Alterations of Hematological Parameters, Hemoglobin and Hematocrit With Liver Enzymes, Aspartate Transaminase and Alanine Transaminase Among Patients With Chronic Kidney Disease Undergoing Hemodialysis in Aljouf Region, Saudi Arabia.
Anemia results from low kidney production of the erythropoiesis-stimulant erythropoietin. Good liver function is crucial to patients with chronic kidney disease (CKD). This study analyzed two hematological parameters (hemoglobin (Hb) and hematocrit (Ht)) and two liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with CKD undergoing hemodialysis (HD). Three hundred and thirty individuals participated in this study. Of them, 159 patients with CKD undergoing HD and 171 healthy individuals as a control group were recruited between January and October 2017. Blood was collected into EDTA containers for complete blood count (CBC) and into additive plain containers for ALT and AST. Relevant case history data were also taken. Obtained results for first and second month of Hb, Ht, AST and ALT of CKD patients undergoing HD were lower (10.2 g/dL and 8.9 for Hb; 27.2% and 24.8% for Ht; 17.8 IU/L and 15.6 IU/L for ALT; 13.9 IU/L and 12.0 IU/L for AST, respectively) (P < 0.05) compared to healthy individuals (15.1 g/dL for Hb; 44.6% for Ht; 28.3 IU/L for ALT and 23.0 IU/L for AST). Furthermore, Hb, Ht, AST and ALT levels were significantly lower (P < 0.05) in their second month compared to the first month. Anemia might emerge in CKD patients because of low Hb concentration and consequent low Ht. Advanced stage CKD causes decreased AST and ALT, as a result of lipid metabolism disturbances. Therefore, anemia and liver diseases are recommended to be treated in CKD patients to alleviate related complications. Renal transplantation must be performed earlier for them to avoid further complications.


Chorionic somatomammotrophin as index of fetal growth.
Concentrations of chorionic somatomammotrophin (hCS) in maternal plasma at the time of delivery and in placental extracts were determined by radioimmunoassay and related to neonatal growth in 111 normal pregnancies. Mean maternal plasma hCS concentration was lower in association with small-for-dates infants, defined by either height or weight, than with well-grown preterm or term infants. Mean placental hCS concentration was not decreased in association with undergrown infants though placental hCS was correlated with maternal hCS (r=0 - 245).


Does inadequate oxygen delivery trigger pressor response to muscle hypoperfusion during exercise?
In dogs running on a treadmill at 2 or 4 mph or 4 mph plus 10% incline, graded reductions in hindlimb perfusion reflexly elicited pressor responses. To test the idea that systemic arterial pressure (SAP) is raised by accumulation in muscle of a nerve-activating "pressor substance" release when O2 delivery becomes inadequate, arterial O2 content (CaO2) was reduced 29.1% by carbon monoxide (CO) inhalation before repeating exercise at 2 mph. We reasoned that the pressor substance, or related substances, should appear in femoral venous blood and be correlated to SAP. [K+] behaved inappropriately as a signal to raise SAP, i.e., when flow was reduced, SAP rose markedly with little or no change in [K+]. SAP was well correlated to pH and [lactate] over the three work loads. Compared with the same work load with normal CaO2, CO shifted the relation between SAP and terminal aortic flow rightward 0.30 l/min (34.5%) and the relation between SAP and PO2 leftward 7.7 mmHg. CO did not affect the relation of SAP to terminal aortic O2 delivery, hindlimb O2 uptake index, pH, or [lactate]. Thus pressor responses are apparently generated when O2 delivery falls below some critical level causing accumulation of a pressor substance the release of which is linked to a metabolic event that precipitates lactate accumulation.


Potential hazards of selenium as a chemopreventive agent.
Clinical and metabolic features of the trace element selenium and the full spectrum of its animal and human toxicity have been reviewed. The difficulties in coming to an easy understanding of the biologic properties of selenium stem from its multiple forms and complex metabolic and biochemical pathways. It is suggested that chemoprevention trials focus on the efficacy of organic and inorganic prototype forms such as selenomethionine and the selenite ion. While some appreciation of the toxic potential of these two prototype forms can be predicted from existing information, additional formal toxicology will be necessary, particularly for selenomethionine.


Sparrows learn adult song and more from memory.
Male swamp sparrows reared in the laboratory and exposed to taped songs during infancy produce accurate imitations of the material following an 8-month interval with no rehearsal. When the first rehearsal occurs, at about 300 days of age, large numbers of syllables are perfected. They are developed through invention and improvisation as well as imitation. Most are discarded at the time of song crystallization. Hence, these songbirds learn more than they manifest in full adult song.


MIL-53 Metal-Organic Framework as a Flexible Cathode for Lithium-Oxygen Batteries.
Li-air batteries possess higher specific energies than the current Li-ion batteries. Major drawbacks of the air cathode include the sluggish kinetics of the oxygen reduction (OER), high overpotentials and pore clogging during discharge processes. Metal-Organic Frameworks (MOFs) appear as promising materials because of their high surface areas, tailorable pore sizes and catalytic centers. In this work, we propose to use, for the first time, aluminum terephthalate (well known as MIL-53) as a flexible air cathode for Li-O2 batteries. This compound was synthetized through hydrothermal and microwave-assisted routes, leading to different particle sizes with different aspect ratios. The electrochemical properties of both materials seem to be equivalent. Several behaviors are observed depending on the initial value of the first discharge capacity. When the first discharge capacity is higher, no OER occurs, leading to a fast decrease in the capacity during cycling. The nature and the morphology of the discharge products are investigated using ex situ analysis (XRD, SEM and XPS). For both MIL-53 materials, lithium peroxide Li2O2 is found as the main discharge product. A morphological evolution of the Li2O2 particles occurs upon cycling (stacked thin plates, toroids or pseudo-spheres).


Stability-indicating HPLC Method for Simultaneous Determination of Montelukast and Fexofenadine Hydrochloride.
A simple, specific, accurate, and stability-indicating reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of montelukast and fexofenadine hydrochloride, using a Lichrospher(®) 100, RP-18e column and a mobile phase composed of methanol:0.1% o-phosphoric acid (90:10 v/v), pH 6.8. The retention times of montelukast and fexofenadine hydrochloride were found to be 10.16 and 12.03 min, respectively. Linearity was established for montelukast and fexofenadine hydrochloride in the range of 2-10 μg/ml and 24-120 μg/ml, respectively. The percentage recoveries of montelukast and fexofenadine hydrochloride were found to be in the range of 99.09 and 99.81%, respectively. Both the drugs were subjected to acid and base hydrolysis, oxidation, photolytic, and thermal degradation conditions. The degradation products of montelukast and fexofenadine hydrochloride were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of montelukast and fexofenadine hydrochloride in bulk drugs and formulations.


Chrysanthemum coronarium L. Extract Attenuates Homocysteine-Induced Vascular Inflammation in Vascular Smooth Muscle Cells.
Hyperhomocysteinemia is a main risk factor for phenotypic modulation of vascular smooth muscle cells (VSMCs) and atherosclerosis. Phenotypic switching and proliferation of VSMCs are related to the progression of vascular inflammation. Chrysanthemum coronarium L. is a leafy vegetable with various biological functions, such as antioxidative, anti-inflammatory, and antiproliferative effects. In this study, we aimed to identify the mechanisms underlying the therapeutic and preventive effects of C. coronarium L. extract (CC) in regulating homocysteine (Hcy)-induced vascular inflammation in human aortic VSMCs. CC did not exhibit cytotoxicity and inhibited Hcy-stimulated VSMC proliferation and migration. In addition, CC promoted Hcy-induced expression of VSMC contractile phenotype proteins, including alpha-smooth muscle actin, calponin, and smooth muscle 22α. CC also decreased Hcy-induced accumulation of reactive oxygen species and expression of inflammatory markers nicotinamide adenine dinucleotide phosphate oxidase-4 and soluble epoxide hydrolase. These results showed that CC attenuates Hcy-induced inflammatory responses, highlighting its potential as a therapeutic or preventive target for Hcy-induced vascular inflammation.


Specific arrests of spermatogenesis in genetically modified and mutant mice.
In naturally occurring mutant mice but also in mice genetically modified for the study of other organs, relatively often a spermatogenic arrest is seen. In a number of cases the arrests appear to be very specific causing apoptosis of germ cells at a particular step in their development, while before this step cells progress normally. These steps include: proliferation/migration of primordial germ cells, the production of differentiating spermatogonia by gonocytes, the regulation of stem cell renewal/differentiation, the differentiation of A(al) into A1 spermatogonia, proliferation of A1-A4 spermatogonia, germ cell density regulation, start of meiosis, epithelial stage IV checkpoint of pachytene spermatocytes, the first meiotic division, the formation of the acrosomic vesicle in spermatids and several other steps in spermatid development. In addition, there are many mice that have not been studied in enough detail for a proper categorization. In this review an overview is given of the various mutations and genetically modified mice showing a direct effect on specific spermatogenic cell types. In addition, the relevance of these models to our understanding of the spermatogenic process is discussed.


Coccidioidomycosis: a regional disease of national importance. Rethinking approaches for control.
Coccidioidomycosis is an increasingly important health problem because of the migration of large numbers of persons to portions of the southwestern United States in which the disease is endemic and because of the increasing numbers of immunosuppressed patients. Most infections due to Coccidioides immitis, although causing significant illness, are self-limited and resolve over a period of weeks to months without specific treatment. It is not known whether antifungal treatment of early infections hastens resolution of the primary illness or prevents complications. Even so, diagnosis of early infections is of value for allaying patient anxiety, lessening the need for further diagnostic studies, decreasing empirical use of antibacterial agents, and facilitating early identification of patients with complications that are more serious. Patients who develop chronic coccidioidal pneumonia or extrapulmonary infection often have complicated courses that require the involvement of various medical, surgical, and radiologic subspecialties for management. Improvement of the ability to control the problem of coccidioidomycosis will require research into the molecular and cellular biology of C. immitis, vaccine development to prevent coccidioidal infection, a better understanding of the soil ecology that supports the fungus in its endemic regions, and discovery of new antifungal drugs. In addition, government agencies, colleges, the military, and employers could improve public health by initiating education programs about the most common manifestations of the disease among persons at risk for infection.


