Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis.
Tanshinone IIA (Tan II A) is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways.


Farm injury hospitalisations in New South Wales (2010 to 2014).
To examine gender differences in the characteristics, treatment costs and health outcomes of farm injuries resulting in hospitalisation of New South Wales (NSW) residents. A population-based study of individuals injured on a farm and admitted to hospital using linked hospital admission and mortality records from 1 January 2010 to 30 June 2014 in NSW. Health outcomes, including injury severity, hospital length of stay (LOS), 28-day readmission and 30-day mortality were examined by gender. A total of 6,270 hospitalisations were identified, with males having a higher proportion of work-related injuries and injuries involving motorbikes compared to females. Females had a higher proportion of equestrian-related injuries. There were no differences in injury severity, with around 20% serious injuries, in mean LOS or 28-day hospital re-admission. Treatment costs totalled $42.7 million, with males accounting for just under 80% of the total. There are some gender differences in the characteristics of farm injury-related hospitalisations. Farm injury imposes modest, but nonetheless relatively considerable, financial costs on hospital services in NSW. Implications for public health: Continued efforts to ameliorate these injuries in a farm environment, which are mainly preventable, will have personal and societal benefits.


Male-Specific Metabolic Considerations Concerning the Prescription of Second-Generation Antipsychotics to Adolescents.
Objectives: Although males and females gain comparable weight when prescribed second-generation antipsychotics (SGAs), males may be uniquely vulnerable to an array of endocrinological, inflammatory, and psychosocial adverse drug effects. Methods: This opinion piece reviews work in each of these three areas for consideration. Results: Androgens may decrease both through hypothalamic-pituitary-gonadal axis dysregulation and as a consequence of increased adiposity. Testosterone has anti-inflammatory properties, and declining levels as well as many other factors may influence overall immunological functioning. Psychosocial stressors are gender specific in obesity, and SGA-induced obesity may affect males in unique and severe ways. Conclusion: This opinion piece supports the framework of the World Federation of Societies of Biological Psychiatry's Task Force on Men's Mental Health to advocate for further studies concerning the adverse drug effects of SGAs as unique manifested in male children, adolescents, and young men.


Roles of NAD (+) , PARP-1, and Sirtuins in Cell Death, Ischemic Brain Injury, and Synchrotron Radiation X-Ray-Induced Tissue Injury.
NAD(+) plays crucial roles in a variety of biological processes including energy metabolism, aging, and calcium homeostasis. Multiple studies have also shown that NAD(+) administration can profoundly decrease oxidative cell death and ischemic brain injury. A number of recent studies have further indicated that NAD(+) administration can decrease ischemic brain damage, traumatic brain damage and synchrotron radiation X-ray-induced tissue injury by such mechanisms as inhibiting inflammation, decreasing autophagy, and reducing DNA damage. Our latest study that applies nano-particles as a NAD(+) carrier has also provided first direct evidence demonstrating a key role of NAD(+) depletion in oxidative stress-induced ATP depletion. Poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins are key NAD(+)-consuming enzymes that mediate multiple biological processes. Recent studies have provided new information regarding PARP-1 and sirtuins in cell death, ischemic brain damage and synchrotron radiation X-ray-induced tissue damage. These findings have collectively supported the hypothesis that NAD(+) metabolism, PARP-1 and sirtuins play fundamental roles in oxidative stress-induced cell death, ischemic brain injury, and radiation injury. The findings have also supported "the Central Regulatory Network Hypothesis", which proposes that a fundamental network that consists of ATP, NAD(+) and Ca(2+) as its key components is the essential network regulating various biological processes.


QM/MM investigation of the concentration effects on the second-order nonlinear optical responses of solutions.
A multiscale approach combining quantum mechanics (QM) and molecular mechanics methods has been employed to investigate the effects of solute-solute interactions and therefore of concentration on the first hyperpolarizability of solutions of nitrobenzene in benzene. First, spatial distributions of solute and solvent molecules are generated using Monte Carlo simulations where the intermolecular interactions are described using the Lennard-Jones potentials and Coulomb terms. Then, a reduced number of statistically-uncorrelated configurations are sampled and submitted to time-dependent Hartree-Fock calculations of the first hyperpolarizability. When only one molecule is described quantum-mechanically and is embedded in the electrostatic polarization field of the solution described by point charges, βHRS and β// as well as the depolarization ratio increase in parallel with the concentration in nitrobenzene. This effect is attributed to the increase of the polarization field associated with the presence of polar nitrobenzene molecules in the surrounding. Then, the first solvation shell is considered explicitly in the QM calculation to address solute-solute interactions effects. When the number of nitrobenzenes in the first solvation shell increases, βHRS and β// normalized to the number of nitrobenzene molecules decrease and this decrease attains roughly 50% when there are 3 nitrobenzene molecules in the first solvation shell. These drastic reductions of the first hyperpolarizability result from (partial) centro-symmetric arrangements between the nitrobenzene molecules, as supported by the relationship between β and the angle between the nitrobenzene charge transfer axes. Moreover, these β decreases originate mostly from the reduction of the dipolar β component, whereas the octupolar one is rather constant as a function of the nitrobenzene concentration.


