Factors influencing nursing students' continued success in a baccalaureate nursing program in Indonesia.
Holistic admission processes are needed to promote diversity in nursing students. Previous research had identified different variables related to the average grade point at the end of the first semester. There is a need to examine if those variables are associated with ongoing student success. The purpose of this study was to analyze experience, attributes, and academic variables for an association with nursing student success. Student success was defined as being an active student at the end of the first year and at the end of the second year of a baccalaureate nursing program in Indonesia. Binary logistic regression analysis was used to determine what relationship, if any, the variables had with student success, measured at the end of the first and second academic years. The data of 341 nursing students enrolled in August 2018 was analyzed. The variables accounted for 40.3% of the variance at the end of the first year and 24.3% of the variance at the end of the second year. There was a significant (p < .05) relationship between being enrolled at the end of the first year and 1) academic variables of first semester grade point average and the admission score of Raven's Advanced Progressive Matrices, and 2) attribute variables of reason for entering nursing and brief calling presence scale. A significant relationship was found between being enrolled at the end of the second year and the attribute variable of grit score. No variables had a strong correlation with other variables. Holistic admission processes and promoting student success can create the future of the nursing workforce. Improving the diversity in admitted nursing students will enhance the diversity in the nursing workforce. To promote the success of all students, a variety of support interventions will need to be developed. As students' calling and grit may play a role in student success, a better understanding is needed. In addition, more research is needed to explore how developing calling and grit throughout the nursing program can impact student success.


Effects of different root coping materials for abutment teeth on secondary caries and periodontal conditions: a retrospective study.
This study evaluated secondary caries and periodontal conditions associated with metal (MCs) and composite resin copings (RCs) of abutment teeth for overdentures. The rates of secondary caries and periodontal problems in 70 root copings (41 MCs, 29 RCs) in 35 patients were retrospectively investigated for a period of 6.9 years. Statistical analysis was performed using chi-square tests and logistic regression (P < .05). No significant differences in secondary caries or periodontal conditions were detected between MCs and RCs. These results suggest that RCs and MCs can be used as root copings of abutment teeth for overdentures.


Trauma and Injury Severity Score (TRISS): is it time for variable re-categorisations and re-characterisations?
Despite its limitations, the Trauma and Injury Severity Score (TRISS) continues to be the most commonly used tool for benchmarking trauma outcome. Since its inception, considerable energy has been devoted to improving TRISS. However, there has been no investigation into the classification or characterisation of the TRISS variables. Using a major nationally representative database, this study aims to explore the adequacy of the existing TRISS model by investigating variable re-categorisations and alternative characterisations in a logistic model used to predict survival in adults after traumatic injury. Data were obtained from the National Trauma Data Bank National Sample Project (NSP). Each variable in the TRISS model was related to discharge status and various categorisations considered using weighted logistic regression. Categorisations were treated nominally,using a series of indicator variables. For each variable and classification level, the best category combination was ascertained using the Bayesian Information Criterion (BIC). All best 5-category classified TRISS variables were combined, as were all best 10-category classified TRISS variables, and their predictive performance assessed against two conventionally defined TRISS models on the unweighted NSP sample using area under the Receiver Operating Characteristic curve (AUC) and BIC statistics. Overall, the weighted sample included 1,124,001 adults with injury events and known discharge status, of whom 1,061,709 (94.5%) were alive at discharge. When separately related to discharge status, each re-classified TRISS variable yielded a superior BIC statistic to its original specification. When investigating predictive performance, complete information was available for 167,239 (79.9%) adults with blunt and 20,643 (82.3%) adults with penetrating injury mechanisms. AUC and BIC estimates for the re-classified TRISS models were superior to the conventionally defined TRISS models. While having better predictive precision, the complexity associated with the best 10-category model resulted in the best 5-category model being preferred for penetrating mechanism injuries and being negligibly inferior for blunt mechanism injuries. Substantial improvements in the predictive power of TRISS were demonstrated by reclassifying the component variables and treating the variable categories nominally. However, before anew TRISS model with updated coefficients can be published, variable interactions and the effect of missing data needs thorough statistical evaluation.


Effects of diltiazem alone and combined with mefruside on cardiovascular response at rest and during exercise, carbohydrate metabolism and serum lipoproteins in patients with systemic hypertension.
The antihypertensive effects of the calcium antagonist diltiazem, both alone and combined with the diuretic mefruside, were assessed over 14 months in 36 patients with essential hypertension. Patients received 180 or 270 mg/day; those with inadequate response were given 270 mg/day plus mefruside, 20 mg/day. Both monotherapy and combination therapy significantly reduced blood pressure (BP) at rest and during exercise. However, adding mefruside did not significantly decrease BP below that achieved with diltiazem alone. After 14 months of therapy, the percentage of responders (patients with at least 10% reduction in diastolic BP at rest) was 64% for all patients, 100% (by definition) for those receiving diltiazem alone and 47% for those receiving the combination. Diltiazem decreased heart rate by 6% (4 beats/min at rest) (p less than 0.05). Combined therapy with mefruside did not further reduce heart rate. There were few adverse effects and no undesirable metabolic effects with either monotherapy or combined therapy. Plasma renin activity, aldosterone levels, carbohydrate metabolism, serum lipoprotein levels and routine laboratory test results were unchanged in both groups at the end of the study. Thus, diltiazem is an effective antihypertensive agent and apparently the combination of diltiazem and mefruside does not potentiate the antihypertensive effect of diltiazem alone during long-term therapy.


Peer review and innovation.
Two important aspects of the relationship between peer review and innovation includes the acceptance of articles for publication in journals and the assessment of applications for grants for the funding of research work. While there are well-known examples of the rejection by journals of first choice of many papers that have radically changed the way we think about the world outside ourselves, such papers do get published eventually, however tortuous the process required. With grant applications the situation differs in that the refusal of a grant necessarily curtails the possible research that may be attempted. Here there are many reasons for conservatism and reservation as to the ability of a grant allocation process based on peer review to deliver truly innovative investigations. Other methods are needed; although such methods need not be applied across the board, they should constitute the methods whereby some 10-20% of the grant monies are assigned. The nomination of prizes for specific accomplishments is one way of achieving innovation although this presumes that investigators or institution already have available the money necessary to effect the innovations; otherwise it is a question of the selection and funding of particular individuals or institutions and requiring them to solve particular problems that are set in the broadest of terms.


University students' perspectives on the benefits and challenges of emergency remote teaching during the Covid-19 pandemic in Ghana.
The advent of Covid-19 changed how education is carried out at the tertiary level in Ghana. Despite the lunch of emergency remote teaching at the University of Ghana in 2020, little research has been done on students' experiences. Using a qualitative descriptive design, this study explored students' experiences regarding the benefits, challenges, and the influence of emergency remote teaching on their self-esteem, academic confidence, and performance. 20 students were interviewed, and their responses were analyzed using thematic analysis. Results showed students had both positive and negative experiences which had diverse impacts on their self-esteem, academic confidence, and performance. Positive experiences resulted from the confidence to participate in class without intimidation, improved IT literacy, self-esteem and academic performance, less distraction and leniency from lecturers. Negative experiences bothered on problems with the learning management system, internet challenges, laziness on the part of students, high cost of internet data, unconducive learning environment, comprehension difficulties, increased workload and cheating by students. The findings underscore the need for university management to consider students' psychological wellbeing and needs when implementing new educational systems and further put measures in place to improve emergency remote teaching and curb academic dishonesty in order to improve tertiary education in Ghana amidst Covid-19.


Klippel-Trenaunay syndrome: report of case affecting oral cavity.
A patient is described with clinical characteristics suggesting a vascular syndrome that included an oral component. After an intraoral biopsy was taken and further evaluation performed, it was determined that the patient exhibited criteria consistent with Klippel-Trenaunay syndrome, a rare congenital vascular disorder.


Stimulus alternation and fast retinal potentials: photopic anc scotopic contributions.
Human retinal oscillatory potentials in response to an alternating checker-board pattern stimulus were studied in two subjects over an intensity range of 7.5 log units. Under scotopic conditions, two wavelets (S1 and S2) could be recorded. At an intensity of 1.9 photopic log Td four high frequency oscillations (O1--O4) were noticed and a discontinuity was observed in the corresponding luminance curve of the b-wave together with a sudden decrease in the magnitude of the standard deviation of the amplitude measures. The oscillations were noticed only on the ascending slope of the b-wave. With increasing stimulus intensity, their latency decreased at a slower rate than that of the b-wave and their number decreased. Each wavelet had an amplitude maximum at a certain stimulus intensity level. It was suggested that O1--O4 were generated by the activation of the photopic system and that S1 and S2 were of scotopic origin.


N-Alkylprotoporphyrin IX formation in 3,5-dicarbethoxy-1,4-dihydrocollidine-treated rats. Transfer of the alkyl group from the substrate to the porphyrin.
Administration of 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) to rats causes the accumulation of N-methylprotoporphyrin IX, a potent inhibitor of ferrochelatase. To clarify the origin of the porphyrin N-methyl group, we have synthesized and administered to rats N-ethyl-3,5-dicarbethoxy-1,4-dihydrocollidine (N-ethyl DDC) and 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP), the DDC analogue with a 4-ethyl rather than 4-methyl group. Only N-methylprotoporphyrin IX is isolated from rats treated with the former agent, and only N-ethylprotoporphyrin IX from those treated with the latter. All four isomers of N-ethylprotoporphyrin IX are formed biologically. The structure of the isolated porphyrins has been confirmed by complete spectroscopic comparison with the four synthetic isomers of N-ethylprotoporphyrin IX. DDEP has been shown to cause NADPH- and time-dependent in vitro loss of hepatic microsomal cytochrome P-450. These results unequivocally establish that the 4-alkyl groups in DDC and dDEP are the source of the N-alkyl group in N-methyl- and N-ethylprotoporphyrin IX, respectively, and strongly suggest that the alkyl group is transferred to the prosthetic heme of cytochrome P-450 during catalytic processing of the substrate by the enzyme. The mechanism of the group transfer is discussed.