Relative importance of CCR5 and antineutrophil cytoplasmic antibodies in patients with Wegener's granulomatosis.
Wegener's granulomatosis (WG) is an idiopathic inflammatory condition characterized by upper and lower airway involvement and often renal dysfunction. Sites of tissue injury include pleomorphic cell populations, and classically mononuclear cell infiltrates that may form granulomas. Vascular inflammation (i.e., vasculitis) is often but not always present. Because CCR5 and its ligands influence mononuclear cell trafficking, we sought to identify their expression in pulmonary lesions and to determine whether genetic variations in genes for CCR5 and its ligands influence susceptibility to WG. Lung biopsies from 4 patients that had classical features of WG were examined for protein expression of CCR5, RANTES, MIP-1alpha and MIP-1beta using immunohistochemistry. One hundred eighteen Caucasian patients with WG and 127 ethnically matched healthy controls were included in the genetic analysis. Genomic DNA samples were amplified by PCR. CCR5 Delta32 and RANTES -28 and -401 polymorphisms were determined by either specific primers or direct sequencing. CCR5+ cells were enriched in lung lesions from patients with WG. Enhanced protein concentrations of RANTES, MIP-1alpha, and MIP-1beta were present in WG lung lesions, indicating redundancy of ligands for CCR5 in affected tissue. Genetic analyses revealed 3 subsets of patients with WG: (1) circulating antineutrophil cytoplasmic antibody (ANCA) positive and CCR5+/+ (58%); (2) CCR5+/+ and ANCA negative (22%); and (3) CCR5 Delta32 and ANCA positive (20%). Among patients in whom ANCA were repeatedly absent, none was found to carry the CCR5 Delta32 allele. Conversely, patients who possessed the CCR5 Delta32 allele were always ANCA positive. CCR5 and its ligands are abundantly present in pulmonary lesions in WG. The absence of a genetic deletion for CCR5 (CCR5 Delta32) in WG patients lacking ANCA suggests that CCR5 may exert a particularly important pathogenetic role in those patients. Another subset of patients (approximately 20%) with WG possessed a genetic deletion for CCR5. That each of these patients was ANCA positive implies that an alternative pathway to CCR5 may exist, for which ANCA may be especially important.


Assessment of attractiveness of cassava as a roosting plant for the melon fly, Bactrocera cucurbitae, and the Oriental fruit fly, B. dorsalis.
Application of bait spray to crop borders is a standard approach for suppression of melon fly, Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae) populations and may also be of value for suppression of oriental fruit fly, B. dorsalis (Hendel) populations. Establishment of preferred roosting hosts as crop borders may help to improve suppression of both fruit fly species by providing sites for bait spray applications. In an area-wide B. cucurbitae suppression trial, the question was raised as to whether cassava, Manihot esculenta Crantz (Euphorbiales: Euphorbiaceae), could be used as a B. cucurbitae roosting host. M. esculenta was of interest as a roosting host because, in contrast to many other identified preferred roosting hosts, it would also be a crop potentially increasing the productivity of the crop production system overall. As a short-lived and shrubby perennial, M. esculenta potentially constitutes a crop with more persistent roosting foliage than an annual crop such as corn, Zea mays L. (Cyperales: Poaceae), that has often been planted as a roosting host for B. cucurbitae control. Using protein-baited traps set amidst potted plants placed adjacent to a papaya Carica papaya L. (Violales: Caricaceae) orchard known to have established populations of B. cucurbitae and B. dorsalis, the effectiveness of M. esculenta as a roosting host was assessed by comparing its attractiveness to that of castor bean, Ricinus communis L (Malpighiales: Euphorbiaceae), previously identified as one of the most attractive roosting hosts for B. cucurbitae, and to corn, a crop which has been planted as a roosting host for help in B. cucurbitae control. The results showed that use of M. esculenta as a roosting host is comparable to use of R. communis by both B. cucurbitae and B. dorsalis. These results provide encouragement to incorporate M. esculenta on a farm as a trap crop (i.e. site for bait spray application). This has the advantage of having the trap crop be a crop on its own (as opposed to castor bean) and, among prospective crops that could be used as a trap crop, has foliage more persistent than an annual trap crop such as corn.


Oxcarbazepine add-on for drug-resistant focal epilepsy.
Epilepsy is a common neurological disorder. In approximately 30% of epilepsy cases, seizures are uncontrolled by one antiepileptic drug (AED). These people require treatment with a combination of multiple AEDs and are described as having drug-resistant epilepsy. Oxcarbazepine is a keto-analogue of carbamazepine, an established AED, and can be used as an add-on treatment for drug-resistant epilepsy. To assess the efficacy and tolerability of oxcarbazepine as an add-on treatment for people with drug-resistant focal epilepsy. The following databases were searched on 24 September 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); Medline (Ovid) 1946 to 21 September 2018; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Originally, we also searched SCOPUS as a substitute for Embase, but this is no longer necessary, because randomised and quasi-randomised controlled trials in Embase are now included in CENTRAL. Randomised controlled trials with parallel-group or cross-over design, recruiting people of any age with drug-resistant focal epilepsy. We accepted any level of blinding and trials could be placebo- or active-controlled. In accordance with the methodological procedures expected by the Cochrane Collaboration, two review authors independently assessed trial eligibility before extracting data and assessing risk of bias. We assessed the primary outcomes: median percentage seizure reduction per 28 days; 50% or greater reduction in seizure frequency; and adverse effects including ataxia, hyponatraemia, and somnolence. We assessed the secondary outcomes: seizure freedom; treatment withdrawal; cognitive effects; and quality of life. We used an intention-to-treat population for all primary analyses. We present results as risk ratios (RR) with 95% confidence intervals (CI), with the exception of adverse effects which we present with 99% CI. We identified six eligible studies, involving 1593 participants. We judged that three studies were at unclear risk of bias and three were at high risk of bias. Bias mainly arose from lack of methodological details and from high attrition rates. Participants were aged 1 month to 65 years, with a diagnosis of drug-resistant focal epilepsy. All studies were either placebo- or alternative-dose-controlled with parallel-group design. The treatment period varied from 9 days to 26 weeks. The median percentage seizure reduction per 28 days (3 studies; moderate-certainty evidence) ranged from 26% to 83.3% for participants randomised to experimental oxcarbazepine compared to 7.6% to 28.7% for participants randomised to control treatment. Oxcarbazepine may increase the responder rate for 50% or greater reduction in seizure frequency compared to control treatment (RR 1.80, 95% CI 1.27 to 2.56; random-effects model; 6 studies; low-certainty evidence). For seizure freedom, the RR was 2.86 (95% CI 1.19 to 6.87; random-effects model; 5 studies; low-certainty evidence), suggesting an advantageous effectiveness of oxcarbazepine over control treatment. Treatment with oxcarbazepine was associated with an increased treatment withdrawal rate compared to control (RR 1.75, 95% CI 1.44 to 2.13; fixed-effect model; 6 studies; moderate-certainty evidence). The largest oxcarbazepine dose used, 2400 mg/d, was associated with a higher treatment withdrawal rate (RR 2.38, 95% CI 1.92 to 2.94; fixed-effect model; 2 studies) compared to control, than 1200 mg/d (RR 1.54, 95% CI 1.21 to 1.95; fixed-effect model; 3 studies) or 600 mg/d oxcarbazepine (RR 0.79, 95% CI 0.55 to 1.15; fixed-effect model; 1 study). Treatment with oxcarbazepine was associated with an increased incidence of multiple adverse effects including: ataxia (RR 2.54, 99% CI 0.86 to 7.54; random-effects model; 5 studies; moderate-certainty evidence); and somnolence (RR 2.03, 99% CI 1.17 to 3.54; random-effects model; 6 studies; low-certainty evidence). Hyponatraemia occurred more frequently with oxcarbazepine treatment but not significantly so (RR 2.53, 99% CI 0.27 to 23.85; fixed-effect model; 6 studies; moderate-certainty evidence). Oxcarbazepine might be effective at reducing seizure frequency when used as an add-on for drug-resistant focal epilepsy. The efficacy outcomes - 50% or greater seizure reduction and seizure freedom - were derived from low-certainty evidence. We are, therefore, uncertain whether the estimated effect size is representative of the true effect. In contrast, the evidence for median percentage seizure reduction and treatment withdrawal were of moderate certainty: thus, we are fairly certain of the effect estimates' reliability. Overall, we are unsure of the true efficacy of oxcarbazepine, but have concerns about its tolerability.


Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic Glioma.
Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are prone to the development of low-grade brain tumors (gliomas) within the optic pathway (optic gliomas). One of the key obstacles to developing successful therapeutic strategies for these tumors is the striking lack of information about the mechanical properties that characterize these tumors relative to non-neoplastic optic nerve tissue. To study the physical changes that may occur when an optic nerve glioma is present, we employed atomic force microscopy to measure the stiffness of healthy versus tumor-bearing optic nerve tissue. We found that the average elastic moduli of non-neoplastic and tumor-bearing optic nerves were ∼3 and ∼6 kPa, respectively. Based on previous studies implicating changes in extracellular matrix remodeling in other, related optic nerve pathological states, we found decreased expression of one major metalloproteinase protein (MMP-2) and unchanged expression of lysyl oxidase and a second metalloproteinase, MMP-9, in murine optic gliomas relative to normal non-neoplastic optic nerve. Collectively, these observations suggest a productive interplay between physical properties of mouse optic nerve gliomas and the extracellular matrix.


