOX toxicity in chemo-patients for which they are kept under life-long investigation for cardiac function. DOX-induced oxidative stress disrupts the integrity of cardiac contractile muscle proteins that alter the rhythmic mechanism and oxygen consumption rate of the heart. DOX is an oxidant and it is further discussed that oxidative stress prompts the damage of contractile components and associated factors, which include Ca2+ load through Ca2+ ATPase, SERCA, ryanodine receptor-2, phospholamban, and calsequestrin, which ultimately results in left ventricular ejection and dilation. Based on data and evidence, the associated proteins can be considered as clinical markers to develop medications for patients. Even with the advancement of various diagnosing tools and modified drugs to mitigate DOX-induced cardiotoxicity, the risk could not be surmounted with survivors of cancer.


Recurrent noncoding somatic and germline WT1 variants converge to disrupt MYB binding in acute promyelocytic leukemia.
Genetic alternations can occur at noncoding regions, but how they contribute to cancer pathogenesis is poorly understood. Here, we established a mutational landscape of cis-regulatory regions (CREs) in acute promyelocytic leukemia (APL) based on whole-genome sequencing analysis of paired tumor and germline samples from 24 patients and epigenetic profiling of 16 patients. Mutations occurring in CREs occur preferentially in active enhancers bound by the complex of master transcription factors in APL. Among significantly enriched mutated CREs, we found a recurrently mutated region located within the third intron of WT1, an essential regulator of normal and malignant hematopoiesis. Focusing on noncoding mutations within this WT1 intron, an analysis on 169 APL patients revealed that somatic mutations were clustered into a focal hotspot region, including one site identified as a germline polymorphism contributing to APL risk. Significantly decreased WT1 expression was observed in APL patients bearing somatic and/or germline noncoding WT1 variants. Furthermore, biallelic WT1 inactivation was recurrently found in APL patients with noncoding WT1 variants, which resulted in the complete loss of WT1. The high incidence of biallelic inactivation suggested the tumor suppressor activity of WT1 in APL. Mechanistically, noncoding WT1 variants disrupted MYB binding on chromatin and suppressed the enhancer activity and WT1 expression through destroying the chromatin looping formation. Our study highlights the important role of noncoding variants in the leukemogenesis of APL.


Rituximab associated necrosis: A case report.
Rituximab is a B-cell-depleting unconjugated monoclonal IgG1 antibody that targets the transmembrane protein CD20. This article reports on a case with the rare complication known as Rituximab-associated mucosal necrosis. The present case report addresses, for the first time, a patient affected by Devic's syndrome presenting with oral manifestations of palatal necrosis after rituximab treatment. The present case raises the possibility of anti-CD20 antibody contributing to the development of palatal mucosal necrosis in some patients. Given the increasing administration of rituximab as a result of its efficacy against several diseases, a report on the potential iatrogenic effects of this drug is essential.


'Toy' laser macular burns in children: 12-month update.
There is increasing evidence that high-powered hand-held laser devices cause retinal injury. We present 12-month follow-up data for three patients that we previously reported with such retinal injuries. A retrospective case series of three children with maculopathy secondary to exposure to high-power hand-held laser devices. All children underwent clinical examination and spectral domain optical coherence tomography (SD-OCT) at presentation and follow-up. Fundus-controlled microperimetry was also undertaken 12-19 months after exposure. Three children sustained macular injury after exposure to a high-powered hand-held laser. Acutely, they presented with a 'vitelliform-like' maculopathy with reduced vision. Over the course of follow-up, the best corrected Snellen acuity in all three patients improved to 'normal' levels (range 6/6-6/9). Long-term deficits in foveal retinal sensitivity were identified in two patients using fundus-controlled microperimetry. SD-OCT imaging showed persistent disruption of the foveal outer photoreceptor layers in all three children. Although visual acuity improved over time, deficits in microperimetry and SD-OCT persisted. All three children had retinal pigment epithelium changes, requiring follow-up for longer-term sequelae of laser injuries such as expansion of retinal atrophy and development of choroidal neovascular membranes.


An autophagy-related lncRNA prognostic risk model for thyroid cancer.
Thyroid cancer (TC) is the most common malignancy of the endocrine system and its incidence is gradually rising. Research has demonstrated a close link between autophagy and thyroid cancer. We constructed a prognostic model of autophagy-related long non-coding RNA (lncRNA) in thyroid cancer and explored its prognostic value. The data used in this study were all obtained from The Cancer Genome Atlas (TCGA) database and the Human Autophagy Database (HADb). We construct a co-expression network by autophagy-related genes and lncRNA to obtain autophagy-related lncRNAs. After univariate Cox regression analysis and multivariate Cox regression analysis, autophagy-related lncRNAs significantly associated with prognosis were identified. Based on the risk score of lncRNA, thyroid cancer patients are divided into high-risk group and low-risk group. A total of 14,142 lncRNAs and 212 autophagy-related genes (ATGs) were obtained from the TCGA database and the HADb, respectively. We performed lncRNA-ATGs correlation analysis and finally obtained 1,166 autophagy-associated lncRNAs. Subsequently, we conducted univariate Cox regression analysis and multivariate Cox regression analysis, nine autophagy-related lncRNAs (AC092279.1, AC096677.1, DOCK9-DT, LINC02454, AL136366.1, AC008063.1, AC004918.3, LINC02471 and AL162231.2) significantly associated with prognosis were identified. Based on these autophagy-related lncRNAs, a risk model was constructed. The area under the curve (AUC) of the risk score was 0.905, proving that the accuracy of risk signature was superior. In addition, multiple regression analysis showed that risk score was a significant independent prognostic risk factor for thyroid cancer. In this study, nine autophagy-related lncRNAs in thyroid cancer were established to predict the prognosis of thyroid cancer patients.


The dynamics of GII.4 Norovirus in Ho Chi Minh City, Vietnam.
Norovirus (NoV) is a major cause of epidemic gastroenteritis in industrialized countries, yet the epidemiological significance of NoV in industrializing countries remains poorly understood. The spatiotemporal distribution of NoV genotypes identified in 2054 enrolled children was investigated between May 2009 and December 2010, in Ho Chi Minh City (HCMC), Vietnam. A total of 315 NoV extracted from stool samples were genotyped and GPS mapped to their source. Genogroup II NoV, particularly GII.4, were predominant, and the GII.4 strains could be subgrouped into GII.4-2006b (Minerva) and GII.4-2010 (New Orleans) variants. There was no spatiotemporal structure among the endemic GII strains; yet a significant spatiotemporal signal corresponding with the novel introduction of GII.4-2010 variant was detected. These data show that NoV GII.4 variants are highly endemic in HCMC and describe a scenario of rapid NoV strain replacement occurring in HCMC in early 2010.


