Alcohol consumption, hazardous drinking, and alcohol dependency among the population of Andaman and Nicobar Islands, India.
Harmful use of alcohol is one of the globally recognized causes of health hazards. There are no data on alcohol consumption from Andaman and Nicobar Islands. The objective of the study was to assess the prevalence and pattern of alcohol use among the population of Andaman and Nicobar Islands, India. A representative sample of 18,018 individuals aged ≥14 years were chosen by multistage random sampling and administered a structured instrument, a modified version of the Gender, Alcohol, and Culture: An International Study (GENACIS) which included sociodemographic details and Alcohol Use Disorders Identification Test (AUDIT). The overall prevalence of alcohol consumption was 35% among males and over 6.0% in females, aged 14 and above. Two out of every five alcohol users fit into a category of hazardous drinkers. One-fourth of the total users (23%) are alcohol dependents. Both the hazardous drinking and dependent use are high among males compared to females. Almost 18.0% of male drinkers and 12.0% of female drinkers reported heavy drinking on typical drinking occasions. The predominant beverages consumed were in the category of homebrews such as toddy and handia. The present study highlights the magnitude of hazardous drinking and alcohol dependence in Andaman and Nicobar Islands, India and the complex sociocultural differences in the pattern of alcohol use. Based on the AUDIT data, among the population of Andaman and Nicobar Islands (aged 14 and above), one out of ten requires active interventions to manage the harmful impact of alcohol misuse.


Sequential analysis of postural control resource allocation during a dual task test.
To investigate the postural control factors influencing the automatic (reflex-controlled) and attentional (high cortical) factors on dual task. We used a dual task model to examine the attentional factors affecting the control of posture, subjecting test subjects to vibration stimulation, one-leg standing and verbal or nonverbal task trials. Twenty-three young, healthy participants were asked to stand on force plates and their centers of pressure were measured during dual task trials. We acquired 15 seconds of data for each volunteer during six dual task trials involving varying task combinations. We observed significantly different sway patterns between the early and late phases of dual task trials, which probably reflect the attentional demands. Vibration stimulation perturbed sway more during the early than the late phases; with or without vibration stimulation, the addition of secondary tasks decreased sway in all phases, and greater decreases in sway were observed in the late phases, when subjects were assigned nonverbal tasks. Less sway was observed during the nonverbal task in a sequential study. The attentional and automatic factors were analyzed during a sequential study. By controlling the postural control factors, optimal parameters and training methods might be used in clinical applications.


Additions to Andiorrhinus (Turedrilus) (Rhinodrilidae, Clitellata) from Eastern Amazonia.
Two new species of the earthworm family Rhinodrilidae (Clitellata), from Maranhão state, Brazil, were studied by dissection. Andiorrhinus (Turedrilus) miricuri n. sp. is the first record of a big earthworm for this region with three pairs of large spermathecae in segments 7-9 and one pair of tubercula pubertatis bands lateral to b line in XX-XXV. Andiorrhinus (Turedrilus) barrosoi n. sp. lacks spermathecae and has one pair of tubercula pubertatis bands lateral to b line in XX-(1/3) XXIV. The earthworms described are from the most threatened region of Amazonia where 75% of forest cover is already lost. More information is urgently necessary to assess their ecology and vulnerability status.


Pseudo Aneurysm of Aberrant Right Gastroepiploic Artery Mimicking Pseudocyst of Pancreas- A Rare Case Report.
Pseudoaneurysm of peripancreatic vessel is a rare complication of pancreatitis. The splenic artery is the most commonly affected vessels close to the pancreas. Pseudoaneurysm of right gastroepiploic artery is rare. It can rupture into Gastro Intestinal (GI) tract, retroperitoneum, peritoneal cavity, biliopancreatic duct or pseudocyst. Clinical diagnosis of unruptured pseudoaneurysm is rarely possible because there are no specific signs and symptoms. We hereby report a case of pseudoaneurysm of aberrant right gastroepiploic artery in 30-year-old male which presented with history of epigastric pain and lump with episode of haematemesis and malena. Diagnosis was suspected on Doppler Ultrasonography (USG), which was later confirmed by CECT and angiography. Patient was treated by coil embolization. The pain and lump in epigastrium disappeared within five to six days. Patient is symptom free after six months of follow up.


[Complicated omental splenosis].
Splenosis results from autotransplantation of splenic tissue, usually after traumatic splenic rupture. The diagnosis is suggested by the history and the presence of multiple nodules on computed tomography. Selective splenic scintigraphy utilising heat denatured red blood cells confirm the diagnosis. Treatment is usually conservative with surgical excision reserved for complicated cases. We report a case of splenosis associated with phlegmon and infectious process, requiring surgical intervention.


White matter changes in treatment refractory schizophrenia: Does cognitive control and myelination matter?
Widespread white matter abnormalities have been reported in schizophrenia, a disorder frequently characterised as a dysconnection syndrome. White matter connectivity in schizophrenia has been predominantly investigated using diffusion weighted imaging, with reductions in fractional anisotropy throughout the brain often interpreted as an indicator of abnormal myelination. However, diffusion weighted imaging lacks specificity and as such a number of microstructural factors besides myelin may be contributing to these results. We utilised multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) in medicated patients with chronic schizophrenia, stratified by treatment response status, and healthy controls, in order to assess myelin water fraction (MWF) in these groups. In addition, we assessed cognitive control using the Stroop task to investigate how response inhibition relates to myelination in patients and controls. Both treatment resistant (n = 22) and treatment responsive (n = 21) patients showed reduced MWF compared to healthy controls (n = 24) in bilateral fronto-occipital fasciculi, particularly evident in the vicinity of the striatum und extending to the cerebellum, with no difference between patient groups. Patients showed greater reaction time interference on the Stroop task compared to healthy controls, with no difference between patient groups. Stroop interference was significantly negatively correlated with MWF in the corpus callosum across groups, and MWF differences in this region mediated the behavioural group effects on the Stroop task. These findings support the suitability of mcDESPOT as a myelin-specific measure of abnormal connectivity in schizophrenia, and suggest that treatment resistant schizophrenia is not characterised by more severe abnormalities in myelination or cognitive control compared to treatment responsive schizophrenia.


Respiratory effects of surgery and pulmonary function testing in the preoperative evaluation.
Advanced age, smoking habit, obesity or malnutrition, the coexistence of hypercapnia, bronchospasm or bronchial hypersecretion, the lack of pre-operative preparation and/or a prolonged duration of anaesthesia can negatively influence respiratory function in patients undergoing abdominal or thoracic surgery. Spirometric testing of pulmonary function is recommended in patients with a history of tobacco use or dyspnoea who are considered for cardiac or upper abdominal surgery and for all patients who are candidated for lung resection. Spirometry can provide cut-off values of acceptable risk in patients that are candidated for abdominal and thoracic surgery. At-risk patients having resective lung surgery should undergo a split lung function study with quantitative lung scanning or computed tomography in order to estimate the function of residual parenchyma after surgery. In patients with borderline estimated values, a cardiopulmonary exercise test is useful to further stratify surgical risk.(www.actabiomedica.it)


Comparison and chemometric analysis of the phenolic compounds and organic acids composition of chinese wines.
Characteristics of 106 wines from 5 major grape varieties and 3 typical geographic regions in China were investigated by means of profiling of organic acids and phenolic compounds analysis. An ultra-performance liquid chromatography method was developed and thus, large number of samples could be determined in a quick and reliable way. The results showed that different origins and varieties were characteristic of various profiles of organic acid and phenolic compounds. In order to investigate possible correlation between organic acids and phenolic compounds content and grape variety and/or geographical origin, analysis of variance and linear discriminant analysis (LDA) were conducted. A satisfactory LDA result for red wines according to geographic origin was obtained, in which the correct classification was 100% and the leave-one-out validation accuracy was 90%. The corresponding results of white wines were 91% and 86%, respectively. When LDA was processed, according to grape varieties, the proportionality of successfully classified wines was 96%, while the leave-one-out validation accuracy was 94%. The organic acids and phenolic compounds profiles were useful in the classification of Chinese wines according to grape variety and geographic origin.


Prevalence of diabetic retinopathy and evaluation of risk factors. A review of 1,005 diabetic clinic patients.
One thousand and five diabetic patients were evaluated ophthalmologically and classified into one of four groups according to the retinopathy status of the worst of their eyes. The presence of various factors and their influence on retinopathy status were evaluated. Race, duration of diabetes, type of treatment, the presence of hypertension, a high serum cholesterol level, smoking and the presence of systemic complications of diabetes were found to have a statistically important influence on retinopathy status. Sex and type of diabetes had no such influence.


Role of the UGT2B17 deletion in exemestane pharmacogenetics.
Exemestane (EXE) is an aromatase inhibitor used for the prevention and treatment of breast cancer. The major metabolic pathway for EXE is reduction to form the active 17β-dihydro-EXE (17β-DHE) and subsequent glucuronidation to 17β-hydroxy-EXE-17-O-β-D-glucuronide (17β-DHE-Gluc) by UGT2B17. The aim of the present study was to determine the effects of UGT2B17 copy number variation on the levels of urinary and plasma 17β-DHE-Gluc and 17β-DHE in patients taking EXE. Ninety-six post-menopausal Caucasian breast cancer patients with ER+ breast tumors taking 25 mg EXE daily were recruited into this study. UGT2B17 copy number was determined by a real-time PCR copy number variant assay and the levels of EXE, 17β-DHE and 17β-DHE-Gluc were quantified by UPLC/MS in patients' urine and plasma. A 39-fold decrease (P<0.0001) in the levels of creatinine-adjusted urinary 17β-DHE-Gluc was observed among UGT2B17 (*2/*2) subjects vs subjects with the UGT2B17 (*1/*1) genotype. The plasma levels of 17β-DHE-Gluc was decreased 29-fold (P<0.0001) in subjects with the UGT2B17 (*2/*2) genotype vs subjects with UGT2B17 (*1/*1) genotype. The levels of plasma EXE-adjusted 17β-DHE was 28% higher (P=0.04) in subjects with the UGT2B17 (*2/*2) genotype vs subjects with the UGT2B17 (*1/*1) genotype. These data indicate that UGT2B17 is the major enzyme responsible for 17β-DHE-Gluc formation in vivo and that the UGT2B17 copy number variant may play a role in inter-individual variability in 17β-DHE levels in vivo.