Elemental superdoping of graphene and carbon nanotubes.
Doping of low-dimensional graphitic materials, including graphene, graphene quantum dots and single-wall carbon nanotubes with nitrogen, sulfur or boron can significantly change their properties. We report that simple fluorination followed by annealing in a dopant source can superdope low-dimensional graphitic materials with a high level of N, S or B. The superdoping results in the following doping levels: (i) for graphene, 29.82, 17.55 and 10.79 at% for N-, S- and B-doping, respectively; (ii) for graphene quantum dots, 36.38 at% for N-doping; and (iii) for single-wall carbon nanotubes, 7.79 and 10.66 at% for N- and S-doping, respectively. As an example, the N-superdoping of graphene can greatly increase the capacitive energy storage, increase the efficiency of the oxygen reduction reaction and induce ferromagnetism. Furthermore, by changing the degree of fluorination, the doping level can be tuned over a wide range, which is important for optimizing the performance of doped low-dimensional graphitic materials.


[Serotonin content in different sections of the brain, liver, intestines and blood of rats predisposed and not predisposed to alcohol consumption].
Experiments were made with white random-bred rats (males) exposed to ethanol. The content of serotonin measured by spectrofluorometry was higher in the hypothalamus, brain stem and intestine, and was lower in the thalamus, striatum liver and blood in the animals predisposed to voluntary alcohol consumption and with lateral position duration 62 +/- 18 min as compared with the animals not predisposed to alcohol consumption and with lateral position duration 196 +/- 23 min, the dose of ethanol being 4.5 g/kg i. p. Thirty minutes after ethanol administration in a dose of 2.5 g/kg i. p. to the alcohol-predisposed rats there was a lowering of the serotonin content in the hypothalamus and an increase in the thalamus, brain stem, liver and blood. Meanwhile in the rats not predisposed to alcohol consumption, the serotonin content rose in the hypothalamus, brain stem, liver, intestine and blood and fell in the thalamus and striatum. It is assumed that the serotoninergic system of the brain may play a role in the formation of "positive" or "negative" attitudes to ethanol in the population of white random-bred rats.


Growth phase mediated regulation of the Actinobacillus pleuropneumoniae ApxI and ApxII toxins.
Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia, a highly contagious and often fatal respiratory tract disease of pigs. The Apx toxins are primary virulence factors of this pathogen, with ApxI and ApxII being produced by all highly virulent strains in North America. Further characterization of these hemolytic toxins is needed to fully understand their role in disease and elucidate the environmental signals and genes that affect their production during infection. Many bacteria regulate genes in response to growth phase, and in this report we examined the effect of growth phase on ApxI and ApxII gene expression. Batch cultures of ApxI- and ApxII-producing strains were grown in heart infusion broth supplemented with beta-NAD, and samples were prepared throughout the growth curve. Maximal gene expression occurred in late exponential or early stationary phase, as indicated by a peak in apx mRNA concentration in Northern blot analysis. The amount of accumulated Apx protein and Apx hemolytic activity confirmed this increase in gene expression. These findings suggest a novel transcriptional regulatory mechanism that enhances Apx gene expression under in vitro conditions of high cell density and/or slow growth rate.


Mercury removal from coal combustion flue gas by modified fly ash.
Fly ash is a potential alternative to activated carbon for mercury adsorption. The effects of physicochemical properties on the mercury adsorption performance of three fly ash samples were investigated. X-ray fluorescence spectroscopy, X-ray photoelectron spectroscopy, and other methods were used to characterize the samples. Results indicate that mercury adsorption on fly ash is primarily physisorption and chemisorption. High specific surface areas and small pore diameters are beneficial to efficient mercury removal. Incompletely burned carbon is also an important factor for the improvement of mercury removal efficiency, in particular. The C-M bond, which is formed by the reaction of C and Ti, Si and other elements, may improve mercury oxidation. The samples modified with CuBr2, CuCl2 and FeCl3 showed excellent performance for Hg removal, because the chlorine in metal chlorides acts as an oxidant that promotes the conversion of elemental mercury (Hg0) into its oxidized form (Hg2+). Cu2+ and Fe3+ can also promote Hg0 oxidation as catalysts. HCl and O2 promote the adsorption of Hg by modified fly ash, whereas SO2 inhibits the Hg adsorption because of competitive adsorption for active sites. Fly ash samples modified with CuBr2, CuCl2 and FeCl3 are therefore promising materials for controlling mercury emissions.


Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies.
Peripheral arterial disease (PAD) is common but commonly unrecognized. Improved recognition of PAD is needed. We used high-throughput proteomic profiling to find PAD-associated biomarkers. Plasma was collected from PAD patients (ankle brachial index of <0.90; n=45) and subjects with risk factors but without PAD (n=43). Plasma was analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to quantify 1619 protein peaks. The peak intensity of a 12-kDa protein was higher in PAD patients. Western blot analyses and immunoaffinity studies confirmed that this protein was beta2-microglobulin (B2M). In a validation study, B2M was measured by ELISA in plasma in age- and gender-matched PAD (n=20) and non-PAD (n=20) subjects. Finally, we studied a larger cohort of subjects (n=237) referred for coronary angiography but without known PAD. Plasma B2M levels were higher in PAD patients than in non-PAD patients with coronary artery disease. Plasma B2M correlated with ankle brachial index and functional capacity. Independent predictors of PAD were diabetes mellitus, age, and the combination of B2M and C-reactive protein level. In PAD patients, circulating B2M is elevated and correlates with the severity of disease independent of other risk factors. These findings might provide a needed biomarker for PAD and new insight into its pathophysiology. Further studies in other populations are needed to confirm the utility of measuring B2M in cardiovascular disease risk assessment.


[Advanced nursing practice in a medical-psychological center].
The introduction of an advanced practice nurse in psychiatry and mental health (APN) at the University Hospital of Nîmes has made it possible to improve the quality and safety of care while controlling costs and ensuring the satisfaction of patients, partners and care teams. A favorable institutional policy, the involvement of the management, psychiatrists and the IPA PSM facilitated the acceptance of this new profession by the care teams and other professionals, despite the existence of statutory and logistical obstacles.


Celiac disease in adults: evaluation with MDCT enteroclysis.
The purpose of this article is to present the MDCT enteroclysis features of the multiple complications of celiac disease and illustrate why this technique is helpful to adult patients with celiac disease. MDCT enteroclysis findings can suggest the diagnosis in adult patients with unknown celiac disease, and many complications of celiac disease can be recognized because of their characteristic appearance. Familiarity with these signs can help in appropriate planning of further diagnostic procedures.


Effects of crude oil and diesel exposures on biochemical activities of polymorphonuclear leukocytes in cattle.
Cattle exposed to low doses of an Alberta crude oil, Pembina Cardium crude oil (PCCO), or a winter diesel oil no. 2 (WDO-2) were assessed for their biochemical activities in polymorphonuclear leukocyte (PMNL) cells (mainly neutrophils). The study used a randomized block design containing five treatment groups (8 animals/group). The animals were dosed per gavage with the test substance on study days 0, 14, 28, and 42. The dosages given (on per kg body weight) were: Group 1 (control), 10 mL/kg of potable water; Group 2, 5 mL/kg WDO-2; Group 3, 2.5 mL/kg PCCO; Group 4, 5 mL/kg PCCO; and Group 5, 10 mL/kg PCCO. Blood was collected at the specified intervals during the pre- and post-exposure periods, and the biochemical activities of isolated PMNL were analyzed. Cattle groups exposed to WDO-2 and PCCO showed moderate and statistically significant reductions (p < 0.01) in the activities of (1) phorbol myristate acetate (PMA) stimulated cellular respiration (respiratory burst), (2) NADPH-oxidase (PMA-stimulated production of superoxide anion), (3) myeloperoxidase, and (4) n-acetylglucosidase as compared to the control group. These biochemical parameters also showed statistically significant (p < 0.01) dose-related periodic (study day) trends. In general, these biochemical activities were decreased after each dosing; however, they subsequently recovered to near the pre-dosing levels. Such a biochemical response in PMNL provides a valuable biological tool to follow exposure effects in cattle accidentally exposed to low doses of petroleum hydrocarbons.


Single-unit activity in the bed nucleus of the stria terminalis during fever.
Arginine vasopressin, released from nerve terminals in the septal region, probably exerts endogenous antipyretic activity. A major source of vasopressin to this area is the bed nucleus of the stria terminalis (BST). In order to characterize electrophysiologically the BST-septal pathway and its potential role in the control of fever, single-unit, extracellular recordings were made from neurons in the BST of anesthetized rats. Afferent and efferent connections were identified by electrical stimulation of the medial amygdaloid nucleus and the ventral septal area (VSA). BST neurons received both inhibitory and excitatory synaptic input from the amygdala and VSA. Efferents to the VSA were identified by stimulus-evoked antidromic spike invasion. Some BST neurons were responsive to peripheral skin temperature (thermoresponsive). The activity of putative vasopressin neurons was studied during prostaglandin E1-induced fever. Although a majority of BST units was unaffected by fever, a proportion of the cells examined increased their firing rates in accordance with reported release of vasopressin in the VSA during fever.


The electronic disability record: purpose, parameters, and model use case.
The active engagement of consumers is an important factor in achieving widespread success of health information systems. The disability community represents a major segment of the healthcare arena, with more than 50 million Americans experiencing some form of disability. In keeping with the "consumer-driven" approach to e-health systems, this paper considers the distinctive aspects of electronic and personal health record use by this segment of society. Drawing upon the information shared during two national policy forums on this topic, the authors present the concept of Electronic Disability Records (EDR). The authors outline the purpose and parameters of such records, with specific attention to its ability to organize health and financial data in a manner that can be used to expedite the disability determination process. In doing so, the authors discuss its interaction with Electronic Health Records (EHR) and Personal Health Records (PHR). The authors then draw upon these general parameters to outline a model use case for disability determination and discuss related implications for disability health management. The paper further reports on the subsequent considerations of these and related deliberations by the American Health Information Community (AHIC).