Temporal sensitivity for achromatic and chromatic flicker across the visual cortex.
The classes of retinal ganglion cells (RGCs) receive different combinations of L, M, and S cone inputs and give rise to one achromatic and two chromatic post-receptoral channels. Beyond the retina, RGC outputs are subject to filtering and normalization along the geniculo-striate pathway, ultimately producing the properties of human vision. The goal of the current study was to determine temporal sensitivity across the three post-receptoral channels in subcortical and cortical regions involved in vision, to better characterize post-retinal temporal processing. We measured functional magnetic resonance imaging (MRI) responses at 7 Tesla from participants viewing a high-contrast, flickering, spatially-uniform wide (~140°) field. Stimulus flicker frequency varied logarithmically between 2 and 64 Hz and targeted the L+M+S, L-M, and S-[L+M] cone combinations. These measurements were used to create temporal sensitivity functions (TSFs) of primary visual cortex (V1) across eccentricity, and spatially averaged responses from lateral geniculate nucleus (LGN), V2/V3, hV4, and MT. Functional MRI responses reflected known properties of the visual system, including higher peak temporal sensitivity to achromatic vs. chromatic stimuli, and low-pass filtering between the LGN and V1. V1 had the slowest peak temporal sensitivity across cortical regions, which increased at higher levels of the visual cortical hierarchy. Unexpectedly, peak temporal sensitivity decreased at greater eccentricities in area V1, especially for achromatic stimuli. Comparison of measured cortical responses to a model of integrated retinal output to our stimuli demonstrates that extensive filtering and amplification is applied to post-retinal signals.


Discrepancy in the expression of autoantibodies in healthy aged individuals.
Sera from 50 healthy old subjects and from 51 young controls were tested by ELISA assays for a panel of autoantibodies, including IgM RF, anti-DNA, anti-F(ab')2, antithyroglobulin, anti-human albumin, anti-human hemoglobin, anti-secretory component from human IgA, and anti-gliadin. In vitro production of anti-DNA as well as anti-F(ab')2 antibodies were measured after stimulation of PBMC by pokeweed mitogen (PWM) in 12 healthy elderly subjects and 11 young controls. Sera from elderly donors contained threefold higher amounts of IgM RF than young controls (P less than 0.001). On the contrary, the levels of anti-DNA as well as anti-F(ab')2 antibodies were similar in both groups (P less than 0.3 for the two determinations). Anti-DNA and anti-F(ab')2 antibodies were also measured in supernates of PWM-stimulated glass nonadherent PBMC cultures from both old and young healthy donors without finding any significant difference between the two groups. Additional ELISA tests were also performed in both elderly and young control sera to detect antibodies against six other different antigens. No significant difference was found in the percentages of positive sera between the two groups. This discrepancy in production of IgM RF compared to other autoantibodies in healthy elderly subjects does not provide support for a general increase of autoantibodies with aging. The biological significance of an increase in IgM RF with aging remains to be determined.


Epidemiological profile of methanol poisoning, El Hajeb, Morocco.
Methanol poisoning is of particular importance in low and middle-income countries. We reported on a methanol poisoning incident that occurred 22 May 2017, in El Hajeb (Morocco). This study aimed to describe the extent of the intoxication, determine its source and implement the necessary preventative measures. We conducted a cross-sectional survey. A standardized questionnaire including socio-economic data, clinical symptoms and time of use was administered face-to-face to cases of methanol poisoning. Biological samples were taken for toxicological analysis. Data were entered and analyzed on Epi Info version 7. Twenty-six cases of methanol poisoning were surveyed with a mean age of 39.7 (SD 11.1) years and a male/female sex ratio of 5.5. All intoxicated cases were of low socioeconomic status. The mean latency period between use and symptom onset was 1.5 (SD 1) days. Reported symptoms were mildly altered consciousness in 14 cases (53.8%), abdominal pain in 10 cases (38.5%), headache in 9 cases (34.6%), vomiting in 8 cases (30.8%) and coma in 7 cases (27.1%). Mortality was 65% and 4 cases developed blindness. Laboratory results confirmed the presence of methanol in the blood with values greater than 0.6 g/L. The dose of methanol in the associated bottle was 217 g/L. Public awareness of the dangers of methanol intoxication is important. Health professionals need to be aware of the clinical signs and what to do in the event of methanol poisoning.


Evaluation of the effectiveness of photodynamic therapy for the endodontic treatment of primary teeth: study protocol for a randomized controlled clinical trial.
The elimination of pathogenic microorganisms from the root canal system is one of the major steps required for successful endodontic treatment. The aim of the proposed study is to conduct a randomized, controlled, clinical trial for the clinical and radiographic evaluation of the effectiveness of photodynamic therapy during the endodontic treatment of primary teeth. Thirty primary anterior teeth in children aged 3 to 6 years old will be randomly divided into 2 groups: a control group, which will receive conventional treatment, and an experimental group, which will be subjected to photodynamic therapy. Microbiological evaluations will be performed before and after endodontic treatment. Moreover, clinical and radiographic evaluations will be performed on the day of treatment as well as 1, 3 and 6 months after treatment. Comparisons will be made of the two study groups. The data will be tabulated and presented in a descriptive, analytical fashion. Depending on the distribution (normal or non-normal), either the t test, ANOVA or the Mann-Whitney test will be used for analysis of the variables. The Wilcoxon test will be used for comparisons before and after treatment. P values<0.05 (95% significance level) will be considered indicative of statistically significant differences. As successful endodontic treatment is directly related to intra-canal bacterial disinfection and considering the difficult task of endodontic treatment in primary teeth, often due to difficulties in controlling young children, the internal anatomy of root canals and root resorption, the alternative of using PDT is a painless,easy-to-administer method that does not lead to microbial resistance and can assist in the achievement of successful endodontic treatment in primary teeth by eliminating the pain children can experience due to retreatment as well as premature tooth loss. The protocol for this study was registered with Clinical Trials number NCT02485210 on 30 july 2015.


Interactions of suboesophageal ganglion and frontal ganglion motor patterns in the locust.
Although locust feeding has been well studied, our understanding of the neural basis of feeding-related motor patterns is still far from complete. This paper focuses on interactions between the pattern of rhythmic movements of the mouth appendages, governed by the suboesophageal ganglion (SOG), and the foregut movements, controlled by the frontal ganglion (FG), in the desert locust. In vitro simultaneous extracellular nerve recordings were made from totally isolated ganglia as well as from fully interconnected SOG-FG and brain-SOG-FG preparations. SOG-confined bath application of the nitric oxide donor, SNP, or the phosphodiesterase antagonist, IBMX, each followed by the muscarinic agonist pilocarpine, consistently induced robust fictive motor patterns in the SOG. This was observed in both isolated and interconnected preparations. In the brain-SOG-FG configuration the SOG-confined modulator application had an indirect excitatory effect on spontaneous FG rhythmic activity. Correlation between fictive motor patterns of the two ganglia was demonstrated by simultaneous changes in burst frequency. These interactions were found to be brain-mediated. Our results indicate the presence of intricate neuromodulation-mediated circuit interactions, even in the absence of sensory inputs. These interactions may be instrumental in generating the complex rhythmic motor patterns of the mandibles and gut muscles during locust feeding or ecdysis-related air swallowing.