Force-dependent mobility and entropic rectification in tubes of periodically varying geometry.
We investigate transport of point Brownian particles in a tube formed by identical periodic compartments of varying diameter, focusing on the effects due to the compartment asymmetry. The paper contains two parts. First, we study the force-dependent mobility of the particle. The mobility is a symmetric non-monotonic function of the driving force, F, when the compartment is symmetric. Compartment asymmetry gives rise to an asymmetric force-dependent mobility, which remains non-monotonic when the compartment asymmetry is not too high. The F-dependence of the mobility becomes monotonic in tubes formed by highly asymmetric compartments. The transition of the F-dependence of the mobility from non-monotonic to monotonic behavior results in important consequences for the particle motion under the action of a time-periodic force with zero mean, which are discussed in the second part of the paper: In a tube formed by moderately asymmetric compartments, the particle under the action of such a force moves with an effective drift velocity that vanishes at small and large values of the force amplitude having a maximum in between. In a tube formed by highly asymmetric compartments, the effective drift velocity monotonically increases with the amplitude of the driving force and becomes unboundedly large as the amplitude tends to infinity.


[Factor VIII and the risk of arterial thrombosis].
The pathomechanism of acute complications of atheromatosis, i.e. arterial thrombosis, still remains unclear. Conventional cardiovascular risk factors can explain only about 50% of cases of arterial thrombosis. The activation of intrinsic and extrinsic pathways of the coagulation system on damaged atherosclerotic plaque is one of the most important mechanisms. The role of clotting factors in the development of arterial thrombosis is also considered. From among a few clotting factors (V, VIII, XIII), factor VIII arouses interest due to the well-known observation that the morbidity for cardiovascular reasons is less among hemophiliacs than in the general population. A high factor VIII level predicts the occurrence of episodes of venous thromboses, but its role in the pathogenesis of arterial thromboses is still unclear. In clinical studies, a high factor VIII level predicts episodes of stroke, myocardial infarct, and acute lower-limb ischemia over a short period of observation. A high factor VIII level may the cause of about 5% of all episodes of arterial thrombosis. The reasons for elevated factor VIII levels in some persons remain unclear. Although heritability can play an important role, the influence of other factors (e.g. activation of the sympathetic nervous system) has been reported. The pathomechanism is the subject of investigation as well. An explanation for the occurrence of severe complications of arterial thrombosis in patients without significant risk factors may result in the development of methods of detection and prevention.


Substitution Model Adequacy and Assessing the Reliability of Estimates of Virus Evolutionary Rates and Time Scales.
Determining the time scale of virus evolution is central to understanding their origins and emergence. The phylogenetic methods commonly used for this purpose can be misleading if the substitution model makes incorrect assumptions about the data. Empirical studies consider a pool of models and select that with the highest statistical fit. However, this does not allow the rejection of all models, even if they poorly describe the data. An alternative is to use model adequacy methods that evaluate the ability of a model to predict hypothetical future observations. This can be done by comparing the empirical data with data generated under the model in question. We conducted simulations to evaluate the sensitivity of such methods with nucleotide, amino acid, and codon data. These effectively detected underparameterized models, but failed to detect mutational saturation and some instances of nonstationary base composition, which can lead to biases in estimates of tree topology and length. To test the applicability of these methods with real data, we analyzed nucleotide and amino acid data sets from the genus Flavivirus of RNA viruses. In most cases these models were inadequate, with the exception of a data set of relatively closely related sequences of Dengue virus, for which the GTR+Γ nucleotide and LG+Γ amino acid substitution models were adequate. Our results partly explain the lack of consensus over estimates of the long-term evolutionary time scale of these viruses, and indicate that assessing the adequacy of substitution models should be routinely used to determine whether estimates are reliable.


Functions of DNA methyltransferase 3-like in germ cells and beyond.
DNA methyltransferase 3-like (DNMT3L) is one of the key players in de novo DNA methylation of imprinting control elements and retrotransposons, which occurs after genome-wide epigenetic erasure during germ cell development. In this review, we summarise the biochemical properties of DNMT3L and discuss the possible mechanisms behind DNMT3L-mediated imprinting establishment and retrotransposon silencing in germ cells. We also discuss possible connections between DNMT3L and non-coding RNA-mediated epigenetic remodelling, the roles of DNMT3L in germ cell development and the implications in stem cell and cancer research.


