Some aspects of antioxidant status in blood from alcoholics.
The effect of ethanol consumption on serum concentration of alpha-tocopherol, erythrocyte activities of superoxide dismutase, glutathione peroxidase, and catalase were studied in 34 male alcoholics and 35 age-matched controls. Serum concentration of alpha-tocopherol was 30% lower in the alcoholics as compared to the controls (p less than 0.001). No significant difference was found in erythrocyte activities of Cu-Zn-containing superoxide dismutase, glutathione peroxidase, or catalase between the groups. Of the 12 alcoholics with subnormal serum alpha-tocopherol, 50% had concomitant neurological clinical scores and cerebellar atrophy, and their neurological scores were significantly higher (82%) than for alcoholics with normal alpha-tocopherol levels (p less than 0.03). However, no significant correlation was observed between levels of alpha-tocopherol and neurological clinical scores or cerebellar atrophy. When entering the study, alcoholics and controls were each randomized into two separate groups, receiving vitamin E supplementation (100 mg/day) or placebo capsules for 10 days, respectively. In the four subgroups, alpha-tocopherol levels increased only in alcoholics receiving vitamin E supplementation (23%) (p less than 0.001). The reduced serum levels of alpha-tocopherol in alcoholics may be normalized by vitamin E supplementation.


Postnatal Growth in a Cohort of Sardinian Intrauterine Growth-Restricted Infants.
Recent studies have shown that infants with intrauterine growth restriction (IUGR) undergo catch-up growth during infancy. The aim of our study was to evaluate the postnatal growth in a cohort of IUGR infants born in a tertiary-level Obstetric University Hospital of Northern Sardinia. An observational retrospective study was conducted on 12 IUGR (group A) and 12 control infants (group B) by measuring the anthropometric parameters of weight (W), length (L) and head circumference (HC) from birth to the 3rd postnatal year. At birth, significant differences were found between group A and group B with regard to all the auxological parameters (W, mean 1846.6 versus 3170.8 g, p < 0.0001; HC, 30.1 versus 34.4 cm, p < 0.0001; L, mean 43.4 versus 49.4 cm, p < 0.0001). During the 1st year, 8 of 12 (70%) IUGR infants exhibited a significant catch-up growth in the 3 anthropometric parameters and a regular growth until the 3rd year of follow-up. The majority but not all infants born with IUGR in our series showed significant postnatal catch-up growth essentially during the first 12 months of life. An improved knowledge of the causes of IUGR will help to develop measures for its prevention and individualized treatment.


Regulatable promoters and gene therapy for Parkinson's disease: is the only thing to fear, fear itself?
Gene therapy for Parkinson's disease has become a clinical reality with three different approaches currently being tested in patients. All three trials employ an adeno-associated virus with a type two serotype (AAV2). To date, no serious adverse events related to the injections of therapeutic vectors have been reported in any patient. This safety profile was predicted based upon, in some cases, exhaustive preclinical testing in both rodent and primate species. Still some argue that regulatable promoters are required so that expression of the transgene can be halted should untoward side effects arise. We argue that given the current empirical data base of AAV2, the lack of regulatable promoters that have been proven to be safe and effective, and the pressing clinical needs of PD patients, the mandatory use of regulatable vectors is not only unnecessary but, in some instances, misguided and potentially dangerous. This commentary will outline the issues related to the use of regulatable promoters for gene therapy for PD and express our opinion as to why mandating the use of such promoters might result in outcomes that are unsafe, unproductive, and counter to the progress of scientifically sound, clinical research.


Improved avidin-biotin immunoperoxidase method for terminal deoxyribonucleotidyl transferase and immunophenotypic characterization of blood cells.
This report describes a simple avidin-biotin immunoperoxidase method for detection of cell surface antigens and terminal deoxyribonucleotidyl transferase (TdT) in blood, bone marrow, and body fluids. It employs enhanced sensitivity avidin-biotin complex (ABC) reagents and includes a step for quenching of endogenous peroxidase activity that does not diminish antigenic reactivity, allowing its application to specimens (such as blood or bone marrow films) that have significant levels of endogenous peroxidase. This quenching step is performed after the secondary (biotinylated) antibody incubation, which also allows for maximum sensitivity. Examples of results obtained with this method are illustrated, and advantages over other immunocytochemical methods are discussed.


A vote for no confidence.
This paper considers the justifications for adhering to a principle of confidentiality within medical practice. These are found to derive chiefly from respect for individual autonomy, the doctor/patient contract, and social utility. It is suggested that these will benefit more certainly if secrecy is rejected and the principle of confidentiality is removed from the area of health care.


Clinical findings after zosteriform spread of herpes simplex virus to the eye of the mouse.
When herpes simplex virus (HSV) is inoculated onto the snout of the inbred strain NIH mouse, clinical disease of the eye ensues only after a delay, due to spread of virus to the eye occurring via neural pathways. This report is concerned with the detailed description of eye disease. Physical signs observed include mydriasis, iritis and keratitis. The incidence of combinations of physical signs has been analysed by the computer and presented as pie-charts to show the complexity and evolution of the eye disease.


Two-dimensional Raman and infrared vibrational spectroscopy for a harmonic oscillator system nonlinearly coupled with a colored noise bath.
Multidimensional vibrational response functions of a harmonic oscillator are reconsidered by assuming nonlinear system-bath couplings. In addition to a standard linear-linear (LL) system-bath interaction, we consider a square-linear (SL) interaction. The LL interaction causes the vibrational energy relaxation, while the SL interaction is mainly responsible for the vibrational phase relaxation. The dynamics of the relevant system are investigated by the numerical integration of the Gaussian-Markovian Fokker-Planck equation under the condition of strong couplings with a colored noise bath, where the conventional perturbative approach cannot be applied. The response functions for the fifth-order nonresonant Raman and the third-order infrared (or equivalently the second-order infrared and the seventh-order nonresonant Raman) spectra are calculated under the various combinations of the LL and the SL coupling strengths. Calculated two-dimensional response functions demonstrate that those spectroscopic techniques are very sensitive to the mechanism of the system-bath couplings and the correlation time of the bath fluctuation. We discuss the primary optical transition pathways involved to elucidate the corresponding spectroscopic features and to relate them to the microscopic sources of the vibrational nonlinearity induced by the system-bath interactions. Optical pathways for the fifth-order Raman spectroscopies from an "anisotropic" medium were newly found in this study, which were not predicted by the weak system-bath coupling theory or the standard Brownian harmonic oscillator model.


Structure of Ptr ToxA: an RGD-containing host-selective toxin from Pyrenophora tritici-repentis.
Tan spot of wheat (Triticum aestivum), caused by the fungus Pyrenophora tritici-repentis, has significant agricultural and economic impact. Ptr ToxA (ToxA), the first discovered proteinaceous host-selective toxin, is produced by certain P. tritici-repentis races and is necessary and sufficient to cause cell death in sensitive wheat cultivars. We present here the high-resolution crystal structure of ToxA in two different crystal forms, providing four independent views of the protein. ToxA adopts a single-domain, beta-sandwich fold of novel topology. Mapping of the existing mutation data onto the structure supports the hypothesized importance of an Arg-Gly-Asp (RGD) and surrounding sequence. Its occurrence in a single, solvent-exposed loop in the protein suggests that it is directly involved in recognition events required for ToxA action. Furthermore, the ToxA structure reveals a surprising similarity with the classic mammalian RGD-containing domain, the fibronectin type III (FnIII) domain: the two topologies are related by circular permutation. The similar topologies and the positional conservation of the RGD-containing loop raises the possibility that ToxA is distantly related to mammalian FnIII proteins and that to gain entry it binds to an integrin-like receptor in the plant host.


Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation.
The rate of RNA polymerase II (Pol II) elongation can influence splice site selection in nascent transcripts, yet the extent and physiological relevance of this kinetic coupling between transcription and alternative splicing (AS) is not well understood. We performed experiments to perturb Pol II elongation and then globally compared AS patterns with genome-wide Pol II occupancy. RNA binding and RNA processing functions were significantly enriched among the genes with Pol II elongation inhibition-dependent changes in AS. Under conditions that interfere with Pol II elongation, including cell stress, increased Pol II occupancy was detected in the intronic regions flanking the alternative exons in these genes, and these exons generally became more included. A disproportionately high fraction of these exons introduced premature termination codons that elicited nonsense-mediated mRNA decay (NMD), thereby further reducing transcript levels. Our results provide evidence that kinetic coupling between transcription, AS, and NMD affords a rapid mechanism by which cells can respond to changes in growth conditions, including cell stress, to coordinate the levels of RNA processing factors with mRNA levels.


[A perception of the development trend of radiological T staging in gastric cancer through UICC/AJCC 8th edition].
More and more emphases were put on pre-therapy staging following the promotion of multidisciplinary team(MDT) collaboration and individualized medicine in gastric cancer. However, the accuracy of traditional radiology staging system which applies mechanically pathological staging is not satisfactory during clinical practice, therefore, the objectivity of treatment decisions is affected. Under such conditions, the newly introduced staging system from Union for International Cancer Control/American Joint Committee on Cancer(UICC/AJCC)(8th edition) divided out an independent cTNM system for the first time, and summarized the application range, operation specification and staging criteria. Although there are still no unified CT signs for staging, the 8th edition staging system has pointed out the directions for future clinical studies and provides new opportunities for radiology. The recent studies published on issue of cT staging are summarized in this article, including the discrimination of T1 cancer on the basis of peptic ulcers, the cross-sectional location of serosal exposure in bare areas, new rule for cancer at esophagogastric junction and the effect of cT4b change on iconography evaluation. The future prospect of radiomics in T staging of gastric cancer is also discussed.


Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing.
Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process. Having the ability to monitor these markers in real-time using in-line sensors would offer significant advantages, allowing faster decision-making and a finer level of process control. In this study, we use Raman spectroscopy as an in-line optical sensor for bioprocess monitoring of an autologous T-cell immunotherapy model produced in a stirred tank bioreactor system. Using reference datasets generated on a standard bioanalyzer, we develop chemometric models from the Raman spectra for glucose, glutamine, lactate, and ammonia. These chemometric models can accurately monitor donor-specific increases in nutrient consumption and metabolite production as the primary T-cell transition from a recovery phase and begin proliferating. Using a univariate modeling approach, we then show how changes in peak intensity within the Raman spectra can be correlated with cell concentration and viability. These models, which act as surrogate markers, can be used to monitor cell behavior including cell proliferation rates, proliferative capacity, and transition of the cells to a quiescent phenotype. Finally, using the univariate models, we also demonstrate how Raman spectroscopy can be applied for real-time monitoring. The ability to measure these key parameters using an in-line Raman optical sensor makes it possible to have immediate feedback on process performance. This could help significantly improve cell therapy bioprocessing by allowing proactive decision-making based on real-time process data. Going forward, these types of in-line sensors also open up opportunities to improve bioprocesses further through concepts such as adaptive manufacturing.


Overexpression of herbaceous peony HSP70 confers high temperature tolerance.
Heat shock proteins (HSPs) are found extensively in Eukaryotes and are involved in stress tolerance. However, their functions in herbaceous peony (Paeonia lactiflora Pall.) under high temperature stress are poorly characterized. In this study, the genomic sequence of P. lactiflora HSP70, designated PlHSP70, was isolated. Its full-length was 3635 bp, and it contained a large 1440-bp intron. The encoded protein with a molecular weight of 71 kDa was localized in the cytoplasm of the cell. PlHSP70 transcription was detected in P. lactiflora and increased with the treatment of high temperature stress. The constitutive overexpression of PlHSP70 in Arabidopsis thaliana obviously conferred tolerance to high temperature stress by affecting different physiological and biochemical indices. Transgenic A. thaliana plants exhibited higher chlorophyll fluorescence values than the wild-type (WT) when exposed to high temperature stress. The accumulation of hydrogen peroxide (H2O2), superoxide anion free radical (O2·-) and relative electric conductivity (REC) were significantly lower in the transgenic A. thaliana plants compared to the WT. In addition, more intact cell membranes, chloroplasts and starch grains, and fewer plastoglobuli were found in the PlHSP70-overexpressing transgenic lines than in the WT. All of these results indicated that PlHSP70 possessed the ability to improve the tolerance to high temperature in transgenic A. thaliana, which could provide a theoretical basis to improve high temperature tolerance of P. lactiflora by future genetic manipulation.


Nasal cytology in the diagnosis and treatment of sinusitis in atopic and nonatopic children.
To investigate the value of nasal cytology in the diagnosis of sinusitis and follow-up of atopic and nonatopic children before and after treatment and to compare the nasal cytologic findings with the radiologic findings. Open randomized investigation. Ministry of Health, Ankara Diskapi Children's Hospital. Fifty-five children with bronchial asthma and/or allergic rhinitis followed by the Allergy Department of the Ministry of Health, Ankara Diskapi Children's Education and Research Hospital and 35 control children were evaluated for the following parameters: symptoms and signs of sinusitis, total serum immunoglobulin E level and eosinophil count, skinprick tests to common allergens, paranasal sinus radiographs, and nasal cytology (by the Rhinoprobe [Synbiotics Inc. London] method and wax paper blow). Nasal cytology, radiologic findings, and treatment. There were no significant correlations between radiologic and cytologic findings in any of the groups (p > .05). In both atopic and nonatopic chronic sinusitis patients, the Rhinoprobe method had results similar to the radiologic findings, and there was a significant relationship (p < .05). Nasal cytology is still a diagnostic tool in the follow-up and evaluation of chronic sinusitis in atopic children but should not be considered an adequate alternative to sinus radiography.


[Laparoscopic versus laparotomic adrenalectomy: preliminary experiences].
The authors report their experience about laparoscopic surgery in the treatment of adrenal tumours. Three laparoscopic right adrenalectomies were performed. From a comparison with five open adrenalectomies, microinvasive surgery is more advantageous than traditional management: recovery is earlier, incisions are smaller, post-operative discomfort is less, physiologic functions recover in a short time, return to full professional activity in one week.


Solution 1H NMR characterization of the axial bonding of the two His in oxidized human cytoglobin.
Solution 1H NMR spectroscopy has been used to determine the relative strengths (covalency) of the two axial His-Fe bonds in paramagnetic, S = 1/2, human met-cytoglobin. The sequence specific assignments of crucial portions of the proximal and distal helices, together with the magnitude of hyperfine shifts and paramagnetic relaxation, establish that His81 and His113, at the canonical positions E7 and F8 in the myoglobin fold, respectively, are ligated to the iron. The characterized complex (approximately 90%) in solution has protohemin oriented as in crystals, with the remaining approximately 10% exhibiting the hemin orientation rotated 180 degrees about the alpha-, gamma-meso axis. No evidence could be obtained for any five-coordinate complex (<1%) in equilibrium with the six-coordinate complexes. Extensive sequence-specific assignments on other dipolar shifted helical fragments and loops, together with available alternate crystal coordinates for the complex, allowed the robust determination of the orientation and anisotropies of the paramagnetic susceptibility tensor. The tilt of the major axis is controlled by the His-Fe-His vector, and the rhombic axes are controlled by the mean of the imidazole orientations for the two His. The anisotropy of the paramagnetic susceptibility tensor allowed the quantitative factoring of the hyperfine shifts for the two axial His to reveal an indistinguishable pattern and magnitudes of the contact shifts or pi spin densities, and hence, indistinguishable Fe-imidazole covalency for both Fe-His bonds.


Striatal Cholinergic Dysregulation after Neonatal Decrease in X-Linked Dystonia Parkinsonism-Related TAF1 Isoforms.
X-linked dystonia parkinsonism is a generalized, progressive dystonia followed by parkinsonism with onset in adulthood and accompanied by striatal neurodegeneration. Causative mutations are located in a noncoding region of the TATA-box binding protein-associated factor 1 (TAF1) gene and result in aberrant splicing. There are 2 major TAF1 isoforms that may be decreased in symptomatic patients, including the ubiquitously expressed canonical cTAF1 and the neuronal-specific nTAF1. The objective of this study was to determine the behavioral and transcriptomic effects of decreased cTAF1 and/or nTAF1 in vivo. We generated adeno-associated viral (AAV) vectors encoding microRNAs targeting Taf1 in a splice-isoform selective manner. We performed intracerebroventricular viral injections in newborn mice and rats and intrastriatal infusions in 3-week-old rats. The effects of Taf1 knockdown were assayed at 4 months of age with evaluation of motor function, histology, and RNA sequencing of the striatum, followed by its validation. We report motor deficits in all cohorts, more pronounced in animals injected at P0, in which we also identified transcriptomic alterations in multiple neuronal pathways, including the cholinergic synapse. In both species, we show a reduced number of striatal cholinergic interneurons and their marker mRNAs after Taf1 knockdown in the newborn. This study provides novel information regarding the requirement for TAF1 in the postnatal maintenance of striatal cholinergic neurons, the dysfunction of which is involved in other inherited forms of dystonia. © 2021 International Parkinson and Movement Disorder Society.


The lesser occipital nerve visualized by high-resolution sonography--normal and initial suspect findings.
The lesser occipital nerve (LON) supplies the lateral part of the occiput and is-together with the greater occipital nerve (GON)-involved in headache pathogenesis. While the GON was described in high-resolution ultrasound (HRUS), the same does not apply to the LON. We aimed at characterizing the LON in HRUS, and present cases of suspect findings in the course of the LON identified by HRUS. The LON was examined bilaterally in eight anatomical specimens with HRUS (n = 16). HRUS-guided ink marking and consecutive dissection was performed. Further, measurements of the LON diameter were performed in 10 healthy volunteers (n = 20), and patient charts were reviewed to identify patients who were considered to have possible pathology of the LON. The LON was identified correctly in all cadavers on both sides and all volunteers except for one side (n = 19). The average diameter was 1.08 ± 0.30 mm. Four patients with pain within the LON territory and presumed peripheral origin of headache (defined as resolution of headache after diagnostic HRUS-guided selective blockade) were identified, and three of these showed interference of the LON with lymph nodes or an accessory muscle belly. We confirm the possibility of visualization of the LON using HRUS. HRUS may be a helpful adjunct tool in the assessment of patients with atypical headache.


Desulfothermus okinawensis sp. nov., a thermophilic and heterotrophic sulfate-reducing bacterium isolated from a deep-sea hydrothermal field.
A novel thermophilic and heterotrophic sulfate-reducing bacterium, strain TFISO9(T), was isolated from a deep-sea hydrothermal field at the Yonaguni Knoll IV in the Southern Okinawa Trough. The cells were motile rods 2.5-5.0 microm in length and 0.6-0.9 microm in width. Strain TFISO9(T) was an obligate heterotroph and reduced sulfate. It grew between 35 and 60 degrees C (optimum 50 degrees C), at pH 5.4-7.9 (optimum pH 5.9-6.4) and with 1.5-4.5 % NaCl (optimum 2.5 %). The fatty acid composition was C(16 : 0) (61.5 %) and 12Me(16 : 0) (38.5 %). The DNA G+C content was 34.9 mol%. The 16S rRNA gene sequence analysis indicated that strain TFISO9(T) belonged to the genus Desulfothermus. Based on physiological and phylogenetic characteristics, strain TFISO9(T) represents a novel species for which the name Desulfothermus okinawensis sp. nov. is proposed. The type strain is TFISO9(T) (=JCM 13304(T)=DSM 17375(T)).