Protein refolding in reversed micelles: Interactions of the protein with micelle components.
A novel process has been developed to improve the refolding yield of denatured proteins. It uses reversed micelles to isolate denatured protein molecules from each other and thus, upon refolding, reduces the intermolecular interactions which lead to aggregation. The feasibility of this process was first demonstrated with Ribonuclease A as a model protein. In the present work, we expanded the scope of this study to better understand both the general mechanisms of protein refolding in reversed micelles and the biotechnological applicability of the process. First, we investigated the interactions between the individual components of the reversed micellar system (the protein molecule, the denaturant guanidine hydrochloride (GuHCl), and the surfactant (AOT)) during the refolding process. We then extended our studies to a more hydrophobic protein, gamma-interferon, which aggregates upon refolding in aqueous solution. However, it was also found to aggregate in our reversed micelle process during the extraction step. Since gamma-interferon is a much more hydrophobic protein than RNase, we hypothesize that interactions between hydrophobic amino acids and the surfactant layer may interfere with refolding. This hypothesis was tested by studying the refolding of chemically modified RNase. The substitution of 55% of the surface lysine residues with hydrophobic caproyl groups caused a significant decrease in the refolding yield of RNase in the reversed micellar system without affecting aqueous solution renaturation. In addition, the extraction efficiency of the enzyme from reversed micelles back into aqueous solution was severely reduced and resulted in aggregation. These experiments indicate that unfolded hydrophobic Proteinsinteract with the Surfactant molecules, which limits their ability to refold in reversed micelles.


Acoustic and thermoacoustic properties of an additive manufactured lattice structure.
With the advent of additive manufacturing, lattice structures can be printed with precisely controlled geometries. In this way, it is possible to realize porous samples with specific acoustic and thermoacoustic characteristics. However, to this aim and prior to the manufacturing process, it is fundamental to have a design tool that can predict the behaviour of the lattices. In the literature, Luu, Perrot, and Panneton [Acta Acust. United Ac. 103, 1050 (2017)] provide a model to characterize transport parameters of fibrous material with a certain fiber orientation with respect to the direction of wave propagation. In this work, finite element numerical simulations are used to improve their model in order to compute the thermoviscous functions of lattice structures composed of cylindrical struts arranged in Tetragonal Body Centred cells. New correlations for transport parameters are suggested, which are finally coupled with the semi-phenomenological model of Johnson-Champoux-Allard-Lafarge to obtain the complex density and bulk modulus of the equivalent fluid. These results are compared with the measurements carried out on two 3-dimensional-printed samples with hybrid impedance tube techniques.


Development of an environmental health tool linking chemical exposures, physical location and lung function.
A challenge in environmental health research is collecting robust data sets to facilitate comparisons between personal chemical exposures, the environment and health outcomes. To address this challenge, the Exposure, Location and lung Function (ELF) tool was designed in collaboration with communities that share environmental health concerns. These concerns centered on respiratory health and ambient air quality. The ELF collects exposure to polycyclic aromatic hydrocarbons (PAHs), given their association with diminished lung function. Here, we describe the ELF as a novel environmental health assessment tool. The ELF tool collects chemical exposure for 62 PAHs using passive sampling silicone wristbands, geospatial location data and respiratory lung function measures using a paired hand-held spirometer. The ELF was tested by 10 individuals with mild to moderate asthma for 7 days. Participants wore a wristband each day to collect PAH exposure, carried a cell phone, and performed spirometry daily to collect respiratory health measures. Location data was gathered using the geospatial positioning system technology in an Android cell-phone. We detected and quantified 31 PAHs across the study population. PAH exposure data showed spatial and temporal sensitivity within and between participants. Location data was used with existing datasets such as the Toxics Release Inventory and the National Oceanic and Atmospheric Administration (NOAA) Hazard Mapping System. Respiratory health outcomes were validated using criteria from the American Thoracic Society with 94% of participant data meeting standards. Finally, the ELF was used with a high degree of compliance (> 90%) by community members. The ELF is a novel environmental health assessment tool that allows for personal data collection spanning chemical exposures, location and lung function measures as well as self-reported information.


Low molecular weight heparin for prevention of thromboembolic complications in cardioversion--rationale and design of the ACE study (Anticoagulation in Cardioversion using Enoxaparin).
The modality and duration of anticoagulation before, during, and after cardioversion of atrial fibrillation--either with or without guidance by transesophageal echocardiography (TEE)--is still an unresolved issue. Intravenous infusion of unfractionated heparin until effective anticoagulation with phenprocoumon or warfarin is used as the standard therapy. However, this approach may be associated with several days of hospitalization because of the necessity for intravenous heparin administration. Moreover, there may be an increased risk of bleeding complications or, conversely, episodes of undercoagulation. Low-molecular weight heparin is an attractive alternative as it not only provide a safe and predictable level of anticoagulation with fewer side effects but can also be administered safely on an outpatient basis. In addition, no anticoagulation monitoring is needed. The ACE study (Anticoagulation in Cardioversion using Enoxaparin) is a randomized, prospective, open-label multicenter trial comparing the safety and efficacy of subcutaneous enoxaparin with intravenous heparin/oral phenprocoumon before and after cardioversion (stratified to TEE guidance or no TEE guidance). This article presents the rationale, design and status of the ACE study.


Substrate requirements for secondary cleavage by HIV-1 reverse transcriptase RNase H.
During and after minus-strand DNA synthesis, human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) degrades the RNA genome. To remove RNA left after polymerization, the RT aligns to cut 18 nucleotides in from the 5' RNA end. The enzyme then repositions, making a secondary cut 8 nucleotides from the RNA 5' end. Transfer of the minus strong stop DNA during viral replication requires cleavage of template RNA. Removal of the terminal RNA segment is a special case because the RNA-DNA hybrid forms a blunt end, shown previously to resist cleavage when tested in vitro. We show here that the structure of the substrate extending beyond the RNA 5' end is an important determinant of cleavage efficiency. A short single-stranded DNA extension greatly stimulated the secondary cleavage. Annealing an RNA segment to the DNA extension was even more stimulatory. Recessing the DNA from a blunt end by even one nucleotide caused the RT to reorient its binding, preventing secondary cleavage. The presence of the cap at the 5' end of the viral RNA did not improve the efficiency of secondary cleavage. However, NC protein greatly facilitated the secondary cut on the blunt-ended substrate, suggesting that NC compensates for the unfavorable substrate structure.


Transition-path sampling of beta-hairpin folding.
We examine the dynamical folding pathways of the C-terminal beta-hairpin of protein G-B1 in explicit solvent at room temperature by means of a transition-path sampling algorithm. In agreement with previous free-energy calculations, the resulting path ensembles reveal a folding mechanism in which the hydrophobic residues collapse first followed by backbone hydrogen-bond formation, starting with the hydrogen bonds inside the hydrophobic core. In addition, the path ensembles contain information on the folding kinetics, including solvent motion. Using the recently developed transition interface sampling technique, we calculate the rate constant for unfolding of the protein fragment and find it to be in reasonable agreement with experiments. The results support the validation of using all-atom force fields to study protein folding.


Relationship between patterns of engraftment in peripheral blood and immune reconstitution after allogeneic bone marrow transplantation for (severe) combined immunodeficiency.
We report the outcome of allogeneic bone marrow transplantation (BMT) as treatment for severe combined immunodeficiency disease (SCID) in 31 patients grafted from 1968 until 1992. The patients received a graft from an HLA-identical related (n = 10), an HLA-haplo-identical related (n = 19), or a closely HLA-matched unrelated (n = 2) donor that resulted in the long-term survival of 6 of 10, 9 of 19, and 0 of 2 children, respectively. Major complications included failure of engraftment and early death caused by respiratory failure. The chimerism pattern and immunologic reconstitution were evaluated in 15 children who survived more than 1 year with sustained engraftment. The pattern of engraftment was investigated within flow-sorted peripheral blood (PB) T- and B-lymphoid, natural killer (NK), and myelomonocytic cell populations using the amplification of variable number of tandem repeats by the polymerase chain reaction. The immunologic reconstitution was assessed by various in vitro and in vivo parameters. Although the number of PB T cells and the in vitro T-cell proliferative response was in the lower region of normal in the majority of cases and even subnormal in some, in all cases donor T-cell engraftment and reconstitution of T-cell immunity was observed. Residual host-type T cells (1% to 5%) were detected in eight cases at multiple occasions. All children showed normal serum IgM and IgG subclass levels and produced specific IgG antibodies after vaccination, irrespective of donor B-cell engraftment. However, three HLA haplo-identical graft recipients with host-type B lymphoid and myeloid cells have a persistent selective IgA deficiency. NK cells were either of donor, host, or mixed origin. Donor NK cell engraftment restored defective in vitro NK cell function of the recipient. We conclude that determination of lineage-specific engraftment patterns provides valuable information for the understanding of the immunologic reconstitution after allogeneic BMT for SCID.


Learning the lessons of moving education online.
Education providers across the world are transferring course delivery from face-to-face to online methods. This article reports on a New Zealand college's experience of transferring a course on nursing research to online delivery, and on an evaluation of the initiative from the perspective of student experiences and achievements. The results and discussion contain lessons for any education providers considering moving courses to online delivery.


Outcome of referred neonates weighing less than 2500 g.
The pattern of morbidity and mortality of 103 neonates weighing less than 2500 g referred to a Nigerian University Teaching Hospital over a period of 30 months (March 1989-August 1991) was studied. Fifty seven (55.3%) weighted less than 1500 g, 80 (77.7%) were preterm while 23 (22.3%) were term, small for gestation. Sepsis, hypothermia, respiratory distress syndrome and birth asphyxia were the commonest problems encountered. These were also the predominant associated causes of death. The corrected mortality rate was 65.3%, the rate being higher for babies weighing less than 1500 g (chi 2 = 4.02, p < 0.05) and for small for gestational age babies (chi 2 = 5.17, p < 0.025). The early neonatal problems stemmed from suboptimal conditions of perinatal resuscitation, thermoregulation and transfer. High mortality was also caused by poor state of facilities at the referral centre. Early materno-foetal transfer during preterm labour to hospitals with facilities for optimal perinatal care would reduce morbidity and mortality.