Managers, myths and misses: target efficiency and health care management education in Australia.
The Australian penchant for monitoring overseas developments in general and health matters is noted. The face validity of the findings of the International Project on Culture and Management (IPCM) is assessed positively and certain structural commonalities of the health systems of the USA and Australia are identified, without attributing causality in the development of managers' attributes. Linkages between Australia, Malaysia and Hong Kong are also explored briefly. In addition, key attributes of the sample of Australian managers are discussed together with the limitations related to emerging forms of provision and organization in health services and to their distribution in the study sample. The IPCM findings may be used in course design but are unlikely to cause any major change, although one may debate on the values of applicants towards health service management education courses. The findings may help to stimulate the establishment of performance measures for management education in Australia.


[Analysis of clinical characteristics of 43 patients with pulmonary mycosis diagnosed by pathology].
To observe the etiological distribution, clinical presentations and imaging features of pulmonary mycosis that is diagnosed by pathology. The etiological distribution, clinical presentations and imaging features of patients with pulmonary mycosis, who were collected in the Affiliated Hospital of Jining Medical University from January 2018 to July 2020, were retrospectively analyzed. The diagnosis of all the patients were confirmed by pathological examination, of lung or bronchi tissue that were obtained through operation, bronchoscope or percutaneous lung puncture biopsy. There were 26 patients' (60.47%, 26/43) pathological specimens were obtained by operation, 14 cases (32.56%, 14/43) were obtained by bronchoscope, and 3 cases (6.98%, 3/43) were obtained by percutaneous lung puncture biopsy. Of the 43 patients who were diagnosed pulmonary mycosis by pathology, 27 patients (62.79%, 27/43) suffered from pulmonary aspergillosis, 11 patients (25.58%, 11/43) suffered from pulmonary cryptococcosis, 3 patients (6.98%, 3/43) suffered from pulmonary mucormycosis, and 2 patients (4.65%, 2/43) suffered from pulmonary candidiasis. There were 27 patients (62.79%, 27/43) with pulmonary fungal disease complicating risk factors of fungal infection, including diabetes mellitus (23.26%,10/43), malignant tumor (16.28%, 7/43), bronchiectasis (9.30%, 4/43), hepatitis B virus (HBV) carrier (6.98%, 3/43), taking glucocorticoids (4.65%, 2/43), pulmonary tuberculosis (4.65%, 2/43), and chemotherapy following colon carcinoma operation (2.33%, 1/43). The common clinical presentations included cough (55.81%, 24/43), expectoration (48.84%, 21/43), hemoptysis (37.21%, 16/43), fever (20.93%, 9/43), gasping (18.60%, 8/43), chest pain (16.28%, 7/43), and hoarseness (3.13%, 1/43). Imaging features of chest included lung nodes in 20 cases (46.51%, 20/43), vascular welt sign in 12 cases (27.91%, 12/43), exudative process in 10 cases (23.26%, 10/43), lung mass or consolidation in 8 cases (18.60%, 8/43), cavitary lesions in 7 cases (16.28%, 7/43), thicken bronchus wall and narrow lumina in 6 cases (13.95%, 6/43), air crescent in 5 cases (11.63%, 5/43). The pulmonary aspergillosis and cryptococcosis are mainly in pulmonary mycosis diagnosed by pathology. The common complications are diabetes mellitus and malignant tumor. The common clinical presentations are cough, expectoration, and hemoptysis. The main imaging features of chest are lung nodes and vascular welt sign can be found in most of pulmonary cryptococcosis.


Non-oestrogen-based and complementary therapies for menopause.
Women are living a significant portion of their adult lives in the post-reproductive phase, and many seek help for debilitating menopausal symptoms. Every individual's experience of menopausal transition is unique. Adopting a holistic approach to managing the menopause using a combination of lifestyle, hormonal, and non-hormonal interventions is key to maximise the quality of life of affected women. However, many opt to use non hormonal options or have contraindications to using hormonal therapy. Studies have shown that several pharmacological non-hormonal medications such as SSRIs, SSRI/SNRIs, Gabapentin, and Pregabalin are effective for managing vasomotor symptoms as well as other menopausal symptoms. Their main side effects are dry mouth, nausea, constipation, reduced libido, and loss of appetite. Clonidine is the only non-hormonal drug which is licenced for control of vasomotor symptoms in the UK, but has several side effects including dizziness and sleep disturbance. Cognitive Behavioural Therapy is recommended as a treatment for anxiety, sleep problems and vasomotor symptoms related to menopausal transition. Evidence for clinical efficacy and safety of herbal remedies and alternative therapies remains weak. Studies with neurokinin receptor 3 antagonists on women with hot flushes have shown improvement in vasomotor symptoms and results of large-scale studies are awaited.