Bimodal multispectral imaging system with cloud-based machine learning algorithm for real-time screening and detection of oral potentially malignant lesions and biopsy guidance.
Screening and early detection of oral potentially malignant lesions (OPMLs) are of great significance in reducing the mortality rates associated with head and neck malignancies. Intra-oral multispectral optical imaging of tissues in conjunction with cloud-based machine learning (CBML) can be used to detect oral precancers at the point-of-care (POC) and guide the clinician to the most malignant site for biopsy. Develop a bimodal multispectral imaging system (BMIS) combining tissue autofluorescence and diffuse reflectance (DR) for mapping changes in oxygenated hemoglobin (HbO2) absorption in the oral mucosa, quantifying tissue abnormalities, and guiding biopsies. The hand-held widefield BMIS consisting of LEDs emitting at 405, 545, 575, and 610 nm, 5MPx monochrome camera, and proprietary Windows-based software was developed for image capture, processing, and analytics. The DR image ratio (R610/R545) was compared with pathologic classification to develop a CBML algorithm for real-time assessment of tissue status at the POC. Sensitivity of 97.5% and specificity of 92.5% were achieved for discrimination of OPML from patient normal in 40 sites, whereas 82% sensitivity and 96.6% specificity were obtained for discrimination of abnormal (OPML + SCC) in 89 sites. Site-specific algorithms derived for buccal mucosa (27 sites) showed improved sensitivity and specificity of 96.3% for discrimination of OPML from normal. Assessment of oral cancer risk is possible by mapping of HbO2 absorption in tissues, and the BMIS system developed appears to be suitable for biopsy guidance and early detection of oral cancers.


Induction of autophagy and interleukin 6 secretion in bystander cells: metabolic cooperation for radiation-induced rescue effect?
We hypothesized that radiation-induced rescue effect (RIRE) shared similar mechanisms with 'metabolic cooperation', in which nutrient-deprived cancer cells prompted normal cells to provide nutrients. Our data demonstrated that X-ray irradiation induced autophagy in HeLa cells, which could last at least 18 h, and proved that the irradiated cells (IRCs) resorted to breaking down their own intracellular components to supply the molecules required for cell-repair enhancement (e.g. to activate the NF-κB pathway) in the absence of support from bystander unirradiated cells (UICs). Furthermore, autophagy accumulation in IRCs was significantly reduced when they were partnered with UICs, and more so with UICs with pre-induced autophagy before partnering (through starvation using Earle's Balanced Salt Solution), which showed that the autophagy induced in UICs supported the IRCs. Our results also showed that interleukin 6 (IL-6) was secreted by bystander UICs, particularly the UICs with pre-induced autophagy, when they were cultured in the medium having previously conditioned irradiated HeLa cells. It was established that autophagy could activate the signal transducer and activator of transcription 3 (STAT3) that was required for the IL-6 production in the autophagy process. Taken together, the metabolic cooperation of RIRE was likely initiated by the bystander factors released from IRCs, which induced autophagy and activated STAT3 to produce IL-6 in bystander UICs, and was finally manifested in the activation of the NF-κB pathway in IRCs by the IL-6 secreted by the UICs.


Nonuniversality of elastic exponents in random bond-bending networks.
We numerically investigate the rigidity percolation transition in two-dimensional flexible, random rod networks with freely rotating cross links. Near the transition, networks are dominated by bending modes and the elastic modulii vanish with an exponent f=3.0+/-0.2, in contrast with central force percolation which shares the same geometric exponents. This indicates that universality for geometric quantities does not imply universality for elastic ones. The implications of this result for actin-fiber networks is discussed.


Dialect is diagnostic.
Folk medical language, as spoken in western Alabama, contains medical dialect terms that have an ancient lineage, with structure and meaning very similar to those of their earliest roots. The dialect has precise medical meanings and is used with astonishing accuracy by patients. Terms and phrases are often diagnostic as well as colorfully descriptive. An appreciation of medical dialect makes practice more fun, history taking and diagnosis easier, and lessens misunderstandings with patients. It sharpens the physician's senses to every level of what patients feel and say, verbal and otherwise. An appreciation of dialect heightens respect for patients and gives the physician a sense of continuity with cultures and ages past. Understanding and respect for medical dialect can be a powerful aid to patient care.


Bone-anchored maxillary protraction in patients with unilateral complete cleft lip and palate and Class III malocclusion.
This prospective controlled study evaluated the effect of bone-anchored maxillary protraction therapy in cleft children with Class III malocclusion using CBCT-derived 3D surface models. Eighteen cleft patients between 10 and 12 years old were included. Intermaxillary elastics were worn after the placement of four zygoma bone plates for 18 months. Uniquely, three age-matched untreated groups including both cleft subjects and non-cleft subjects with Class III malocclusion served as controls. Profile photos and CBCT scans for each patient were taken before (T0) and 18 months after the protraction (T1). 3D measurements were made on CBCT surface models from the treatment group using tomographic color mapping method. Cephalometric measurements were made on lateral cephalogram reconstructed from the CBCT scans and were compared with those obtained from the control groups. Two thirds of the treatment subjects showed improved lip projection towards more convex facial profile. The most significant skeletal changes on 3D surface models were observed at the zygomatic regions (mean 1.5-mm forward, downward, and outward displacement) and at the maxillary complex (mean 1.5-mm forward displacement). Compared with the control groups, the treatment subjects showed significant increase in the SNA and ANB angles, increased Wits appraisal, a more forward movement of point A and overjet improvement (p < 0.05). BAMP in cleft patients gives a significant forward displacement of the zygomaxillairy complex in favor of the Class III treatment. This treatment method shows clearly favorable outcome in cleft patients after 1.5 years of BAMP.


Diaphragmatic dysfunction in sepsis due to severe acute pancreatitis complicated by intra-abdominal hypertension.
Objective This study aimed to examine the mechanism of diaphragmatic dysfunction in sepsis due to severe acute pancreatitis (SAP) with intra-abdominal hypertension (IAH) in a rat model. Methods The rats were assigned at random to four groups: (1) control (n = 5), (2) SAP (n = 5), (3) SAP+IAH (n = 5), and (4) SAP+IAH+SS-31 (n = 5). Length and force output of the diaphragm were analysed in vivo. Histopathological examinations were performed by haematoxylin-eosin. Oxidative stress levels related to protease in diaphragmatic mitochondria were detected with a colorimetric technique. Results In the septic rat model due to SAP complicated by IAH, myofibres were increased. Muscle contractile function was significantly lower in the SAP+IAH group compared with the SAP and control groups. Glutathione peroxidase and superoxide dismutase levels were significantly lower and malondialdehyde levels were higher in the SAP and SAP+IAH groups compared with the control group. Notably, SS-31 could reverse atrophy of myofibres in SAP+IAH rats, as well as contractile dysfunction and mitochondrial dysfunction in the diaphragm. Conclusions Diaphragmatic structure and biomechanics are altered in septic rats due to SAP and IAH. This finding is mainly due to an increase in release of mitochondrial reactive oxygen species.


Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is significantly affected by environmental regulators impacting on genetic predisposition. Lifestyle changes can significantly modulate the phenotype of this disease. Diet, exercise, smoking, stress, and other factors adversely affect reproductive outcomes in PCOS. These influences can be modulated by structure change in an individual or group. Lifestyle choices should be discussed in this group of patients. The role of insulin sensitizers, including metformin, has still to be determined in this condition.


Combination of lentiviral and genome editing technologies for the treatment of sickle cell disease.
Sickle cell disease (SCD) is caused by a mutation in the β-globin gene leading to polymerization of the sickle hemoglobin (HbS) and deformation of red blood cells. Autologous transplantation of hematopoietic stem/progenitor cells (HSPCs) genetically modified using lentiviral vectors (LVs) to express an anti-sickling β-globin leads to some clinical benefit in SCD patients, but it requires high-level transgene expression (i.e., high vector copy number [VCN]) to counteract HbS polymerization. Here, we developed therapeutic approaches combining LV-based gene addition and CRISPR-Cas9 strategies aimed to either knock down the sickle β-globin and increase the incorporation of an anti-sickling globin (AS3) in hemoglobin tetramers, or to induce the expression of anti-sickling fetal γ-globins. HSPCs from SCD patients were transduced with LVs expressing AS3 and a guide RNA either targeting the endogenous β-globin gene or regions involved in fetal hemoglobin silencing. Transfection of transduced cells with Cas9 protein resulted in high editing efficiency, elevated levels of anti-sickling hemoglobins, and rescue of the SCD phenotype at a significantly lower VCN compared to the conventional LV-based approach. This versatile platform can improve the efficacy of current gene addition approaches by combining different therapeutic strategies, thus reducing the vector amount required to achieve a therapeutic VCN and the associated genotoxicity risk.


The relationship between theory of mind and the executive functions: Evidence from patients with frontal lobe damage.
"Theory of mind" (ToM) refers to the ability to predict others' thoughts, intentions, beliefs, and feelings. Evidence from neuropsychology and functional imaging indicates that ToM is a domain-specific or modular architecture; however, research in development psychology has suggested that ToM is the full development of the executive functions in individuals. Therefore, the relationship between ToM and the executive functions needs to be clarified. Since the frontal lobe plays a critical role in the abilities of ToM and the executive functions, patients with frontal lobe damage were recruited for the present study. Assessments of ToM and the executive functions were performed on 23 patients with frontal lobe damage and 20 healthy controls. When controlling for the executive functions, significant differences between the patient and normal groups were found in the affective component of ToM, but not in the cognitive component. The present study suggests that in various social situations, executing ToM abilities requires logical reasoning processes provided by the executive functions. However, the reasoning processes of affective ToM are independent of executive functions.


Risk-based objectives for the allocation of chemical, biological, and radiological air emissions sensors.
This article addresses the problem of allocating devices for localized hazard protection across a region. Each identical device provides only local protection, and the devices serve localities that are exposed to nonidentical intensities of hazard. A method for seeking the optimal allocation Policy Decisions is described, highlighting the potentially competing objectives of maximizing local risk reductions and coverage risk reductions. The metric for local risk reductions is the sum of the local economic risks avoided. The metric for coverage risk reductions is adapted from the p-median problem and equal to the sum of squares of the distances from all unserved localities to their closest associated served locality. Three graphical techniques for interpreting the Policy Decisions are presented. The three linked graphical techniques are applied serially. The first technique identifies Policy Decisions that are nearly Pareto optimal. The second identifies locations where sensor placements are most justified, based on a risk-cost-benefit analysis under uncertainty. The third displays the decision space for any particular policy decision. The method is illustrated in an application to chemical, biological, and/or radiological weapon sensor placement, but has implications for disaster preparedness, transportation safety, and other arenas of public safety.