Tau loss attenuates neuronal network hyperexcitability in mouse and Drosophila genetic models of epilepsy.
Neuronal network hyperexcitability underlies the pathogenesis of seizures and is a component of some degenerative neurological disorders such as Alzheimer's disease (AD). Recently, the microtubule-binding protein tau has been implicated in the regulation of network synchronization. Genetic removal of Mapt, the gene encoding tau, in AD models overexpressing amyloid-β (Aβ) decreases hyperexcitability and normalizes the excitation/inhibition imbalance. Whether this effect of tau removal is specific to Aβ mouse models remains to be determined. Here, we examined tau as an excitability modifier in the non-AD nervous system using genetic deletion of tau in mouse and Drosophila models of hyperexcitability. Kcna1(-/-) mice lack Kv1.1-delayed rectifier currents and exhibit severe spontaneous seizures, early lethality, and megencephaly. Young Kcna1(-/-) mice retained wild-type levels of Aβ, tau, and tau phospho-Thr(231). Decreasing tau in Kcna1(-/-) mice reduced hyperexcitability and alleviated seizure-related comorbidities. Tau reduction decreased Kcna1(-/-) video-EEG recorded seizure frequency and duration as well as normalized Kcna1(-/-) hippocampal network hyperexcitability in vitro. Additionally, tau reduction increased Kcna1(-/-) survival and prevented megencephaly and hippocampal hypertrophy, as determined by MRI. Bang-sensitive Drosophila mutants display paralysis and seizures in response to mechanical stimulation, providing a complementary excitability assay for epistatic interactions. We found that tau reduction significantly decreased seizure sensitivity in two independent bang-sensitive mutant models, kcc and eas. Our results indicate that tau plays a general role in regulating intrinsic neuronal network hyperexcitability independently of Aβ overexpression and suggest that reducing tau function could be a viable target for therapeutic intervention in seizure disorders and antiepileptogenesis.


Stabilization of Pb²⁺ and Cu²⁺ contaminated firing range soil using calcined oyster shells and waste cow bones.
Pb(2+) and Cu(2+) contamination at army firing ranges poses serious environmental and health risks to nearby communities necessitating an immediate and prompt remedial action. In this study, a novel mixture of calcined oyster shells (COSs) and waste cow bones (WCBs) was utilized to immobilize Pb(2+) and Cu(2+) in army firing range soils. The effectiveness of the treatment was evaluated based on the Korean Standard leaching test. The treatment results showed that Pb(2+) and Cu(2+) immobilization in the army firing range soil was effective in significantly reducing Pb(2+) and Cu(2+) leachability upon the combined treatment with COS and WCB. A drastic reduction in Pb(2+) (99%) and Cu(2+) leachability (95%) was obtained as compared to the control sample, upon treatment with 5 wt.% COS and 5 wt.% WCB. The combination treatment of COS and WCB was more effective for Pb immobilization, than the treatment with COS or WCB alone. The 5 wt.% COS alone treatment resulted in 95% reduction in Cu(2+) leachability. The SEM-EDX results suggested that Pb(2+) and Cu(2+) immobilization was most probably associated with the formation of ettringite, pozzolanic reaction products and pyromorphite-like phases at the same time.


Seroprevalence of anti-Gymnorhynchus gigas (Trypanorhyncha, Gymnorhynchidae) antibodies in a Spanish population.
The somatic products released from ingested larvae of Gymnorhynchus gigas parasitizing fish induce a Th2 response capable of causing allergic disorders. The objective of the present work was to evaluate the prevalence of anti-Gymnorhynchus gigas antibodies in a Spanish population and established a possible relationship with fish consumption habits. We studied 305 residents in Madrid, with neither clinical symptoms suggestive of gastrointestinal or allergic disorders, nor pathologies related to ingestion of fish that could cause disease. Specific antibody levels were measured by ELISA: 11.8%, 20%, 15.7%, 21%, and 7.5% of the total studied sera were IgA, Ig's, IgG, IgM, and IgE positive, respectively. Seropositivity was not more prevalent among fresh fish consumers and did not increase with frequency of fish consumption. IgE values were lower in the group that never ingested smoked fish. Anti-G. gigas antibody levels were higher in the group that reported frequent consumption of marinated fish. The use of cooking methods with the least heating efficacy (frying, or frying in batter, and microwaving) did not affect seropositivity percentages among consumers. Infection with live plerocercoids is not necessary for seropositivity, and the antibody production, in this case, is due to the absorption of antigens from the parasite following the digestion process. The human health risks of allergic reactions due to parasite antigens remain active after freezing the fish.


Application of the principles of systems biology and Wiener's cybernetics for analysis of regulation of energy fluxes in muscle cells in vivo.
The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener's cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener's cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures - intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations of cytosolic ADP, Pi and Cr/PCr ensures metabolic stability necessary for normal function of cardiac cells.


[The relationship of damage to and death of ascitic tumor cells during starvation to the ATP and free calcium content in the cells].
Ascite tumor cells EL-4 were incubated in conditions of energy starvation (Hanks salt solution with rothenone and without glucose) at 37 degrees C for 3 hours. Under these conditions, some structural cell damages appeared within the first hours: enlarging and flattening of the cells, blebbing, vacuolization of the cytoplasm, nuclear chromatin condensation. Later on, a share of cells with obvious damage decreased, whereas that of the cells stained with trypan blue (dead cells) much increased (up to 90% after a 3 hour incubation). The cellular ATP decreased abruptly (up to 10% of the control) during the first 10 minutes of starvation. Free Ca2+ concentration increased within 1 hour of incubation more than two-fold. The conditions promoting Ca2+ influx (ionophore A23187 + Ca2+ in medium) accelerated the damage and cell death. However, the increase in free Ca2+ concentration did not trigger any damage in the energy-starved cells, since in the Ca2(+)-depleted medium (no increase in free Ca2(+)-concentration) the development of damages was not prevented. The damage initiation was irreversible: the addition of glucose to cell suspensions after 0.5-1 hour of their incubation in energy-starved condition did not prevent the development of damage, while ATP content in these cells was much increased.


[Assessment of respiratory deterioration with spirometry].
Respiratory impairment was evaluated in 342 smokers and exsmokers patients, aged 21 to 79 years; 195 were male and 147 female, The American Thoracic Society (ATS) recommendations were followed. Pulmonary function tests: VC, FEV1, FVC and FEV1/FVC% were performed, using a Spirometer Spyro Analyzer, model ST-200, Fukuda Sangyo. The actual values of these tests, were compared with predictive values of Corzo, in order to evaluate the severity of respiratory impairment. In this work, respiratory impairment was found in 104 patients (30%) of 342 studied, distributed as follows: 20 (19.2%) in 20-39 years group, 35 (33.7%) in 40-59 years group and 49 (47.1%) in 60-79 years group. In relation to degree of impairment, 55 patients (52.9%) were mildly impaired, 35 (33.7%) moderately impaired and 14 (13.4%) severely impaired. It was found that 60% (21) moderately impaired patients and 64.3% (9) severely impaired were in 60-79 years group. They also had a larger history of cigarette smoking or smoked more than 30 cigarettes daily. Also a higher frequency of obstructive ventilatory defect causing respiratory impairment was found.


Efficient beam converter for the generation of high-power femtosecond vortices.
We describe an optical beam converter for an efficient transformation of Gaussian femtosecond laser beams to single- or double-charge vortex beams. The device achieves a conversion efficiency of 75% for single- and 50% for double-charge vortex beams and can operate with high-energy broad bandwidth pulses. We also show that the topological charge of a femtosecond vortex beam can be determined by analyzing its intensity distribution in the focal area of a cylindrical lens.


The Relationship Between Circulating Endogenous Cannabinoids and the Effects of Smoked Cannabis.
Background: The endogenous cannabinoid system (ECS), including the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), plays an integral role in psychophysiological functions. Although frequent cannabis use is associated with adaptations in the ECS, the impact of acute smoked cannabis administration on circulating eCBs, and the relationship between cannabis effects and circulating eCBs are poorly understood. Methods: This study measured the plasma levels of AEA, 2-AG, and Δ-9-tetrahydrocannabinol (THC), subjective drug-effects ratings, and cardiovascular measures at baseline and 15-180 min after cannabis users (n=26) smoked 70% of a cannabis cigarette (5.6% THC). Results: Cannabis administration increased the ratings of intoxication, heart rate, and plasma THC levels relative to baseline. Although cannabis administration did not affect eCB levels relative to baseline, there was a significant positive correlation between baseline AEA levels and peak ratings of "High" and "Good Drug Effect." Further, baseline 2-AG levels negatively correlated with frequency of cannabis use (mean days/week) and with baseline THC metabolite levels. Conclusions: In a subset of heavy cannabis smokers: (1) more frequent cannabis use was associated with lower baseline 2-AG, and (2) those with lower AEA got less intoxicated after smoking cannabis. These findings contribute to a sparse literature on the interaction between endo- and phyto-cannabinoids. Future studies in participants with varied cannabis use patterns are needed to clarify the association between circulating eCBs and the abuse-related effects of cannabis, and to test whether baseline eCBs predict the intoxicating effects of cannabis and are a potential biomarker of cannabis tolerance.