Transposition of Saccharomyces cerevisiae Ty1 retrotransposon is activated by improper cryopreservation.
Ty1 is a retrotransposon of the yeast Saccharomyces cerevisiae whose transposition at new locations in the host genome is activated by stress conditions, such as exposure to UV light, X-rays, nitrogen starvation. In this communication, we supply evidence that cooling for 2 h at +4 degrees C followed by freezing for 1 h at -10 degrees C and 16 h at -20 degrees C also increased Ty1 transposition. The mobility of Ty1 was induced by cooling at slow rates (3 degrees C/min) and the accumulation of trehalose inside cells or the cooling at high rates (100 degrees C/min) inhibited significantly the induction of the transposition. The freeze-induced Ty1 transposition did not occur in mitochondrial mutants (rho-) and in cells with disrupted SCO1 gene (Deltasco1 cells) evidencing that the Ty1 transposition induced by cooling depends on the mitochondrial oxidative phosphorylation. We also found that the freeze induced Ty1 transposition is associated with increased synthesis and accumulation of superoxide anions (O2-) into the cells. Accumulation of O2- and activation of Ty1 transposition were not observed after cooling of cells with compromised mitochondrial functions (rho-, Deltasco1), or in cells pretreated with O2- scavengers. It is concluded that (i) elevated levels of reactive oxygen species (ROS) have a key role in activation the transposition of Ty1 retrotransposon in yeast cells undergoing freezing and (ii) given the deleterious effect of increased ROS levels on cells, special precautions should be taken to avoid ROS production and accumulation during cryopreservation procedures.


Oral nystatin prophylaxis of Candida spp. colonization in ventilated critically ill patients.
Colonization of multiple body sites is a leading risk factor for Candida spp. infection in intensive care unit (ICU) patients. We evaluated whether oral nystatin prophylaxis reduces Candida spp. colonization in ventilated ICU patients. Prospective, randomized, open-label study with blinded assessment of the objective primary evaluation criterion in the medical-surgical ICU of a teaching hospital. The study included 98 consecutive patients mechanically ventilated for at least 48 h (mean age 58+/-19 years; mean SAPS II 40+/-11), assigned to either treatment group (n=51) or control group (n=47). Study groups were comparable for age, SAPS II, reason for admission, and immune status. Patients were randomized to receive oral nystatin (treatment group; 3x10(6) U per day) or no nystatin (control group). Multiple body sites (trachea, stomach, rectum, urine, groin, and blood) were tested for Candida spp. on admission and then every 3 days by mycologists blinded to group assignment, and the colonization index was determined. Colonization by Candida spp. developed in 25% of controls but in none of the treated patients. In multivariate analysis, the absence of nystatin prophylaxis and ICU length of stay were independently associated with Candida spp. colonization. No invasive candidiasis was diagnosed in either study group. Oral nystatin prophylaxis efficiently prevented Candida spp. colonization in ICU patients at low risk of developing invasive candidiasis. Further studies are needed to determine whether this strategy remains efficient in reducing Candida spp. infections in higher risk ICU patients.


A Novel Radiofrequency Device to Monitor Changes in Pulmonary Fluid in Dialysis Patients.
Fluid monitoring is an important management strategy in patients with chronic kidney disease (CKD) and heart failure (HF). The µCor™ Heart Failure and Arrhythmia Management System uses a radiofrequency-based thoracic fluid index (TFI) to track pulmonary edema. During hemodialysis, the acute removal of fluid through ultrafiltration offers a model for measuring a patient's fluid status. The objective of the study was to assess the relationship between the device measured TFI and ultrafiltration volume (UFV). Patients undergoing chronic dialysis with and without heart failure were enrolled in the study. The relationship between TFI and UFV in each individual subject was assessed by calculating the Pearson correlation coefficient (r). The average correlation across all subjects was calculated through the use of the Fisher's z transform. Responder analysis was performed to assess the magnitude of change in TFI before and after dialysis. Twenty subjects were enrolled in the trial. The mean volume of fluid removal was 3.63 L (SD 0.88 L). The mean correlation based on Fisher's transform was 0.95 CI (0.92-0.99). Responder analysis showed that the mean reduction of TFI after dialysis was 5.5% ± 3.8. The µCor system provides radiofrequency-based measurements of thoracic fluid which correlate well with total body fluid removal in a real-world setting. Fluid management based on the radar-derived TFI may provide benefits to dialysis patients and serves as a potential model for pulmonary edema common to the clinical course of heart failure.


Regulatory control of glycopyrrolate in performance horses using validated UHPLC/MS-MS methods.
We describe a validated, rapid, sensitive, and specific UHPLC-MS/MS method to detect and quantify glycopyrrolate in 0.5 mL of horse urine. Further, we investigated the elimination of glycopyrrolate in urine after both intravenous and oral administration of clinically relevant doses to Thoroughbred horses. Quantification was performed by weighted, linear regression analysis using a deuterated analogue of glycopyrrolate as internal standard (IS). The method was characterized by a linear range of 5-2500 pg/mL, a lower limit of quantification of 5 pg/mL and a limit of detection of 1 pg/mL. The intra and inter-batch imprecisions were <10% RSD and accuracy of the method ranged between 94 and 104%. Glycopyrrolate remained detectable in urine samples collected through 168 h after intravenous administration and through 24h after oral administration. Analytical method validation requirements for linearity, specificity, precision, accuracy, stability, dilution integrity, matrix effect, and ruggedness have been fulfilled. The urine method described in this report is simple and efficient and is the first reported method with sufficient sensitivity, accuracy, and precision to regulate the use of glycopyrrolate in urine samples collected more than one day after dosing of horses. Urine to plasma glycopyrrolate concentration ratios were calculated and were approximately 100:1 in samples collected from 24h through the end of sample collection.


The Hippo pathway effector TAZ induces TEAD-dependent liver inflammation and tumors.
The Hippo signaling pathway regulates organ size and plays critical roles in maintaining tissue growth, homeostasis, and regeneration. Dysregulated in a wide spectrum of cancers, in mammals, this pathway is regulated by two key effectors, YAP and TAZ, that may functionally overlap. We found that TAZ promoted liver inflammation and tumor development. The expression of TAZ, but not YAP, in human liver tumors positively correlated with the expression of proinflammatory cytokines. Hyperactivated TAZ induced substantial myeloid cell infiltration into the liver and the secretion of proinflammatory cytokines through a TEAD-dependent mechanism. Furthermore, tumors with hyperactivated YAP and TAZ had distinct transcriptional signatures, which included the increased expression of inflammatory cytokines in TAZ-driven tumors. Our study elucidated a previously uncharacterized link between TAZ activity and inflammatory responses that influence tumor development in the liver.


Studies of the pharmacokinetic properties of nimorazole.
The pharmacokinetics of the hypoxic radio-sensitizer nimorazole were studied in 19 individuals after single oral doses of between 0.5-3.5 g. HPLC measurements showed, after a rapid absorption, a linear relationship between peak plasma concentration and given dose. Mean elimination half life was 3.1 h. A tendency to a dose-dependent variation in the apparent volume of distribution, total body clearance and elimination half life suggest non-linear pharmacokinetics of nimorazole. Tumour concentrations measured in 5 patients gave tumour/plasma ratios between 0.8-1.3. No toxicity was observed. The results indicate that nimorazole may have potential as a clinically useful hypoxic radiosensitizer.