Thiol-ene "click" reaction triggered by neutral ionic liquid: the "ambiphilic" character of [hmim]Br in the regioselective nucleophilic hydrothiolation.
Thiol-ene "click" chemistry has emerged as a powerful strategy to construct carbon-heteroatom (C-S) bonds, which generally results in the formation of two regioisomers. To this end, the neutral ionic liquid [hmim]Br has been explored as a solvent cum catalyst for the synthesis of linear thioethers from activated and inactivated styrene derivatives or secondary benzyl alcohols and thiols without the requirement of using a metal complex, base, or free radical initiator. Furthermore, detailed mechanistic investigations using (1)H NMR spectroscopy and quadrupole time-of-flight electrospray ionization mass spectrometry (Q-TOF ESI-MS) revealed that the "ambiphilic" character of the ionic liquid promotes the nucleophilic addition of thiol to styrene through an anti-Markovnikov pathway. The catalyst recyclability and the extension of the methodology for thiol-yne click chemistry are additional benefits. A competitive study among thiophenol, styrene, and phenyl acetylene revealed that the rate of reaction is in the order of thiol-yne>thiol-ene>dimerization of thiol in [hmim]Br.


Effects of creep value and occlusal force on marginal adaptation of amalgam filling.
Creep of amalgam is thought to be a factor determining poor marginal adaptation. Clarification of the relationship between creep of amalgam in the cavity and creep value (American Dental Association specification no. 1; ADA #1) is essential to an understanding of the mechanism of marginal fracture and service life. However, only elastic stress analyses of amalgam in a cavity have been reported in the dental field. Therefore, the creep of amalgam in a class I cavity was simulated by an axisymmetric elastic creep finite-element method. The stress and time dependencies of the creep rate of amalgam were incorporated into this calculation. Creep values of 1.0 and 3.0% (ADA #1) were selected as amalgam properties. When the occlusal force on the amalgam filling was assumed in the vertical direction along the axis of the tooth, the rate of extrusion and rate of opening of the gap at the cavity margin were revealed by the simulation. The computed results show that the gap and extrusion were developed in direct proportion of the creep value and proportionally with the square of the occlusal force. Simulated results are in agreement with clinical findings of the service lives of restorations, i.e., a poor adaptation to the margin can be seen for 4-to-10-year-old amalgam fillings.


A volume-dependent apneic threshold during NREM sleep in the dog.
We determined the causes of central apnea that commonly follow the hyperpnea resulting from brief airway occlusion during non-rapid-eye-movement (NREM) sleep. Ventilation and end-tidal gases were measured before, during, and after 214 trials of 15-20 s of tracheal occlusion in three dogs during NREM sleep. Airway occlusion was accompanied by progressive increases in inspiratory effort and was followed by transient one- to four-breath hyperapneas, with subsequent central apnea [3-15 times eupneic control expiratory duration (TE)] in 62% of occlusion trials. Significant TE prolongation after hyperventilation did not occur until tidal volume (VT) was three times greater than control; i.e., there was a volume-dependent apneic threshold. Transient electroencephalogram arousal at the end of the occlusion often augmented VT, thereby contributing to the subsequent central apnea; however, arousal was not required for the apnea to occur. Significant transient hypocapnia (up to -12 Torr arterial PCO2) commonly occurred after release of airway occlusion but was not closely correlated with the length of central apnea. During vagal blockade, after release of airway occlusion, significant transient hyperventilation occurred but at VT < 40% greater than control, and TE prolongation was markedly reduced. In summary, after release of airway occlusion in NREM sleep, 1) VT greater than three times eupnea was necessary to cause central apnea, 2) transient arousal at the termination of airway occlusion caused longer apneas by augmenting VT, and 3) transient hypocapnia per se made a significant but minor contribution to the postocclusion central apnea.


Detection of herpesviruses and periodontal pathogens in subgingival plaque of patients with chronic periodontitis, generalized aggressive periodontitis, or gingivitis.
Herpesviruses may be related to the etiology of aggressive periodontitis (AgP) and chronic periodontitis (CP) by triggering periodontal destruction or by increasing the risk for bacterial infection. This case-control study evaluated the presence of herpes simplex virus type I (HSV-1), Epstein-Barr virus type I (EBV-1), human cytomegalovirus (HCMV), Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia (previously T. forsythensis) in patients with generalized AgP (AgP group), CP (CP group), or gingivitis (G group) and in healthy individuals (C group). Subgingival plaque samples were collected with paper points from 30 patients in each group. The nested polymerase chain reaction (PCR) method was used to detect HSV-1, EBV-1, and HCMV. Bacteria were identified by 16S rRNA-based PCR. HSV-1, HCMV, and EBV-1 were detected in 86.7%, 46.7%, and 33.3% of the AgP group, respectively; in 40.0%, 50.0%, and 46.7% of the CP group, respectively; in 53.3%, 40.0%, and 20.0% of the G group, respectively; and in 20.0%, 56.7%, and 0.0% of the C group, respectively. A. actinomycetemcomitans was detected significantly more often in the AgP group compared to the other groups (P <0.005). P. gingivalis and T. forsythia were identified more frequently in AgP and CP groups, and AgP, CP, and G groups had higher frequencies of P. intermedia compared to the C group. In Brazilian patients, HSV-1 and EBV-1, rather than HCMV, were more frequently associated with CP and AgP.


The surgical approach in non-border digit complex dislocations of the metacarpophalangeal joint.
Complex dislocations of the metacarpophalangeal (MCP) joint of the hand are uncommon. Most are irreducible by closed means and require open reduction. The structure most frequently blocking reduction is the volar plate, which is often interposed between the metacarpal head and the base of the proximal phalanx by the partially torn deep transverse metacarpal ligaments and MCP collateral ligaments. A review of the literature reveals controversy concerning which surgical approach, dorsal or volar, should be used to reduce these dislocations. We present an unusual case of a closed dorsal complex dislocation of the middle finger MCP joint to advocate the dorsal approach.


The contribution of two isozymes to the pyruvate kinase activity of Vibrio cholerae: One K+-dependent constitutively active and another K+-independent with essential allosteric activation.
In a previous phylogenetic study of the family of pyruvate kinase EC (126.96.36.199), a cluster with Glu117 and another with Lys117 were found (numbered according to the rabbit muscle enzyme). The sequences with Glu117 have been found to be K+-dependent, whereas those with Lys117 were K+-independent. Interestingly, only γ-proteobacteria exhibit sequences in both branches of the tree. In this context, it was explored whether these phylogenetically distinct pyruvate kinases were both expressed and contribute to the pyruvate kinase activity in Vibrio cholerae. The main findings of this work showed that the isozyme with Glu117 is an active K+-dependent enzyme. At the same substrate concentration, its Vmax in the absence of fructose 1,6 bisphosphate was 80% of that with its effector. This result is in accordance with the non-essential activation described by allosteric ligands for most pyruvate kinases. In contrast, the pyruvate kinase with Lys117 was a K+-independent enzyme displaying an allosteric activation by ribose 5-phosphate. At the same substrate concentration, its activity without the effector was 0.5% of the one obtained in the presence of ribose 5-phosphate, indicating that this sugar monophosphate is a strong activator of this enzyme. This absolute allosteric dependence is a novel feature of pyruvate kinase activity. Interestingly, in the K+-independent enzyme, Mn2+ may "mimic" the allosteric effect of Rib 5-P. Despite their different allosteric behavior, both isozymes display a rapid equilibrium random order kinetic mechanism. The intracellular concentrations of fructose 1,6-bisphosphate and ribose 5-phosphate in Vibrio cholerae have been experimentally verified to be sufficient to induce maximal activation of both enzymes. In addition, Western blot analysis indicated that both enzymes were co-expressed. Therefore, it is concluded that VcIPK and VcIIPK contribute to the activity of pyruvate kinase in this γ-proteobacterium.


Class II genes of the human major histocompatibility complex. Organization and evolutionary relationship of the DR beta genes.
The genes of the polymorphic HLA-DR molecules are located within the human major histocompatibility complex. We have studied the HLA-DR genes of an HLA homozygous individual typed to be DR4, Dw4, and DRw53. Fourteen cosmid and phage clones from genomic libraries were isolated and grouped into three clusters comprising a total of 165 kilobases. These clusters contain four DR beta genes. Nucleotide sequence determination showed that two of the genes encode beta chains that carry the DR4 and DRw53 specificities, respectively, while the other two genes are presumably pseudogenes. Comparisons of the nucleotide sequences of all four DR beta genes of the DR4 haplotype show that the genes are extensively similar, approximately 90% in both exons and introns. All four genes are equally similar to each other. These observations are consistent with the notion that the genes arose by duplications that were followed by homogenization through gene conversion. The existence of more than one DR beta gene homologue but only a single DR alpha gene homologue in mouse, rabbit, and cattle suggests that the DR beta gene duplications occurred at or early during mammalian speciation.


Litonit: evaluation of clinical effectiveness.
Clinical data are presented on a new anti-alcoholic drug, litonit. A substantial reduction in the pathological addiction to alcohol takes place under the effect of litonit, and a stable aversive reaction to alcohol develops. The new drug is distinguished by its low toxicity, good tolerance, and its failure to cause disorders of the liver and kidneys even after chronic administration.


Separation-of-function mutants of yeast Ku80 reveal a Yku80p-Sir4p interaction involved in telomeric silencing.
The Saccharomyces cerevisiae Ku heterodimer comprising Yku70p and Yku80p is involved in telomere maintenance and DNA repair by the pathway of non-homologous end joining. It is also a key regulator of transcriptional silencing of genes placed in close proximity to telomeres. Here, we describe the identification of separation-of-function mutants of Yku80p that exhibit defects in silencing but not DNA repair and show that these mutations map to an evolutionarily conserved domain within Yku80p. Furthermore, we reveal that Yku80p interacts with the silent information regulator protein Sir4p and that this interaction is mediated by the N-terminal 200 amino acid residues of Sir4p. Notably, this interaction also requires the region of Yku80p that contains the sites of the silencing defective mutations. Finally, we show that these mutations impair the Yku80p-Sir4p interaction and recruitment of Sir3p to telomeric regions in vivo. Taken together with other data, these findings indicate that the Yku80p-Sir4p interaction plays a vital role in the assembly of telomeric heterochromatin.