T cell selection during the evolution of CD8+ T cell memory in vivo.
Memory T cell responses are frequently highly restricted in terms of receptor usage. How and when such clonotypic dominance is established remains poorly understood. Here we have investigated the evolution of the T cell responses to an epitope from Epstein-Barr virus (EBV), (FLRGRAYGL), by analyzing TCR use of clones specific for this epitope, derived from peripheral blood mononuclear cells taken from individuals early during primary EBV infection and up to 3 years later. We show that, in a given individual, particular T cell clonotypes are selected early during the primary response to this epitope and that the same clonotypes dominate the late memory response. In one individual direct analysis of HLA-B8-restricted FLRGRAYGL-specific T cells, isolated from peripheral blood lymphocytes taken during primary EBV infection using a tetrameric MHC-peptide complex, confirmed the early selection of the dominant clonotypes.


Uniqueness and nonuniqueness in the Einstein constraints.
The conformal thin-sandwich (CTS) equations are a set of four of the Einstein equations, which generalize the Laplace-Poisson equation of Newton's theory. We examine numerically solutions of the CTS equations describing perturbed Minkowski space, and find only one solution. However, we find two distinct solutions, one even containing a black hole, when the lapse is determined by a fifth elliptic equation through specification of the mean curvature. While the relationship of the two systems and their solutions is a fundamental property of general relativity, this fairly simple example of an elliptic system with nonunique solutions is also of broader interest.


Metformin and alpha lipoic acid ameliorate hypothyroidism and its complications in adult male rats.
The current study evaluates the effect of metformin (MET) and /or alpha lipoic acid (ALA) on hypothyroidism and its adverse effects on the cardiac, renal, and, hepatic functions in rats. Rats were divided into five groups: control, rat model of hypothyroidism induced by propylthiouracil (PTU), rat model of hypothyroidism treated with MET, rat model of hypothyroidism treated with ALA, and rat model of hypothyroidism treated with MET and ALA. At the end of the experiment, body weight gain was determined and the blood samples were collected from orbital plexus to measure the serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) by ELISA, glucose level, the activities of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and the levels of urea and creatinine spectrophotometrically. Rat model of hypothyroidism revealed a significant decrease in T4 (p < 0.001) and T3 (p < 0.001) and a significant increase in TSH (p < 0.005). This was accompanied by a significant decrease in the body weight gain (p < 0.025) and a significant increase in LDH (p < 0.001), CK-MB (p < 0.001) AST (p < 0.01), ALT (p < 0.016), ALP (p < 0.001), glucose (p < 0.001), urea (p < 0.001) and creatinine (p < 0.001). MET restored T4, T3 and TSH to control values. Treatment with ALA restored T3 and TSH levels. Treatment with Met and /or ALA reduced the levels of glucose, urea and creatinine and the activities of LDH, CK-MB, AST, ALT, and ALP to control-like values. Only ALA improved the reduced body weight gain induced by hypothyroidism. The present findings indicate the ameliorative effects of MET and /or ALA on hypothyroidism and its adverse effects on cardiac, renal and hepatic functions. The online version contains supplementary material available at 10.1007/s40200-022-01063-7.


BC-spiro-estradiols. Synthesis and estrogen receptor binding affinity of four new estradiol isomers.
The synthesis of four new isomers of estradiol in which the ring A to ring C planes are perpendicular to each other as a result of a spiro BC ring junction is described. Heterocyclic analogs and carbocyclic homologs of these compounds are also reported. Estrogen receptor binding studies show that the spiro compounds with the natural stereochemistry at C9 bind almost as strongly as estradiol but with greater β to α selectivity. These studies show that the estrogen receptors can readily accommodate isomers of estrogen with substantially different fixed shapes than the native ligand.


Cerebral thrombophlebitis revealing SARS-CoV-2 infection: About one case.
SARS-CoV-2 infection is a pandemic that continues to ravage the world, the list of its complications continues to grow longer every day. We report the case of a patient admitted to intensive care for cerebral thrombophlebitis revealing a SARS-CoV-2 infection. The inflammatory nature of SARS-CoV-2 infection exposes an increased risk of thrombosis.In this article, we will discuss its mechanism and the anticoagulant treatment modalities. Besides the typical clinical signs, SARS-CoV-2 infection can manifest as thromboembolic complications such as pulmonary embolism, deep vein thrombosis, and less frequently cerebral thrombophlebitis.


The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction.
Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3',5'-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.


Correlations of CT-findings and neuropathological investigations in cranio-cerebral trauma.
For direct comparison of computerized tomograms (CT) and autopsy findings after cranio-cerebral trauma 86 brain specimens were sectioned along the horizontal planes of CT-scanning. A high reliability of the new x-ray method was found in about 72% of the investigated cases. The causes of insufficient correspondence in other cases were discussed.


Flexor digitorum brevis transfer for floating toe prevention after Weil osteotomy: a cadaveric study.
A floating toe deformity occurs in many patients who undergo Weil osteotomies. It is likely caused by the failure of the windlass mechanism in shortening the metatarsal. For patients who require a proximal interphalangeal (PIP) joint arthroplasty or fusion in addition to a Weil osteotomy, the transfer of the flexor digitorum brevis (FDB) tendon to the PIP joint might restore the windlass mechanism and decrease the incidence of floating toes. Fourteen cadaveric foot specimens were examined to determine the effects of changing metatarsal length as well as tensioning the FDB tendon on the angle of the metatarsophalangeal (MTP) joint as a measure of a floating toe. Shortening and lengthening the second metatarsal resulted in a significant change in MTP angle (P = .03 and .02, respectively), though there was no clear relationship found between the amount of change in metatarsal length and the change in MTP angle. Transferring the FDB to a PIP arthroplasty site plantarflexed the MTP joint and corrected floating toes; the change in angle was significant compared with the control and shortening groups (P = .0001 and .002, respectively). This study supports the theory that change in length of the metatarsal, possibly via the windlass mechanism, plays a role in the pathophysiology of the floating toe deformity. Tensioning and transferring the FDB tendon into the PIP joint helped prevent the floating toe deformity in this cadaveric model. Continued research in this subject will help to refine methods of prevention and correction of the floating toe deformity.


Effects of initial cell seeding density for the tissue engineering of the temporomandibular joint disc.
Tissue engineering may provide a better treatment modality for postoperative discectomy patients. The TMJ disc is an ideal candidate for tissue engineering approaches because of its lack of an intrinsic regenerative ability. Unfortunately, basic knowledge related to TMJ disc tissue engineering is still at an infancy level and not on par to that related to articular cartilage tissue engineering. The objective of this study was to examine the effects of initial cell density of TMJ disc cells seeded in nonwoven poly-glycolic acid (PGA) scaffolds on the biochemical and biomechanical properties of constructs examined at 0, 3, and 6 weeks after seeding. Low, medium, and high seeding densities were chosen to be 15, 30, and 120 million cells per ml of scaffold, which were seeded using a spinner flask. Significant differences were found temporally and as a function of seeding density in morphology, total collagen, GAG content, and permeability of the constructs, but not in aggregate modulus. The high seeding density group outperformed the low and medium groups in collagen and GAG content at all time points measured. The high-density group produced a total of 55.37 +/- 3.56 microg of collagen per construct, maintained 15.77 +/- 1.86 microg of GAG per construct, and only shrunk to 50% of the original scaffold size. Permeability of the constructs at 6 weeks was decreased by 70% compared to 0 weeks.


Isoprinosine and NPT 15392: immunomodulation and cancer.
These data demonstrate that both Isoprinosine and NPT 15392 are active nontoxic biological response modifiers that qualify for studies in cancer patients. Because of their immunomodulating properties, these agents are expected to be most appropriate in the treatment of immunosuppressed patients who are prone to infection or recurrence following cytoreductive therapy.


HLA-D/DR restriction of proliferative T cell responses to antigen. Enrichment of antigen-specific T cell blasts and evidence of preferential HLA-D/DR restriction.
Antigen-specific T cell blasts may be separated from alloreactive cells on Percoll gradients. The absence of alloreactivity allowed us to study HLA-D/DR restriction of proliferative T cell responses towards PPD and HSV antigens using allogeneic antigen-presenting cells. An overriding impact of self HLA-D/DR determinants as restriction elements for in vivo sensitized T cells was demonstrated. Furthermore, evidence was obtained that the proliferative PPD response might be preferentially restricted by HLA-D/DR 1.


Glycoconjugates for glucose transporter-mediated cancer-specific targeting and treatment.
First observed in 1920s, the Warburg effects have inspired scientists to harness the unique glucose metabolism of cancer cells for targeted therapy for a century. Carbohydrate-drug conjugates are explicitly designed for selective uptake by cancer cells overexpressing glucose transporters. We summarize the progress in developing glycoconjugates for cancer-specific targeting and treatment over the past decade (2010-2020) and point to some future directions in this field.


Non-invasive evaluation of transdermal drug delivery using 3-D transient triplet differential (TTD) photoacoustic imaging.
Transdermal drug delivery (TDD) is less invasive and avoids first-pass metabolism, making it an attractive method for treating various diseases such as diabetes and hypertension. However, current methods for evaluating TDD systems lack in vivo descriptions of drug distribution in the skin. In this study, we demonstrate the capability of the Transient Triplet Differential (TTD) method, a non-invasive and background-free photoacoustic imaging technique, for accurately mapping drug distribution and evaluating different TDD systems. Our findings show that the TTD method can provide high sensitivity and specificity for targeted drug extraction and visualize 3D drug distribution in the skin. Furthermore, in vivo experiments confirmed the potential of the TTD method in evaluating the clinical performance of TDD. It's predictable that the TTD method can be a reliable and non-invasive approach for evaluating TDD systems and offer valuable insights into TDD research and development.