Antidepressant-like effects of a methanol extract of Leonotis nepetifolia in mice.
This study evaluated the antidepressant-like effects of a methanol extract of Leonotis nepetifolia in behavioural tests in mice. Our results showed that a single administration of the extract significantly reduced immobility behaviour in the tail suspension test, while three administrations were necessary to diminish immobility behaviour in the forced swimming test. A daily dose of the extract for 28 days improved body weight gain and significantly reduced corticosterone levels of mice exposed to chronic unpredictable mild stress. Metabolic profiling of the extract revealed that nepetaefolin, methoxynepataefolin, and 7-O-β-glucoside luteolin were the main products. Acute and repeated administration of the extract produced antidepressant-like effects in animals subjected to chronic stress. Our results suggest the hypothalamus-hypophysis-adrenal axis participates in the antidepressant actions of the extract. These results show that alterations in behaviour elicited by stress can be prevented with L. nepetifolia treatment.


Cytogenetic analysis of an immature teratoma of the ovary and its metastasis after chemotherapy-induced maturation.
We report a case of an immature teratoma of the ovary, grade 3, in which cytogenetic studies were performed on the primary tumor at diagnosis and on a metastasis resected 1 year after removal of the primary tumor. The patient was treated with cisplatin, bleomycin, and etoposide (VP-16) combination chemotherapy. The metastatic tumor was composed of mature teratoma with only small foci of immature tissue. Despite the different histologic appearance of the primary tumor and the metastasis, there was no detectable difference in karyotype between the primary and metastatic tumors. Both showed a pseudodicentric chromosome derived from chromosome 1 and monosomy for chromosome 4. Flow cytometry analysis of the metastatic tumor showed a diploid DNA content, in agreement with the cytogenetic findings. From this case it would appear that chemotherapy-induced maturation of metastatic immature ovarian teratoma is not associated with regression of the malignant karyotype or selection of a karyotypically distinct population of tumor cells.


Recombinant interleukin-2 limits the replication of Mycobacterium lepraemurium and Mycobacterium bovis BCG in mice.
BALB/c mice were infected with Mycobacterium lepraemurium (MLM) in the foot pad or with M. bovis BCG intravenously with 5 x 10(7) bacilli. Recombinant interleukin-2 (IL-2) was injected intraperitoneally as a single dose (20,000 u), single course of 5 injections (400 u each) or 6 monthly courses starting 3 days or 60 days after the MLM infection. BCG infected mice received a single dose (1000 u) or 5 daily injections of 100 or 1000 u each. IL-2 significantly reduced the total bacterial counts in the footpad, lymph node and liver of MLM infected mice (50-85%) by 6 months and viable counts in the spleen (30-50%) by 60 days after BCG infection. The courses of IL-2 started at 60 days were more effective than at 3 days after MLM infection (P less than 0.05-0.001) and in the case of BCG, 100 u of IL-2 was better than 1000 u (P less than 0.05-0.01). These results indicate that IL-2 limits mycobacterial infections in mice, and raise the question of its possible use in humans.


MicroRNA 27a-3p Regulates Antimicrobial Responses of Murine Macrophages Infected by Mycobacterium avium subspecies paratuberculosis by Targeting Interleukin-10 and TGF-β-Activated Protein Kinase 1 Binding Protein 2.
Mycobacterium avium subspecies paratuberculosis (MAP) persistently survive and replicate in mononuclear phagocytic cells by adopting various strategies to subvert host immune response. Interleukin-10 (IL-10) upregulation via inhibition of macrophage bactericidal activity is a critical step for MAP survival and pathogenesis within the host cell. Mitogen-activated protein kinase p38 signaling cascade plays a crucial role in the elevation of IL-10 and progression of MAP pathogenesis. The contribution of microRNAs (miRNAs) and their influence on the activation of macrophages during MAP pathogenesis are still unclear. In the current study, we found that miRNA-27a-3p (miR-27a) expression is downregulated during MAP infection both in vivo and in vitro. Moreover, miR-27a is also downregulated in toll-like receptor 2 (TLR2)-stimulated murine macrophages (RAW264.7 and bone marrow-derived macrophage). ELISA and real-time qRT-PCR results confirm that overexpression of miR-27a inhibited MAP-induced IL-10 production in macrophages and upregulated pro-inflammatory cytokines, while miR-27a inhibitor counteracted these effects. Luciferase reporter assay results revealed that IL-10 and TGF-β-activated protein kinase 1 binding protein 2 (TAB 2) are potential targets of miR-27a. In addition, we demonstrated that miR-27a negatively regulates TAB 2 expression and diminishes TAB 2-dependent p38/JNK phosphorylation, ultimately downregulating IL-10 expression in MAP-infected macrophages. Furthermore, overexpression of miR-27a significantly inhibited the intracellular survival of MAP in infected macrophages. Our data show that miR-27a augments antimicrobial activities of macrophages and inhibits the expression of IL-10, demonstrating that miR-27a regulates protective innate immune responses during MAP infection and can be exploited as a novel therapeutic target in the control of intracellular pathogens, including paratuberculosis.


Primary amines inhibit recycling of alpha 2M receptors in fibroblasts.
Receptor-mediated endocytosis of alpha 2M-protease complexes by normal human skin fibroblasts in culture was inhibited by the primary amines, methylamine and mono-dansylcadaverine. The latter was effective at a concentration two orders of magnitude lower than methylamine. Several observations indicated an intracellular mode of action of these amines, excluding interference with binding of alpha 2M to the receptor. Inhibition of endocytosis was dissociated from lysosomotropic effects of these amines by kinetic analysis of endocytosis. As opposed to chloroquine and alkaline incubation conditions (pH 8.0), the amines reduced the maximal rate of endocytosis considerably, indicating a reduction in number of available receptors. This was confirmed by measuring binding at 4 degrees C. Continuous recycling of receptors is indicated by the absence of down-regulation of number of receptors under conditions saturating for endocytosis of alpha 2M complexes. We postulate that the primary amines, methylamine and mono-dansylcadaverine, interfere with the recycling of alpha 2M receptors, while the chemical nature of the amines and the conditions under which inhibition becomes apparent point to the involvement of transglutaminase in this recycling.


Chronic undernutrition and cognitive abilities.
This review attempts to summarize recent developments in our understanding of the relationship between childhood malnutrition and cognitive abilities. The first questions briefly discussed relate to methods: the definition of malnutrition and the selection of suitable methods of measuring cognitive abilities. Next are considered the effects on mental development of undernutrition, social background and the behavioural patterns of mothers. The consequences of an episode of severe malnutrition in infancy and of confinement in hospital represent a special but important case. The review ends with a discussion of the factors that influence recovery and of strategies for intervention which might be included in a health care programme.


New opinion on the subtypes of poststroke depression in Chinese stroke survivors.
Poststroke depression (PSD) is the most common complication of stroke. However, some stroke survivors with depression cannot meet the diagnostic criteria of PSD. The aim of this study was to propose the new conception of stroke patients with depression and then make them to receive reasonable diagnosis and treatment. We first put forward the opinion that the general PSD should consist of PSD disorder (PSDD) and PSD symptoms (PSDS) according to the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5) and ZhongDa diagnostic criteria - first edition (ZD-1), respectively. The ZD-1 was established based on the suggestions of 65 Chinese chief doctors considering that the symptoms of PSDS might be different from those of PSDD and the duration of DSM-5 was too strict. Then, 166 stroke inpatients were recruited, and the study was conducted using the diagnosis and classification of PSD to verify the new concept. A total of 24 (14.46%) and 80 (48.19%) stroke patients were diagnosed with PSDD and PSDS, respectively, according to individual diagnosis criteria. Moreover, patients meeting the diagnostic criteria of PSDD should satisfy the criteria of PSDS first. The distribution frequencies of depressive symptoms were different, which suggested that there might be discrepant depressive symptoms between PSDS and PSDD. The present study proposes new opinion about the classification and diagnosis of depression in stroke survivors. The definition and criteria of PSDS are beneficial to explore phenomenological consistency and provide useful information for early recognition and appropriate interventions.


The distribution of pneumatisation in the skeleton of the adult domestic fowl.
The occurrence of pneumatisation in the skull of the adult domestic fowl was investigated in eight birds by gross and histological examination. It was found to occur regularly throughout the neurocranium and in the quadrate and variably in the mandible, but to be absent in the facial skeleton. Close agreement was found between gross and histological examination. The entire skeletons of fifty one adult birds all from the same hatch and kept under the same conditions were examined grossly for evidence of the occurrence and extent of pneumatisation. Previous findings for the skull were confirmed with the additional information that pneumatisation in the pterygoid was variable. Variation in the extent of skull pneumatisation was less than in the postcranial skeleton, where only cervical vertebrae 5-9 were found to be regularly pneumatised. The humerus and coracoid were variably pneumatised, often unilaterally. The os coxae and sternum had a very low incidence of pneumatisation. The three cockerels in the group appeared to be relatively well pneumatised. Some possible factors governing the occurrence and extent of pneumatisation in the skeleton are discussed.


Interactions of vanadium(V)-citrate complexes with the sarcoplasmic reticulum calcium pump.
Among the biotargets interacting with vanadium is the calcium pump from the sarcoplasmic reticulum (SR). To this end, initial research efforts were launched with two vanadium(V)-citrate complexes, namely (NH(4))(6)[V(2)O(4)(C(6)H(4)O(7))(2)].6H(2)O and (NH(4))(6)[V(2)O(2)(O(2))(2)(C(6)H(4)O(7))(2)].4H(2)O, potentially capable of interacting with the SR calcium pump by combining kinetic studies with (51)V NMR spectroscopy. Upon dissolution in the reaction medium (concentration range: 4-0.5mM), both vanadium(V):citrate (VC) and peroxovanadium(V):citrate (PVC) complexes are partially converted into vanadate oligomers. A 1mM solution of the PVC complex, containing 184microM of the PVC complex, 94microM oxoperoxovanadium(V) (PV) species, 222microM monomeric (V1), 43microM dimeric (V2) and 53microM tetrameric (V4) species, inhibits Ca(2+) accumulation by 75 %, whereas a solution of the VC complex of the same vanadium concentration, containing 98microM of the VC complex, 263microM monomeric (V1), 64microM dimeric (V2) and 92microM tetrameric (V4) species inhibits the calcium pump activity by 33 %. In contrast, a 1 mM metavanadate solution, containing 460microM monomeric (V1), 90.2microM dimeric (V2) and 80microM tetrameric (V4) species, has no effect on Ca(2+) accumulation. The NMR signals from the VC complex (-548.0ppm), PVC complex (-551.5ppm) and PV (-611.1ppm) are broadened upon SR vesicle addition (2.5mg/ml total protein). The relative order for the half width line broadening of the NMR signals, which reflect the interaction with the protein, was found to be V4>PVC>VC>PV>V2=V1=1, with no effect observed for the V1 and V2 signals. Putting it all together the effects of two vanadium(V)-citrate complexes on the modulation of calcium accumulation and ATP hydrolysis by the SR calcium pump reflected the observed variable reactivity into the nature of key species forming upon dissolution of the title complexes in the reaction media.