A literature-based algorithm for the assessment, management, and monitoring of drug-induced QTc prolongation in the psychiatric population.
Certain psychotropics and a number of other medications used to treat medical conditions in psychiatric patients can increase the risk of prolonging the corrected QT (QTc) interval on the electrocardiogram, which puts patients at risk of life-threatening ventricular arrhythmias such as torsades de pointes. Pharmacists are often consulted about medications which are known to prolong the QTc interval. Although this information is often accessible, advising how to identify, assess, manage, and refer psychiatric patients at risk for drug-induced QTc prolongation is more challenging. The objective of this project was first to review the literature, which describes guidelines and recommendations for the assessment and management of drug-induced QTc prolongation, and then to design an algorithm to be used by pharmacists working closely with mental health professionals or who provide care to psychiatric patients. A review of the literature was undertaken. Predefined keywords were used to perform the database search in MEDLINE, EMBASE, and International Pharmaceutical Abstracts to identify reviews, reports and guidelines on the assessment, prevention and monitoring of drug-induced QTc prolongation with an emphasis on psychotropic medications and management in the psychiatric population. The electronic database search retrieved 637 relevant citations. These were initially screened by title and all duplicates were removed. The abstracts were then reviewed for relevancy based on the inclusion/exclusion criteria. Additional citations were retrieved from the bibliography of the articles identified in the initial search. A total of 79 articles describing QTc prolongation in the psychiatric population were thoroughly examined, but only 31 articles were selected to guide the development of the algorithm. The literature-based algorithm developed provides a stepped-based approach for the assessment, monitoring, and management of drug-induced QTc prolongation in the psychiatric population. The algorithm may assist mental health clinicians in the decision-making process when psychiatric patients are prescribed medications known to increase the QTc interval.


Occupational medicine in the petroleum industry: an historical perspective.
The development of occupational health in the petroleum industry has been reviewed from the early years of the 20th century through the 1970s. Approximately 50 years after its chaotic beginning, the industry began to realize its obligations to its employees and undertook activities that were already standard practice in a number of other business enterprises. After a belated start and slow progress for several decades, by mid-century practically all of the major oil companies were involved in the principal activities of modern occupational health. Significant advances had been made in applying preventive measures in a variety of environments throughout the world. Over the following 30 years the level of clinical practices and the associated professional disciplines of industrial hygiene, toxicology and epidemiology demonstrated the industry's leadership to its peers as well as to society in general.


Establishing a Rural General Surgery Residency Program: Identifying Community Stakeholder Perception and Obstacles of a de Novo Residency in Rural Appalachia.
Rural healthcare has become more challenging over the past several years with increasingly limited access to surgical care in the rural setting. The Accreditation Council for Graduate Medical Education (ACGME) has recently introduced the Rural Track Program (RTP) initiative to combat physician shortage in rural areas. We intend to start the first Rural General Surgery Residency program under the RTP designation in rural Appalachia. 430 community stakeholders were surveyed regarding the anticipated impact of a new training program. Questions focused on the understanding of a Residency Program, the care provided by residents, impact on availability of local care, current geographical limitation of surgical care, and potential benefits/obstacles of the training program. Over 90% of all surveyed approved of training surgeons locally, with the local government believing that the program would be a good investment for the community. Several locals had been treated by resident physicians at other facilities and the majority were satisfied with the care they received. Several families frequently travel to larger cities for surgical care, with 96% of all respondents believing that the program would provide better access to care locally. Our study demonstrated that the community is familiar with healthcare in a training facility and welcoming to a local training program, while believing that trainees will have a positive impact on local surgical care in rural Appalachia. We will continue to work with the local community and healthcare personnel while developing the program and tailor our Residency to the rural setting as able.


Determinants of hip pain in adult patients with severe cerebral palsy.
The purpose of our investigation was to study the relationship between radiographic results of the femoral head and pain in people with severe cerebral palsy. We conducted a cross-sectional study on hip radiography results and pain in 160 patients with severe cerebral palsy. Eighteen percent of our patients had hip pain in hip-loading situations. Migration and deformity were closely related. There was a significant association with hip pain (odds ratio, 2.79; 95% confidence interval 1.01-7.70). There is a high prevalence of hip pain after unsuccessful femoral bone surgery. Migration and deformity of the femoral head are strongly interrelated, and are associated with pain.


Cross-contamination of lettuce (Lactuca sativa L.) with Escherichia coli O157:H7 via contaminated ground beef.
A lettuce outbreak strain of E. coli O157:H7 was used to quantitate the pathogen's survival in ground beef and its transfer to hands, cutting board surfaces, and lettuce. Overnight storage of inoculated beef at 4 degrees C resulted in no pathogen growth, while room-temperature storage allowed multiplication. Hamburger patty formation allowed the transfer of bacteria to hands. Contaminated fingers subsequently transferred the pathogen to lettuce during handling. E. coli was transferred from hamburgers to cutting board surfaces; overnight storage of boards decreased the numbers of recoverable pathogens by approximately 1 log CFU. A 15-s water rinse failed to remove significant numbers of pathogens from cutting boards whether it was applied immediately after contamination or following overnight room-temperature storage. Three lettuce leaves were successively applied to a single contaminated cutting board area both immediately after contamination and after overnight room-temperature storage of contaminated boards. Another set of leaves was pressed onto boards immediately following contamination and was then stored overnight at 4 degrees C before pathogen enumeration. The numbers of pathogens transferred to the first pressed leaves were larger than those transferred to the second or third leaves. There were no significant differences in the numbers of pathogensrecovered from leaves pressed immediately after contamination whether pathogens were enumerated immediately or following overnight storage at 4 degrees C. However, fewer pathogens were transferred to leaves pressed to boards stored overnight at room temperature prior to contact with lettuce. Twenty-five lettuce pieces were successively pressed onto one area on a board containing 1.25 x 10(2) CFU of E. coli. Pathogens were transferred to 46% of the leaves, including the 25th exposed leaf.


Using group-based trajectory modeling to examine heterogeneity of symptom burden in patients with head and neck cancer undergoing aggressive non-surgical therapy.
Treatment-related symptom burden varies significantly among patients undergoing radiotherapy or chemoradiotherapy, yet such variation is typically not reflected in the results from single-group studies. We applied group-based trajectory modeling (GBTM) to describe the heterogeneity of symptom burden among patients with head and neck cancer and to identify subgroups with distinct symptom-development trajectories. Patients (n = 130) were recruited pretherapy and rated multiple symptoms weekly for 10 weeks via the M. D. Anderson Symptom Inventory. With the mean of five most severe symptoms over time as an outcome measure, GBTM was used to identify patient subgroups with distinct symptom trajectories. Linear mixed-effects modeling (LMM) was applied to compare with GBTM's ability to describe the longitudinal symptom data. The five most severe symptoms were problems with taste, difficulty swallowing or chewing, problems with mucus, fatigue, and dry mouth. A two-group GBTM model identified 68 % of patients as having high symptom burden, associated with older age, worse baseline performance status, and chemoradiotherapy treatment. A four-group GBTM model generated one stable group (4 % of patients) and three groups varying in symptom severity with both linear and quadratic functions over time. LMM revealed symptom-change patterns similar to that produced by GBTM but was inferior in identifying risk factors for high symptom burden. For cancer patients undergoing aggressive therapy, GBTM is capable of identifying various symptom-burden trajectories and provides severity groupings that will aid research and may be of clinical utility. These results may be generalizable to other cancer types and treatments.


Substantial within-animal diversity of Salmonella isolates from lymph nodes, feces, and hides of cattle at slaughter.
Lymph nodes (mandibular, mesenteric, mediastinal, and subiliac; n = 68) and fecal (n = 68) and hide (n = 35) samples were collected from beef carcasses harvested in an abattoir in Mexico. Samples were analyzed for Salmonella, and presumptive colonies were subjected to latex agglutination. Of the isolates recovered, a subset of 91 was characterized by serotyping, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility phenotyping. Salmonella was isolated from 100% (hide), 94.1% (feces), 91.2% (mesenteric), 76.5% (subiliac), 55.9% (mandibular), and 7.4% (mediastinal) of samples. From the 87 typeable isolates, eight Salmonella enterica serotypes, including Kentucky (32.2%), Anatum (29.9%), Reading (17.2%), Meleagridis (12.6%), Cerro (4.6%), Muenster (1.1%), Give (1.1%), and Mbandaka (1.1%), were identified. S. Meleagridis was more likely (P = 0.03) to be recovered from lymph nodes than from feces or hides, whereas S. Kentucky was more likely (P = 0.02) to be recovered from feces and hides than from lymph nodes. The majority (59.3%) of the Salmonella isolates were pansusceptible; however, multidrug resistance was observed in 13.2% of isolates. Typing by PFGE revealed that Salmonella strains generally clustered by serotype, but some serotypes (Anatum, Kentucky, Meleagridis, and Reading) were comprised of multiple PFGE subtypes. Indistinguishable PFGE subtypes and, therefore, serotypes were isolated from multiple sample types, and multiple PFGE subtypes were commonly observed within an animal. Given the overrepresentation of some serotypes within lymph nodes, we hypothesize that certain Salmonella strains may be better at entering the bovine host than other Salmonella strains or that some may be better adapted for survival within lymph nodes. Our data provide insight into the ecology of Salmonella within cohorts of cattle and offer direction for intervention opportunities.


[Results of a trial of a plague monoclonal antibody erythrocyte diagnostic agent].
Plague antibody monoclonal erythrocyte diagnosticum was studied in serological tests simultaneously with commercial plague antibody erythrocyte diagnosticum prepared on the basis of hyperimmune horse serum and with commercial plague antigenic erythrocyte diagnosticum. In this investigation the suspensions of numerous strains of Yersinia pestis, other closely related and heterologous organisms, experimentally infected wild and laboratory animals, as well as samples of materials obtained from small rodents caught in several natural foci of plague, were studied. The monoclonal diagnosticum was, practically, not inferior to the similar commercial preparation with respect to the frequency of positive results and the activity of the materials under study in serological tests, but showed greater specificity, as it reacted strictly with Y. pestis capsular antigen.