Area level indirect exposure to extended conflicts and early childhood anthropometric outcomes in India: a repeat cross-sectional analysis.
Protracted, internal conflicts with geographic variations within countries, are an important understudied community exposure for adverse child health outcomes. Violent events from the Uppsala Conflict Data Program (UCDP) between January 2016-December 2020 and January 2010-December 2015, were included as exposure events for children sampled in National Family Health Surveys (NFHS) 5 (2019-21) and NFHS 4 (2015-16), respectively. Geocoded data from UCDP were merged with residential clusters from NFHS, to identify children living in villages or urban blocks situated at <= 50 km from conflict sites. Within these clusters, which we defined as conflict exposed, we studied risks of stunting, underweight and wasting in children, prenatally, and in 0-3 years. We assessed sensitivity on a subsample of siblings with discordant conflict exposures. For NFHS 5, exposure to violence between 0 and 3 years was associated with 1.16 times (95% CI 1.11-1.20) higher risks of stunting, 1.08 (1.04, 1.12) times higher risks of underweight, and no change in wasting. In-utero violence exposure was associated with 1.11 times (95% CI 1.04-1.17) higher risks of stunting, 1.08 (95% CI 1.02-1.14) times higher risks of underweight, and no change in wasting, among children <= 2 years. In 17,760 siblings of 8333 mothers, exposure to violence during 0-3 years, was associated with a 1.19 times higher risk of stunting (95% CI - 0.24 to 0.084). Incremental quartiles of violence exposure had higher risks of stunting and underweight until quartile 3. In-utero and early childhood indirect exposure to protracted conflicts were associated with increased stunting and underweight in India. Given the continued exposures of such historically and contextually rooted internal conflicts in many LMICs, chronic violence exposures should be targeted in public health policies as important social and political determinant of child health.


Cigarette smoke preparations, not electronic nicotine delivery system preparations, induce features of lung disease in a 3D lung repeat-dose model.
Cigarette smoking is a risk factor for several lung diseases, including chronic obstructive pulmonary disease, cardiovascular disease, and lung cancer. The potential health effects of chronic use of electronic nicotine delivery systems (ENDS) is unclear. This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in a repeat-dose exposure to evaluate and compare the effect of combustible cigarette and ENDS preparations. We show that 1-h daily exposure of NHBE cultures over a 10-day period to combustible cigarette whole smoke-conditioned media (WS-CM) increased expression of oxidative stress markers, cell proliferation, airway remodeling, and cellular transformation markers and decreased mucociliary function including ion channel function and airway surface liquid. Conversely, aerosol conditioned media (ACM) from ENDS with similar nicotine concentration (equivalent-nicotine units) as WS-CM and nicotine alone had no effect on those parameters. In conclusion, primary NHBE cultures in a repeat-dose exposure system represent a good model to assess the features of lung disease. This study also reveals that cigarette and ENDS preparations differentially elicit several key endpoints, some of which are potential biomarkers for lung cancer or chronic obstructive pulmonary disease (COPD).


New multifactorial burn resuscitation formula offers superior predictive reliability in comparison to established algorithms.
The Parkland-Baxter formula is a widely utilized resuscitation guideline for the initial management of fluid deficits in burn victims. Implementation of resuscitation formulas has helped to reduce the incidence of shock and hypovolemic organ failure such as acute renal failure in the setting of burn trauma. However, it has been shown that indiscriminate implementation of these formulas may inappropriately suit individual patient's requirements. In our experience resuscitation by the Parkland formula often forced corrections in order to reach predefined resuscitation goals. Given these findings we felt the need to refine formula based resuscitation strategies. Reviewing a subset of 81 burn admissions we screened for predictive parameters in addition to total body surface area burned (TBSA burned) and body weight influencing resuscitation volume requirements. Using multivariate linear regression analysis (MRA) various parameters were integrated in a stepwise forward mathematical selection procedure resulting in a modified resuscitation formula. A new formula including body weight, TBSA burned, inhalation injury (IHI), high blood alcohol level (BAL) and a compensating factor for advanced age was set up. The new formula was compared to the original Parkland formula. Both were assessed for predictive reliability (PR(+/-20%)). Using this strategy we were able to improve PR(+/-20%) from 28.4% to 51.9%. Optimal fluid resuscitation of severe burn victims is a complex clinical challenge. Rigid-formula based resuscitation schemes often fail to match all subtleties of current clinical practice but need to provide a reliable starting point for fluid resuscitation. We demonstrate a new multifactorial formula resulting in a better guide to initial fluid resuscitation.


Knee arthroscopy after yttrium or osmic acid injection.
This study presents the macroscopic and histologic results of 35 knee arthroscopies performed on patients with rheumatoid arthritis, some months after an yttrium or osmic acid intraarticular injection. The procedure was most often performed after a failure of the injection or a relapse of synovitis. Arthroscopy provides an understanding of the cause of synoviorthesis failure--insufficient action of the product on the synovitis or its poor diffusion, fibri-nonecrotic deposits, or cartilaginous lesions--and may be used both diagnostically and therapeutically.


Towards therapy using RNA interference.
Small interfering RNA (siRNA) molecules are short sequences of double-stranded RNA 19-27 bp in length, which suppress expression of target genes by inducing the breakdown of the cognate mRNA through mechanisms that are still being elucidated. siRNA molecules can be chemically synthesized or prepared through digestion of larger double-stranded RNA molecules using recombinant dicer or RNAase III enzyme. siRNA molecules can also be encoded by plasmid or virus vectors or expressed in transgenic animals. Design of siRNA sequences that efficiently suppress target genes can sometimes be challenging, although digestion of large double-stranded RNA species with recombinant dicer or RNAase III may remove the necessity for testing multiple candidate siRNA. Exogenous siRNA can suppress translation for varying amounts of time depending on the half-life of the protein targeted. Vector-mediated approaches may improve duration but their use can be limited by the permanency and efficiency of transduction. Potential therapeutic targets for siRNA include viral and non-viral pathogens, cancer, neurodegenerative diseases, septic shock and macular degeneration. Suppression of expression via siRNA is also an extremely useful research tool for ascertaining gene function. Looking ahead to clinical applications, it will be important to know the consequences of inadvertent suppression of non-targeted sequences. If safety can be established, siRNA has the potential to significantly impact the field of molecular medicine.


Nurse versus family caregiver perspectives on hospitalized older patients: an exploratory study of agreement at admission and discharge.
Staff nurses and family caregivers of hospitalized elderly patients (> or = age 70) play crucial roles in the health care and recovery of patients. This exploratory study identified and compared nurse and family caregiver perceptions about the patient's health condition, needs to stay healthy, and problems in self-care at admission and discharge. Agreement between nurse and caregiver reports at both time points was assessed. Overall, findings confirmed a lack of agreement between nurses and family caregivers. At both time points, fewer nurses than caregivers focused on disease in describing the patients' health condition, and there was low agreement about diseases when mentioned. Although the great majority of nurses and caregivers reported one or more patient needs to stay healthy, and problems with self-care, there was little agreement about specific needs or problems mentioned at either time point. Findings may be attributed, in part, to current limitations on staff nurses' bedside time or insufficient opportunities, skills, or both to communicate with families about patients as part of comprehensive discharge planning. Organizational factors in large tertiary care hospitals may serve as a deterrent to nurse-family caregiver contact and communication during hospitalization.


Tissue distribution and association of heavy metal accumulation in a free-living resident passerine bird tree sparrow Passer montanus.
Passerine birds have been increasingly used as effective sentinels of ecosystem contamination. They can provide direct evidence of the bioavailability and accumulation of heavy metal elements in the environment. In this study, the bioaccumulation of four heavy metals (Cu, Zn, Pb, and Cd) and Ca in different organs and tissues (feathers, internal organs, skeletons, and muscles) of an urban bird, tree sparrow (Passer montanus), collected from a polluted site [Baiyin (BY)] and a relatively unpolluted site [Liujiaxia (LJX)], and their associations were investigated. There were significantly higher and lower concentrations of heavy metals and Ca, respectively, in different organs and tissues of sparrows in BY than those in LJX. However, except for Pb, the heavy metal levels were below the threshold of sublethal effects. Age-dependent variations in metals were quantified, and it was found that adult bird contained higher concentration of different organs and tissue metals, except for feathers, compared with nestlings and juveniles. The tissue distribution of heavy metals in sparrows of different ages and sex was similar in the two study sites, and heavy metal elements were mainly accumulated in the feathers. This study further investigated the correlation between heavy metals in different organs and tissues and found that the correlations between them were strong in nestlings and adults but weak in juveniles. In addition, Pb and Cd in internal organs, skeletons, and muscles of young sparrows can be estimated using feathers, whereas Cu and Zn were found in adult sparrows. Altogether, our results suggest that tree sparrows will serve as valuable biomonitors of environmental heavy metal pollution and will underscore the importance of tissue types in avian ecotoxicology field studies.


Eliciting perspectives of the key study population: An effective strategy to inform advertisement, content and usability of an online survey for a national investigation.
This short communication demonstrates how conducting a focus group with members of a proposed study population of interest can help inform the suitability of study interventions and appeal of recruitment strategies prior to study commencement. People living with HIV (PLWH) were recruited to participate in a focus group to elicit feedback on the content and design of an online survey on sweetener knowledge and consumption; and usability of the survey which was ultimately launched nationally. Ten participants (age 55 years, 60% male, 70% non-Caucasian, 60% income < $25,000) attended and rotated through three stations and completed questionnaires to evaluate survey content, advertisement imagery and taglines, and ability to access and navigate the survey platform. Participants also engaged in open dialogue to discuss potential community and web-based recruitment strategies familiar to PLWH. Findings from the focus group helped investigators identify and select advertisement and recruitment strategies that were appealing to PLWH, refine and improve clarity/layout of the survey content, and enhance usability of an online survey intended for PLWH in the United States, age 18 years and older. Prospectively engaging individuals from a key study population in the early phase of study development is an effective strategy to assist in the development of study interventions and recruitment/advertisement materials designed for a specific population.


Pharmacotherapy for the pseudobulbar affect in individuals who have sustained a traumatic brain injury: a systematic review protocol.
The objective of this systematic review is to synthesize current evidence on the effectiveness of pharmacotherapy as compared to all comparators for the management of pseudobulbar affect in adults 16 years and over who have sustained a traumatic brain injury. The specific review question is: What is the effectiveness of pharmacotherapy for the management of pseudobulbar affect in adults 16 years and over who have sustained a traumatic brain injury?