Association between residential proximity to environmental pollution sources and childhood renal tumors.
Few risk factors for childhood renal tumors are well established. While a small fraction of cases might be attributable to susceptibility genes and congenital anomalies, the role of environmental factors needs to be assessed. To explore the possible association between residential proximity to environmental pollution sources (industrial and urban areas, and agricultural crops) and childhood renal cancer, taking into account industrial groups and toxic substances released. We conducted a population-based case-control study of childhood renal cancer in Spain, including 213 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996-2011), and 1278 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries, the 30 urban areas with ≥75,000 inhabitants, and the agricultural crops located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. Excess risk (OR; 95%CI) of childhood renal tumors was observed for children living near (≤2.5km) industrial installations as a whole (1.97; 1.13-3.42) - particularly glass and mineral fibers (2.69; 1.19-6.08), galvanization (2.66; 1.14-6.22), hazardous waste (2.59; 1.25-5.37), ceramic (2.35; 1.06-5.21), surface treatment of metals (2.25; 1.24-4.08), organic chemical industry (2.22; 1.15-4.26), food and beverage sector (2.19; 1.18-4.07), urban and waste-water treatment plants (2.14; 1.07-4.30), and production and processing of metals (1.98; 1.03-3.82) -, and in the proximity of agricultural crops (3.16; 1.54-8.89 for children with percentage of crop surface ≥24.35% in a 1-km buffer around their residences). Our study provides some epidemiological evidence that living near certain industrial areas and agricultural crops may be a risk factor for childhood renal cancer.


One-Dimensional Nanostructures of Polypyrrole for Shielding of Electromagnetic Interference in the Microwave Region.
Polypyrrole one-dimensional nanostructures (nanotubes, nanobelts and nanofibers) were prepared using three various dyes (Methyl Orange, Methylene Blue and Eriochrome Black T). Their high electrical conductivity (from 17.1 to 60.9 S cm-1), good thermal stability (in the range from 25 to 150 °C) and resistivity against ageing (half-time of electrical conductivity around 80 days and better) were used in preparation of lightweight and flexible composites with silicone for electromagnetic interference shielding in the C-band region (5.85-8.2 GHz). The nanostructures' morphology and chemical structure were characterized by scanning electron microscopy, Brunauer-Emmett-Teller specific surface measurement and attenuated total reflection Fourier-transform infrared spectroscopy. DC electrical conductivity was measured using the Van der Pauw method. Complex permittivity and AC electrical conductivity of respective silicone composites were calculated from the measured scattering parameters. The relationships between structure, electrical properties and shielding efficiency were studied. It was found that 2 mm-thick silicone composites of polypyrrole nanotubes and nanobelts shield almost 80% of incident radiation in the C-band at very low loading of conductive filler in the silicone (5% w/w). Resulting lightweight and flexible polypyrrole composites exhibit promising properties for shielding of electromagnetic interference in sensitive biological and electronic systems.


Numeric and morphological studies of the African lion (Panthera leo leo) pectoral limb.
The Importance of the appendicular skeleton in the conformation, shape and physiology of wild animals especially carnivores for adaptation and survival cannot be overemphasized, as limited and obsolete information on the bones of the forelimb necessitated this study. Matured adult African lions (Male and female) that weighed 173 kg and 112 kg were obtained at different times after post mortem examinations of their carcasses. Bone preparation was achieved via cold water maceration after proper skin and muscle removal to a barest minimum. The acromion process of the scapula consisted of a ventral hamate and caudal suprahamate processes. The Clavicle was absent in this species. The musculospiral groove of the humerus was more or less absent while its supracondyloid foramen and crest were positioned above the medial condyle and lateral condyle respectively. The radio-ulna presented a twisted appearance with the radius slightly curved thereby creating an extensive interosseous space that spanned its entire length. The seven (7) carpal bones were uniquely arranged in two rows while the 5 metacarpals anchored 5 digits with 3 phalanges except the first with 2 phalanges each. Two sesamoid bones were located on the ventral surface of each Metacarpophalangeal joint. None was seen on its dorsal surface. The 3rd phalanx had a unique appearance with a crescent plate projecting from the ventral cavity. The average total number of bones constituting the pectoral limb was 80. Numerical information and detailed anatomical features of the pectoral limb bones of the African lion (Panthera leo leo) have added some valuable literature to science. This further serves as a baseline data for future scientific exposition on this species.


Growth characteristics of algae during early stages of phytoplankton bloom in Lake Taihu, China.
Three treatments, sediment plus lake water (S+W), sterilized sediment plus lake water (SS+W), and sediment plus filtered lake water (S+FW), were recruited to investigate the growth characteristics of algae during pre-bloom and the importance of algal inocula in the water column and sediment. The results showed that in the water column, biomass of all algae increased in all treatments when recruitment was initiated, whereas this tendency differed among treatments with further increment of temperature. The process of algal growth consisted of two stages: Stage I, the onset of recruitment and Stage II, the subsequent growth of algae. Compared with S+W, in Stage I, SS+W significantly increased the biomass of cyanophytes by 178.70%, and decreased the biomass of non-cyanophytes by 43.40%; In Stage II, SS+W notably stimulated the growth of all algae, thus incurring the occurrence of phytoplankton bloom. Further analyses revealed that both metabolic activity and photochemical activity of algae were enhanced in SS+W, which resulted from the releasing of nutrients from sediment. These results suggest that algal growth in Stage II and algal inocula in the water column can be important factors for the formation of phytoplankton bloom. In addition, possible mechanisms promoting algal recruitment and subsequent growth of algae were explored.


Progression of inflammation during immunodeficient mouse skeletal muscle regeneration.
The skeletal muscle injury triggers the inflammatory response which is crucial for damaged muscle fiber degradation and satellite cell activation. Immunodeficient mice are often used as a model to study the myogenic potential of transplanted human stem cells. Therefore, it is crucial to elucidate whether such model truly reflects processes occurring under physiological conditions. To answer this question we compared skeletal muscle regeneration of BALB/c, i.e. animals producing all types of inflammatory cells, and SCID mice. Results of our study documented that initial stages of muscles regeneration in both strains of mice were comparable. However, lower number of mononucleated cells was noticed in regenerating SCID mouse muscles. Significant differences in the number of CD14-/CD45+ and CD14+/CD45+ cells between BALB/c and SCID muscles were also observed. In addition, we found important differences in M1 and M2 macrophage levels of BALB/c and SCID mouse muscles identified by CD68 and CD163 markers. Thus, our data show that differences in inflammatory response during muscle regeneration, were not translated into significant modifications in muscle regeneration.