Vasopeptidase inhibition improves insulin sensitivity and endothelial function in the JCR:LA-cp rat.
The insulin-resistant, hyperinsulinemic, normoglycemic, and obese JCR:LA-cp rat was used to study the effects of ramipril (an ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidases) on insulin sensitivity and vascular function. Both compounds reduced the surge of plasma insulin in a meal tolerance test by approximately 50%. Ramipril had no effect on acetylcholine-induced relaxation but increased the sensitivity to sodium nitroprus-side at low concentrations. AVE7688 significantly reduced the EC50 for acetylcholine to relax phenylephrine-contracted aortic rings. None of the compounds affected the baseline coronary flow and reactive hyperemia. Coronary flow response to bradykinin in AVE7688- and ramipril-treated rat hearts showed a significantly lower EC50 than in control rats. Maximum flow rate was not different between groups. In summary, both ramipril and AVE7688 had significant hypoinsulinemic and insulin-sensitizing effects. Whereas ramipril had limited vascular effects, AVE7688 had more marked beneficial vascular effects, probably of endothelial origin and possibly related to lowered insulin levels.


[Clinical observation on auricular magnetotherapy for convalescent stroke patients with depression].
To observe the effect of auricular magnetotherapy on depression and quality of life in stroke patients with depression after recovery. Ninety-three stroke patients with depression were randomly divided into a conventional group(a control group), a conventional combined with magnetotherapy group (an observation 1 group), a conventional combined with vaccaria seed group (an observation 2 group), 31 cases in each group. Conventional treatments were applied in the three groups. On the basis of conventional treatments, auricular magnetotherapy was added in the observation 1 group, and in the observation 2 group, vaccaria seed was applied at gan (CO12), xin (CO15), pi (CO13), shen (CO10), shenmen (TF4), pizhixia (AT4), press 3 times a day, replace once every 3 days, alternate ears and treating for 4 weeks. The scores of 17 Hamilton Depression Scales (HAMD-17) and stroke-specific quality of life scales (SS-QOL) were observed before and after treatment in each group. Depression was assessed at follow-up 4 weeks after treatment, and the clinical efficacy of each group was compared. A total of 83 cases completed the test. After treatment and follow-up, the scores of HAMD decreased in the observation 1 group and observation 2 group compared with that before treatment (all P<0.01). The total score of HAMD in the observation 1 group was lower than that in the observation 2 group and control group (all P<0.01). After treatment, the depression, suicide, initial insomnia, middle insomnia, final insomnia, work and interest dimension scores in the observation 1 group were lower than those in the observation 2 group and control group (P<0.05, P<0.01). Compared with that before treatment, the total score of SS-QOL in the observation 1 group increased (P<0.01), and there was no significant difference in total score of SS-QOL before and after treatment in the observation 2 group and control group (both P>0.05). After treatment, the total score of SS-QOL in the observation 1 group and observation 2 group were higher than that in the control group (P<0.01, P<0.05), there was no significant difference between the two groups (P>0.05). The scores of energy, family characters, and emotional dimensions in the observation 1 group were higher than those in the observation 2 group and control group (P<0.05, P<0.01). The score of personality and upper limb function were higher than those in the control group (P<0.05, P<0.01); the score of the family role dimension of the observation 2 group was significantly higher than that in the control group (P<0.01). The total effective rate in the observation 1 group was 72.4% (21/29), which was higher than 44.4% (12/27) in the observation 2 group (P<0.05) and 11.1% (3/27) in the control group (P<0.01). Auricular magnetotherapy can improve the depressive symptoms of convalescent stroke patients with depression and improve their quality of life.


Exploring the relationship between anellovirus load and clinical variables in hospitalized COVID-19 patients: Implications for immune activation and inflammation.
Anelloviruses have been linked with host-immunocompetence and inflammation. Here, we studied the anellovirus load in hospitalized COVID-19 patients. We collected samples of patients recruited in the DAWN-Plasma trial that received convalescent plasma (CP) therapy (four plasma units) combined with standard of care (SOC) or SOC of alone. Plasma samples were collected on day 0 and 6 of hospitalization and we quantified anellovirus load. With multivariate models, clinical variables were associated with changes in anellovirus load. Samples were collected on day 0 and 6 of 150 patients (103 CP + SOC and 47 SOC). Anellovirus load was higher on day 0 compared to day 6 and we found a significant drop in SOC patients. Patients receiving immunosuppressive drug had a lower anellovirus load (coefficient: 1.021, 95% confidence interval [CI] 0.270-1.772, P = 0.008), while patients admitted to the emergency room displayed a higher abundance on day 0 (1.308, 95% CI 0.443-2.173, P = 0.003). Unspecific markers of inflammation and organ damage, D-dimer (0.001, 95% CI <0.001-0.001, P = 0.001) and lactate dehydrogenase (0.002, 95% CI 0.001-0.004, P = 0.044), were positively associated with anellovirus load. Finally, anellovirus load on day 0 (-39.9, 95% CI -75.72 to -4.27, P = 0.029) was negatively associated with SARS-CoV-2 antibody response on day. The results showed associations between clinical variables and anellovirus load in COVID-19 patients. Many variables share properties related to host immunocompetence or inflammation. Therefore, we expect that anellovirus abundance displays the net state of immune activation.


Presumed Furosemide-associated Bilateral Angle-Closure Glaucoma.
To report a case of presumed furosemide-associated bilateral angle-closure glaucoma. Retrospective case report with spectral domain anterior segment optical coherence tomography imaging. A 21-year-old African American woman in her 17th week of pregnancy presented with acute angle-closure glaucoma in both eyes after being started on furosemide in her first trimester for fluid overload. Intraocular pressures were elevated in the low 40s mm Hg bilateral (OU) and anterior chambers were shallow with narrow grade 1 angles on gonioscopy (Schaffer classification). Medical history included type 1 diabetes mellitus, chronic kidney disease, and 2 prior failed pregnancies complicated by fluid overload. She was started on 60 mg of prednisone daily along with topical brimonidine in both eyes twice daily. After 3 days, her intraocular pressures normalized. At 1 week, slit-lamp examination showed deepened anterior chambers and gonioscopy confirmed widened angles. Oral prednisone was titrated down slowly for the remainder of her uneventful pregnancy. On follow-up 1 month after delivery, intraocular pressures and best-corrected visual acuities reached preterm baseline values of 15 mm Hg OU and 20/30 OU. This is the first reported case of furosemide-associated bilateral angle-closure glaucoma. Similar idiosyncratic reactions following exposure to other sulphonamide-containing drugs have been described. We propose discontinuation of the offending agent and treatment with oral prednisone in similar clinical settings.


From rapid smoking to the Internet: five decades of cessation research.
This review summarizes the author's smoking cessation research from the 1960s into the 21st century. Both contextual and personal factors that led the author to undertake cessation research and to move from intensive clinical interventions to brief, population-focused interventions, especially in healthcare settings, are described. Suggestions are offered as to how research can address the problem of inconsistent delivery of effective interventions in healthcare settings.


Centered reduced moments and associate density functions applied to alkaline comet assay.
The single cell gel electrophoresis assay is a sensitive, rapid, and visual technique for deoxyribonucleic acid (DNA) strand-break detection in individual mammalian cells, whose application has significantly increased in the past few years. The cells are embedded in agarose on glass slides followed by lyses of the cell membrane. Thereafter, damaged DNA strands are electrophoresed away from the nucleus towards the anode giving the appearance of a comet tail. Nowadays, charge coupled device cameras are attached at optical microscopes for recording the images of the cells, and digital image processing is applied for obtaining quantitative descriptors. However, the conventional software is usually expensive, inflexible and, in many cases, can only provide low-order descriptors based in image segmentation, determination of centers of mass, and Euclidean distances. Associated density functions and centered reduced moments offer an effective and flexible alternative for quantitative analysis of the comet cells. We will show how the position of the center of mass, the lengths and orientation of the main semiaxes, and the eccentricity of such images can be accurately determined by this method.


The archives of the Canadian Dermatology Association.
This article describes some details of the archival material of the Canadian Dermatology Association (CDA). Covering its 75 years of existence, these archives consist of seven items: (1) 38 volumes of bound archives; (2) tri-annual issues since 1975 of the CDA Journal/Bulletin (a socio-political historical newsletter); (3) members' files containing extensive biographical material; (4) a collection of 150 books and other pamphlets; (5) since 1995, the scientific peer-reviewed official journal of the CDA (Journal of Cutaneous Medicine and Surgery); (6) a sporadic collection of photographs, meeting tape recordings, and protocols of patient presentations at the annual meetings; and (7) a miscellany of historical articles on Canadian dermatologists, dermatology published in older medical Journals, and two books published separately.


Long-term course and outcome in panic disorder: a naturalistic follow-up study.
Fifty-five of 102 consecutively evaluated patients with panic disorder seen in consultation at a specialty anxiety and mood disorders clinic were reinterviewed from 15 to 60 months later after naturalistic treatment in the community. Over the follow-up period, most patients displayed improvement in panic attack frequency and severity, phobic avoidance, depression, and major role functioning, although only five (10%) were asymptomatic on all measures at follow-up. The majority of patients with impaired interpersonal functioning showed no improvement on this measure. Thirty percent of the patients were panic-free at 12 months and 28% at the time of follow-up, with 43% experiencing at least three panic-free months during the follow-up period. Comorbid agoraphobia, major depression, and Axis II disorders were associated with worse outcome on selected measures of symptomatic and functional impairment. However, the strongest predictors of overall improvement were avoidance coping for outcome at 12 months and Axis I comorbidity for outcome at the time of the follow-up evaluation.