Cerebral Proliferative Angiopathy in a Child, Five Years after an Intraventricular Hemorrhage and Negative Catheter Angiography.
Cerebral proliferative angiopathy (CPA) is a rare cerebrovascular disease comprised of a diffuse network of blood vessels, often spread over several lobes. Due to the presence of normal brain tissue within the malformation, complete resection is not desirable. Several imaging characteristics help to distinguish CPA from brain arteriovenous malformations. We report the case of a patient diagnosed with CPA five years after a spontaneous intraventricular hemorrhage and an initial negative angiogram. The radiologist should be able to differentiate CPA from brain AVM to prevent potentially harmful treatment.


Emotion perception abnormalities across sensory modalities in bipolar disorder with psychotic features and schizophrenia.
Emotion perception deficits are a well-established feature of schizophrenia (SZ). Individuals with SZ have difficulty labeling emotional stimuli across auditory, visual, and audio-visual modalities and also misattribute threat towards neutral stimuli. The relationship between a history of psychosis and similar abnormalities in bipolar disorder (BD) is less clear. The current study set out to examine emotion perception across sensory modalities in a sample of 24 stabilized individuals meeting criteria for SZ, 24 remitted individuals meeting criteria for BD with psychotic features, 24 remitted individuals meeting criteria for BD without psychotic features, and 24 healthy controls. Results indicated that the bipolar with psychotic features group had intermediary performance between the SZ group and the other two groups for auditory, visual, and audio-visual items, with particularly poor performance in identifying angry stimuli. The SZ group misattributed neutral stimuli as negative when they were in visual format, but as positive when they were in auditory or audio-visual formats. The bipolar with psychotic features group had a trend towards misattributing more neutral visual stimuli as negative. These findings indicate that emotion perception deficits are present in BD with psychotic features and comparatively spared in BD without psychotic features, and that a similar bias of misattributing negative emotions to neutral visual stimuli may be present across diagnostic boundaries.


Childhood medulloblastoma-a single institution's historical perspective on survival and functional morbidity.
To compare results from a third (1995-2010) cohort of children with medulloblastoma with two previous series (J Neurosurg 86:13-21, 1997; Arch Dis Child 54:200-203, 1979) to analyse the effects of management changes aimed at improving both overall and event-free survivals (OS and EFS) and functional outcomes. Review of neuro-oncology and imaging databases and previously published results. There was no statistically significant improvement in the 5-year OS for 104 children diagnosed 1995-2010, 61.5% (95% CI, 52.9, 71.6), compared with 50% of the 80 children presenting 1980-1990 (J Neurosurg 86:13-21, 1997) (difference 11.5%; 95% CI, 2.8, 25.4). Five-year OS for 96 children suitable for risk-stratification was overall 66% (95% CI, 57.9, 75.8); standard risk 77.8% (95% CI, 67.4, 89.7); high risk < 3 years 50.0% (95% CI, 32.3, 77.5); high risk ≥ 3 years 54.5% (95% CI, 37.2, 79.9); 5-year EFS were standard risk 68.5% (95% CI, 57.2, 82.1); high risk < 3 years 40.0% (95% CI, 23.4, 68.4); and high risk ≥ 3 years 36.4% (95% CI, 20.9, 63.2); overall 55.2% (95% CI, 46.1, 66.1). Of 62/63 ≥ 5-year survivor, 9 died later from tumour relapse and 4 from second malignancy. Functional outcomes of 62 of the 63 ≥ 5-year survivors: 67.7% had educational issues requiring remedial input; 18% restricted mobility indoors and outdoors; 59.7% hearing impairment (42% prescribed aids). 1. Comparison of this single-institution series with its predecessor found that revised chemotherapy and RT protocols and greater accuracy of risk stratification did not result in statistically significant improvements in either survival or treatment-related functional disability. 2. Extended (> 5-year) follow-up is essential if 20% of late deaths from relapse and second malignancies are not to be overlooked.


Effect of a short-term infusion of glutamine on muscle protein metabolism postoperatively.
The acute effect of a short-term postoperative infusion of glucose supplemented with glutamine (0.285 g/kg body weight), on muscle protein metabolism, was studied by analyses of free amino acid concentrations and determinations of protein synthesis. A glutamine-glucose infusion was given for 5.5 h to 6 patients 2-3 days after elective surgery for colon cancer. The free glutamine concentration was 5.72 +/- 0.96 mmol/kg wet weight (ww) before and 6.14 +/- 1.10 mmol/kg ww 4 h after the glutamine infusion. The rate of protein synthesis was 1.26 +/- 0.15%/24 h before the infusion and 1.12 +/- 0.16%/24 h during its latter part. The percentage of polyribosomes was 42.2 +/- 3.4% before and 40.9 +/- 1.3% after the infusion. The results showed no difference in these biochemical parameters, indicating that a short-term infusion of glutamine given postoperatively is insufficient to affect protein metabolism in human skeletal muscle.


Assessment for Tactile Perception in Children With Cerebral Palsy.
Impaired tactile perception frequently accompanies motor deficits in children with cerebral palsy (CP). Assessing tactile perception precisely for children with CP remains challenging because of a lack of assessments with robust psychometric evidence or standard procedures. To develop a standardized assessment tool, the Tactile Perceptual Test (TPT), for measuring tactile perception in children with CP and to examine its psychometric properties. Observational study design. University research laboratory and medical center. Children with CP (n = 100) and typical development (TD; n = 50). The TPT includes four subtests measuring stereognosis, roughness, hardness, and heaviness. Three comparator instruments, Semmes-Weinstein monofilaments, Two-Point Discrimination, and the stereognosis subtest of the Revised Nottingham Sensory Assessment, were used for convergent validity. Good test-retest reliability was confirmed for all of the TPT subtests. The values of minimal detectable change were acceptable. Moderate correlations between the TPT and comparator instruments were found, as expected. For known-groups validity, the significant difference was confirmed between children with CP and those with TD. The TPT is a reliable and valid measure for multiple subdomains of tactile perception in children with CP. This tactile assessment may help clarify tactile performance to provide appropriate, precise interventions. What This Article Adds: The TPT measures tactile perception in children with CP. It has four subdomains of tactile perception that could facilitate prioritization of tactile treatment of specific subdomains and thereby aid in the provision of appropriate interventions.


Glucagon receptor blockage inhibits β-cell dedifferentiation through FoxO1.
Glucagon-secreting pancreatic α-cells play pivotal roles in the development of diabetes. Glucagon promotes insulin secretion from β-cells. However, the long-term effect of glucagon on the function and phenotype of β-cells had remained elusive. In this study, we found that long-term glucagon intervention or glucagon intervention with the presence of palmitic acid downregulated β-cell-specific markers and inhibited insulin secretion in cultured β-cells. These results suggested that glucagon induced β-cell dedifferentiation under pathological conditions. Glucagon blockage by a glucagon receptor (GCGR) monoclonal antibody (mAb) attenuated glucagon-induced β-cell dedifferentiation. In primary islets, GCGR mAb treatment upregulated β-cell-specific markers and increased insulin content, suggesting that blockage of endogenous glucagon-GCGR signaling inhibited β-cell dedifferentiation. To investigate the possible mechanism, we found that glucagon decreased FoxO1 expression. FoxO1 inhibitor mimicked the effect of glucagon, whereas FoxO1 overexpression reversed the glucagon-induced β-cell dedifferentiation. In db/db mice and β-cell lineage-tracing diabetic mice, GCGR mAb lowered glucose level, upregulated plasma insulin level, increased β-cell area, and inhibited β-cell dedifferentiation. In aged β-cell-specific FoxO1 knockout mice (with the blood glucose level elevated as a diabetic model), the glucose-lowering effect of GCGR mAb was attenuated and the plasma insulin level, β-cell area, and β-cell dedifferentiation were not affected by GCGR mAb. Our results proved that glucagon induced β-cell dedifferentiation under pathological conditions, and the effect was partially mediated by FoxO1. Our study reveals a novel cross talk between α- and β-cells and is helpful to understand the pathophysiology of diabetes and discover new targets for diabetes treatment.NEW & NOTEWORTHY Glucagon-secreting pancreatic α-cells can interact with β-cells. However, the long-term effect of glucagon on the function and phenotype of β-cells has remained elusive. Our new finding shows that long-term glucagon induces β-cell dedifferentiation in cultured β-cells. FoxO1 inhibitor mimicks whereas glucagon signaling blockage by GCGR mAb reverses the effect of glucagon. In type 2 diabetic mice, GCGR mAb increases β-cell area, improves β-cell function, and inhibits β-cell dedifferentiation, and the effect is partially mediated by FoxO1.


Stable lariats bearing a snoRNA (slb-snoRNA) in eukaryotic cells: A level of regulation for guide RNAs.
Small nucleolar (sno)RNAs guide posttranscriptional modifications essential for the biogenesis and function of their target. The majority of snoRNAs in higher eukaryotes are encoded within introns. They are first released from nascent transcripts in the form of a lariat and rapidly targeted by the debranching enzyme and nuclear exonucleases for linearization and further trimming. In this study, we report that some snoRNAs are encoded within unusually stable intronic RNAs. These intronic sequences can escape the debranching enzyme and accumulate as lariats. Stable lariats bearing a snoRNA, or slb-snoRNA, are associated with snoRNA binding proteins but do not guide posttranscriptional modification. While most slb-snoRNAs accumulate in the nucleus, some can be exported to the cytoplasm. We find that this export competes with snoRNA maturation. Slb-snoRNAs provide a previously unknown layer of regulation to snoRNA and snoRNA binding proteins.


Lung function in infants and young children: functional residual capacity, tidal volume, and respiratory rats.
Functional residual capacity was measured by the closed-circuit, helium-equilibration method in 121 normal children 3 months to 6 years of age. Prediction equations for functional residual capacity for normal children of this age range are presented for the first time. This study demonstrates that some aspects of lung functiok can be studied relatively conveniently in young children.