The Lichtenstein technique is being used adequately in inguinal hernia repair: national analysis and review of the surgical technique.
it is estimated that approximately 20 million people undergo inguinal hernia surgery annually in the world, with the Lichtenstein technique being the most performed surgical procedure. The objective of this study is to analyze the knowledge of the technical principles used in the Lichtenstein technique. Survey-type intersectional study approved by the research ethics committee of São Camilo University Center (CAAE: 70036523.1.0000.0062). During the research period, 11,622 e-mails were sent to members of the main national surgical societies with research on the technical principles of Lichtenstein surgery. The survey was carried out using an electronic form with 10 multiple-choice questions. The form was answered anonymously on the SurveyMonkey and Google Forms platforms. 744 responses were received to the electronic form. Based on this number of respondents, our survey has a confidence level of 95% with a margin of error of 3.5%. It was observed that there is no standardization of the technique among the majority of responders (53.4%). Many surgeons still perform digital dissection of the spermatic cord (47%). A small number of interviewees (15.2%) performed sutures with absorbable thread in the region of the internal oblique aponeurosis, while more than half (55.2%) continued to perform sutures with non-absorbable thread. Most surgeons use a small overlap or fix the mesh juxtaposed to the pubic symphysis (51%). Our research identified that a small percentage of respondents adequately know the technical principles of Lichtenstein surgery. The result brings us new insights into the need to review Lichtenstein technique.


Treatment effect of natalizumab on relapse outcomes in multiple sclerosis patients despite ongoing MRI activity.
Natalizumab treatment significantly reduced the annualised relapse rate and MRI activity over 2 years compared with placebo in phase III trials when administered as monotherapy in AFFIRM or in combination with interferon β-1a (IFNβ) in SENTINEL. The post hoc analyses reported here sought to determine the effect of natalizumab treatment on relapse activity in the minority of patients who continued to show MRI activity (ie, ≥ 1 gadolinium enhancing (Gd+) lesions or new or enlarging T2 hyperintense lesions) over 2 years in these trials. These analyses demonstrated that natalizumab treatment, both alone (AFFIRM) and in combination with IFNβ (SENTINEL), resulted in a reduced annualised relapse rate despite the presence of Gd+ lesions (p=0.004 and p=0.008, respectively) or new or enlarging T2 hyperintense lesions (each p<0.0001). Thus patients treated with natalizumab show clinical benefit even in the presence of continued MRI activity. Long term clinical outcome of these patients has not been studied.


Maintaining remission in lamivudine-resistant patients with a virological response to adefovir add-on lamivudine after stopping lamivudine therapy.
We examined the durability of the virological response after discontinuing lamivudine (LVD) in chronic hepatitis B (CHB) patients with LVD-resistant hepatitis B virus (HBV), who responded to LVD plus adefovir (ADV) combination therapy, and the outcome of switching to ADV monotherapy compared to maintaining combination therapy. This study enrolled 72 patients with undetectable viral loads (≤12 IU/ml) and normal alanine aminotransferase levels after ADV add-on therapy for at least 6 months in LVD-resistant CHB patients. The enrolled patients were randomly assigned to continue with LVD-ADV combination therapy or switch to ADV monotherapy (n = 36 per group). Virological rebound was defined as HBV DNA detection at more than 12 IU/ml by quantitative polymerase chain reaction determined on two consecutive measurements. During 96 weeks of follow-up, 100% (36/36) of the patients in the LVD-ADV combination maintained group had persistently undetectable HBV DNA, compared with 94.4% (34/36) patients in the ADV monotherapy switched group. These two patients had undetectable HBV DNA after switching back to LVD-ADV combination therapy. There were no significant differences in the HBsAg levels between the two treatment groups during the 96-week follow-up period. In our study, switching to ADV monotherapy resulted in sustained HBV DNA suppression in 94.4% of the patients for 96 weeks. Prior complete viral suppression with LVD-ADV combination therapy conferred a significant advantage in patients who switched to ADV monotherapy. LVD may be discontinued in patients who show a complete virological response to LVD-ADV combination therapy for at least 6 months.


New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits.
Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs.


Apolipoprotein E ε4 Allele-Based Differences in Brain Volumes Are Largely Uniform Across Late Middle Aged and Older Hispanic/Latino- and Non-Hispanic/Latino Whites Without Dementia.
Hispanics/Latinos are at an equal or a greater risk for Alzheimer's disease (AD), yet risk factors remain more poorly characterized as compared to non-Hispanic/Latino Whites. Among non-Hispanic/Latino White cohorts, the apolipoprotein E (APOE) ε4 allele is one of the strongest risk factors for AD with subtle declines in episodic memory and brain volumes detectable in the preclinical stages. We examined whether the APOE ε4 status had a differential impact on cognition and brain volumes among cognitively healthy and mild cognitively impaired Hispanics/Latinos (n = 86; ε4 n = 23) compared to a well-matched group of non-Hispanic/Latino Whites (n = 92; ε4 n = 29). Neither the APOE ε4 status nor the interaction between the ε4 status and ethnicity was associated with cognitive performance. The APOE ε4 status was associated with white matter and not with gray matter volumes. APOE ε4 carriers had a significantly smaller total brain white matter volumes, as well as smaller right middle temporal and left superior temporal volumes. The Hispanics/Latinos had significantly smaller left middle frontal gray matter volumes, yet marginally larger overall white matter volumes, than the non-Hispanic/Latino Whites. Exploratory analysis within the Hispanic/Latino sample found that those people whose primary language was Spanish had larger total brain white matter volumes compared primarily to the English speakers. Importantly, primary language differences only held for Hispanic/Latino ε4 carriers and did not differentiate Hispanic/Latino non-carriers, underscoring the need for further investigation into the impacts of language and acculturation on cognitive aging among the fastest growing ethnic minority group in the United States.


Tranylcypromine Plus Amitriptyline for Electroconvulsive Therapy-Resistant Depression: A Long-Term Study.
Few therapeutic options are available for patients with electroconvulsive therapy-resistant major depressive disorder (ECT-r MDD), leaving a substantial proportion of this population beyond treatment possibilities. The combination of monoamine oxidase inhibitors and tricyclic antidepressants could be a potential strategy for managing ECT-r MDD, and the specific association of amitriptyline and tranylcypromine may offer additional tolerability advantages. Although promising, in our knowledge, no studies have examined until now the effectiveness of this combination in ECT-r MDD. We report a retrospective cohort of 31 patients with ECT-r MDD treated in an open-label fashion with the combination of amitriptyline and tranylcypromine. Overall, 80.6% of the sample met response criteria at the end of the first 12 weeks of treatment. Seventy-six percent (19 of 25) of the responders were followed for a mean of 9.37 ± 3.86 years. During this follow-up period, none of the patients had a recurring depressive episode. The combination was well tolerated, whereas minor adverse effects were common, and no severe or life-threatening events were reported throughout the study. These findings indicate that the combination tranylcypromine and amitriptyline is a potentially safe and effective candidate for future investigation in the treatment and long-term maintenance of ECT-r MDD.


[Neonatal infection with Salmonella apapa after contact with a reptile in the home].
Salmonella apapa is transmitted by reptiles, e.g., bearded dragons. To date only few cases of S. apapa-related human infections have been reported. Because the bacteria are transmitted through the feces of animals or direct contact with low infection doses, infection in early infancy is possible. We report an 18-day-old newborn with sepsis caused by Salmonella apapa. Salmonella apapa was isolated from the feces of a bearded dragon living along with the family.


The two human trypsinogens. Inhibition spectra of the two human trypsins derived from their purified zymogens.
The two human anionic trypsinogens 1 and 2 were purified from human pancreatic juice by gel filtration on Sephadex G-100 and by chromatography on DEAE-cellulose. After activation of their respective zymogens by porcine enterokinase, human trypsins 1 and 2 were studied for their reaction with a wide variety of proteinase inhibitors. Kunitz pancreatic trypsin inhibitor and human pancreatic secretory trypsin inhibitor completely inhibited both human trypsins at a stoichiometric inhibitor-to-enzyme ratio of one to one. In contrast, bovine pancreatic secretory trypsin inhibitor (Kazal's inhibitor) failed to inhibit either human trypsin. The inhibition of both human trypsins by porcine pancreatic secretory trypsin inhibitor was demonstrated. The reactions of the trypsins with chicken ovomucoid, Ascaris lumbricoides (type suis), human sperm and blood plasma trypsin inhibitors were studied. The most striking difference between the two human trypsins was the reaction with soybean trypsin inhibitor (Kunitz). Trypsin 2 was completely inhibited in a one-to-one molar ratio while trypsin 1 was poorly inhibited. The presence of a prekallikrein in human pancreatic juice is discussed.


Broadband chromatic dispersion measurements in higher-order modes selectively excited in optical fibers using a spatial light modulator.
We propose an improvement of the interferometric method used up to now to measure the chromatic dispersion in single mode optical fibers, which enables dispersion measurements in higher-order modes over a wide spectral range. To selectively excite a specific mode, a spatial light modulator was used in the reflective configuration to generate an appropriate phase distribution across an input supercontinuum beam. We demonstrate the feasibility of the proposed approach using chromatic dispersion measurements of the six lowest order spatial modes supported by an optical fiber in the spectral range from 450 to 1600 nm. Moreover, we present the results of numerical simulations that confirm sufficient selectivity of higher-order mode excitation.


P-wave Indices as Predictors of Atrial Fibrillation: The Lion from a Claw.
The P wave, representing the electrical fingerprint of atrial depolarization, contains information regarding spatial and temporal aspects of atrial electrical-and potentially structural-properties. However, technical and biological reasons, including-but not limited to-the low amplitude of the P wave and large interindividual variations in normal or pathologic atrial electrical activity, make gathering and utilizing this information for clinical purposes a rather cumbersome task. However, even crude ECG descriptors, such as P-wave dispersion, have been shown to be of predictive value for assessing the probability that a patient already has or will shortly present with AF. More sophisticated methods of analyzing the ECG signal, on a single- or multi- beat basis, along with novel approaches to data handling, namely machine learning, seem to be leading up to more accurate and robust ways to obtain clinically useful information from the humble P wave.