Stereopsis and visual acuity: Bilateral trifocal versus blended extended depth of focus and diffractive bifocal intraocular lenses.
To compare stereopsis and visual acuity (VA) between bilateral implantation of trifocal intraocular lenses (IOL) and blended implantation of an extended depth of focus (EDOF) IOL with a bifocal IOL. This is a non-randomized, prospective comparative study included 74 eyes of 37 patients who underwent phacoemulsification and bilateral implantation of AT LISA tri 839MP IOL (bilateral group; 21 patients) or blended implantation of Tecnis Symfony ZXR00 and Tecnis ZLB00 IOL (blended group; 16 patients). The primary outcomes were stereoacuity and binocular VA. The secondary outcomes were visual defocus curve, quality of life, and patient satisfaction. Follow-up was performed 3 months after the surgery. The mean near stereoacuity was 49.76 ± 22.67 and 120.63 ± 90.94 seconds of arc (arcsec) in the bilateral and blended groups, respectively (P < 0.001). Near stereoacuity was positively correlated with VA difference of two eyes (r = 0.896, P < 0.001). The mean binocular uncorrected visual acuity at 40 cm, 80 cm, 5 m, and corrected distance visual acuity at 5 m of the bilateral and blended groups was not statistically significant different. The bilateral group had better VA at a vergence from -2.5 to -4.0 D. Both groups obtained high quality of life and patient satisfaction scores. The bilateral and blended groups achieved good binocular VA, quality of life, and high patient satisfaction. However, the near stereoacuity of the blended group was worse.


The regulation of neuroendocrine function: Timing is everything.
Hormone secretion is highly organized temporally, achieving optimal biological functioning and health. The master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates the timing of circadian rhythms, including daily control of hormone secretion. In the brain, the SCN drives hormone secretion. In some instances, SCN neurons make direct synaptic connections with neurosecretory neurons. In other instances, SCN signals set the phase of "clock genes" that regulate circadian function at the cellular level within neurosecretory cells. The protein products of these clock genes can also exert direct transcriptional control over neuroendocrine releasing factors. Clock genes and proteins are also expressed in peripheral endocrine organs providing additional modes of temporal control. Finally, the SCN signals endocrine glands via the autonomic nervous system, allowing for rapid regulation via multisynaptic pathways. Thus, the circadian system achieves temporal regulation of endocrine function by a combination of genetic, cellular, and neural regulatory mechanisms to ensure that each response occurs in its correct temporal niche. The availability of tools to assess the phase of molecular/cellular clocks and of powerful tract tracing methods to assess connections between "clock cells" and their targets provides an opportunity to examine circadian-controlled aspects of neurosecretion, in the search for general principles by which the endocrine system is organized.


Smoking and Socio-demographic correlates of BMI.
The aim of the current study was to examine the associations between Body Mass Index (BMI) and socio-demographic factors and to examine the relationship between BMI, smoking status and ethnicity. The Singapore Mental Health Study (SMHS) surveyed Singapore Residents (Singapore Citizens and Permanent Residents) aged 18 years old and above. BMI was calculated using height and weight which were self-reported by respondents. Socio-demographic characteristics and smoking status were recorded in a standardized data collection form. Six thousand and six hundred sixteen respondents completed the study (response rate of 75.9 %) which constituted a representative sample of the adult resident population in Singapore. Ethnicity, gender and education status were associated with obesity. There was an interaction effect between ethnicity smoking status, and BMI. Indian and Malay smokers were less likely to be obese compared to Chinese smokers. The relationship between ethnicity and BMI was thus reversed when smoking was taken into account. The study identified certain subgroups and risk factors that are associated with obesity. There is a need for further research to explore and identify genetic, metabolic and ethnic differences that underlie the interaction between ethnicity and smoking status which affects BMI.


Bacterial endotoxin lipopolysaccharide induces up-regulation of glyceraldehyde-3-phosphate dehydrogenase in rat liver and lungs.
Bacterial endotoxin or lipopolysaccharide (LPS) can trigger inflammatory responses and cause damage in organs such as liver and lungs when it is introduced into mammals, but the exact molecular events that mediate these responses have remained obscure. In this study, by using 2D gel electrophoresis and cDNA microarray analysis, we found that both protein and mRNA levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were significantly increased in rat liver and lungs after treatment with LPS. The results were further confirmed by Western blot and Northern blot. Given the known role of GAPDH in inducing apoptosis, our results suggest that LPS-induced GAPDH up-regulation may be an important mechanism responsible for the damage induced by Gram negative bacteria in mammalian tissue and GAPDH may be involved in the signaling pathway of LPS induced apoptosis. Our results also demonstrate that GAPDH is not a suitable internal control in gene expression studies, especially when bacterial infection is involved.


Genetic relationships among strains of Salmonella enteritidis in a national epidemic in Switzerland.
A collection of Salmonella enteritidis strains isolated in Switzerland (1965-90) was characterized. The phage type and plasmid profile of isolates were compared with the copy number and insertion loci of the DNA insertion element IS200. Three clonal lines of S. enteritidis were identified by IS200 profile; the various phage types were subtypes reproducibly associated with one of these lines. All human and poultry isolates contained a 38 Mda plasmid which hybridized with a mouse virulence-associated gene probe. In S. enteritidis, the IS200 profile is a race-specific molecular marker of the chromosome, and may be particularly applicable for studying the epidemiology of less common serovars.


A DNA polymerase activity associated with the skeletal framework of the plasma membranes of a rat hepatoma.
A DNA polymerase activity has been identified in the plasma membranes isolated from a rat hepatoma (the Zajdela Ascitic Hepatoma). The enzyme activity was found specifically associated with the detergent insoluble skeleton of the plasma membranes from which it cannot be dissociated by conventional methods. The properties of the enzyme are indistinguishable from those of DNA polymerase-alpha.


Factors Associated with Post-Acute Sequelae of SARS-CoV-2 (PASC) After Diagnosis of Symptomatic COVID-19 in the Inpatient and Outpatient Setting in a Diverse Cohort.
The incidence of persistent clinical symptoms and risk factors in Post-Acute Sequelae of SARS-CoV-2 (PASC) in diverse US cohorts is unclear. While there are a disproportionate share of COVID-19 deaths in older patients, ethnic minorities, and socially disadvantaged populations in the USA, little information is available on the association of these factors and PASC. To evaluate the association of demographic and clinical characteristics with development of PASC. Prospective observational cohort of hospitalized and high-risk outpatients, April 2020 to February 2021. One thousand thirty-eight adults with laboratory-confirmed symptomatic COVID-19 infection. Development of PASC determined by patient report of persistent symptoms on questionnaires conducted 60 or 90 days after COVID-19 infection or hospital discharge. Demographic and clinical factors associated with PASC. Of 1,038 patients with longitudinal follow-up, 309 patients (29.8%) developed PASC. The most common persistent symptom was fatigue (31.4%) followed by shortness of breath (15.4%) in hospitalized patients and anosmia (15.9%) in outpatients. Hospitalization for COVID-19 (odds ratio [OR] 1.49, 95% [CI] 1.04-2.14), having diabetes (OR, 1.39; 95% CI 1.02-1.88), and higher BMI (OR, 1.02; 95% CI 1-1.04) were independently associated with PASC. Medicaid compared to commercial insurance (OR, 0.49; 95% CI 0.31-0.77) and having had an organ transplant (OR 0.44, 95% CI, 0.26-0.76) were inversely associated with PASC. Age, race/ethnicity, Social Vulnerability Index, and baseline functional status were not associated with developing PASC. Three in ten survivors with COVID-19 developed a subset of symptoms associated with PASC in our cohort. While ethnic minorities, older age, and social disadvantage are associated with worse acute COVID-19 infection and greater risk of death, our study found no association between these factors and PASC.