Emotion dysregulation across the spectrum of pathological eating: Comparisons among women with binge eating, overeating, and loss of control eating.
Emotion regulation difficulties influence the etiology and maintenance of binge eating and eating disorders, but differential associations between emotion dysregulation and objective binge eating (OBE) components have not been examined. We compared emotion dysregulation dimensions in women with OBEs (n = 27), overeating only (n = 25), loss of control (LOC) only (n = 32), or no pathological eating (n = 137). Women with OBEs had significantly more difficulty with overall emotion dysregulation, access to strategies, and impulse control when upset than other groups. Women with OBEs and women with overeating did not differ on poor emotional clarity, whereas women with OBEs and women with LOC did not differ on non-acceptance of emotions. The combination of overeating and LOC eating is associated with the greatest emotion dysregulation, but certain emotion regulation facets may differentially relate to overeating and LOC. Identifying emotion-related treatment targets for core eating disorder symptoms is important.


Inhibitory Effects of Vernonia amygdalina Leaf Extracts on Free Radical Scavenging, Tyrosinase, and Amylase Activities.
Cytotoxicity and instability are the limitations when using bioactive compounds in cosmetic and pharmacology products. This study assesses Vernonia amygdalina leaf extracts for their antityrosinase, antiamylase, and antioxidant activities. Group A extracts were obtained using an aqueous solvent system [70% (v/v) of methanol (BTL70ME), ethanol (BTL70ET), and acetone (BTL70AC)]. Group B extracts were obtained using organic solvents of varying polarities. The results displayed that all extracts exhibited antityrosinase, antiamylase, and antioxidant activities in vitro. The most potent antityrosinase activity was observed in BTL70AC, with a half-maximal inhibitory concentration (IC50) value of 20 μg/mL. BTL_Ethyl acetate and BTL70AC showed potential antiamylase activity. BTL_Isopropanol and BTL_Ethanol exhibited potential antioxidant activity, with IC50 values of 4.0 μg/mL. The total phenolic content of BTL70ME, BTL70ET, and BTL70AC was 72.29±14.14, 65.98±11.91, and 69.37±7.72 mg gallic acid/g extract, respectively. The total flavonoid content was 53.04±5.22, 44.35±13.17, and 61.74±13.17 mg quercetin/g extract, respectively. Group A extracts contained polyphenols, flavonoids, saponins, terpenoids, steroids, and cardiac glycosides. These biological properties can potentially be attributed to the types and quantities of phytochemicals present. Bioactive compounds in the extracts may exert synergistic effects in vitro by interfering with the conformational changes of tyrosinase during substrate binding. Both groups of extracts have the potential to suppress biomolecule degradation, promote antiaging and antimelasma effects, and their phytochemicals can help lower blood glucose levels in diabetes.


For Fiddlers on the Roof and in the Pit: Healthcare and Epidemiology of Playing-Related Problems in Violinists.
Musicians, specifically violinists, may experience pain or loss of function as a result of poor playing hygiene, environmental factors, and insufficient guidance from teachers, parents, conductors, and physicians. The causal occurrence of these pathologies and the efficacy of general treatment, along with referral to other specialists for adjunct therapies and rehabilitation, were examined in this literature review. A systematic PubMed search was conducted in May 2022 to gain insight into the current state of the published literature. Inclusion criteria were cross-sectional or comparative studies that address relevant pathologies among violinists by specialty. The search resulted in 25 cross-sectional, 5 comparative studies, and 1 case review including a total of 6010 musicians, among them at least 920 violinists. Orthopedists, neurologists, dentists/orthodontists, dermatologists, and audiologists are most commonly consulted to treat violinists' complaints. Other internists and various paramedical specialists can equally be affected and should be sensitive to the complaints of musicians. In conclusion, the field of performing arts medicine is extremely wide and requires multidisciplinary specialist attention. The studies chosen highlight that violinists may suffer great discomfort at the hands of their instrument and merit adequate guidance from physicians in order to be able to continue playing in a safe, ergonomic way.


Healing responses following transverse root fracture: a historical review and case reports showing healing with (a) calcified tissue and (b) dense fibrous connective tissue.
The understanding and management of transverse intra-alveolar root fractures has evolved to its current high level of sophistication and clinical success from foundations laid down by histological studies as early as the mid-nineteenth century. The aim of the review was to highlight those earlier histological reports and studies that have contributed to the current understanding of the biological processes involved in the healing of transverse root fractures. Healing of a transverse root fracture by calcified tissue was demonstrated histologically by Howe in 1926, while Boulger in 1928 showed the two other patterns of root fracture healing, namely the interposition of fibrous connective tissue and the interposition of bone and periodontal ligament around both fractured segments. Other major histological reports around that time came from members of the so-called 'The Vienna group of Illinois', who had a significant influence in the development of oral biology worldwide. Other important reports and an experimental study emanated from Germany and Switzerland in the late 30s and early 40s, followed in the 1950s and early 1960s by histological material principally from Sweden, Denmark, France, the USA and Britain. Jens Andreasen and Erik Hjörting-Hansen's landmark paper in 1967 included new histological reports and a classification of healing responses following transverse root fractures. The expansion of knowledge related to root fractures since that time has been exponential, with major contributions from Scandinavia and several other countries. Accompanying the historical review are two case reports with histology of root fracture healing by (a) calcified tissue and (b) dense fibrous connective tissue. The role of the pulp and the periodontal ligament in the repair process is described and the clinical significance discussed with particular emphasis to diagnosis and orthodontic management.


Copper(II) Thiosemicarbazone Complexes and Their Proligands upon UVA Irradiation: An EPR and Spectrophotometric Steady-State Study.
X- and Q-band electron paramagnetic resonance (EPR) spectroscopy was used to characterize polycrystalline Cu(II) complexes that contained sodium 5-sulfonate salicylaldehyde thiosemicarbazones possessing a hydrogen, methyl, ethyl, or phenyl substituent at the terminal nitrogen. The ability of thiosemicarbazone proligands to generate superoxide radical anions and hydroxyl radicals upon their exposure to UVA irradiation in aerated aqueous solutions was evidenced by the EPR spin trapping technique. The UVA irradiation of proligands in neutral or alkaline solutions and dimethylsulfoxide (DMSO) caused a significant decrease in the absorption bands of aldimine and phenolic chromophores. Mixing of proligand solutions with the equimolar amount of copper(II) ions resulted in the formation of 1:1 Cu(II)-to-ligand complex, with the EPR and UV-Vis spectra fully compatible with those obtained for the dissolved Cu(II) thiosemicarbazone complexes. The formation of the complexes fully inhibited the photoinduced generation of reactive oxygen species, and only subtle changes were found in the electronic absorption spectra of the complexes in aqueous and DMSO solutions upon UVA steady-state irradiation. The dark redox activity of copper(II) complexes and proligand/Cu(II) aqueous solutions towards hydrogen peroxide which resulted in the generation of hydroxyl radicals, was confirmed by spin trapping experiments.


PERSON-Personalized Expert Recommendation System for Optimized Nutrition.
The rise of personalized diets is due to the emergence of nutrigenetics and genetic tests services. However, the recommendation system is far from mature to provide personalized food suggestion to consumers for daily usage. The main barrier of connecting genetic information to personalized diets is the complexity of data and the scalability of the applied systems. Aiming to cross such barriers and provide direct applications, a personalized expert recommendation system for optimized nutrition is introduced in this paper, which performs direct to consumer personalized grocery product filtering and recommendation. Deep learning neural network model is applied to achieve automatic product categorization. The ability of scaling with unknown new data is achieved through the generalized representation of word embedding. Furthermore, the categorized products are filtered with a model based on individual genetic data with associated phenotypic information and a case study with databases from three different sources is carried out to confirm the system.


Implementing nonsmoking policies in the private sector and assessing their effects.
Nonsmoking policies are being implemented increasingly in worksites across the country. This cross-sectional study examined attitudes toward worksite nonsmoking policies and worksite norms about smoking and cessation. Data were collected by telephone interview from 711 smokers and recent ex-smokers employed in seven worksites in Bloomington, Minnesota, in 1986. The findings indicated widespread support for nonsmoking policies even among smokers. Support for nonsmoking policies was especially high among respondents interested in quitting smoking, those concerned about the health effects of smoking, those reporting high coworker support for prior cessation attempts, and those working with a high proportion of nonsmokers. Support for nonsmoking policies was also correlated with smoking cessation in the 18 months prior to the survey. The clustering of these social norms is indicative of a worksite "culture" that may either support nonsmoking or inhibit cessation.


[Ultrasound-assisted thrombolysis in acute ischemic stroke].
Numerous experimental studies,in vitro and in animal models, have demonstrated that ultrasound can accelerate clot lysis. This effect is probably related to the cavitation of microbubbles contained in the medium exposed to ultrasound. Clinical studies show that transcranial application of low-intensity, low-frequency ultrasound identical to that routinely used for diagnostic purposes can improve recanalization rates in patients with acute ischemic stroke. These promising findings should be confirmed in larger studies and using MR or CT angiography to assess recanalization independently. The optimal method of ultrasound-assisted thrombolysis has not been determined yet. Experimental data suggest that it may be enhanced by coadministration of microbubbles used as contrast agents.


Dual-emissive metal-organic framework: a novel turn-on and ratiometric fluorescent sensor for highly efficient and specific detection of hypochlorite.
Hypochlorite (ClO-) is widely used as a disinfectant, whose residue content in water should be strictly controlled due to the potential threat to human health in an inappropriate concentration. Herein, dual-emissive metal-organic frameworks with a UiO-66 prototype structure, PDA/Eu/PDA-UiO-66-NH2(x), were elegantly designed and prepared by a mixed ligand assembly and sequential post-synthesis strategy. Since blue emission is sensitive to ClO-, PDA/Eu/PDA-UiO-66-NH2(40) was selected as a model nanosensor for ratiometric and turn-on sensing of ClO- while red emission acts as a reference signal. Remarkably, PDA/Eu/PDA-UiO-66-NH2(40) shows high efficiency and specificity toward ClO- detection, as verified by a very short response time of 15 s, a wide linear range of 0.1-60 μM, a low detection limit of 0.10 μM, and excellent selectivity toward common competing ions. The recovery experiments show that the recoveries of spiking ClO- in tap water range from 96 to 103%. The rigidification of the coordinated H2N-BDC2- ligands should be responsible for the turn-on fluorescence of PDA/Eu/PDA-UiO-66-NH2(40). This work not only shows a highly efficient and specific fluorescent nanosensor for ClO- detection but also presents the first MOF-based fluorescent probe for turn-on and ratiometric sensing of ClO-.