The Barriers to Universal Health Coverage in India and the Strategies to Address Them: A Key Informant Study.
India has adopted several policies toward improving access to healthcare and has been an enthusiastic signatory to several global health policies to achieve Universal Health Coverage (UHC). However, despite these policy commitments, there has been limited success in realizing these goals. The COVID-19 pandemic has highlighted the urgent need for health system re-design and amplified the calls for such reforms. We seek to understand the views of a diverse group of policy actors in India to address the following research questions: what are the (i) conceptualizations of UHC, (ii) main barriers to realizing UHC, and (iii) policy strategies to address these barriers. We collected data through in-depth interviews with 38 policy actors from diverse backgrounds and analyzed using the Framework Method to develop themes both inductively and deductively using the Control Knob Framework of health systems. There was congruence in the conceptualization of UHC by policy actors. Quality of care, equity, financial risk protection, and a comprehensive set of services were the most commonly cited features. The lack of a comprehensive systems approach to health policies, inadequate and inefficient health financing mechanisms, and fragmentation between public and private sectors were identified as the main barriers to UHC. Contrasting views about specific strategies, health financing, provider payments, organization of the delivery system, and regulation emerged as the key policy interventions to address these barriers. This is the first systematic examination of a diverse set of policy actors' problem analyses and suggestions to advance UHC goals in India. The study underscores the need to recognize the complex and interlinked nature of health system reforms and initiate a departure from path-dependent vertical interventions to bring about transformative change.


Inactivation efficacy of low-pressure plasma treatment against seed-borne tomato pathogen Clavibacter michiganensis and effect of seed setting position and mesh sheet usage.
Clavibacter michiganensis, a gram-positive actinomycete, is a major seed-borne tomato pathogen. We investigated the inactivation efficacy of low-pressure plasma treatment against C. michiganensis inoculated on tomato seeds by placing them on a mesh sheet above the bottom dielectric glass plate. The 2- and 5-minute plasma treatment reduced C. michiganensis populations on the tomato seeds by 0.8 and 1.8 log cfu/seed, respectively. The reduction rates were similar to those of C. michiganensis on shirona (cruciferous) seeds, which have different shapes and surface structures. In contrast, the inactivation of C. michiganensis cells using plasma was more difficult than that of X. campestris cells. Additionally, it was found that placing seeds on a mesh sheet laid on the dielectric glass plate was remarkably effective in inactivating the pathogens on tomato seeds. Since the tomato seeds were susceptible to damage from plasma treatment, methods to reduce its damage need to be investigated.


A qualitative study on health stigma and discrimination in the first year of the COVID-19 pandemic: Lessons learnt from a public health perspective.
Stigmatisation, misinformation and discrimination have been magnified globally due to the COVID-19 pandemic. The healthcare sector was not spared from this. We conducted a transnational study, using the Health Stigma and Discrimination framework (HSDF) to explore public perception and reactions to the COVID-19 pandemic in a multicultural context. Findings from the Asian arm of the study, sited in Singapore, are reported in this paper. This phenomenological research deployed semi-structured informant interviews using non-probability sampling approaches to recruit members of the public. Interviews were coded independently by two researchers and thematic analysis was used to analyse the responses. Twenty-nine members of the public (23-80 years old) were interviewed between Oct 2020 to Feb 2021. Five major themes were identified: (i) perception of stigma amongst respondents, (ii) experiences of stigma amongst respondents, (iii) views on what drove stigma and misinformation, (iv) facilitators in preventing and reducing stigma and misinformation, and (v) ageist attitudes towards older adults. Overall, construction workers living in dormitories, healthcare workers, and to some extent tourists from China, were perceived to have been stigmatised and shunned by the public. Place-based stigmatisation was common; participants responded by avoiding places that had confirmed cases of COVID-19. Perceived stigma was temporary and not enduring, driven at the outset by fear of being infected. This study also identified the role played by trust in reducing stigmatisation. The relative absence of politicising of issues and high-quality information readily disseminated to the public were reported as factors that could have reduced and prevented stigma and misinformation on the various groups. Ageist attitudes were observed in some participants with older adults being labelled as vulnerable, susceptible to misinformation and being less able to cope during the pandemic. Through the lens of the HSDF, this study provided an exploratory account of the nature of stigma that resulted from the COVID-19 pandemic in an Asian context. It also shed light on facilitators in preventing and reducing stigma during an outbreak especially the role of trust and communications during a public health crisis.


High-level expression of bovine alpha s1-casein in milk of transgenic mice.
The bovine alpha s1-casein gene, isolated from a cosmid library, was introduced into the murine germline. Transgene expression occurred in all transgenic mice, and was confined to the lactating mammary gland. Half of the mouse lines (five out of ten) expressed at relatively high expression levels (> 1 mg ml-1). The highest levels of expression were obtained with a transgene containing 14.2 kb of 5' flanking sequence, in two cases expression levels comparable to (10 mg ml-1) or well above (20 mg ml-1) alpha s1-casein levels in bovine milk were obtained. Transcription initiation occurred at the same site in the bovine alpha s1-casein gene in transgenic mouse as in the cow. A marked induction of expression occurred at parturition rather than at mid-pregnancy, and thus resembled the bovine rather than the murine developmental expression pattern. Bovine alpha s1-casein specific immunoblotting and RIA were developed for characterization and quantification of the recombinant protein. Using these assays, the properties of the recombinant protein could not be distinguished from those of the natural bovine protein. In spite of the high-level tissue-specific and correctly regulated developmental expression of the transgene, expression levels were integration-site dependent. This may indicate that not all cis-acting regulatory elements involved in bovine alpha s1-casein expression were included in the transgene.


Three-Dimensional Kinetic Adaptations of Gait throughout Pregnancy and Postpartum.
Biomechanical adaptations that occur during pregnancy can lead to changes on gait pattern. Nevertheless, these adaptations of gait are still not fully understood. The purpose was to determine the effect of pregnancy on the biomechanical pattern of walking, regarding the kinetic parameters. A three-dimensional analysis was performed in eleven participants. The kinetic parameters in the joints of the lower limb during gait were compared at the end of the first, second, and third trimesters of pregnancy and in the postpartum period, in healthy pregnant women. The main results showed a reduction in the normalized vertical reaction forces, throughout pregnancy, particularly the third peak. Pregnant women showed, during most of the stance phase, medial reaction forces as a motor response to promote the body stability. Bilateral changes were observed in hip joint, with a decrease in the participation of the hip extensors and in the eccentric contraction of hip flexors. In ankle joint a decrease in the participation of ankle plantar flexors was found. In conclusion, the overall results point to biomechanical adjustments that showed a decrease of the mechanical load of women throughout pregnancy, with exception for few unilateral changes of hip joint moments.


Grape RNA-Seq analysis pipeline environment.
The avalanche of data arriving since the development of NGS technologies have prompted the need for developing fast, accurate and easily automated bioinformatic tools capable of dealing with massive datasets. Among the most productive applications of NGS technologies is the sequencing of cellular RNA, known as RNA-Seq. Although RNA-Seq provides similar or superior dynamic range than microarrays at similar or lower cost, the lack of standard and user-friendly pipelines is a bottleneck preventing RNA-Seq from becoming the standard for transcriptome analysis. In this work we present a pipeline for processing and analyzing RNA-Seq data, that we have named Grape (Grape RNA-Seq Analysis Pipeline Environment). Grape supports raw sequencing reads produced by a variety of technologies, either in FASTA or FASTQ format, or as prealigned reads in SAM/BAM format. A minimal Grape configuration consists of the file location of the raw sequencing reads, the genome of the species and the corresponding gene and transcript annotation. Grape first runs a set of quality control steps, and then aligns the reads to the genome, a step that is omitted for prealigned read formats. Grape next estimates gene and transcript expression levels, calculates exon inclusion levels and identifies novel transcripts. Grape can be run on a single computer or in parallel on a computer cluster. It is distributed with specific mapping and quantification tools, but given its modular design, any tool supporting popular data interchange formats can be integrated. Grape can be obtained from the Bioinformatics and Genomics website at: http://big.crg.cat/services/grape.


Recoverable (R)- and (S)-binap-Ag(I) complexes for the enantioselective 1,3-dipolar cycloaddition reaction of azomethine ylides.
The first enantioselective 1,3-dipolar cycloaddition reaction of amino acid derived azomethine ylides and maleimides catalyzed by very stable and recyclable chiral (R)- or (S)-binap-AgClO(4) complexes is described. The reactions are performed at room temperature, in good yields, with high endo diastereoselectivity and enantioselectivity, the complex being recovered by simple filtration.


Prognostic value of in vitro measurements of platelet aggregability and fibrinolytic activity in patients with reversible cerebral ischemic attacks.
Platelet aggregability and fibrinolytic activity were studied repeatedly in 83 patients with reversible cerebral ischemic attacks over a median follow-up period of 26 months. Platelet hyperaggregability, defined as in vitro secondary aggregation obtained by adenosine diphosphate concentration less than or equal to 1 mumol/l, was demonstrated in 36.1% or the patients examined 5-8 days after the attack, but only in 6% of age- and sex-matched blood donors (p less than 0.001). Fibrinolytic activity was reduced in 57.8% of the patients, as compared with 20.5% of the controls. At the time of follow-up only 8% of the survivors showed platelet hyperaggregability, whereas the fibrinolytic activity was still reduced in 44.4%. Over the observation period 21.7% of the patients had a stroke or died. No significant correlation was found between abnormalities of platelet aggregability or of fibrinolytic activity, when observed 5-8 days after the ischemic episode, and the subsequent risk of stroke or death. It is concluded that in patients with recent cerebral ischemic attacks the demonstration of platelet hyperaggregability or reduced fibrinolytic activity appears to be without prognostic significance.


Time course of in vivo insulin sensitivity after a single bout of exercise in rats.
After a single bout of treadmill running (20 m.min-1, 1 hour), the time course of the in vivo insulin sensitivity was determined in previously untrained rats. The glucose infusion rate (GIR, mg.kg-1.min-1) as an index of insulin sensitivity was assessed by the euglycemic insulin clamp technique 1 (1h-post-Ex group), 3 (3h-post-Ex), 6 (6h-post-Ex) and 24 hours after exercise (24h-post-Ex), n = 8 in each group. GIRs increased with time from 5.72 +/- 1.02 (1h-post-Ex), to 7.58 +/- 1.07 (3h-post-Ex), 10.31 +/- 1.52 (6h-post-Ex) and 10.23 +/- 1.62 (24h-post-Ex) vs control (5.51 +/- 0.63); the GIR in the 6h-post-Ex and the 24h-post-Ex were significantly higher than those in the control and the 1h-post-Ex groups (p less than 0.05). The rate of increase was equivalent to that observed after long-term training in our previous study. GIR of alpha-adrenergic blockade infused 1 hour after exercise (1h-post-Ex alpha) significantly increased (8.32 +/- 0.96) compared to the control and no exercise alpha-blocker-infused control (C alpha) (p less than 0.05). But no significant difference was shown between 1h-post-Ex and 1h-post-Ex alpha groups. In the beta-blocker-infused group, GIR did not show a significant increase. These results indicate that an increase in the in vivo insulin sensitivity after a single bout of exercise is not evident until 6 hours post-exercise. The delay in the sensitivity might partly be explained by the suppression caused by catecholamines via the alpha-mechanism.