[The physiological validation of the use of iodinol in physiotherapy].
Experiments on 43 thyroidectomized Wistar male rats with experimental hypothyroidism have shown a favourable effect of iodinole electrophoresis but not galvanization on the disease. The effect was assessed by organ weight and intraorgan water concentration.


Mexiletine related chronic defibrillation threshold elevation: case report and review of the literature.
Many antiarrhythmic drugs may produce a rise in defibrillation threshold. Mexiletine is a frequently used antiarrhythmic drug in patients with an implantable cardioverter defibrillator, usually thought of as producing no or minimal effects on the defibrillation threshold. The current case report presents a patient with an endocardial implantable cardioverter defibrillator being treated with mexiletine, which precluded the ability to defibrillate the patient.


[Update in interstitial lung disease 2023].
The notable advances in interstitial lung disease (ILD) published in Chinese and international authoritative journals from November 2022 to October 2023 were systematically reviewed in our annual review. The year 2023 brought significant advances about mechanism, diagnosis and treatment of idiopathic pulmonary fibrosis, connective tissue diseases associated ILD, sarcoidosis, progressive pulmonary fibrosis and rare ILDs. The related global and/or Chinese commentaries and guidelines were also reviewed in our paper. We also highlighted the important findings of epidemiologic and health economic data on idiopathic pulmonary fibrosis and sarcoidosis.


Pre-resectional Radiofrequency Ablation as a Neoadjuvant in situ Tumor Vaccine.
A lack of effective immune response against cancer is one of the major risk factors for developing local recurrence and distant metastases after curative resectional surgery. Prior studies revealed that systemic antitumor immunity is elicited by radiofrequency ablation (RFA) of tumor lesions, which is mainly considered a palliative procedure for unresectable tumors or for inoperable patients. Recently, we discovered an oncological benefit that depends on the adaptive arm of the antitumor immune response when RFA is performed in a neoadjuvant setting prior to surgical resection in preclinical murine models.


Mining the fecal proteome: from biomarkers to personalised medicine.
Fecal proteomics has gained increased prominence in recent years. It can provide insights into the diagnosis and surveillance of many bowel diseases by both identifying potential biomarkers in stool samples and helping identify disease-related pathways. Fecal proteomics has already shown its potential for the discovery and validation of biomarkers for colorectal cancer screening, and the analysis of fecal microbiota by MALDI-MS for the diagnosis of a range of bowel diseases is gaining clinical acceptance. Areas covered: Based on a comprehensive analysis of the current literature, we introduce the range of sensitive and specific proteomics methods which comprise the current 'Proteomics Toolbox', explain how the integration of fecal proteomics with data processing/bioinformatics has been used for the identification of potential biomarkers for both CRC and other gut-related pathologies and analysis of the fecal microbiome, outline some of the current fecal assays in current clinical practice and introduce the concept of personalised medicine which these technologies will help inform. Expert commentary: Integration of fecal proteomics with other proteomics and genomics strategies as well as bioinformatics is paving the way towards personalised medicine, which will bring with it improved global healthcare.


Lipid and apolipoprotein predictors of atherosclerosis in youth: apolipoprotein concentrations do not materially improve prediction of arterial lesions in PDAY subjects. The PDAY Research Group.
We compared serum lipid and apolipoprotein predictors of atherosclerosis in cases from the multicenter study, Pathobiological Determinants of Atherosclerosis in Youth (PDAY). The lipid measures included HDL cholesterol (HDL-C) and non-HDL-C, and the apolipoprotein measures included concentrations of apoA1, apoB, and Lp(a), and sizes of the apo(a) proteins. We tested whether the apolipoprotein measures predicted atherosclerotic lesions as well as the more traditional lipid measures. We estimated extent of lesions as fatty streaks or raised lesions (fibrous plaques, complicated or calcified lesions) in 3 sites: thoracic aorta, abdominal aorta, and right coronary artery. Neither apoA1 nor apoB measures were as strongly or consistently correlated with extent of lesions as the corresponding lipid measure (HDL-C and non-HDL-C, respectively). Beyond the basic model that included sex, age, race, smoking status, hypertension, and the lipid measures, apoA1 and apoB added only an average 1.3% increased explanatory ability to the model, whereas HDL-C plus non-HDL-C added an average 2.5%. The results suggest that the traditional lipid measures are more useful than apolipoprotein measures for detecting young persons at high risk of precocious atherosclerosis. Because of large racial differences, the two Lp(a)-related measures, Lp(a) concentrations and apo(a) size, were evaluated in blacks and whites separately. Under these circumstances, neither of the Lp(a)-related measures was strongly or consistently correlated with extent of lesions.


Characterizing Ethiopian cattle production systems for disease burden analysis.
This paper addresses knowledge gaps in the biomass, productivity and value of livestock for the pastoral, mixed crop-livestock and specialized dairy systems in Ethiopia. Population size, reproductive performance, mortality, offtake and productivity of cattle were calculated from official statistics and a meta-analysis of data available in the published literature. This information was then used to estimate biomass and output value for 2020 using a herd dynamics model. The mixed-crop livestock system dominates the Ethiopian cattle sector, with 55 million cattle (78% total population) and contributing 8.52 billion USD to the economy through the provision of meat, milk, hides and draft power in 2021. By comparison, the pastoral (13.4 million head) and specialized dairy (1.8 million head) systems are much smaller. Productivity varied between different production systems, with differences in live body weight, productivity and prices from different sources. The estimated total cattle biomass was 14.8 billion kg in 2021, i.e., 11.3 billion kg in the mixed crop-livestock system, 2.60 billion kg in the pastoral system and 0.87 billion kg in the specialized dairy system. The total economic asset values of cattle in the mixed crop-livestock, pastoral and specialized dairy systems were estimated as 24.8, 5.28 and 1.37 billion USD, respectively. The total combined output value (e.g., beef, milk and draft power) of cattle production was 11.9 billion USD, which was 11.2% of the GDP in Ethiopia in 2021. This work quantifies the importance of cattle in the Ethiopian economy. These estimates of herd structure, reproductive performance, productivity, biomass, and economic value for cattle production systems in Ethiopia can be used to inform high-level policy, revealing under-performance and areas to prioritize and provide a basis for further technical analysis, such as disease burden.


Bullous degeneration of the left lower lobe in a heroin addict.
A 34 yr old heroin addict was referred because of chest pain caused by air-trapping in a bulla in the left lower lobe. There was a marked difference between the functional residual capacity measured by body-plethysmography and helium dilution. A slow wash-in and wash-out were demonstrated by ventilation scintigraphy with Xenon133. Bullous degeneration is a known complication of intravenous drug abuse. Usually these bullae are found in the upper lobes. Possible causative mechanisms are discussed.


Transcatheter gelfoam embolization in abdominal, retroperitoneal, and pelvic hemorrhage.
Clinical experience with Gelfoam embolization for arterial hemorrhage in 55 patients is described. This technique controlled hemorrhage in 51 patients (92.7%). Two patients (3.6%) died of complications related to embolization. Gelfoam can be a permanent occluding agent which does not require subselective catheter position for effectiveness and safety. The advantages of Gelfoam are its availability, low cost, the ease and speed with which it can be applied through conventional catheters, and its safety and effectiveness if properly applied. The data presented here, and those in the literature, indicate that transcatheter therapeutic embolization for arterial bleeding below the diaphragm is by far the safest and most effective method available.


Outcomes of Hardware Removal Surgery for Children.
Hardware removal is among the most common orthopedic procedures performed in the United States. The goal of this study was to report the outcomes of deep hardware removal for children. This study received institutional review board approval. Patients younger than 18 years who underwent deep hardware removal between 2007 and 2017 were studied. We reviewed 227 procedures involving 132 boys and 95 girls. Mean follow-up was 25 months (range, 14-36 months). Mean age at the time of surgery was 12.8 years (range, 2-17 years). Mean time from initial surgery to hardware removal was 8.4 months (range, 1-72 months). Of the 227 cases, 75 used a tourniquet. Mean tourniquet time was 30.1 minutes (range, 1-118 minutes). Mean length of surgery was 44.0 minutes (range, 4-173 minutes). Mean resident level performing the surgery was postgraduate year 3 (range, postgraduate year 2 to fellow). There were 3 complications. Locations of the implanted hardware included: femur, 85; humerus, 49; tibia, 46; hip/pelvis, 17; ulna, 11; miscellaneous foot, 10; radius, 6; and fibula, 3. Indications for surgery included surgeon recommendations in 122 cases; symptomatic hardware in 68 cases, and parent wishes in 37 cases. Hardware removal for children was safe, and the outcomes were excellent. Complications of hardware removal at a teaching hospital can be minimized when a more senior resident is the primary surgeon. Despite the challenging and historically troublesome nature of deep hardware removal, the current study shows that hardware removal for children is safe and effective. [Orthopedics. 2022;45(2):e91-e95.].