[Drinking alcohol among junior high school students: reflecting drinking culture].
Using a data obtained from a junior high school students survey on drug use, perception of alcohol drinking for junior high school students and role of adults in drinking were examined. 78% of the junior high school students had ever drunk alcohol at least once. The results revealed that experience of drinking alcohol accompanied by family did not have a close relationship with regularity of daily life routine, school lives and family lives for the students. It was, however, strongly suggested that experience of drinking alcohol only with peers had a close relationship with undesirable daily life routine, school lives and family lives for the students. Furthermore, lifetime prevalence of cigarette smoking and that of solvent inhalation for the male students with experience of drinking only with friends were 11 to 13 times and 5 to 8 times higher, respectively, than the male students without experience of drinking only with friends. These were 22 times and 3 to 5 times, respectively, for female students. As for observance of the law which prohibits drinking alcohol for those under 20 years old, over a half of the students consider that alcohol drinking for minors was acceptable depending on the time and circumstances. This was greatly different from the observance of the laws against cigarette smoking and solvent inhalation. The author considers that this may reflect adult alcohol drinking culture in Japan.


Enantioselective Construction of Trifluoromethoxylated Stereogenic Centers by a Nickel-Catalyzed Asymmetric Suzuki-Miyaura Coupling of Secondary Benzyl Bromides.
Trifluoromethoxy-substituted stereogenic centers can be constructed with high enantioselectivity by a nickel-catalyzed Suzuki-Miyaura coupling of readily available α-bromobenzyl trifluoromethyl ethers with a variety of aryl pinacol boronates. The coupling proceeds under mild reaction conditions, and a variety of common functional groups, such as fluoride, chloride, bromide, ester, enolizable ketone, nitro, cyano, amino, and vinyl moieties, were well tolerated. Furthermore, the reaction can be easily scaled up to gram quantities without a decrease in enantioselectivity.


Adrenal cysts - optimal laparoscopic treatment.
Adrenal cysts develop in up to about 0.2% of the overall population. They may account for up to 11% of all pathologies of adrenal glands. Is laparoscopic resection of adrenal cysts a method for the treatment of these pathologies? In the years 2010-2017, a total of 27 patients underwent surgery due to adrenal cysts; those included 18 (66.7%) women and 9 (33.3%) men aged 29 to 84 years (mean age: 42.7). Cyst diameter ranged from 55 to 130 mm. After exclusion of hormonal hyperactivity, parasitic cysts, or, to the best possible extent, cancer lesions, patients were qualified for adrenal-sparing laparoscopic surgery. All patients were subjected to laparoscopic surgery. Cystic wall resection was performed in 15 (55.6%) patients while adrenalectomy was performed in the remaining 12 (44.4%) patients. The decision regarding the extent of the surgery was made intraoperatively. Histopathological assessment revealed pathological adrenal lesions in as few as 3 (11.1%) patients, with the rest of the study population, i.e. 24 (88.9%), presenting with normal adrenal tissue. Laparoscopic resection of adrenal cysts appears to be recommendable as a method for the treatment of these pathologies. It is simpler than adrenalectomy and associated with low risk of any pathological lesion remaining within the adrenal gland following careful intraoperative assessment by an experienced surgeon.


Current approaches for identifying high-risk non-muscle invasive bladder cancer.
Management of high risk non-muscle invasive bladder cancer (NMIBC) is challenging. It is vital to detect recurrences early and predict which tumors are likely to progress. Areas covered: This manuscript reviews the current approaches available for detection and surveillance of high risk NMIBCs. A literature review was utilized to evaluate risk factors for recurrence and progression as well as evaluating approaches including pathological aspects of NMIBC, molecular subtyping, methods for tumor visualization, urine cytology, urinary molecular markers, molecular tissue markers as well as the scoring systems and nomograms. Expert commentary: Clinical and pathological factors are still the mainstay of prediction of recurrence and progression. However, genomic information such as molecular subtyping may improve understanding of prognosis. White light cystoscopy is still a dominant approach but enhanced cystoscopy is likely superior for detection of cancer especially carcinoma in situ. Urinary biomarkers are evolving; however, they are not ready to replace cystoscopy and trials are still necessary to determine optimal clinical utility. Prognostic scoring systems and nomograms are available for counseling the patients but there is room to improve predictive accuracy.


The spatial regulation of condensin activity in chromosome condensation.
Condensin mediates chromosome condensation, which is essential for proper chromosome segregation during mitosis. Prior to anaphase of budding yeast, the ribosomal DNA (RDN) condenses to a thin loop that is distinct from the rest of the chromosomes. We provide evidence that the establishment and maintenance of this RDN condensation requires the regulation of condensin by Cdc5p (polo) kinase. We show that Cdc5p is recruited to the site of condensin binding in the RDN by cohesin, a complex related to condensin. Cdc5p and cohesin prevent condensin from misfolding the RDN into an irreversibly decondensed state. From these and other observations, we propose that the spatial regulation of Cdc5p by cohesin modulates condensin activity to ensure proper RDN folding into a thin loop. This mechanism may be evolutionarily conserved, promoting the thinly condensed constrictions that occur at centromeres and RDN of mitotic chromosomes in plants and animals.


Pharmacokinetics of intraperitoneal cefazolin and ceftazidime coadministered to CAPD patients.
Guidelines for empiric treatment of PD-related peritonitis published in 2000 recommend concurrent intraperitoneal (IP) cefazolin and ceftazidime. The pharmacokinetics (PK) of these agents combined have not been studied. This study was designed to determine the PK of combined IP cefazolin and ceftazidime in CAPD patients. Prospective PK study in seven non-infected CAPD patients. Patients had a peritoneal equilibration test (PET), then received one IP dose of cefazolin and ceftazidime (15 mg/kg each) co-administered over a 4-hour dwell, then performed three CAPD exchanges over the next 16 hours. Serum and dialysate samples collected over the 20-hour study period were assayed for drug concentrations by HPLC. PK parameters. Correlations were tested between PET and PK parameters using the Pearson-product correlation coefficient. Serum cefazolin and ceftazidime levels exceeded the minimum inhibitory concentrations for susceptible organisms (8 mg/L) throughout the 20 hour study period. Mean cefazolin and ceftazidime PK parameters included: bioavailability, 71% and 63%; elimination rate constant, 0.031 and 0.045 h -1 ; total clearance, 5.8 and 16.0 ml/min; peritoneal clearance, 1.6 and 3.9 ml/min; renal clearance, 2.3 and 3.9 ml/min, respectively. Predictive equations suggest that 1000 mg IP of cefazolin and of ceftazidime every 24 hours would produce average steady-state trough serum cefazolin and ceftazidime concentrations of 70 +/- 52 mg/L and 17 +/- 7 mg/L, respectively. There was no correlation between PET and PK parameters. Co-administration did not adversely affect the PK of either agent. IP cefazolin and ceftazidime (15 mg/kg) produced adequate serum and dialysate concentrations in CAPD patients for 20 hours. PK predictions suggest that most patients would achieve adequate cefazolin and ceftazidime concentrations with 1000 mg IP once-daily. Anuric patients and those with significant residual renal function may require a more individualized approach.


T lymphocyte development and maturation in horses.
Monoclonal antibodies specific for equine T lymphocyte subpopulations were produced and procedures for the continuous culture of equine lymphocytes were developed. These reagents and procedures were used to analyse the appearance, maturation and functions of T lymphocytes in normal horses and in T lymphocyte deficient horses with severe combined immunodeficiency (SCID). T lymphocytes appeared as early as the 75th day of fetal development and were normally distributed prior to birth of normal foals. Analysis of thymic T lymphocyte differentiation in SCID foals revealed the presence of both prothymocytes and mature thymocytes, but a virtual absence of cortical thymocytes. The data obtained support the hypothesis that two distinct pathways of T lymphocyte differentiation exist within the thymus. Although the gene defect in foals with SCID blocks the production of mature B and T lymphocytes, such foals do possess large granular lymphocytes which are cytotoxic following induction with interleukin 2. This suggests that lymphoid cells with natural killer cell activity are spared by the gene defect resulting in SCID in horses.


Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer's disease.
Acetylcholinesterase (AChE) is one of the key targets of drugs for treating Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were carried out in order to study 60 tacrine derivatives and their AChE-inhibitory activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q(2) = 0.552 and r(2) = 0.983 and an optimal CoMSIA model with q(2) = 0.581 and r(2) = 0.989. These QSAR models also showed that the steric and H-bond fields of these compounds are important influences on their activities. The interactions between these inhibitors and AChE were further explored through molecular docking and molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279, and Phe330) at the binding site of AChE were identified. The results of this study improve our understanding of the mechanisms of AChE inhibitors and afford valuable information that should aid the design of novel potential AChE inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest-energy structure obtained from MD simulation (magenta) onto those of the structure of the initial molecular docking model (green).