Safety and long-term outcome of laparoscopic antireflux surgery in patients in their eighties and older.
The elderly have more severe reflux disease and paraesophageal hernias than younger patients, leading to a high failure rate of medical therapy. Laparoscopic antireflux surgery has an overall mortality of 0.1% and a low morbidity, making it a safe and beneficial procedure for the elderly. We performed a retrospective study of octo- and nonogenerians with a mean follow-up of 3.1 years after laparoscopic fundoplication. Thirty (3.5%) patients who were in their eighties or older are reported. Preoperative symptoms, esophageal testing, postoperative symptoms, and satisfaction rate were analyzed. Fifty-seven percent of patients had paraesophageal hernias. Mean duration of procedures was 146 +/- 49 min, blood loss was 76 +/- 101 ml, and hospitalization was 2.2 +/- 1.0 days. There was one conversion to laparotomy, two intraoperative complications, and no deaths. Follow-up data were available in 93% of patients. Mean follow-up time was 3.1 years. Two died of unrelated causes. At follow-up 96% stated that their surgical outcome was satisfactory. Two patients were suffering from severe symptoms. Overall well-being at follow-up was 7.5 (range 3-10) on a 10-point scale in comparison to 2.2 (range 1-5) before surgery (p = 0.03). Laparoscopic surgery is a good option for the treatment of severe gastroesophageal reflux disease in octo- and nonagenarians.


Effect of anatase nanoparticles (TiO2) on parsley seed germination (Petroselinum crispum) in vitro.
Nano priming is a new method for the increase of seedling vigor and improvement of germination percentage and seedling growth. The experiments to evaluate the effect of different concentrations of nano-anatase on germination parameters of parsley as a completely randomized design with five replications were performed in a tissue culture laboratory of the Department of Horticulture, Shahid Chamran University of Ahvaz. In addition, nano-anatase at four concentrations (10, 20, 30, and 40 mg/ml) was added to the Murashige and Skoog medium. At the end of the experiment, the percentage of germination, germination rate index, root and shoot length, fresh weight of seedlings, vigor index, and chlorophyll content were evaluated. The results showed that an increase in the concentration of nano-anatase caused a significant increase in the percentage of germination, germination rate index, root and shoot length, fresh weight, vigor index, and chlorophyll content of seedlings. The best concentration of nano-anatase was 30 mg/ml.


Neural correlates of visuospatial imagery.
We studied changes in regional cerebral blood flow (rCBF) in 10 healthy right-handed subjects during a visuospatial imagery task. The subject's task consisted of drawing imagined lines connecting encircled numbers in ascending order and estimating the number of lines crossing. Compared with a control task in which there were no crossed lines, there were significant rCBF increases in the cingulate gyrus, the adjacent superior frontal gyrus and in the left inferior parietal cortex. The rCBF changes of the latter area correlated with task performance time. Since these activation areas are close to those in imagery of movement trajectories, we concluded that they appear to be a subsystem for processing mental visuospatial images.


A comparative study on characteristics and leaching toxicity of fluidized bed and grate furnace MSWI fly ash.
Grate furnace and fluidized bed are the most widely used technologies for municipal solid waste incineration (MSWI), which play significant roles in characteristics of MSWI fly ash. A comparative study of the physicochemical characteristics, microstructure morphology and leaching toxicity of fluidized bed and grate furnace MSWI fly ash was conducted in this work, and some resource utilization and disposal treatments were proposed. Results showed that calcium salt and chlorine salt formed the dominant components of MSWI fly ash. CaO-SiO2-Al2O3 ternary system indicated that MSWI fly ash had potential pozzolanic activity, similar to coal fly ash and blast furnace slag. The total Pb, Cd and Zn contents in fluidized bed MSWI fly ash was only 1/2, 1/3 and 2/3 of grate furnace MSWI fly ash, respectively. Leachability of Pb in MSWI fly ash collected from Dalian, Shanghai, Zhuji and Hangzhou was 4.25 mg/L, 3.83 mg/L, 3.84 mg/L and 3.68 mg/L, 28.3, 25.5, 25.6 and 24.5 times as much as the national standard limitation (GB16889-2008), respectively. However, grate furnace MSWI fly ash with high chloride and unstable chemical speciation distribution of heavy metals would pose more environmental risk toits immobilization and disposal. Fluidized bed fly ash is a promising candidate for preparing the Portland cement clinker, microcrystalline glass and ceramics due to its high Si and Al content. Grate furnace MSWI fly ash is more appropriate for Alinite cement preparation because of high chloride content.


Non-serogroup O1/O139 agglutinable Vibrio cholerae: a phylogenetically and genealogically neglected yet emerging potential pathogen of clinical relevance.
Somatic antigen agglutinable type-1/139 Vibrio cholerae (SAAT-1/139-Vc) members or O1/O139 V. cholerae have been described by various investigators as pathogenic due to their increasing virulence potential and production of choleragen. Reported cholera outbreak cases around the world have been associated with these choleragenic V. cholerae with high case fatality affecting various human and animals. These virulent Vibrio members have shown genealogical and phylogenetic relationship with the avirulent somatic antigen non-agglutinable strains of 1/139 V. cholerae (SANAS-1/139- Vc) or O1/O139 non-agglutinating V. cholerae (O1/O139-NAG-Vc). Reports on implication of O1/O139-NAGVc members in most sporadic cholera/cholera-like cases of diarrhea, production of cholera toxin and transmission via consumption and/or contact with contaminated water/seafood are currently on the rise. Some reported sporadic cases of cholera outbreaks and observed change in nature has also been tracable to these non-agglutinable Vibrio members (O1/O139-NAGVc) yet there is a sustained paucity of research interest on the non-agglutinable V. cholerae members. The emergence of fulminating extraintestinal and systemic vibriosis is another aspect of SANAS-1/139- Vc implication which has received low attention in terms of research driven interest. This review addresses the need to appraise and continually expand research based studies on the somatic antigen non-serogroup agglutinable type-1/139 V. cholerae members which are currently prevalent in studies of water bodies, fruits/vegetables, foods and terrestrial environment. Our opinion is amassed from interest in integrated surveillance studies, management/control of cholera outbreaks as well as diarrhea and other disease-related cases both in the rural, suburban and urban metropolis.


Determinants of direct-care staff turnover in group homes for individuals with mental retardation.
A model of direct-care human service staff turnover was proposed and tested with 236 direct-care staff members in nine private, nonprofit New Jersey agencies. A path analysis of the data was conducted. Four variables were found to contribute to current job satisfaction: agreement of the job with personal goals and values, burnout, satisfaction with supervision, and employment history. In turn, current job satisfaction led to intention to quit, which led to actual turnover. Implications for the human service field and future research were explored.


Improving ACE inhibitor use in patients hospitalized with systolic heart failure: a cluster randomized controlled trial of clinical practice guideline development and use.
The efficacy of angiotensin-converting enzyme (ACE) inhibitors in treating heart failure is well established, but there is concern that these agents are underutilized. This study aimed to evaluate the effect of developing and implementing Clinical Practice Guidelines (CPGs) on the quality of care given to patients receiving ACE inhibitors for systolic heart failure. Twenty cardiology units in Lorraine (France) were randomized to an experimental (n = 10) or a control group (n = 10). In each experimental unit, doctors were involved in drafting and implementing CPGs; those at control units were not. Practice surveys were conducted in all units before and after the intervention; 723 patients with heart failure and less than 75 years old were included. The main outcome was compliance with the CPGs. Before intervention, clinicians in both groups were already compliant with CPGs relating to indications and contra-indications, adverse effects management, concomitant therapy and monitoring of biologic factors. After intervention, adherence to others CPGs was generally better in the experimental group. Compliance with the CPG relating to ACE inhibitor dose on discharge was higher in the experimental group (P = 0.003). Compliance with CPGs relating to increasing ACE inhibitors doses (P < 0.0001) and the contents of the discharge letter (P = 0.02) improved in all units between the two periods. These results suggest that doctors involved in drafting and implementing CPGs are more likely to comply with them.


Unipolar depression/bipolar depression: connections and controversies.
The modern dichotomous divide between unipolar and bipolar depressive disorders derives from several monographs that appeared in the mid-twentieth century. Studies of illness course and differing symptomatic profiles in unipolar and bipolar illness support this interpretation, but more recent descriptions of 'bipolar spectrum disorders' and genetic findings suggest otherwise. Whether these illnesses represent categories or points on a continuum remains an unresolved question.


Stochastic inequality probabilities for adaptively randomized clinical trials.
We examine stochastic inequality probabilities of the form P (X > Y) and P (X > max (Y, Z)) where X, Y, and Z are random variables with beta, gamma, or inverse gamma distributions. We discuss the applications of such inequality probabilities to adaptively randomized clinical trials as well as methods for calculating their values.


Interferon is effective in hairy-cell leukaemia.
Seventeen patients with hairy-cell leukaemia (HCL) and peripheral cytopenias were given human lymphoblastoid interferon (Wellferon), 3 megaunits daily or 6 megaunits on alternate days intramuscularly, for 4-24 weeks. Twelve of the patients had undergone splenectomy, three had no palpable spleen and had therefore not been offered surgery, and two patients with substantial splenomegaly were given interferon (IFN) as treatment of first choice. Toxic effects were minor except in one patient who experienced a severe form of somnolence syndrome. In all patients hairy cells (HCs) were cleared from the blood and platelet and Hb levels improved in 2-14 weeks. Neutrophils were improved in 14/17 of the patients. In the two patients with splenomegaly, the spleen became impalpable after 5-8 weeks therapy, and haematological improvement occurred at 12-14 weeks. HC infiltration of the marrow was reduced in all patients, but was complete (less than 5%) in only two, both of whom had impalpable spleens. Immunological surface-marker studies confirmed that light-chain-restricted B cells disappeared from the blood in parallel with the clearance of morphological HCs. There was no evidence of HC maturation and no increase in phenotypic NK cells. T cells were moderately reduced and the relatively greater reduction of Leu 2a+ suppressor cells resulted in increased Leu 3a+/2a+ helper/suppressor ratios in 11/17 of the patients. Early experience in the six patients who have stopped IFN suggests that, after an initial further increase in Hb and neutrophil levels, HCs gradually return with slow deterioration of haematological parameters. Interferon is now the treatment of choice for patients becoming cytopenic post-splenectomy or for patients without splenomegaly. IFN is effective first-line therapy in patients with splenomegaly, but further work is needed to establish whether the agent should replace splenectomy in such patients. Some form of maintenance or re-treatment therapy will probably be necessary.