Interleukin-1 Gene Cluster Polymorphisms and its Haplotypes may Predict the Risk to Develop Cervical Cancer in Tunisia.
Our study aimed to evaluate the association between IL-1α (4845 G/T), IL-1β (-511C/T) and IL-1RN (VNTR) polymorphisms and risk of cervical cancer. This case-control study investigates three polymorphisms in 130 patients and 260 controls by PCR-restriction fragment length polymorphism (RFLP). The IL-1RN (VNTR) A1/A3 genotype appear as a cervical cancer risk factor (p = 0.048; OR = 2.92; 95 % CI = 1.00-8.74), moreover, the L/2* decreased the risk (p = 0.011; OR = 0.47; 95 % CI = 0.25-0.88) and may be a protective factor against this pathology. Stratified analysis according to the FIGO stage subgroup revealed that the IL-1β-511 T/T genotype and T allele may be a protective factors against cervical cancer development for patients with early stage (p = 0.030; OR = 0.46; 95 % CI = 0.22-0.96) (p = 0.020; OR = 0.68; 95 % CI = 0.48-0.97). However, for the patients with advanced FIGO stage, IL-1RN-VNTR L/2* genotype appear as a protective factor for this pathology (p = 0.023; OR = 0.29; 95 % CI = 0.08-0.99). The (G-T-L) haplotype showed a significant decreased frequency in cervical cancer patients as compared to controls (p = 0.032; OR = 0.53; 95 % CI = 0.29-0.95). In contrast, the (T-T-2*) combination appear a risk factor for the development of cervical cancer (p = 0.018; OR = 1.57; 95 % CI = 1.07-2.30). Our study suggested that IL1 cluster polymorphisms and haplotypes may be a genetic risk factor for cervical cancer.


Sympathetic nerve activity after thoracoscopic cardiac resynchronization therapy in congestive heart failure.
Sympathetic benefits of thoracoscopic cardiac resynchronization therapy (TCRT) in congestive heart failure (CHF) are unknown. We determined cardiac hemodynamics, functional status, and muscle sympathetic nerve activity (MSNA) in a group of TCRT patients. We aimed to compare these patients with CHF patients with cardiac asynchrony (ASY) to substantiate the beneficial effects of TCRT. Eleven patients resynchronized by TCRT 6 +/- 1 months before study inclusion (SYN) and 10 matched ASY patients underwent blood pressure, heart rate, and MSNA recordings. All underwent functional status, cardiac index, and left ventricular ejection fraction (LVEF) assessments. SYN patients had shorter QRS duration and interventricular mechanical delays, longer 6 minute walking distance and lower New York Heart Association class (all P < .05) than ASY patients. MSNA of 56 +/- 2 bursts/min in ASY patients was higher than in SYN patients (48 +/- 3 bursts/min, P < .05). Cardiac index was higher in SYN patients than in ASY patients (2.8 +/- 0.2 versus 1.9 +/- 0.2 L.min.m2, P < .05, respectively). MSNA was highest in the patients with the lowest LVEF (r = -0.49, P < .05), cardiac index (r = -0.48, P < .05) and 6-minute walking distance (r = -0.50, P < .05). Lower sympathetic nerve activities in TCRT patients are related to more favorable cardiac indexes and six minute walking distances suggesting a sympathetic, hemodynamic, and functional improvement by TCRT.


Proapoptotic activity of Caenorhabditis elegans CED-4 protein in Drosophila: implicated mechanisms for caspase activation.
CED-4 protein plays an important role in the induction of programmed cell death in Caenorhabditis elegans through the activation of caspases. However, the precise mechanisms by which it activates caspases remain unknown. To investigate the conservation of CED-4 function in evolution, transgenic Drosophila lines that express CED-4 in the compound eye were generated. Ectopic expression of CED-4 in the eyes induced massive apoptotic cell death through caspase activation. An ATP-binding site (P-loop) mutation in CED-4 (K165R) causes a loss of function in its ability to activate Drosophila caspase, and an ATPase inhibitor blocks the CED-4-dependent caspase activity in Drosophila S2 cells. Immunoprecipitation analysis showed that both CED-4 and CED-4 (K165R) bind directly to Drosophila caspase drICE, and the overexpression of CED-4 (K165R) inhibits CED-4-, ecdysone-, or cycloheximide-dependent caspase activation in S2 cells. Furthermore, CED-4 (K165R) partially prevented cell death induced by CED-4 in Drosophila compound eyes. Thus, CED-4 function is evolutionarily conserved in Drosophila, and the molecular mechanisms by which CED-4 activates caspases might require ATP binding and direct interaction with the caspases.


Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation.
Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p ≤ 0.001]. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2-4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 [95% CI: 1.06-3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.


Comparison of the cytoplasmic antigens of leprosy-derived corynebacteria and some mycobacteria.
The immunological relationship between leprosy-derived corynebacteria (LDC) and reference mycobacteria was analysed by crossed immunoelectrophoresis with intermediate gel. For this purpose, three reference systems (LDC15/anti-LDC15, LDC18/anti-LDC8, and LDC8/anti-LDC8) were developed. They showed 15 to 20 distinct antigenic components in LDC cytoplasm. Extensive cross-reactivity was observed among different LDC isolates, affecting 3 to 17 components. Moreover, several components were shown to cross-react with mycobacteria when anti-bacillus Calmette-Guérin (BCG), anti-Mycobacterium leprae, other antisera and lepromatous leprosy sera were incorporated in the intermediate gel. The major cross-reactive component, antigen M, was present in all LDC isolates and cross-reacted with antigen 7 of M. leprae and antigen 60 of M. bovis BCG. The thermostability of these antigens and the specificity of the cross-reacting antigens were assessed. The data underline the degree of immunochemical homogeneity within the LDC group of micro-organisms and relatedness with M. leprae and other mycobacteria.


How to perform transcaval access and closure for transcatheter aortic valve implantation.
Transcaval, or caval-aortic, access is a promising approach for fully percutaneous transcatheter aortic valve implantation in patients without good conventional access options. This tutorial review provides step-by-step guidance to planning and executing the procedure, along with approaches to remedy complications.


Synovial chondromatosis: a case series and review of the literature.
This case series reviews 2 patients worked up and treated for unilateral synovial chondromatosis of the temporomandibular joint (TMJ). The first was a 58-year-old female evaluated and treated for synovial chondromatosis of the left TMJ using an arthrotomy of the joint to remove the cartilaginous and osteocartilaginous nodules. The second is a 63-year-old male who was evaluated and treated for synovial chondromatosis of the right TMJ with the removal of extracapsular masses and an arthrotomy with intra-joint removal of nodules. Six-year radiographic follow-up demonstrated no recurrence of the pathology in his case. The cases are reviewed in this article, along with a current review of the literature.