Different routes of donor-derived hematopoietic stem cell transplantation for donor-specific chimerism induction across MHC barrier.
Transplantation of donor-derived stem cells can improve organ allograft survival in animal models. This study was designed to investigate the effect of different routes of bone marrow cell (BMC) transplantation on donor-specific tolerance induction across MHC barrier under short-term CsA monotherapy and alphabetaTCR/CsA treatment protocols. Forty-eight BMC transplantations were performed between BN(RT1(n)) donors and LEW(RT1(1)) recipients. Intraosseous and intravenous BMC transplantation was studied in six groups of eight animals each receiving 35 x 10(6) (n = 4) and 70 x 10(6) (n = 4) bone marrow cells. Groups I and II (controls) received BMC transplantation but no treatment, groups III and IV CsA monotherapy, and groups V, VI alphabetaTCR/CsA protocol for 7 days. Flow cytometry monitored immunodepletion and donor-specific chimerism for MHC class I RT1(n)/CD4, RT1(n)/CD8 and RT1(n)/CD45RA antigens. All animals survived without graft-versus-host disease. At day 63 under CsA monotherapy a low level of chimerism for RT1(n)/CD4 was induced after intraosseous (1.9%) and intravenous (0.8%) transplantation of (70 x 10(6)) BMC. Under alphabetaTCR/CsA protocol chimerism for RT1(n)/CD4 revealed 6.5% and 0.9% in intraosseous and intravenous (70 x 10(6)) BMC transplantation, respectively. The total number of chimerism in intraosseous and intravenous (70 x 10(6)) BMC transplantation groups was 9.9% and 3.4%, respectively. Following intraosseous BMC transplantation under alphabetaTCR/CsA protocol chimerism was 50% higher in a group receiving 70 x 10(6) (9.9%) vs 35 x 10(6) (4.9%) BMC. Intraosseous transplantation of donor BMC under alphabetaTCR/CsA protocol was 75% more efficient in induction of donor-specific chimerism compared to intravenous transplantation.


Conductivity Optimization of Tysonite-type La1-xBaxF3-x Solid Electrolytes for Advanced Fluoride Ion Battery.
Use of lithium ion batteries is currently the method of choice when it comes to local stationary storage of electrical energy. In the search for an alternative system, fluoride ion batteries (FIBs) emerge as a candidate due to their high theoretical capacity, and no lithium is needed for its operation. To improve the cycling performance and lower the working temperature of a solid-state battery, one of the critical components is the electrolyte, which needs advanced performance. This paper aims at developing an electrolyte with enhanced ionic conductivity for fluoride ions, to be used in a FIB. Tysonite La1-xBaxF3-x (0 ≤ x ≤ 0.15) solid solutions were synthesized by a facile wet chemical method, and its ionic conductivity was analyzed using electrochemical impedance spectroscopy. A composition study shows that the conductivity reaches a maximum of 1.26 × 10-4 S·cm-1 at 60 °C for the La0.95Ba0.05F2.95 pellet sintered at 800 °C for 20 h, which is 1 order of magnitude higher than that for the as-prepared pellet and 2 times higher than the conductivity of sintered ball-milled batches. The reason for this dramatic increment is the more efficient decrement of grain boundary resistance upon sintering. Morphological, chemical, and structural characterizations of solid electrolytes were studied by X-ray diffraction, scanning electron microscopy , energy dispersive X-ray spectroscopy, physisorption by the Brunauer-Emmett-Teller method, and transmission electron microscopy. Electrochemical testing was carried out for the FIB cell using La0.95Ba0.05F2.95 as electrolyte due to its highest conductivity among the compositions, Ce as anode, and BiF3 as a cathode. The cycling performance was found to be considerably improved when compared to our earlier work, which used the ball-milled electrolyte.


Performance and comfort on near-eye computer displays.
Very small high-resolution displays (SVGA, 800 x 600 pixels) worn near the eye and imaged to create a virtual image have potential as alternatives to traditional computer displays. Twenty-two subjects performed text-based tasks on five displays: monocular virtual, binocular head-mounted virtual, hard copy, flat panel, and a small format portable display. Outcome measures included performance speed, symptoms, visual acuity, and heterophoria. In a second experiment, subjects performed a proscribed routine of head and body movements designed to elicit motion-related symptoms. Performance speed on monocular virtual was generally comparable with performances on flat panel and hard copy. Overall, performance speeds on the binocular virtual display were about 5% slower than normalized performances, 6.75% slower compared with the traditional flat panel and hard copy displays. Symptoms of eyestrain and blurry vision were significantly higher on monocular virtual than on other displays. No significant changes in visual acuity or heterophoria occurred with any of the displays. Motion-related symptoms with the head mounted near-eye display were not significantly different than with other displays tested. Performance and comfort on the near-eye displays in this study was more similar to traditional displays than in many previous studies with head mounted displays. This is likely due to lack of task movement, partial instead of full immersion, better display resolution, and concordance of the accommodative and vergence stimuli.


Corneal topography matching by iterative registration.
Videokeratography is used for the measurement of corneal topography in overlapping portions (or maps) which must later be joined together to form the overall topography of the cornea. The separate portions are measured from different viewpoints and therefore must be brought together by registration of measurement points in the regions of overlap. The central map is generally the most accurate, but all maps are measured with uncertainty that increases towards the periphery. It becomes the reference (or static) map, and the peripheral (or dynamic) maps must then be transformed by rotation and translation so that the overlapping portions are matched. The process known as registration, of determining the necessary transformation, is a well-understood procedure in image analysis and has been applied in several areas of science and engineering. In this article, direct search optimisation using the Nelder-Mead algorithm and several variants of the iterative closest/corresponding point routine are explained and applied to simulated and real clinical data. The measurement points on the static and dynamic maps are generally different so that it becomes necessary to interpolate, which is done using a truncated series of Zernike polynomials. The point-to-plane iterative closest/corresponding point variant has the advantage of releasing certain optimisation constraints that lead to persistent registration and alignment errors when other approaches are used. The point-to-plane iterative closest/corresponding point routine is found to be robust to measurement noise, insensitive to starting values of the transformation parameters and produces high-quality results when using real clinical data.


Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis.
Harlequin ichthyosis is a rare and severe congenital erythrodermic ichthyosis characterized at birth by hyperkeratotic plates covering the entire body, ectropion, eclabium, poorly developed ears, and contractures of the hands and feet. Two Chinese children, a 2-year-old boy and an 11-year-old girl, presented with these classic features as well as alopecia and loss of eyebrows and eyelashes. The boy was small for his age and was found to have hypothyroidism at the age of 18 months; he is currently on thyroxine replacement therapy. At 6 years of age, the girl developed symmetrical polyarthritis associated with positive rheumatoid factor and radiologic evidence of erosive arthritis, suggestive of juvenile rheumatoid arthritis. She received prednisolone, nonsteroidal anti-inflammatory drugs (NSAIDs), and subsequently methotrexate for her arthritis, with clinical and radiologic improvement. Early therapy with oral retinoids in both children accelerated shedding of the hyperkeratotic plates as well as improved ectropion and eclabium. There was no major adverse reaction to oral retinoids. The development of juvenile rheumatoid arthritis in survivors with harlequin ichthyosis has not been previously described. The use of prednisolone and NSAIDs in the girl did not affect the skin condition, but the addition of methotrexate led to a decrease in erythema. The association with autoimmune disease is probably coincidental. The psychosocial impact of this severe lifelong disease on the two families was enormous. Early retinoid therapy may improve the disorder and help increase survival rates. A multidisciplinary approach, including psychosocial support of the affected families, is vital in the management of this lifelong disease.


Drug-induced immune thrombocytopenic purpura secondary to sunitinib.
SUNITINIB (SUTENT: Pfizer, New York, NY, U.S.A.) is an oral multi-targeted tyrosine kinase inhibitor approved for use in various solid tumour malignancies. Many side effects secondary to sunitinib have been documented. In particular, sunitinib administration is known to result in thrombocytopenia, with the cause being attributed to myelosuppression. Here, we present the first case report to demonstrate immune-mediated thrombocytopenia secondary to sunitinib administration.


Experimental myofascial trigger point creation in rodents.
Myofascial pain syndrome is one of the most common forms of muscle pain. In this syndrome, pain is originated by the so-called trigger points, which consists of a set of palpable contraction knots in the muscle. It has been proposed that a high, spontaneous neurotransmission may be involved in the generation of these contraction knots. To confirm this hypothesis, we exposed mouse muscles to an anticholinesterasic agent to increase the neurotransmision in the synaptic cleft in two different conditions, in vivo and ex vivo experiments. Using intracellular recordings, a sharp increase in the spontaneous neurotransmission in the levator auris longus muscle and a lower increase in the diaphragm muscle could be seen. Likewise, electromyography recordings reveal an elevated endplate noise in gastrocnemius muscle of treated animals. These changes are associated with structural changes such as abundant neuromuscular contracted zones observed by rhodaminated α-bungarotoxin and the presence of abundant glycosaminoglycans around the contraction knots, as shown by Alcian PAS staining. In a second set of experiments, we aimed at demonstrating that the increases in the neurotransmission reproduced most of the clinical signs associated to a trigger point. We exposed rats to the anticholinesterase agent neostigmine, and 30 min afterward we observed the presence of palpable taut bands, the echocardiographic presence of contraction knots, and local twitch responses upon needle stimulation. In summary, we demonstrated that increased neurotransmission induced trigger points in both rats and mice, as evidenced by glycosaminoglycans around the contraction zones as a novel hallmark of this pathology. NEW & NOTEWORTHY In rodents, when neostigmine was injected subcutaneously, the neuromuscular neurotransmission increased, and several changes can be observed: an elevated endplate noise compared with normal endplate noise, as evidenced by electromyographyc recording; many muscular fibers with contraction knots (narrower sarcomeres and locally thickened muscle fiber) surrounded by infiltration of connective tissue like glycosaminoglycans molecules; and palpable taut bands and local twitch responses upon needle stimulation. Several of these signs are also observed in humans with muscle pain.


The comparison of stepping responses following perturbations applied to pelvis during overground and treadmill walking.
Treadmills are used frequently in rehabilitation enabling neurologically impaired subjects to train walking while being assisted by therapists. Numerous studies compared walking on treadmill and overground for unperturbed but not also perturbed conditions. The objective of this study was to compare stepping responses (step length, step width and step time) during overground and treadmill walking in a group of healthy subjects where balance assessment robots applied perturbing pushes to the subject's pelvis in sagittal and frontal planes. During walking in both balance assessment robots (overground and treadmill-based) with applied perturbations the stepping responses of a group of seven healthy subjects were assessed with a motion tracking camera. The results show high degree of similarity of stepping responses between overground and treadmill walking for all perturbation directions. Both devices reproduced similar experimental conditions with relatively small standard deviations in the unperturbed walking as well as in perturbed walking. Based on these results we may conclude that stepping responses following perturbations can be studied on an instrumented treadmill where ground reaction forces can be readily assessed which is not the case during perturbed overground walking.


Radioimmunoassay of hepatitis b antigen and antibody in dialysis and transplant patients.
57 dialysis patients, 29 of whom had been exposed to hepatitis in 1968-69, were re-examined for hepatitis B antigen (HB-Ag) and antibody (HB-Ab) by means of radioimmunoassay (RIA) and counter immunoelectrophoresis (CIE). Infected patients were followed for five years. Compared to CIE, RIA did not detect additional HB-Ag-positive patients, but antibody could persistently be detected in seven out of fifteen patients previously supposed to have escaped infection. tnine surviving HB-Ag-positive transplant patients remained carriers for 50-72 months. None developed clinical signs of chronic hepatic failure.