Acute ischaemic stroke or transient ischaemic attack and the need for inpatient echocardiography.
To determine the diagnostic yield of echocardiography and its utility in changing medical management; and to derive a risk score to guide its use in patients with in-hospital stroke or transient ischaemic attack (TIA). We carried out a retrospective chart review from January 2009 to June 2010 of patients with acute ischaemic stroke or TIA who had undergone transthoracic echocardiography (TTE) or transoesophageal echocardiography (TOE). Clinical and imaging findings at baseline were noted and 'potential clinically relevant findings' identified on TTE and TOE. A multivariable logistic regression was used to identify predictors of potential clinically relevant findings on TTE or TOE and derive a risk score. Of 370 patients, 307 (83.0%) had TTE and 63 (17.0%) had additional TOE. Potential clinically relevant findings on echocardiography were noted in 28 (7.6%) patients. Change in medical management was noted in 19/307 (6.2%) patients on TTE and in 7/63 (11.1%) patients on TOE. Male sex (OR 3.05, 95% CI 1.19 to 7.84; p=0.021), abnormal admission ECG (OR 4.39, 95% CI 1.79 to 10.79; p=0.001), and embolic pattern imaging at baseline (OR 2.38, 95% CI 1.05 to 5.40; p=0.038) were independent predictors of findings on TTE or TOE. A risk score including these three variables had modest discrimination (c-statistic 0.69, 95% CI 0.59 to 0.80). Echocardiography detected potential clinically relevant findings in a minority of patients (7.6%), but these findings changed medical management 90.5% of the time. A risk score using sex, ECG abnormality, and embolic pattern imaging at baseline could help predict which patients are more likely to have these echo findings.


Discovering sequence-structure motifs from protein segments and two applications.
We present a novel method for clustering short protein segments having strong sequence-structure correlations, and demonstrate that these clusters contain useful structural information via two applications. When applied to local tertiary structure prediction, we achieve approximately 60% accuracy with a novel dynamic programming algorithm. When applied to secondary structure prediction based on Support Vector Machines, we obtain a approximately 2% gain in Q3 performance by incorporating cluster-derived data into training and classification. These encouraging results illustrate the great potential of using conserved local motifs to tackle protein structure predictions and possibly other important problems in biology.


Aerobic methylcyclohexane-promoted epoxidation of stilbene over gold nanoparticles supported on Gd-doped titania.
Aerobic partial oxidations of alkanes and alkenes are important processes of the petrochemical industry. The radical mechanisms involved can be catalyzed by soluble salts of transition metals (Co, Cu, Mn...). We show here that the model methylcyclohexane/stilbene co-oxidation reaction can be efficiently catalyzed at lower temperature by supported gold nanoparticles. The support has little influence on gold intrinsic activity but more on the apparent reaction rates which are a combination of catalytic activity and diffusion limitations. These are here minimized by using gadolinium-doped titania nanocrystallites as support for gold nanoparticles. This material is obtained by mild hydrolysis of a new Gd(4)TiO(O(i)Pr)(14) bimetallic oxoalkoxide. It leads to enhanced wettability of the < 3 nm gold particles in the tert-butyl hydroperoxide (TBHP)-initiated epoxidation of stilbene in methylcyclohexane; Au/TiO(2):Gd(3+) is in turn as active as the state-of-the-art hydrophobic Au/SiO(2) catalyst. The rate-determining step of this reaction is identified as the gold-catalyzed homolytic decomposition of TBHP generating radicals and initiating the methylcyclohexane-mediated epoxidation of stilbene, yielding a methylcyclohexan-1-ol/trans-stilbene oxide mixture. Methylcyclohexan-1-ol can also be obtained in the absence of the alkene in the gold-catalyzed solvent-free autoxidation of methylcyclohexane, evidencing the catalytic potential of gold nanoparticles for low temperature C-H activation.


Ineffectiveness of the 2014-2015 H3N2 influenza vaccine.
The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Nasopharyngeal samples of vaccinated and non-vaccinated patients presenting with Influenza-like-illness (ILI) were collected from over 20 outpatient clinics located in different geographic parts of Israel and were tested for the presence of influenza viruses (influenza A and influenza B). Here we show, that in the 2014-2015 season, the vaccine that included the A/Texas/50/2012 H3N2 virus was ineffective. Significant numbers of individuals vaccinated with the 2014-2015 vaccine, of all ages, were infected with influenza A (H3N2), manifesting similar symptoms as the non-vaccinated group. We further demonstrate that the Israeli circulating influenza A(H3N2) virus was different than that included in the 2014-2015 northern hemisphere vaccine, and that antibodies elicited by this vaccine were significantly less efficient in neutralizing influenza A(H3N2) infection.


A bovine low molecular weight bone morphogenetic protein (BMP) fraction.
A low MW bone morphogenetic protein fraction (BMP) is quantitatively extracted from bovine bone matrix by an inorganic-organic CaCl2-urea solvent mixture and fractionated by ion exchange and gel chromatography. The BMP fraction induces differentiation of perivascular mesenchymal type cells into cartilage and bone inside the mouse's thigh, outside of double walled diffusion chamber, in muscle pouches in the rabbit anterior abdominal wall, and in 0.8 cm trephine defects in the rat's skull. Bovine BMP may consist of electrophoretic components ranging from 12 K to 30 K in MW. The main components correspond to a MW of 23 K, 18 K and 12 K when they are compared with the mobilities of standard proteins. Because it was invariably present in all of the fractions with osteoinductive activity, circumstantial evidence leads to a 17 to 18 K component for a BMP. The possibility of a diameter monomer system for BMP activity also warrants consideration. The polypeptide portion constitutes only about 80% to 85% of the dry weight of the mixture of the three electrophoretic components, and suggests that the BMP fraction contains glycoproteins. Characteristically, glycoproteins migrate anomalously on SDS gels and create doubt about whether the major bands represent true MW. Nevertheless, the data clearly point to the low MW protein fractions for the direction of future work on BMP.


COVID-19 in Children: Molecular Profile and Pathological Features.
Although the World Health Organization has declared the end of the COVID-19 pandemic, doctors continue to register new cases of the disease among both adults and children. Unfortunately, the course of COVID-19 in children can have a severe form, with death being a potential outcome. The absence of published works discussing the pathological morphology of COVID-19 in children prevents the objective analysis of the disease's pathogenesis, including among the adult population. In this vein, the objective of our study is to identify the morphological features of the lungs' involvement and evaluate virus-host interactions in the case of COVID-19 in patients at a pediatric medical practice. We present the results of the study of the lungs of three children who died due to COVID-19, highlighting the predominant involvement of their respiratory organs at different stages of the disease (5, 21, and 50 days). This article presents data obtained from histopathological and immunohistochemical investigations, taking into account the results of clinical and laboratory indicators and intravital and postmortem SARS-CoV-2 PCR investigations. The common finding of all of the examined COVID-19 cases is the involvement of the endothelium in microcirculation vessels, which are considered to be a primary target of various pathogenic influencing factors. We also discuss both the significance of apoptosis as a result of virus-host interactions and the most likely cause of endothelium cell destruction. The results of this study could be useful for the development of endothelium-protective therapy to prevent the progression of disseminated intravascular coagulation syndrome.


Paraoxonase 1 L55M, Q192R and paraoxonase 2 S311C alleles in atherothrombosis.
Increased oxidative stress is known to play a role in the pathogenesis of atherosclerosis, and polymorphisms in genes encoding for enzymes involved in modulation of oxidant stress, such as paraoxonases (PONs), provide a potentially powerful approach to study the risk of disease susceptibility. Aim of our study is to investigate the possible association among PONs polymorphisms, clinical and metabolic factors, and atherothrombotic events in an Italian population. We evaluated in 105 subjects, with or without atherosclerotic risk factors, the presence of PON1 L55M, PON1 Q192R, and PON2 S311C genetic variants, as well as lipid profile, the concentration of aminothiols (blood reduced glutathione, plasma total glutathione, homocysteine, cysteine, cysteinyl glycine), and malondialdehyde as markers of lipid peroxidation. Clinical, biochemical, and genetic variables were correlated with a history of atherothrombosis. Previous atherothrombotic events were found in 42 patients (40 %): myocardial infarction in 24, stroke or transient ischemic attack in 18. By multiple logistic regression analysis, hypertension (OR = 5.538; 95 % CI 2.202-13.902, P < 0.001), HDL-cholesterol concentration (OR = 0.947; 95 % CI 0.910-0.985, P = 0.007), and the presence of C allele in PON2 gene (OR = 3.595; 95 % CI 1.247-10.361, P = 0.018) were independently associated with atherothrombotic events. Our study sheds light on the role of PON2 as a possible cofactor in determining the risk of events together with the well-known risk markers HDL-cholesterol and hypertension.


POTENTIAL LIFE PROGNOSTIC MARKER FOR MESENCHYMAL TUMOR RESEMBLING UTERINE LEIOMYOSARCOMA.
Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), both uterine mesenchymal tumors, are distinguished by the number of cells exhibiting mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiating between benign and malignant tumors, is difficult. For example, cotyledonoid dissecting leiomyoma (CDL) or uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which a differential diagnosis is challenging. To date, a standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of CDL or STUMP in the differential diagnosis have not been defined. Several clinical studies have reported that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The immunohistochemical biomarkers reported so far cannot effectively help determine the malignant potential of CDL or STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by using next-generation molecular techniques can facilitate disease prediction, diagnosis, treatment, and prognosis. We examined the oncological properties of STUMP in adults using molecular pathological techniques on tissue excised from patients with uterine mesenchymal tumor. In a clinical study conducted by our medical team, the results of gene expression profiling indicated factors that may be associated with malignancy of uterine mesenchymal tumors. We herein describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies. It is expected that the establishment of a diagnostic method targeting the characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.