Overcrowded housing reduces COVID-19 mitigation measures and lowers emotional health among San Diego refugees from September to November of 2020.
Refugee communities are vulnerable to housing insecurity, which drives numerous health disparity outcomes in a historically marginalized population. The COVID-19 pandemic has only worsened the ongoing affordable housing crisis in the United States while continuing to highlight disparities in health outcomes across populations. We conducted interviewer-administered surveys with refugee and asylum seekers in San Diego County at the height of the COVID-19 pandemic to understand the social effects and drivers of COVID-19 in one of the largest refugee communities in the United States. Staff from a community-based refugee advocacy and research organization administered the surveys from September-November 2020. 544 respondents participated in the survey, which captured the diversity of the San Diego refugee community including East African (38%), Middle Eastern (35%), Afghan (17%), and Southeast Asian (11%) participants. Nearly two-thirds of respondents (65%) reported living in overcrowded conditions (> 1 individual per room) and 30% in severely crowded conditions (> 1.5 individuals per room). For each additional person per room, self-reported poor emotional health increased. Conversely, family size was associated with a lower likelihood of reporting poor emotional health. Crowded housing was significantly associated with a lower probability of accessing a COVID-19 diagnostic test, with every additional reported person per room there was approximately an 11% increase in the probability of having never accessed a COVID-19 testing. Access to affordable housing had the largest effect size and was associated with fewer people per room. Overcrowding housing is a structural burden that reduces COVID-19 risk mitigation behaviors. Improved access to affordable housing units or receiving vouchers could reduce overcrowded housing in vulnerable refugee communities.


Impact of Perioperative Steroid Administration in Patients Undergoing Major Hepatectomy with Extrahepatic Bile Duct Resection: A Randomized Controlled Trial.
To date, five randomized controlled trials have assessed the clinical benefit of perioperative steroid administration in hepatectomy; however, all of these studies involved a substantial number of 'minor' hepatectomies. The benefit of steroid administration for patients undergoing 'complex' hepatectomy, such as major hepatectomy with extrahepatic bile duct resection, is still unclear. This study aimed to evaluate the clinical benefit of perioperative steroid administration for complex major hepatectomy. Patients with suspected hilar malignancy scheduled to undergo major hepatectomy with extrahepatic bile duct resection were randomized into either the control or steroid groups. The steroid group received hydrocortisone 500 mg immediately before hepatic pedicle clamping, followed by hydrocortisone 300 mg on postoperative day (POD) 1, 200 mg on POD 2, and 100 mg on POD 3. The control group received only physiologic saline. The primary endpoint was the incidence of postoperative liver failure. A total of 94 patients were randomized to either the control (n = 46) or steroid (n = 48) groups. The two groups had similar baseline characteristics; however, there were no significant differences between the groups in the incidence of grade B/C postoperative liver failure (control group, n = 8, 17%; steroid group, n = 4, 8%; p = 0.188) and other complications. Serum bilirubin levels on PODs 2 and 3 were significantly lower in the steroid group than those in the control group; however, these median values were within normal limits in both groups. Perioperative steroid administration did not reduce the risk of postoperative complications, including liver failure following major hepatectomy with extrahepatic bile duct resection.


Emil Kraepelin's ideas on transcultural psychiatry.
Prevailing degeneration theory and an increasing number of people in inpatient mental treatment aroused the famous German psychiatrist Emil Kraepelin's (1856-1926) interest to investigate whether the mental illnesses typical for Europe were also characteristic for 'primitive peoples'. He thus dedicated a period spent in the Dutch East Indies (Java) in 1904 to transcultural psychiatric research. This paper endeavours to compile Kraepelin's key findings, aiming to make readers aware of what kind of transcultural research Kraepelin did and what conclusions he came up with. At the same time it provides some background for the question of whether Kraepelin can really be referred to as the founder of transcultural psychiatry. Kraepelin assumed that illnesses with exterior causes depended on the type of stimulants widely used in a given culture. Since he found little evidence for progressive paralysis, he concluded that European brains were particularly prone to sequelae of syphilis. For endogenous psychoses he postulated differences in both symptoms and courses, depressions being rarer and milder, and ceasing sooner. By contrast, he found dementia praecox (mainly covered by the concept of schizophrenias later) to be the most prevalent mental illness in Java, explicitly different in form from that in Europe.


The effects of hypoxia acclimation, exercise training and fasting on swimming performance in juvenile qingbo (Spinibarbus sinensis).
To investigate the effects of hypoxia acclimation, exercise training and fasting on the swimming performance of juvenile qingbo (Spinibarbus sinensis), we measured the critical swimming speed (U (crit)), resting and excess post-exercise oxygen consumption (EPOC) of control, hypoxia-acclimated, exercise-acclimated and fasting fish at 25°C. The muscle and plasma metabolites before and after a bout of exhaustive exercise (produced by chasing) were also measured. The fish were acclimated to hypoxia (48 h at 1.0 mg L(-1), 12.5% air saturation), exercise training (2 weeks at 60% of U (crit), 6 h daily) or fasting (2 weeks). All treatments resulted in significantly lower resting oxygen consumption ([Formula: see text]O(2rest)) but had no effect on the magnitude of EPOC. Hypoxia acclimation had no effect on U (crit) or peak post-exercise oxygen consumption ([Formula: see text]O(2peak)) but produced a higher depletion of muscle [glycogen] post-chasing (P < 0.05). Exercise training produced a significant increase in U (crit), higher liver [glycogen] pre-chasing and higher depletion of muscle [glycogen] post-chasing. Fasting resulted in a significant decrease in U (crit), [Formula: see text]O(2peak), muscle and liver [glycogen]. These results suggested that hypoxia acclimation had no effect on swimming performance in qingbo. Exercise training produced improved swimming performance by increasing the stored energy and the metabolic capacity of muscle. Fasting had a profound effect on swimming performance through both decreased respiratory capacity and a depleted energy store.


Does adjusting for biological maturity when calculating child weight status improve the accuracy of predicting future health risk?
The aim of this study was to assess whether adjusting the weight categorisation of children for their biological maturity status could improve the accuracy of predicting weight status and cardiometabolic risk at age 17. Data from 1525 participants (787 female) from the ALSPAC study were analysed. Participants' weight status at age 11 was estimated using first standard chronological age and sex adjusted BMI cut-offs, and again using maturity adjusted BMI cut-offs. Each BMI category at age 11 was regressed against cardiometabolic risk score and BMI category at age 17, controlling for sex, ethnicity and socio-economic status. At age 11 years, 22% of boys and 46% of girls who were categorised as overweight or having obesity based on chronological age were re-categorised into a lower BMI category after adjusting for biological maturity. Biologically adjusted BMI categories better predicted BMI category at age 17 compared with non-adjusted BMI categories (∆BIC = - 21.69); the odds of having obesity at age 17 were 18.28 times greater with each increase in BMI category at age 11. Adjusted and non-adjusted BMI status at 11 years showed equivalent accuracy in predicting cardiometabolic risk at age 17; the odds ratio of high cardiometabolic risk was 1.85, with heightened risk in boys, particularly early maturers. The traditional method of categorising adolescents into a BMI category may over-predict overweight and obesity, particularly in girls. Adjusting for biological maturity when estimating weight status through calculating adolescents' BMI classification was equivalent to standard approaches in predicting other cardiovascular risk at age 17.


BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis.
The execution phase of apoptosis is characterized by marked changes in cell morphology that include contraction and membrane blebbing. Little is known about the mechanisms underlying this process. We report here the identification of a novel member of BNIPL family, designated Bcl-2/adenovirus E1B 19kDa interacting protein 2 like-2 (BNIPL-2), which interacts with Bcl-2 and Cdc42GAP. We found that the human BNIPL-2 shares homology to human BNIP-2 and also possesses a BNIP-2 and Cdc42GAP homology (BCH) domain. Deletion experiments indicated that the BCH domain of BNIPL-2 is critical for its interactions with the Bcl-2 and Cdc42GAP and also for its cell death-inducing function. Our data showed that BNIPL-2 may be a linker protein located at the front end of Bcl-2 pathway for DNA fragmentation and Cdc42 signaling for morphological changes during apoptosis. We propose that BNIPL-2 protein may play an important role in regulation of both pathways for DNA fragmentation and for formation of membrane blebs in apoptotic cells.


The first Nocticola Bolivar 1892 (Blattodea: Nocticolidae) from New Guinea.
A new species of highly troglobitic cockroach, Nocticola baumi n. sp., is described from limestone caves of Papua Province, Indonesia. The new species is the first Nocticola reported in New Guinea island and differs from other known Nocticola spp. by the combination of the following characters: compound eyes and ocelli absent, tegmina fully developed extending beyond the abdomen, hind wings absent, legs extremely long. The discovery of the genus on New Guinea bridges the gap between Oriental and Australian distribution of the genus and stresses the unknown diversity of the genus.


Na+/H+ exchange in porcine cerebral capillary endothelial cells is inhibited by a benzoylguanidine derivative.
Na+/H+ exchange activity has been examined in endothelial cells isolated from porcine brain capillaries. Intracellular pH (pHi) changes were monitored using a confocal laser scanning microscope and the pH-sensitive fluorescence indicator 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF). Acid load of the brain capillary endothelial cells was performed with a NH4Cl (20 mM) prepulse. In bicarbonate-free solutions pHi recovered within 3 to 10 min. Removal of extracellular Na+ ions demonstrated that H+ extrusion after an acid load of the cells was Na+ dependent. The Na+/H+ exchange could be completely blocked by EIPA (5-(N-ethyl-N-isopropyl)amiloride) as well as by the novel inhibitor 3-methylsulfonyl-4-piperidinobenzoyl guanidine hydrochloride (HOE 694) in concentrations of 1 to 10 microM, respectively. EIPA and HOE 694 in a concentration of 0.1 microM caused a partial block of Na+/H+ exchange.


Rapid point-of-care test to detect broad ranges of protective antigen-specific immunoglobulin G concentrations in recipients of the U.S.-licensed anthrax vaccine.
Currently, there is no routine monitoring of an immune response to the anthrax vaccine. Simple on-site tests are needed to evaluate the antibody response of anthrax-vaccinated individuals in the Armed Forces and others at high risk. Using a prototype lateral flow assay (LFA) (R. E. Biagini, D. L. Sammons, J. P. Smith, B. A. MacKenzie, C. A. F. Striley, J. E. Snawder, S. A. Robertson, and C. P. Quinn, Clin. Vaccine Immunol. 13:541-546, 2006), we investigated the agreement between a validated anthrax protective antigen (PA) immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and the LFA for 335 unvaccinated and vaccinated subjects. We also investigated the performance of the LFA under the following conditions: thermal shock (i.e., thermal cycling between temperature extremes), high temperature/high relative humidity, high temperature/low relative humidity, and low temperature/low relative humidity. With the anti-PA ELISA used as a standard, the LFA was shown to be optimally diagnostic at 11 microg/ml anti-PA-specific IgG. At this concentration, the LFA specificity and sensitivity were 98% (95% confidence interval [CI], 97% to 100%) and 92% (CI, 88% to 97%), respectively. Receiver operating characteristic curve analysis yielded an area under the curve value of 0.988 (CI, 0.976 to 1.00), suggesting that the LFA is an extremely accurate diagnostic test. For < or = 4 or > or = 50 microg/ml PA-specific IgG, the LFA results for each environmental condition were identical to those obtained in the laboratory. These data indicate that this rapid point-of-care test would be a feasible tool in monitoring the serological antibody responses of individuals that have been vaccinated against anthrax.


Aging and hormones of the hypothalamo-pituitary axis: gonadotropic axis in men and somatotropic axes in men and women.
Neuroendocrinology of the aging (male) gonadal and (male and female) somatotropic axes will be reviewed. A companion chapter discusses reproductive hormonal changes in aging women. Both the gonadal and growth-hormone/insulin-like growth factor (GH/IGF-I) axes function as ensembles. The ensembles comprise tripartite interactions among the brain (hypothalamus), anterior pituitary gland (gonadotrope and somatotrope cells) and target organs (testis, liver, muscle, fat and brain). Compelling evidence indicates that combined hypothalamic and gonadal adaptations operate in the reproductive axis of older men, and multiple hypothalamic adaptations prevail in the GH axis of elderly men and women. Evolving investigative methods allow more precise parsing of the particular mechanisms that subserve such age-related changes, and suggest novel interventional strategies to evaluate the physiological impact of the dynamic alterations discerned in aging individuals.


Diverse effects of mutations in the signal sequence on the secretion of beta-lactamase in Salmonella typhimurium.
Mutations in the beta-lactamase structural gene that alter the signal peptide were used to study secretion into the periplasm of Salmonella typhimurium. Processing and cellular location of mutant gene products were followed by pulse-chase and cell-fractionation experiments and by trypsin accessibility in intact and lysed spheroplasts. The precursor proteins examined never appear as a free species in the periplasm. Two of the signal-sequence mutants accumulate a precursor form that is trypsin-accessible in intact spheroplasts; the precursors synthesized by the remaining mutants resemble wild-type in that they remain trypsin-inaccessible. One of the latter mutants does produce mature protein, but at a very reduced rate. It thus appears that signal-sequence mutations can affect more than one step in the secretion process, and that processing of the signal peptide is not required for the protein to be translocated (at least partially) across the inner membrane.


Preoperative hyperthermochemoradiotherapy for esophageal carcinoma.
In order to acquire an improved prognosis, preoperative hyperthermia combined with chemotherapy and radiotherapy (HCR) has been performed in our department for patients with esophageal carcinoma. The experimental and clinical investigations that have been continuously performed in our department were introduced with regard to the therapeutic effect brought by HCR for carcinoma, chiefly for esophageal carcinoma. A series of our investigations have demonstrated the excellent anticancer effect of HCR for esophageal carcinoma. Preoperative HCR has contributed to improvements in the prognosis of patients with esophageal carcinoma and is expected to make marked progress in the future with further development of anticancer agents and improvements in the hyperthermia devices.


Incidental learning of image-mediated or pronounced words after right temporal lobectomy.
The use of visual images in word recall by patients with right temporal lobectomy was studied by testing the incidental learning of 40 (20 abstract, 20 concrete) words that had been either carefully pronounced or the referent visualized. When tested immediately after presentation of the list, the right temporal-lobe group (N = 30) did not differ from a matched normal control group, but in delayed recall 2 hours later the patient group showed impaired recall of concrete words that had been visualized. Recall of visualized abstract words was also poor but not significantly so, while pronounced words, whether abstract or concrete, were recalled normally. Further analysis revealed an impaired recall for visualized concrete words in both immediate and delayed testing in patients having a large right hippocampal removal, indicating an important role of the mesial temporal structures in image recall.