Connecting Health and Social Services for Patients with Complex Care Needs: A Pan-Canadian Comparative Policy Research Program.
Comprehensive primary healthcare for patients with complex care needs requires connections to other health services, social services and community supports. This descriptive comparative policy research program used publicly available documents and informant interviews to examine progress toward integrated comprehensive care through the lens of services needed by children and youth (0-25 years) and community-dwelling older adults (≥ 65 years) with high functional health needs. This article describes five projects. The following three findings emerged across all the projects: Canada indeed has multiple health systems; numerous integrated service delivery solutions are being trialled and most focus on medical services; and it is an ongoing challenge for ministries of health to engage physicians and physician associations in integration.


Age- and Gender-Specific Diagnostic Value of the Albumin-to-Creatinine Ratio for the Early Screening of Chronic Kidney Disease Among Middle-Aged and Elderly Males in Southeast China.
To evaluate the potential diagnostic value of the albumin-to-creatinine ratio (ACR) in screening for early kidney injury in a physically examined population from Southeast China. A total of 13,250 candidates were selected. Urinary ACR values <30, 30-300, and >300 mg/g were utilized as positive cut-off points to denote normal proteinuria, microalbuminuria, and macroalbuminuria, respectively. Age, systolic blood pressure, diastolic blood pressure, body mass index, waistline, fasting blood glucose, glycated hemoglobin, triglycerides, and high-density lipoprotein cholesterol were significantly different among the three groups. eGFR was negatively correlated with the levels of sCr, BUN, and UA in the microalbuminuria and macroalbuminuria groups. Furthermore, there was a significant difference in CKD stage between the normal and abnormal urine ACR groups. Meanwhile, for the 20-40 years patients, the eGFR, sCr and BUN showed no significant difference between microalbuminuria group compared with the normal proteinuria group; in contrast, for the 41-60 years and >61 years patients, eGFR, sCr, BUN and UA were all markedly increase in microalbuminuria and macroalbuminuria group in comparison with the normal proteinuria group. Finally, for the 41-60 males, only eGFR significantly decreased in microalbuminuria group compared with the normal proteinuria group, while for the 41-60 females, only UA showed no significant difference between microalbuminuria group and normal proteinuria group. On the other hand, for the >61 males, eGFR, sCr and BUN all significantly changed between microalbuminuria group and normal proteinuria group, while for the >61 females, eGFR, sCr and BUN all showed no significant difference between microalbuminuria group and normal proteinuria group, as well as microalbuminuria group and macroalbuminuria group. We proposed using the urinary ACR for the screening of physically examined patients, especially among the elderly males. This approach would assist in the early diagnosis and treatment of renal damage.


Synthesis and characterization of nitrosyl diruthenium complexes. Interaction between NO and CO across the metal-metal bond.
Two neutral diruthenium complexes and one anionic diruthenium complex, Ru2(dpf)4(NO), Ru2(dpf)4(NO)2, and [Ru2(dpf)4(NO)]-, where dpf is diphenylformamidinate anion, were synthesized and characterized as to their electrochemical and spectroscopic properties. Two of the compounds, Ru2(dpf)4(NO) and Ru2(dpf)4(NO)2, were also structurally characterized. Ru2(dpf)4(NO) undergoes reversible one-electron reductions under N2 at E1/2=0.06 and -1.24 V in CH2Cl2, 0.1 M TBABr. These processes are shifted to E1/2=0.18 and -0.78 V under CO due to the trans-coordination of a CO molecule which stabilizes the singly and doubly reduced forms of the metal-metal bonded complexes, thus leading to easier reductions. CO does not coordinate to Ru2(dpf)4(NO), but it does bind to the singly reduced species to generate [Ru2(dpf)4(NO)(CO)]- under a CO atmosphere in solution; characteristic NO and CO bands are seen for this compound at nuNO=1674 cm(-1) and nuCO=1954 cm(-1). Ru2(dpf)4(NO)2 displays a reversible one-electron reduction at E1/2=-1.24 V versus SCE and an irreversible reduction at Epc=-1.96 V in CH2Cl2, 0.1 M TBAP under N2. There are also two reversible one-electron oxidations at E1/2=0.24 and 1.15 V. Spectroelectrochemical monitoring of the Ru2(dpf)4(NO)2 oxidation processes in a thin-layer cell shows only a single NO vibration for each electrogenerated product and nuNO is located at 1726 (neutral), 1788 (singly oxidized), or 1834 (doubly oxidized) cm(-1). Finally, a labile CO complex, [Ru2(dpf)4(NO)(CO)]-, could be generated by passing CO into a solution of [Ru2(dpf)4(NO)]-. Formation of the mixed CO/NO adduct was confirmed by electrochemistry and infrared spectroscopy. Analysis of the NO and CO stretching vibration frequencies for [Ru2(dpf)4(NO)(CO)]- by in-situ FTIR spectroelectrochemistry and comparisons with data for Ru2(dpf)4(NO) and Ru2(dpf)4(CO) reveal the presence of a strong interaction between NO and CO across the Ru-Ru bond.


The angular position of a refuge affects escape responses in staghorn sculpin Leptocottus armatus.
The effect of the presence and angular position of a refuge on the direction and kinematics of mechanically-induced escape responses was observed in staghorn sculpins Leptocottus armatus using high-speed video. The results showed that the angular position of the refuge did not affect locomotor performance (speed and acceleration), although it did affect the escape trajectories. Therefore, the angular position of a refuge can modulate the direction taken by the L. armatus during the early stages of their escape response and this response can be affected by both repulsive (i.e. threats) and attractive (i.e. refuges) points of reference.


Banoxantrone Coordinated Metal-Organic Framework for Photoacoustic Imaging-Guided High Intensity Focused Ultrasound Therapy.
Photoacoustic (PA) imaging with high spatial resolution has great potential as desired monitoring means in the high-intensity focused ultrasound (HIFU) surgery of tumor. However, its penetration depth in the tissue is insufficient for achieving accurate intraoperative navigation, leading to residual tumor tissue. Nanomedicine provides a new opportunity for PA imaging to guide HIFU surgery. Studies have found that the hypoxic heterogeneity of tumor is effectively reversed by HIFU. Herein, a specific metal-organic framework nanosystem, constructed by coordination of banoxantrone (AQ4N) and Mn2+ , is designed based on HIFU to reverse the hypoxic heterogeneity of tumors. It can provide exogenous light-absorbing substances, thus improving the penetrability of PA imaging signal through the deep tissue and achieving clearer PA imaging for guiding HIFU surgery. In turn, AQ4N, in the hypoxic homogenous environment of the tumor provided by HIFU, is activated sequentially to specifically treat the residual hypoxic tumor cells. This combination treatment manifests higher tumor suppressors activation and lower expression of genes related to tumor progression. This strategy addresses the dissatisfaction with PA imaging-guided HIFU therapy and is promising for translation into a clinical combination regimen.


Bone Mineral Density Is Negatively Associated With Arterial Stiffness in Men With Hypertension.
Hypertension (HTN) and osteoporosis are associated with the development and progress of atherosclerosis. However, little research has been conducted to examine the relationship between arterial stiffness and bone mineral density (BMD) in men with HTN. This cross-sectional study recruited 355 men with HTN and 353 control patients without HTN. Brachial-ankle pulse wave velocity (baPWV) and BMD measurements were performed. BMD was decreased and baPWV was elevated in patients with HTN compared with control patients (femoral neck [FN] BMD in the HTN and control groups were 0.662±0.195 g/cm2 and 0.713±0.204 g/cm2 , respectively [P=.001], and baPWV in the HTN and control groups were 1403.3±156.8 cm/s and 1354.8±136.0 cm/s, respectively [P<.001]). Multiple linear regression analysis demonstrated that FN BMD was negatively associated with increased baPWV in HTN. Reduced FN BMD may be an independent factor for baPWV in patients with HTN.


[Urethral prolapse. Case report].
The article reports on the case of a girl of 11 1/2 years of age who was referred to hospital with an urethral prolapse. The prolapsed urethral mucosa was excised and the wound closed by suturing.


Pediatric patients with congenital heart disease: thrombin generation measured by calibrated automated thrombography.
The aim of this study was to investigate the possible suitability of the calibrated automated thrombography to determine the coagulation status of pediatric patients with congenital heart disease. Thrombin generation was measured in 60 patients with congenital heart disease using the calibrated automated thrombography and compared to data using standard coagulation parameters such as prothrombin, antithrombin, tissue factor pathway inhibitor, prothrombin fragment 1.2 (F 1.2), and activated partial thromboplastin time. A significant positive correlation was observed between prothrombin and the endogenous thrombin potential (P < 0.01; r = 0.295) as well as between prothrombin and peak height (P < 0.01; r = 0.581). A significant negative correlation was seen between tissue factor pathway inhibitor and endogenous thrombin potential (P < 0.01; r = -0.480) and between tissue factor pathway inhibitor and peak height (P < 0.01; r = -0.234). No statistically significant correlation was found between antithrombin and parameters of continuous thrombin generation. Significant correlation was seen neither between activated partial thromboplastin time and F1.2 nor between activated partial thromboplastin time and prothrombin. The data presented here indicate that calibrated automated thrombography measurements determine thrombin generation more accurately and therefore reflect better the coagulation status of pediatric patients with congenital heart disease then standard global coagulation assays such as activated partial thromboplastin time.