Prevalence, severity and underdiagnosis of COPD in the primary care setting.
Chronic obstructive pulmonary disease (COPD) is a common disease with a steadily increasing prevalence and mortality. However, recent epidemiological estimates differ depending on the population studied and methods used. To investigate the prevalence, severity and burden of COPD in a primary care setting. From 4730 patients registered in a single primary care practice, all 2250 patients aged 40 years or more were invited to participate. Participants completed a questionnaire on smoking, respiratory symptoms, education and social status. A physical examination was followed by pre- and post-bronchodilator (BD) spirometry. Of the eligible patients, 1960 (87%) participated. 92% of spirometric tests met the ATS criteria. Airflow limitation was demonstrated in 299 (15%) of the participants pre-BD and in 211 (11%) post-BD. COPD was diagnosed in 183 patients (9.3%). Of these patients, the degree of post-BD airflow limitation was mild in 30.6%, moderate in 51.4%, severe in 15.3% and very severe in 2.7%. Only 18.6% of these patients had previously been diagnosed with COPD; almost all of these had severe or very severe airflow limitation. As a result of the study, a diagnosis of asthma was made in 122 patients. The prevalence and underdiagnosis of COPD in adult patients in this primary care setting made case finding worthwhile. Large numbers of newly detected patients were symptomatic and needed treatment. Limiting investigations to smokers would have reduced the number of COPD diagnoses by 26%.


Ecology of malaria infections in western lowland gorillas inhabiting Dzanga Sangha Protected Areas, Central African Republic.
African great apes are susceptible to infections with several species of Plasmodium, including the predecessor of Plasmodium falciparum. Little is known about the ecology of these pathogens in gorillas. A total of 131 gorilla fecal samples were collected from Dzanga-Sangha Protected Areas to study the diversity and prevalence of Plasmodium species. The effects of sex and age as factors influencing levels of infection with Plasmodium in habituated gorilla groups were assessed. Ninety-five human blood samples from the same locality were also analysed to test for cross-transmission between humans and gorillas. According to a cytB PCR assay 32% of gorilla's fecal samples and 43·1% human individuals were infected with Plasmodium spp. All Laverania species, Plasmodium vivax, and for the first time Plasmodium ovale were identified from gorilla samples. Plasmodium praefalciparum was present only from habituated individuals and P. falciparum was detected from human samples. Although few P. vivax and P. ovale sequences were obtained from gorillas, the evidence for cross-species transmission between humans and gorillas requires more in depth analysis. No association was found between malaria infection and sex, however, younger individuals aged ≤6 years were more susceptible. Switching between two different Plasmodium spp. was observed in three individuals. Prolonged monitoring of Plasmodium infection during various seasons and recording behavioural data is necessary to draw a precise picture about the infection dynamics.


Protein structural class identification directly from NMR spectra using averaged chemical shifts.
Knowledge of the three-dimensional structure of proteins is integral to understanding their functions, and a necessity in the era of proteomics. A wide range of computational methods is employed to estimate the secondary, tertiary, and quaternary structures of proteins. Comprehensive experimental methods, on the other hand, are limited to nuclear magnetic resonance (NMR) and X-ray crystallography. The full characterization of individual structures, using either of these techniques, is extremely time intensive. The demands of high throughput proteomics necessitate the development of new, faster experimental methods for providing structural information. As a first step toward such a method, we explore the possibility of determining the structural classes of proteins directly from their NMR spectra, prior to resonance assignment, using averaged chemical shifts. This is achieved by correlating NMR-based information with empirical structure-based information available in widely used electronic databases. The results are analyzed statistically for their significance. The robustness of the method as a structure predictor is probed by applying it to a set of proteins of unknown structure. Our results show that this NMR-based method can be used as a low-resolution tool for protein structural class identification.


The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia.
On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).


[Validation of the French language version of the Parkinson's Disease Questionnaire - PDQ-39].
After Alzheimer's disease, Parkinson's disease (PD) is the second most frequent degenerative disease of the central nervous system. The consequences of PD at the functional, social and emotional levels warrant a better understanding the patient's perceptions as measured using a specific instrument rather than restricting the medical approach to the clinical evaluation of the motor component. In 1996, we began implementation of a project to transculturally validate the single specific instrument that had been published and was available at that time: PDQ-39. The scale consists in a 39-item questionnaire enabling determination of an overall quality-of-life score and scores for 8 specific dimensions: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort. Eighty-nine patients taking part in an open-label study of the safety of a combination of pergolide and dopa therapy were included and followed up on D15 and after 8 weeks. The process of "Forward-Backward" translation, conducted in close liaison with the authors, enabled semantic and linguistic validation of the French language version. The content was validated by PD experts. At baseline, the patients presented quality-of-life scores that were particularly impaired for the dimensions exploring Mobility, Emotional well-being and Bodily discomfort. The main metric properties of the scale were confirmed. The PDQ-39 scores were closely correlated with the related concepts investigated by generic scale, SF-36. The PDQ-39 scores were correlated with the "Mental and Mood Status", "Everyday Activities" and "Motor Status" dimensions determined by the UPDRS. The reliability, expressed by Cronbach coefficients alpha, showed strong consistency of the instrument, very similar to the data for the original version. In contrast to what was observed with SF-36, the scale was particularly sensitive to clinical changes. The initial results make PDQ-39 a precious tool for the optimization of management of patients presenting with PD.


Papain-Based Solubilization of Decellularized Extracellular Matrix for the Preparation of Bioactive, Thermosensitive Pregels.
Solubilized, gel-forming decellularized extracellular matrix (dECM) is used in a wide range of basic and translational research and due to its inherent bioactivity can promote structural and functional tissue remodeling. The animal-derived protease pepsin has become the standard proteolytic enzyme for the solubilization of almost all types of collagen-based dECM. In this study, pepsin was compared with papain, α-amylase, and collagenase for their potential to solubilize porcine liver dECM. Maximum preservation of bioactive components and native dECM properties was used as a decisive criterion for further application of the enzymes, with emphasis on minimal destruction of the protein structure and maintained capacity for physical thermogelation at neutral pH. The solubilized dECM digests, and/or their physically gelled hydrogels were characterized for their rheological properties, gelation kinetics, GAG content, proteomic composition, and growth factor profile. This study highlights papain as a plant-derived enzyme that can serve as a cost-effective alternative to animal-derived pepsin for the efficient solubilization of dECM. The resulting homogeneous papain-digested dECM preserved its thermally triggered gelation properties similar to pepsin digests, and the corresponding dECM hydrogels demonstrated their enhanced bioadhesiveness in single-cell force spectroscopy experiments with fibroblasts. The viability and proliferation of human HepaRG cells on dECM gels were similar to those on pure rat tail collagen type I gels. Papain is not only highly effective and economically attractive for dECM solubilization but also particularly interesting when digesting human-tissue-derived dECM for regenerative applications, where animal-derived materials are to be avoided.


Contraction in voltage-clamped, internally perfused single heart cells.
We studied contraction in single voltage-clamped, internally perfused myocytes isolated from guinea pig ventricles. The microscopic appearance of the cell was observed and recorded with a television system, while contractile shortening was measured 1,000 times/s using a linear photodiode array. Uniform, synchronous sarcomere shortening occurred in response to depolarizations that triggered a slow inward current (Isi). Changes in Isi caused by altering the amplitude of the voltage step, the extracellular [Ca2+], or the holding potential were accompanied by immediate parallel changes in the extent and velocity of shortening. In particular, twitch shortening during depolarization was immediately decreased when large voltage steps decreased Isi, and was eliminated by depolarizations that exceeded +75 mV, the apparent reversal potential for Ca2+. In these cases, shortening was associated with the tail current during repolarization. Increases in the amplitude, duration, and the rate of the depolarizing step increased the extent and speed of sarcomere shortening over the course of four to five contractions without a simultaneous parallel increase of Isi. Large prolonged depolarizations caused an asynchronous, nonuniform, oscillatory shortening of the cell and potentiated future twitch contractions. Increases in the duration of the depolarizing step immediately prolonged contraction; otherwise, interventions that altered the extent, velocity, and time course of shortening in intact, nonperfused cells did not affect the time course of the contraction in the internally perfused single cells. Our results provide direct support for the hypothesis that Isi both induces and grades the size of the Ca2+ release from the sarcoplasmic reticulum of intact cardiac muscle. In addition, a separate, depolarization-dependent process unrelated to Isi grades the size of contraction, presumably by modulating Ca2+ accumulation in the intracellular stores, and affects its time course.


A method for extracting rate constants from initial rates of stopped-flow kinetic data: application to a physiological electron-transfer reaction.
The most commonly used methods for analysis of stopped-flow kinetic data require performing a series of measurements in which one reactant is varied at concentrations significantly greater than the concentration of the other reactant. For enzyme-catalysed reactions this may not be possible, because the dissociation constants for the enzyme-substrate complex are often of the same order of magnitude as the high concentrations of enzyme that must frequently be used in stopped-flow studies. An alternative method of data analysis is presented which allows the determination of microscopic rate constants from initial rates of stopped-flow kinetic data in which substrate is varied in a range of concentrations approximately the same as the enzyme. This method also provides a simple and accurate method for determining k4, the rate of the reverse reaction. This method has been used to describe a physiological electron transfer reaction between a quinoprotein, methylamine dehydrogenase, and a copper protein, amicyanin. At 20 degrees C, the rate of the electron-transfer reaction from methylamine dehydrogenase to amicyanin was 24 s-1, and the dissociation constant for complex-formation was 1.9 microM.


Satisfaction with services among people with progressive neurological illnesses and their carers in Australia.
The current study investigated the types of support networks and services accessed by people with progressive neurological illness, as well as the assessment of the usefulness of these services. The participants were 25 people with multiple sclerosis, 15 people with motor neurone disease, 23 people with Parkinson's disease, and six people with Huntington's disease. Twenty-eight professionals who worked with people with these illnesses and 41 carers of people with these illnesses also were interviewed. The results demonstrate that all of the groups of respondents indicated a strong need for basic services (e.g. home help), as well as specialized services (e.g. support groups). These two services also were identified as the most useful services by all of the groups of respondents. The similarities and differences between the groups, as well as the patients and carers, are examined. These findings demonstrate the importance of providing basic services for people with progressive neurological illnesses.