Optical inclinometer based on a single long-period fiber grating combined with a fused taper.
A new concept to measure rotation angles based on a fiber-optic modal Mach-Zehnder interferometer is demonstrated by using a nonadiabatic taper cascaded with a long-period fiber grating. Information about the magnitude of the rotation angle can be obtained from the measurement of the interference pattern visibility, and under certain conditions it is also possible to obtain the sign of the rotation angle from the induced phase variation in the fiber interferometer.


Laparoscopic or open distal pancreatectomy for benign and malignant lesions of the pancreas?
Minimally-invasive techniques were adopted relatively late for pancreatic procedures due to their complexity. Today, minimally-invasive distal pancreatectomy is the procedure of choice for the treatment of benign or premalignant pancreatic lesions due to the advantages inherent to laparoscopy. Data on the efficacy of minimally-invasive distal pancreatectomy in oncologic surgery is still limited and larger prospective series are needed prior to its widespread use for the treatment of pancreatic cancer. This review addresses various aspects of distal pancreatectomy, with emphasis on recent developments and open controversies.


Long-Term Outcomes of Depression Treatment With Hypnotherapy or Cognitive Behavioral Therapy.
In a recent randomized controlled trial of mild to moderate depression, hypnotherapy (HT) was noninferior to cognitive behavioral therapy (CBT) after 6 months of outpatient treatment. In the present article, we extended the results in a secondary analysis and investigated how HT compares with CBT 1) during the course of the self-rated depressive symptoms throughout the 12-month follow-ups, 2) with regard to the rates of full remission, and 3) for the time to remission after treatment. Of the 152 randomized patients with current depression, 136 were available for the follow-up analyses. The course of self-rated depressive symptoms during follow-ups was analyzed with linear mixed-effects models. Time to a full remission, defined as eight consecutive weeks without depression, was compared between groups in a survival analysis. The self-reported depressive symptoms could be maintained on a low symptom level during the 12-month follow-up for both HT and CBT. Overall, both treatments achieved comparably high long-term remission rates of 73% after a median of 30 weeks. Outpatient psychotherapy with HT achieved good long-term results mostly comparable to CBT.


A deep connection between the Vapnik-Chervonenkis entropy and the Rademacher complexity.
In this paper, we derive a deep connection between the Vapnik-Chervonenkis (VC) entropy and the Rademacher complexity. For this purpose, we first refine some previously known relationships between the two notions of complexity and then derive new results, which allow computing an admissible range for the Rademacher complexity, given a value of the VC-entropy, and vice versa. The approach adopted in this paper is new and relies on the careful analysis of the combinatorial nature of the problem. The obtained results improve the state of the art on this research topic.


Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury.
Radiation-induced lung injury (RILI) is a serious complication of radiation therapy. Development of an effective drug that selectively protects normal lung tissues and sensitizes tumor cells to radiotherapy is an unmet need. 2-Methoxyestradiol (2ME2) possesses polypharmacological properties, which qualifies it as an effective radioprotector. Our aim is to explore the potential protective effects of 2ME2 against early and late stages of RILI and the underlying mechanisms. BALB/c mice were either treated with 2ME2 (50 mg/kg/day i.p., for 4 weeks); or received a single dose of 10 Gy ionizing radiation (IR) delivered to the lungs; or 10 Gy IR and 2ME2. Animal survival and pulmonary functions were evaluated. Immune-phenotyping of alveolar macrophages (AM) in the broncho-alveolar lavage fluids (BALF) was determined by flow cytometry. ELISA was used to evaluate the expression levels of TNF-α, TGF-β; and IL-10 in BALF. Lung tissues were used for histopathological examination or immunofluorescence staining for CD68 (pan-macrophage marker), Arginase-1 (Arg1, M2-specific marker), inducible nitric oxide synthase (iNOS, M1-specific marker) and HIF-1α. VEGF and γH2AX expression in lung tissues were detected by western blot. The results demonstrated that 2ME2 improved the survival, lung functions and histopathological parameters of irradiated mice. Additionally, it attenuated the radiation-induced AM polarization and reduced the pneumonitis and fibrosis markers in lung tissues. Significant reduction of TNF-α and TGF-β with concomitant increase in IL-10 concentrations were observed. Moreover, the expression of HIF-1α, VEGF and γH2AX declined. 2ME2 is a promising radioprotectant with fewer anticipated side effects.


Clinical Inertia: A Wider Perspective and Proposed Classification Criteria.
Clinical inertia is very common in day-to-day practice, and the factors contributing to that can be physician-related, patient-related, or health-care-related. Clinical inertia is commonly described in chronic asymptomatic illness. We searched the PubMed and Scopus databases for original articles and reviews. Based on the search result, in this review article, we redefine various terminologies to avoid confusion and propose classification criteria for the early identification of clinical inertia. Clinical inertia is also present in acute illness and in symptomatic disease. Early identification of clinical inertia is difficult because of very vague terminologies which have been used interchangeably as well as because of the lack of definitive classification criteria. In this article, we redefine clinical inertia and propose criteria for early identification, which will be useful for both clinicians and academicians. This review will help clinicians to identify and rectify various aspects of clinical inertia.


Using stable-isotope-labeled proteins for hydrogen exchange studies in complex mixtures.
The use of mass spectrometry to measure hydrogen exchange rates for individual proteins in complex mixtures is described. Incorporation of stable-isotope-labeled (SIL) amino acids into a protein of interest during overexpression in bacteria produced distinctive isotope patterns in mass spectra of peptic peptides from the labeled protein. The isotope pattern was used as a signature for peptides originating from the SIL protein. In addition, stable-isotope labeling simplified identification of the peptic peptides by providing partial amino acid composition information. Despite the complex isotope patterns associated with SIL peptides, hydrogen exchange rates could still be measured for peptides from SIL protein and were found to be the same as exchange rates for unlabeled protein. Hydrogen exchange in a single protein of interest was measured in a complex mixture of proteins, a bacterial cell lysate. This methodology, which includes easy recognition of peptic peptides from the protein(s) of interest during hydrogen exchange studies in heterogeneous systems, will permit analysis of structural properties and dynamics of large protein complexes and complex protein systems.


Impact of water temperature and stressor controllability on swim stress-induced changes in body temperature, serum corticosterone, and immobility in rats.
The present study compared the effects of three different water temperatures (20, 25, and 30 degrees C) and stressor controllability on several physiological and behavioral endpoints in an intermittent swim stress paradigm. The escape latency of rats in the 20 and 25 degrees C water was less than that observed for the 30 degrees C group. Both escape and yoked groups at 20 and 25 degrees C exhibited moderate to severe hypothermia following the swim stress session that returned to prestress levels 30-40 min post-stress. At 30 degrees C core body temperature (Tb) only decreased by 1 degree C for either swim group. Following swim, serum corticosterone (CORT) levels were significantly elevated in both escape and yoked groups in comparison to confined and home cage controls. The confined control group showed a significant elevation that was approximately halfway between the home cage control and the swim stress groups. At 30 degrees C, there was still a significant elevation of serum CORT in both swim groups in comparison to confined and home cage controls. Therefore, 30 degrees C appears to be the optimal water temperature to evaluate stress controllability effects in the current paradigm. In a final experiment, swim stressor controllability effects were examined in a 5 min forced swim test (FST) 24 h following the initial stress exposure. Rats exposed to yoked-inescapable swim stress at 30 degrees C exhibited more immobility than their escapable swim stress and confined counterparts, while the escape and confined controls did not differ. These results demonstrate that the behavioral deficits observed in the FST are attributable to the stress of inescapable swim and not swim stress per se.


On the physical interpretation of the nuclear molecular orbital energy.
Recently, several groups have extended and implemented molecular orbital (MO) schemes to simultaneously obtain wave functions for electrons and selected nuclei. Many of these schemes employ an extended Hartree-Fock approach as a first step to find approximate electron-nuclear wave functions and energies. Numerous studies conducted with these extended MO methodologies have explored various effects of quantum nuclei on physical and chemical properties. However, to the best of our knowledge no physical interpretation has been assigned to the nuclear molecular orbital energy (NMOE) resulting after solving extended Hartree-Fock equations. This study confirms that the NMOE is directly related to the molecular electrostatic potential at the position of the nucleus.