Socio-economic determinants of maternal health care utilization in Kailahun District, Sierra Leone, 2020.
Ascertaining the key determinants of maternal healthcare service utilization and their relative importance is critical to priority setting in policy development. Sierra Leone has one of the world's highest maternal death ratios in the context of a weak health system. The objectives of this study were to determine; the level of utilization of Antenatal Care (ANC), Skilled Delivery Attendants (SDA), Postnatal Care (PNC) services, and factors that influence the utilization of these services. We conducted a community-based cross-sectional study involving 554 women of reproductive age (15-49 years) who had at least one delivery in the last 3 years and lived in the Kailahun District, Sierra Leone from November 2019 to October 2020. Data were analysed using analysed using bivariate, multivariate and multinomial logistic regression models. The median age of respondents was 25 years (Q1 = 17 years, Q3 = 30 years). Eighty-nine percent (89%) had 4 or more ANC visits. Only 35.9% of women were delivered by SDA. Women residing in urban areas had over six-fold increased odds of utilizing SDA as compared to women residing in rural areas (AOR = 6.20, 95% CI = 3.61-10.63). Women whose husbands had a primary level of education had 2.38 times increased odds of utilizing SDA than women whose husbands had no education (AOR = 2.38, 95% CI = 1.30-4.35). Women that walked longer distances (30-60 min) to seek healthcare had 2.98 times increased odds of utilizing SBA than those that walked shorter distances (< 30 min) (AOR = 2.98, 95% CI = 1.67-5.33). Women who had a secondary/vocational level of education had 2.35 times increased odds of utilizing the standard PNC category as compared to those with no education (OR = 2.35, 95% CI = 1.19-4.63). The majority of women had 4 or more ANC visits yet the use of skilled birth attendants was low. Urban residence and education were significantly associated with the use of the standard PNC category. To improve the utilization of maternal health care services, national healthcare policies should target the advancement of education, train skilled Maternal Healthcare (MHC) attendants, rural infrastructure, and the empowerment of women.


The effect of prolonged clamping and vascular stasis on the patency of arterial and venous microanastomoses.
During free tissue transfer, an artery and one or two veins must be sutured. Either the artery or the vein can be repaired first, but the optimal order of vascular repair has not been established. Maintaining a clamp on a vessel is associated with vessel injury, and releasing the clamp may cause bleeding and vascular stasis. The purpose of this study was to determine if the order of vessel repair and the length of vascular clamping affects surgical outcome. Free flaps were created on Sprague-Dawley rats (400-450 g) as follows: Bilateral abdominal skin flaps (3 x 3 cm) based on the superficial inferior epigastric vessels were elevated. The femoral artery and vein were tied and divided distal to the branching of the inferior epigastric vessels. Proximal to the branching, the artery and vein were divided. The animals were then randomized into four groups as follows: In group I (N=16), the artery was repaired and then the clamps were released to revascularize the flap. Venous stasis occurred as the vein was being repaired because of the venous clamp. In group II (N=15), the artery was repaired, but the clamp was maintained to prevent blood from coming in contact with the fresh arterial anastomosis and to prevent venous stasis. The vein was then repaired. In group III (N=15), the vein was repaired first but the venous clamp was not released until the artery was repaired. In group IV (N=15), the vein was repaired first and the clamps were released, allowing venous blood to contact the fresh anastomosis while the artery was being repaired. After final clamp removal, all anastomoses were assessed immediately for evidence of thrombosis. Five days postoperatively the skin flap was evaluated for evidence of necrosis and the anastomosis was inspected for evidence of late thrombosis. The anastomoses were resected for histopathological evaluation. Flap success was compared between groups using chi-squared analysis. Eleven of 16 flaps failed (69%) in group I, and 3 of 15 flaps failed (20%) in each of groups II, III, and IV. Statistical significance was reached in comparing group I with the other three groups (p < 0.01). All failures in group I were caused by immediate venous thrombosis. The other failures were secondary to arterial thrombosis. Histopathological analysis failed to demonstrate any differences between the groups. According to these results, arterial repair followed by clamp release prior to the completion of the venous repair results in a low success rate, probably secondary to venous stasis within the draining vein while the venous anastomosis is being completed. If the arterial repair is performed first, then it is recommended that the arterial clamp be maintained until the venous repair is completed. If the vein is repaired first, then it can be clamped or unclamped with similar results.


Biosynthesis of the light-harvesting chlorophyll a/b protein. Control of messenger RNA activity by light.
1. Antibodies raised against the 26000-Mr polypeptides of the light-harvesting chlorophyll a/b proteins of pea leaves specifically immunoprecipitated two 32000-Mr polypeptides synthesized when pea leaf poly(A)-containing RNA was translated in vitro. On the basis of immunochemical relatedness and by comparison of their partial tryptic digestion products, the 32000-Mr products formed in vitro are identified as precursors to the authentic polypeptides of the light-harvesting chlorophyll a/b complex. 2. The specificity of the immunoprecipitation permitted the development of an assay for the cellular levels of translationally active light-harvesting protein mRNA in plants exposed to different light regimes. Low levels of the mRNAs were detectable in dark-grown plants. Exposure to continuous illumination caused these levels to increase by at least ten-fold and led to the appearance of large quantities of the light-harvesting chlorophyll a/b complex. In plants exposed to intermittent illumination (2 min of white light every 2 h for 2 days), the light-harvesting complex did not accumulate, although levels of mRNA specifying the polypeptides of the complex were high (50% of those in continuously illuminated plants). 3. Messenger RNAs encoding the light-harvesting proteins were detected in polysomes of intermittently illuminated leaves. These polysomes were active in a wheat-germ 100 000 X g supernatant "run-off" system, to form light-harvesting protein precursors, under conditions when only nascent polypeptide chains initiated in vivo were elongated and terminated. These results demonstrate that the inability of intermittently illuminated leaves to accumulate the light-harvesting proteins is not due to a selective inhibition of the translation of the corresponding mRNAs. 4. Intermittently illuminated leaves were labelled with [35S]methionine in darkness, and incorporation of radioisotope into the light-harvesting proteins and their precursors was assayed immunologically. No pool of untransported or unprocessed 32000-Mr precursor polypeptides could be detected in the soluble fraction (cytoplasm and stroma). However, low levels of the mature 26000-Mr polypeptides were detected in the membrane fraction. It is concluded that the newly synthesized light-harvesting chlorophyll a/b protein fail to accumulate in intermittently illuminated leaves because they undergo rapid turnover. The site of light-harvesting protein breakdown is probably the thylakoid membrane, and the cause of breakdown is probably the absence of chlorophyll a and chlorophyll b molecules that are required for eventual stabilization of the proteins within the photosynthetic membrane.


Pupal emergence pattern in cactophilic Drosophila and the effect of host plants.
Drosophila buzzatii and D. koepferae are sibling cactophilic species. The former breeds primarily on prickly pears (genus Opuntia) whereas the latter breeds on columnar cacti of the genera Cereus and Trichocereus, although with certain degree of niche overlapping. We examined the interspecific differences in diurnal temporal patterns of adult emergence from puparia and evaluated whether this behavior is affected by rearing in the different cactus hosts available in nature. We detected important host-dependent genetic variation for this trait differentially affecting the emergence schedule of these species. Diurnal pattern of emergence time was directly correlated with developmental time and negatively correlated with adult wing size, suggesting that early emergences are at least indirectly correlated with increased fitness. We discussed our results in terms of their putative effects on fitness and the genetic-metabolic pathways that would be presumably affected by host's nutritional-chemical differences.


Small bowel adenocarcinoma: a rare but aggressive disease.
Unlike the colon and rectum, the small intestine is associated with a very low rate of tumor occurrence. Adenocarcinomas represent the most frequent of these rare digestive tumors and are often fatal as a result of tardy diagnosis. Regardless of the stage, surgery usually remains the cornerstone of small bowel adenocarcinoma therapy. Because of the rarity of the disease, very few significant clinical trials have identified any efficient nonsurgical treatment; however, recent data indicate these tumors might be sensitive to chemotherapy alone or in association with radiation therapy. Conversely, a great deal of progress has been achieved in diagnosis of the tumor, whether by adaptation of existing techniques or development of new ones. We reviewed the clinical aspects of this rare but aggressive disease, focusing on new diagnostic procedures as well as on recent advances in their therapeutic management.


[Assessment of custodial suicide risk--jail and prison suicides in Austria 1975-1996].
Although incarceration is a high-risk situation for suicide all over the world, hardly any results have been published concerning the situation of custodial suicide in German-speaking countries. We investigated the case notes of all suicides occuring in Austrian prisons between 1975 and 1996 (n= 207). Beside an evaluation of gender and preferred methods of suicide the suicide risk of different circumstances of custody was studied. Suicide rates of distinguishable, important subgroups of prisoners were calculated using the official statistical data of the Ministry of Justice. The suicide rate for people on remand and offenders classified as mentally ill was 231/100,000 vs. 191/100,000, that was about eight times higher than the suicide rate in Austria's general population. The suicide rate for sentenced offenders was 80/100,000, about three times as high as the suicide rate in Austria's general population (1980-1990: 26.4/100,000). The suicide risk increased with the length of the announced sentence. The suicide rate in custody was highest for prisoners on remand and mentally ill offenders. Female offenders had a high suicide risk, too. The common assumption that the suicide risk in jails and prisons is highest shortly after admission should be confirmed based on better methodology or be reconsidered.


Origins of Cardiovascular Surgery at the Mayo Clinic.
Sixty years ago, at the Mayo Clinic in Rochester, Minnesota, an ambitious group of pioneers, led by Dr John W. Kirklin and supported by a multidisciplinary team of physicians and technicians embarked on a planned series of surgical cases using a heart-lung machine to allow direct visualization of the inside of the opened human heart to repair otherwise fatal congenital intracardiac defects. Their success sparked the beginning of a new era of open-heart surgery. In this historical article, we discuss the contributions of a few key figures of this revolution and also share the story of the first successful cardiac surgery operation using cardiopulmonary bypass performed at Mayo Clinic.


The role of histamine in the acute inflammatory responses to intradermal platelet activating factor.
1. The role of histamine in PAF-induced acute inflammatory responses (flare and weal) in the skin has been evaluated in a series of three separate studies. 2. Terfenadine, a potent H1-selective histamine antagonist virtually abolished the flare response and significantly inhibited the weal response. 3. Histamine depletion in the skin using compound 48/80 resulted in similar effects on the flare and weal response. Two consecutive daily injections of compound 48/80 were found to deplete comprehensively skin sites of histamine and the ability of skin to respond to PAF was completely restored within 2 weeks of compound 48/80 treatment. 4. Intradermally injected PAF was associated with acute rises in plasma histamine in blood drawn from a draining vein with peak concentrations occurring within 5 min of injection. 5. No difference in PAF-induced flare and weal response was found between atopic and non-atopic subjects and this was reflected in the peak plasma histamine results. A significantly higher baseline plasma histamine was found in the atopic group, however, when compared with the non atopic group. 6. It is concluded that histamine has an important role in the acute inflammatory responses to intradermally injected PAF, although there does appear to be a significant direct vascular component in the PAF-induced weal response.