Seasonal epidemiology of ticks and aspects of cowdriosis in N'Dama village cattle in the Central Guinea savannah of Côte d'Ivoire.
In the Central Guinea savannah of Côte d'Ivoire, cattle breeding started only approximately 30 years ago. The impact of parasitism on the overall health status and productivity of the trypanotolerant N'Dama cattle in this area is unknown. In close collaboration with national veterinary institutions and local farmers, we studied spectrum, burden and seasonal dynamics of ticks (including aspects of cowdriosis) on N'Dama village cattle. In a longitudinal study, three randomly selected cattle herds (traditional farming type) of one village were examined repeatedly for ticks. Spectrum, burden, seasonal epidemiology of ticks were assessed. In these traditional herds (which lack (ecto)parasite management), all animals were infested by ticks at monthly counts. Five different tick species were identified; the four genera in order of frequency were: Amblyomma (overall prevalence 96%), Boophilus (47%), Hyalomma (<1%) and Rhipicephalus (<1%). Amblyomma variegatum was the most-abundant tick on cattle in all seasons. Seroprevalence of Cowdria ruminantium was 31% (95% CI: 26, 36%). Most of the animals typically carried low tick burdens. N'Dama cattle seem well adapted to their environment and can resist the tick burdens under this traditional farming system.


The contribution of Ruscoe Clarke and his team to knowledge relevant to blood loss after injury.
The major contributions of Ruscoe Clarke, made between 1947 and 1959 at the Birmingham Accident Hospital, are recalled. He and his team measured the red cell volumes. By these and other means we estimated the average blood loss from a series of civilian injuries. It was found that the lowest haemoglobin level 4-14 days after injury was a useful clue in retrospect of the degree to which blood lost had been replaced by blood transfusion. We showed that early transfusion of the correct volume of whole blood appeared to lead to the best chance of quick and full recovery from serious injury. We stressed the need to assess the blood transfusion requirement more precisely.


Mortality and Readmission After Cervical Fracture from a Fall in Older Adults: Comparison with Hip Fracture Using National Medicare Data.
To examine the prevalence of cervical spine fractures after falls in older Americans, to show changes in recent years, and to compare 12-month outcomes between individuals with cervical and hip fracture after falls. Retrospective study of Medicare data from 2007 to 2011. Acute care hospitals. Individuals aged 65 and older with cervical or hip fracture after a fall. Cervical fracture rate, 12-month mortality, and readmission rate after injury. Rates of cervical fracture increased from 4.6 per 10,000 in 2007 to 5.3 per 10,000 in 2011; rates of hip fracture decreased from 77.3 per 10,000 in 2007 to 63.5 per 10,000 in 2011. Participants with cervical fracture with and without spinal cord injury (SCI) were more likely than those with hip fracture to receive treatment at large hospitals (59.4% and 54.1% vs 28.1%, P < .001), teaching hospitals (49.3% and 40.0% vs 13.4%, P < .001), and regional trauma centers (46.3% and 38.5% vs 13.0%, P < .001). Participants with cervical fracture without (24.7%) and with SCI (41.7%) had greater risk-adjusted mortality at 1 year than those with hip fracture (22.7%) (P < .001). By 1 year, 73.4% of participants with cervical fracture with and 59.5% without SCI and 59.3% of those with hip fracture had died or were readmitted to the hospital (P < .001). Cervical spinal fractures occur in one of every 2,000 Medicare beneficiaries annually and appear to be increasing over time. Participants with cervical fracture had greater mortality than those with hip fracture. Given the increasing prevalence and the poor outcomes in this population, hospitals need to develop processes to improve care for these vulnerable individuals.


Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1β production.
Monocyte activation is consistently reported in patients with schizophrenia (SZ). We aimed to study the ultrastructure of monocytes and monocyte production of IL-1β in drug-free patients with SZ and controls. Monocytes from young (18-30 y.o.) healthy and SZ men in relapse were studied. Electron microscopy and morphometry were applied to estimate areas of monocytes, volume density (Vv), areas, and number of organelles. The production IL-1β by monocytes was estimated by the ELISA method. Group differences were examined using ANCOVA. Pearson's correlation coefficients were used to examine the effects of possible confounding variables. Correlation analyses were applied to detect the relationships between the parameters of monocytes measured and between the parameters measured and the IL-1β production. Area of nucleolus, Vv and area of mitochondria and lysosomes, and the number of lysosomes were significantly increased in patients as compared to controls. Area of mitochondria was correlated significantly with Vv and area of lysosomes, and the number of lysosomes was significantly correlated with area of monocyte and Vv of vacuoles only in the control group. The production of IL-1β by monocytes was higher in patients than in controls (p = 0.01) and was correlated with Vv of lysosomes (r = 0.68, p = 0.04) and area of lysosomes (r = 0.78, p = 0.013). The data provide new evidence for over activation of monocytes in SZ and disturbed metabolic relationships between lysosomes, mitochondria, and vacuoles.


Formation and Geological Sequestration of Uranium Nanoparticles in Deep Granitic Aquifer.
The stimulation of bacterial activities that convert hexavalent uranium, U(VI), to tetravalent uranium, U(IV), appears to be feasible for cost-effective remediation of contaminated aquifers. However, U(VI) reduction typically results in the precipitation of U(IV) particles less than 5 nanometers in diameter, except for environmental conditions enriched with iron. Because these tiny particles are mobile and susceptible to oxidative dissolution after the termination of nutrient injection, in situ bioremediation remains to be impractical. Here we show that U(IV) nanoparticles of coffinite (U(SiO4)1-x(OH)4x) formed in fracture-filling calcium carbonate in a granitic aquifer. In situ U-Pb isotope dating demonstrates that U(IV) nanoparticles have been sequestered in the calcium carbonate for at least 1 million years. As the microbiologically induced precipitation of calcium carbonate in aquifer systems worldwide is extremely common, we anticipate simultaneous stimulation of microbial activities for precipitation reactions of calcium carbonate and U(IV) nanoparticles, which leads to long-term sequestration of uranium and other radionuclides in contaminated aquifers and deep geological repositories.


Infantile Hemangiomas: Pathogenesis and Review of Propranolol Use.
Infantile hemangiomas are complex benign vascular tumors that present after birth. Hemangioma lesions have a predictable course of growth, but little is understood about the mechanism behind their development. Infantile hemangiomas are considered proliferative lesions of the endothelial cells. To effectively manage infants with infantile hemangiomas, a clear understanding of the pathogenic pathways is important and can assist the healthcare provider with effective treatment. This understanding will facilitate a relationship of support with the families of affected infants. EBSCO host and Ovid database search for key words of infantile hemangiomas, propranolol, vascular lesion, and proliferative lesion was utilized. Articles on pathophysiology along with recent research studies were include in the search. The use of propranolol is a recent development in the treatment of infantile hemangiomas, which has shown a high rate of response in decreasing the size and reducing the potential for life-long complications. Different studies have shown the same success rate with the use of propranolol but with different variables. As a healthcare team member, better identification and customized care of these patients can reduce the rare but devastating complications of infantile hemangiomas. Future research can help identify the most effective dose and course of propranolol administration.


Improved fluorescent labeling of chitin oligomers: Chitinolytic properties of acidic mammalian chitinase under somatic tissue pH conditions.
Acidic mammalian chitinase (AMCase) has been implicated in various pathophysiological conditions including asthma, allergic inflammation and food processing. AMCase is most active at pH 2.0, and its activity gradually decreases to up to pH 8. Here we analyzed chitin degradation by AMCase in weak acidic to neutral conditions by fluorophore-assisted carbohydrate electrophoresis established originally for oligosaccharides analysis. We found that specific fragments with slower-than-expected mobility as defined by chitin oligosaccharide markers were generated at pH 5.0∼8.0 as by-products of the reaction. We established an improved method for chitin oligosaccharides suppressing this side reaction by pre-acidification of the fluorophore-labeling reaction mixture. Our improved method specifically detects chitin oligosaccharides and warrants quantification of up to 50nmol of the material. Using this strategy, we found that AMCase produced dimer of N-acetyl-d-glucosamine (GlcNAc) at strong acidic to neutral condition. Moreover, we found that AMCase generates (GlcNAc)2 as well as (GlcNAc)3 under physiological conditions.


Fenestration of supraclinoid internal carotid artery and associated aneurysm: embryogenesis, recognition, and management.
Fenestration of internal carotid artery (ICA) is extremely rare and may be associated with aneurysms arising from the fenestrated segment. Here we report two cases with successful surgical clipping of associated saccular aneurysms, and we systematically review the 12 previously reported cases. In one case of 39-year-old female patient, the aneurysm and fenestration were found incidentally in the course of a workup for headaches and a thyroid nodule. In the second case, a 32-year-old female patient, the aneurysm was associated with subarachnoid hemorrhage in the setting of suspected postpartum eclampsia. In both instances the fenestration involved the supraclinoid ICA, and the aneurysm arose from the duplicated segment proximal to the origin of the posterior communicating artery. The aneurysms were more proximal than typical posterior communicating artery aneurysms, and fenestration was suspected by rotational three-dimensional angiography, and confirmed at surgery. In both instances the aneurysm was approached via an extended pterional craniotomy. In one case, partial anterior clinoidectomy was necessary, along with decompression of the optic nerve canal for optimal exposure of the aneurysm neck. Clip reconstruction was successful, obliterating the aneurysm and preserving ICA patency. ICA fenestration should be considered when one analyzes ventral supraclinoid ICA aneurysms. In these and other reported cases, aneurysm is generally amenable to surgical clipping despite broad neck incorporating the fenestrated arterial segment.