The build-up of the thrombospondin extracellular matrix. An apparent dependence on synthesis and on preformed fibrillar matrix.
Thrombospondin (TSP) is a multifunctional protein synthesized by several cell types in culture, among them endothelial cells, and incorporated into the extracellular matrix (ECM) of these cells. In vitro it has been detected in most interstitial spaces, and its presence has been suggested to be developmentally controlled. With the aim of elucidating the role of TSP in the extracellular matrix, we studied the build-up of this protein in the matrix as a function of cell type density and age in culture. The development of the TSP matrix was compared to that of fibronectin (FN) and of von Willebrand Factor (VWF) in the same cultures using our monoclonal anti-TSP antibody B7-3 and monospecific anti-FN or anti-VWF antibodies. In cultures of bovine aortic endothelial cells (BAEC) we observed that both the pattern and distribution of TSP in the matrix changed with cell density and time in culture; it started as a completely amorphous dense layer of protein when the cells were sparse and changed to well organized fibrils when the cells had been confluent for a while. The first appearance of the fibrillar arrays of TSP coincides perfectly with that of the FN fibers; extracellular VWF also was first detected at this point. From this time in culture, there was an increasing coincidence of the TSP with the FN and the VWF matrices suggesting the formation of a complex multicomponent structure of the fibrillar network.(ABSTRACT TRUNCATED AT 250 WORDS)


Exercise adherence: beliefs of adults with knee osteoarthritis over 2 years.
Exercise is an established treatment to alleviate pain and improve function among adults with knee osteoarthritis (KOA). However, long-term adherence to exercise is poor and effective approaches to support adherence are limited. Here, we report on an ancillary study to a randomized controlled trial (RCT) where the primary outcome was 2-year adherence to a home based strength-training program. The aims of this current study were to (i) explore experiences, feelings, and perspectives related to long-term adherence to exercise among adults with painful KOA participating in a 2-year RCT, and (ii) identify factors that influenced long-term adherence to exercise. Methods: We purposively recruited 25 subjects and conducted in-depth interviews at the 2-year RCT assessment. In the RCT participants completed a 6-week group exercise program followed by automated telephone calls. Findings: Three conceptual categories describing beliefs about exercise were identified: (1) monitoring; (2) knowledge of how to manage their exercise behaviors; and (3) benefits of exercise. Monitoring provided by peers and instructors during group exercise, and telephone technology were valued by participants. Participants who reported low adherence expressed ambivalence about the benefits of exercise and a desire for more social support. Those who reported high adherence exhibited self-determination and self-efficacy. Conclusions: A novel finding is the conceptual link of self-determination to high adherence to strength-training exercises over 2 years among adults with KOA. Implications for physical therapists include identifying patients' autonomy, competence, and relatedness needs to foster intrinsic control for exercise behavior.


Immunotherapy and Transarterial therapy of HCC: What the interventional radiologist needs to know about the changing landscape of HCC treatment?
Hepatocellular carcinoma (HCC) is the fourth most common cancer worldwide and its incidence is increasing in Australia. Transarterial therapy, predominantly transarterial chemoembolization (TACE) but increasingly transarterial radioembolization (TARE), plays an important role in patients with intermediate-stage disease and preserved liver function. However, despite advances in TACE, TARE and adjunctive procedures, overall survival has only modestly increased over the last 20 years. Immunotherapy has emerged as a newer cancer treatment and uses antibodies directed at checkpoint inhibitors to upregulate T-cell mediated tumour-specific death. These drugs have been shown to increase survival in patients with HCC and have changed the landscape for advanced disease. Trials are now ongoing combining transarterial therapy and immunotherapy. This manuscript introduces these trials and interventional radiologists should be aware of the changing landscape so that they can partner with immunotherapy and remain relevant in the HCC multidisciplinary group as immunotherapy use increases.


Heat engines with single-shot deterministic work extraction.
We introduce heat engines working in the nanoregime that allow one to extract a finite amount of deterministic work. Using the resource theory approach to themodynamics, we show that the efficiency of these cycles is strictly smaller than Carnot's, and we associate this difference with a fundamental irreversibility that is present in single-shot transformations. When fluctuations in the extracted work are allowed there is a trade-off between their size and the efficiency. As the size of fluctuations increases so does the efficiency and optimal efficiency is attained for unbounded fluctuations, while a certain amount of deterministic work is drawn from the cycle. Finally, we show that when the working medium is composed of many particles, by creating an amount of correlations between the subsystems that scale logarithmically with their number, Carnot's efficiency can also be approached in the asymptotic limit along with deterministic work extraction.


Comparative study of the transcatheter and transthoracic device closure treatments for atrial septal defect: A Chinese single-institution experience.
The purpose of this study was to compare patient populations, safety, feasibility, complications, and total costs of the transcatheter and transthoracic device closure treatments for secundum atrial septal defect.From January 2014 to December 2014, we enrolled 155 patients with secundum atrial septal defects in our hospital. The patients were divided into 2 groups: the 70 patients in group A underwent transcatheter device closure, and the 85 patients in group B underwent transthoracic intraoperative device closure with a right lateral mini-thoracotomy.In group A, the total occlusion rate was 94.3% immediately after the operation, 100% at 3 months, and 100% at 12 months of follow-up; the group A results were not statistically different from the group B results (94.1%, 98.8%, 98.8%, respectively). There was a statistically significant difference in the minor complication rate (P < 0.05), and there were no reported deaths. There was a greater indicated scope using the transthoracic closure device to treat atrial septal defects. In our comparative study, the patients in group B had longer intensive care unit stays and hospital stays than group A (P < 0.05).Both of the device closure treatment options for secundum atrial septal defect are safe and feasible. The transcatheter device closure approach has the advantages of more cosmetic results, less trauma, and a shorter hospital stay than the transthoracic approach. On the contrary, the transthoracic closure device is an economical alternative choice, particularly for patients who are not eligible for the transcatheter closure device.


First evidences that the ectomycorrhizal fungus Paxillus involutus mobilizes nitrogen and carbon from saprotrophic fungus necromass.
Fungal succession in rotting wood shows a surprising abundance of ectomycorrhizal (EM) fungi during the late decomposition stages. To better understand the links between EM fungi and saprotrophic fungi, we investigated the potential capacities of the EM fungus Paxillus involutus to mobilize nutrients from necromass of Postia placenta, a wood rot fungus, and to transfer these elements to its host tree. In this aim, we used pure cultures of P. involutus in the presence of labelled Postia necromass (15 N/13 C) as nutrient source, and a monoxenic mycorrhized pine experiment composed of labelled Postia necromass and P. involutus culture in interaction with pine seedlings. The isotopic labelling was measured in both experiments. In pure culture, P. involutus was able to mobilize N, but C as well, from the Postia necromass. In the symbiotic interaction experiment, we measured high 15 N enrichments in all plant and fungal compartments. Interestingly, 13 C remains mainly in the mycelium and mycorrhizas, demonstrating that the EM fungus transferred essentially N from the necromass to the tree. These observations reveal that fungal organic matter could represent a significant N source for EM fungi and trees, but also a C source for mycorrhizal fungi, including in symbiotic lifestyle.


Protein and energy requirements of animals treated with beta-adrenergic agonists: a discussion.
Much recent work has established the efficacy of certain beta-adrenergic agonists in promoting muscle growth. These compounds also lower the deposition of body lipid. Establishing whether treatment of animals with beta-adrenergic agonists alters their metabolism in ways that affect the efficiency of nutrient use will become important if these compounds are to find a place in animal production. Currently the biological basis of amino acid and energy requirements is being reexamined; this paper discusses whether we have sufficient information to conclude that the current dietary recommendations are appropriate for animals receiving beta-adrenergic agonists. When dietary protein is not a primary nutritional limitation to the rate of protein deposition, beta-adrenergic agonists should increase the efficiency with which the existing protein intake is used in growth. Alternatively, diets that supply a higher essential/nonessential amino acid ratio might be desirable. Whether additional nonprotein energy should be fed to these animals remains an open question. On one hand, the compounds increase energy expenditure and probably increase the maintenance energy needs of the recipient animals; on the other, feeding diets of higher energy density may lead to the resumption of undesirably high rates of fat deposition.


The natural course of diabetic neuropathy. A follow-up.
Out of an unselected group of 160 patients with diabetic neuropathy 51 patients were followed up for an average of 5, 6 years by repeated neurological examinations and by means of a questionnaire. The control of the diabetes was requested from the house physicians. The patients were classified as presenting (1) a symmetrical, predominantly sensory neuropathy (2) a mixed syndrome with additional autonomic neuropathy and (3) multiple mononeuropathy. Individual symptoms and objective signs of neuropathy revealed a remarkable variety of changes. The outlook in multiple mononeuropathy and distal paresis was favorable while autonomic failures, in particular of male sexual function, progressed. There seemed to be some beneficial effect of improved glycemic control. However, despite satisfactory metabolic control some progression of diabetic neuropathy occured.


Cortical dysplasia in congenital muscular dystrophy with central nervous system involvement (Fukuyama type).
We report five cases of congenital muscular dystrophy with central nervous system involvement of the Fukuyama type (FCMD) in which cerebral cortical dysplasia was not uniform even in the same brain. We have categorized the dysplasia into three major patterns, each with a predictable topography despite individual variations. Cerebellar micropolygyria was localized to the dorsal halves of each hemisphere. Aberrant fascicles of myelinated nerve fibers, closely associated with micropolygyria, were found in the subarachnoid space of the dorsal cerebellar surface in all but one case. We discuss the characteristics of the cortical dysplasia of FCMD, particularly in relation to that of Walker's lissencephaly, pathogenesis, and the relationship between lesions of the central nervous system and skeletal muscle.


Liquid chromatography-tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid.
Analysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated. The method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2-->87.0 (SA) and m/z 311.2--> 90.0 ((13)C(3)-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients' samples with known differences in SA metabolites like meningitis (n=6), brain tumour (n=2), leukaemia (n=5), and Salla disease (n=1). Limit of detection (LOD) was 0.54 microM for FSA and 0.45 mM for TSA. Intra- and inter-assay variation for FSA (21.8 microM) were 4.8% (n=10) and 10.4% (n=40) respectively. Intra- and inter-assay variation for TSA (35.6 microM) were 9.7% (n=10) and 12.8% (n=40) respectively. Tested patients showed values of TSA above established reference value. The validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses.


Aerographite: ultra lightweight, flexible nanowall, carbon microtube material with outstanding mechanical performance.
An ultra lightweight carbon microtube material called Aerographite is synthesized by a novel single-step chemical vapor deposition synthesis based on ZnO networks, which is presently the lightest known material with a density smaller than μg/cm(3). Despite its low density, the hierarchical design leads to remarkable mechanical, electrical, and optical properties. The first experiments with Aerographite electrodes confirm its applicability.


Experimental investigation of an American five-string banjo.
An experimental investigation of an American five-string banjo is reported. The acoustic spectra of the strings are analyzed and it is found that in many ways banjo strings behave in a manner similar to those on a piano. The terminating impedance presented to the strings at the bridge is reported and it is found to be generally much lower than the characteristic impedance of the strings. It is also shown that, for a properly tuned banjo, the mode shapes of the membrane are symmetric about the center even though there is a large asymmetric force due to the off-center placement of the bridge. Finally, high-speed electronic speckle-pattern interferometry was used to study the motion of the membranic head after a string is plucked, and it is found that the motion is dominated by a rocking motion of the bridge.