Overproduction of p53 antigen makes established cells highly tumorigenic.
The p53 cellular tumour antigen, long known to be overproduced in a variety of neoplastically transformed cells, was recently shown to be directly involved in transformation. Thus, p53 can complement activated Ha-ras in transforming secondary rat embryo fibroblasts into grossly altered, tumorigenic cells. Moreover, p53 can also be shown to possess immortalizing activity. Our previous results indicated, however, that the contribution of p53 to the transformation was not synonymous with immortalization, suggesting that the two activities of the protein are probably separable. We demonstrate here that this is indeed the case, as overproduction of p53 in an established cell line, while not causing gross morphological changes, endows these cells with an overt tumorigenic potential. Furthermore, the tumorigenic efficiency of such cell lines may be correlated with the extent of p53 over-production.


[Modification of organ perfusion by calcium blocker and converting enzyme inhibitor in the conscious rat with heart failure].
The present study examined the regional vascular effects (radioactive microspheres) of converting-enzyme inhibition (captopril, 1 mg/kg) and calcium-antagonism (diltiazem, 1 mg/kg) in a rat model of cardiac failure due to large myocardial infarction (n = 18, infarct size 40% of the left ventricle) both at rest and during submaximal treadmill exercise. Diltiazem increased renal, gastrointestinal, coronary and cutaneous blood flow at rest by 29%, 28%, 26% and 37% (p less than 0.05 each) and enhanced skeletal muscle blood flow during exercise by 16% (p less than 0.05). Captopril improved primarily renal and coronary blood flow at rest (by 59% and 23%, respectively, p less than 0.05) and reduced vascular resistance in the gastrointestinal bed by 25% (p less than 0.05) without significant effects in other circulatory beds. We conclude that the regional vascular effects elicited by converting-enzyme inhibition and calcium antagonism differ considerably in this animal model of congestive heart failure and may be clinically important. The favourable regional vascular profile of diltiazem deserves further clinical investigation.


Do not put too much value on conventional medicines.
About 80% of the population of the developing countries still use traditional medicines for their health care. The rational use of traditional medicines in primary health care should be based on the Guidelines for the Assessment of Herbal Medicines as developed by the World Health Organization (WHO). The protection of intellectual property on traditional medicines should also be based on the guidelines for the protection of intellectual property on traditional medicines to be developed by the World Intellectual Property Organization (WIPO). The knowledge of traditional medicines hidden and lost should be researched and the loss of natural resources used as traditional medicines should be prevented. As a new emerging field in ethnopharmacology, treatment guidelines and evidence-based evaluation guidelines for ethnoergogenics, and protection guidelines of intellectual property for ethnoergogenics should be developed and put into practice according to guidelines of the WHO and WIPO, respectively.


Fatal paralytic ileus complicating phenothiazine therapy.
The occurrence of fatal paralytic ileus with peritonitis in a patient receiving phenothiazines and an antiparkinsonian agent is described. Although sporadic reports of this complication have appeared, it has not been emphasized in the literature. Only by being alert to this problem can one hope to achieve earlier diagnosis and begin prompt and appropriate treatment.


Anatomy of the biceps brachii osseous footprint: study of 100 radii and literature review.
Biceps brachii (BB) tendon rupture is frequent in young males and may require surgical repair. Non-anatomic reinsertion leads to loss of strength in supination. The main aim of the present study was to describe the anatomy of the osseous footprint of the distal BB tendon. The dimensions of the footprint of the distal BB insertion were analyzed in 100 dry cadaver radii, using MicroScribe 3D software. Insertion area, assimilated to an ellipse, was calculated from 4 points (medial, lateral, cranial and caudal) determining the two axes of the ellipse. Mean footprint length, width and area were 18 mm (range, 7-24 mm), 9 mm (range, 4-15 mm), and 129 mm2 (range, 46-266 mm²), respectively. Intra- and inter-observer correlation coefficients were satisfactory: κ = 0.75 and κ = 0.7, respectively. The present study reported BB footprint dimensions in 100 radii, providing a basis to guide surgical treatment of distal BB tendon rupture. Non-anatomical restoration of the BB tendon footprint leads to poorer clinical and biomechanical results; precise knowledge of the footprint is necessary for anatomical repair.


Novel mitochondrial and cytosolic purification pipeline for compartment-specific metabolomics in mammalian disease model tissues.
Mitochondria represent an important milieu for studying the pathogenesis of several major diseases. The need for organelle-level metabolic resolution exists, as mitochondrial/cytosolic metabolites are often diluted beyond detection limits in complex samples. Compartment-specific studies are still hindered by the lack of efficient, cost-effective fractioning methods-applicable to laboratories of all financial/analytical standing. We established a novel mitochondrial/cytosolic purification pipeline for complimentary GC-TOF-MS and 1H-NMR metabolomics using robust, commercially available fractionation strategies. Magnetic based mitochondria isolation kits (MACS) were adapted for this purpose, accompanied by cytosolic filtering. Yield was assessed through the percentage recovery of citrate synthase (CS; a mitochondrial marker), purity by immunoblotting against compartment-specific proteins and integrity interrogated through the respiratory coupling ratio (RCR). The effects of the kit-based buffers on MS/NMR analyses of pure metabolite standards were evaluated. Finally, biological applicability to mammalian disease models was shown using Ndufs4 mouse brain tissue. With minor modifications, MACS produced around 60% more mitochondria compared to a differential centrifugation method. Less than 15% of lysosomal LAMP-2 protein was found in the MACS isolates, confirming relative purity-while RCR's above 6 indicate sufficient mitochondrial integrity. The filtering approach effectively depleted mitochondria from the cytosolic fraction, as indicated by negligible Hsp60 and CS levels. Our GC-MS pilot yielded 60-70 features per fraction, while NMR analyses could quantify 6-10 of the most abundant compounds in each fraction. This study provides a simple and flexible solution for mitochondrial and cytosolic metabolomics in animal model tissues, towards large-scale application of such methodologies in disease research.


Contribution of villus and intervillus epithelium to intestinal transmural potential difference and response to theophylline and sugar.
A chamber design is described which permits isolation of villus or intervillus epithelium from proximal segments of Amphiuma intestine and measurement of the transpithelial potential difference (psi ms) and short-circuit current (Isc) produced by each. In media containing Cl- and 10 mequiv./l HCO3- the villus generated a basal psi ms of 0.8 mV (serosa negative) and Isc of 12 microA/cm2 while the intervillus psi ms and Isc were not different from zero. Acetazolamide altered the villus psi ms by 1.2 mV; the intervillus psi ms by only 0.3 mV. Transepithelial gradients of HCO3- appeared to generate diffusion potentials across the intervillus but not the villus epithelium. The actively transported sugar galactose elevated psi ms by 0.6 +/- 0.1 mV in the intervillus epithelium and by 1.5 +/- 0.2 mV in the villus epithelium for a response ratio (0.6/1.5) = 0.4. The response ratio for valine was 0.3. In contrast, the response ratios for theophylline (0.7) and cyclic AMP (0.7) were significantly higher. These observations indicate that the entire epithelium is responsive to theophylline and cyclic AMP while Na+-dependent solute transport and the basal electrogenic ion transport processes are primarily functions of the cells lining the intestinal villus.


Properties of a novel nitric oxide-stimulated ADP-ribosyltransferase.
A novel ADP-ribosyltransferase is present in the cytosolic fraction of various cells. The kinetic behavior and physical properties of this enzyme's activity are clearly distinguished from other known cytosolic ADP-ribosyltransferases. Agents that release nitric oxide, such as sodium nitroprusside, greatly stimulated this activity, although this effect was dependent on the presence of intact thiol groups. Dithiothreitol, reduced glutathione, or cysteine was needed for activation of the enzyme, while N-ethylmaleimide inhibited enzyme activity. High concentrations of phosphate had a slight stimulatory effect, while high concentrations of sodium chloride and thiocyanate were inhibitory. ATP also inhibited this activity. This cytosolic ADP-ribosyltransferase is clearly distinguished from other known and characterized cytosolic transferases. Its activation by biologically active nitric oxide suggests an important role for this enzymatic activity.


Sucrose malabsorption in children: noninvasive diagnosis by interval breath hydrogen determination.
To assess whether malabsorption of specific sugars is easily detected in a pediatric population by interval measurement of breath hydrogen excretion, hydrogen concentration was determined following administration of oral sucrose to six sucrose-intolerant children with congenital sucrase-isomaltase deficiency and in 16 sucrose-tolerant control subjects. Breath samples were collected by means of a newly devised nasal prong technique not requiring active patient cooperation and suitable for use in all age groups. Breath hydrogen concentrations obtained by samples collected by this method correlated highly (r = 0.94) with the previously validated modified Haldane-Priestley tube method for sampling alveolar air. Identification of sucrose-intolerant individuals was achieved on the basis of hydrogen excretion: peak values, expressed as parts per million above baseline (deltappm), equalled 114 +/- 63 (mean +/- SD) versus 2.4 +/- 3.6 deltappm in control subjects (P = 0.007). Best discrimination between the groups occurred at 90 minutes postingestion. The findings validate this simple method for collection of expired air and demonstrate that breath hydrogen determination permits the noninvasive detection of sucrose malabsorption in children.


Atmospheric wet deposition serves as an important nutrient supply for coastal ecosystems and fishery resources: Insights from a mariculture area in North China.
To determine the ecological effects of atmospheric wet deposition of dissolved nutrients on the coastal waters around the Yangma Island, rain and snow samples were collected and analyzed at a shore-based site for one year. The wet deposition fluxes of dissolved inorganic nitrogen and phosphorus (DIN and DIP) and dissolved organic nitrogen and phosphorus were 69.2, 0.136, 13.3 and 0.143 mmol m-2 a-1, respectively. In summer, the new production fueled by wet deposition accounted for 19.3 % of that in seawater and 16.4 % of the amount of particulate organic carbon ingested by the scallops cultivated in the study area, indicating the potential contribution of wet deposition to fishery resources. Meanwhile, precipitation increased the seasonal average DIN/DIP ratios in surface seawater by 17.7 %, 16.3 %, 23.4 % and 6.5 % in spring, summer, autumn and winter, respectively, which could change the composition of ecological community and cause obvious negative impact on the ecosystem and mariculture.