Role of Charge Traps in the Performance of Atomically Thin Transistors.
Transient currents in atomically thin MoTe2 field-effect transistors (FETs) are measured during cycles of pulses through the gate electrode. The curves of the transient currents are analyzed in light of a newly proposed model for charge-trapping dynamics that renders a time-dependent change in the threshold voltage as the dominant effect on the channel hysteretic behavior over emission currents from the charge traps. The proposed model is expected to be instrumental in understanding the fundamental physics that governs the performance of atomically thin FETs and is applicable to the entire class of atomically thin-based devices. Hence, the model is vital to the intelligent design of fast and highly efficient optoelectronic devices.


An interaction model for OH + H2O-mixed and pure H2O overlayers adsorbed on Pt(111).
A model potential for the adsorbate-adsorbate interaction among OH and H2O molecules adsorbed on a Pt(111) surface has been developed solely based on first-principle calculations. By combining this directional-dependent model potential for the lateral interaction with a lattice model of Ising type, large length scale structure calculations can be made. The strength of different hydrogen bonds can be analyzed in detail from this model potential. It is found that the hydrogen bond between OH and H2O molecules is stronger than that between two H2O molecules (0.4 eV per pair as compared to 0.2 eV per pair, respectively). Via the computed chemical potential for water in mixed OH + H2O overlayers the water uptake as a function of oxygen precoverage on Pt(111) has been determined. The results compare very well with recent experiments.


Production of recombinant albumin by a herd of cloned transgenic cattle.
Purified plasma derived human albumin has been available as a therapeutic product since World War II. However, cost effective recombinant production of albumin has been challenging due to the amount needed and the complex folding pattern of the protein. In an effort to provide an abundant source of recombinant albumin, a herd of transgenic cows expressing high levels of rhA in their milk was generated. Expression cassettes efficiently targeting the secretion of human albumin to the lactating mammary gland were obtained and tested in transgenic mice. A high expressing transgene was transfected in primary bovine cell lines to produce karyoplasts for use in a somatic cell nuclear transfer program. Founder transgenic cows were produced from four independent cell lines. Expression levels varying from 1-2 g/l to more than 40 g/l of correctly folded albumin were observed. The animals expressing the highest levels of rhA exhibited shortened lactation whereas cows yielding 1-2 g/l had normal milk production. This herd of transgenic cattle is an easily scalable and well characterized source of rhA for biomedical uses.


Fully differential molecular-frame measurements for the electron-impact dissociative ionization of H2.
We present fully differential state-resolved experimental data for the dissociative ionization of molecular hydrogen induced through electron impact. Molecular-frame ionization cross sections are derived for transitions from the X{1}Sigma{g}{+} molecular ground state to the 1ssigma{g}, 2psigma{u}, 2ssigma{g}, and 2ppi{u} states of H2+. For transitions to the 2ssigma{g} and 2ppi{u} states, a strong orientation dependence in the cross sections is revealed, with "side-on" preferred to "end-on" collisions and a propensity for the fragment proton to emerge along the normal to the scattering plane.


Current status of autonomic nerve-preserving surgery for mid and lower rectal cancers: Japanese experience with lateral node dissection.
Surgical practices for treatment of rectal cancer in Japan have changed from extended dissection along perivascular or parietal plane to pelvic autonomic nerve-preserving procedures without compromising radicality of surgical resection. Previous surgical results suggested the significant advantages of extended surgery in survival and local recurrence rate of Dukes B and C patients. More than 15 percent of patients with cancer in the lower rectum have extramesorectal spread to lateral pelvic nodes that can be removed by lateral dissection for local control and cure. Initially the total nerve-preserving procedure has been introduced for a complete preservation of para-aortic and intrapelvic nervous system in patients with early-stage cancer not requiring para-aortic and lateral lymph-node dissection. However, the concept of aggressive surgery for advanced rectal cancer has led to various types of pelvic autonomic nerve-preserving procedures, in which extended lymph-node dissection plus nerve-preserving technique with resection of one or more autonomic nervous segments has been performed. During two decades, total pelvic autonomic nerve-preserving procedure with lateral lymph-node dissection has been used increasingly for Dukes C lesion without increased local recurrence. The overall status of pelvic autonomic nerve-preserving procedures according to clinical experiences in Japan is reviewed in the context of cadaveric anatomic findings, Japanese vs. Western techniques and concepts, and our own clinical data.


[Pulmonary mycobacteriosis caused by Mycobacterium peregrinum in a young, healthy man].
A 24-year-old male never-smoker with no contributory medical history was referred to our division because of chronic productive cough and fever. His chest CT showed pulmonary consolidation including nodular shadows around the bronchovascular bundle in both upper lobes and right middle lobe. Sputum smears were negative but cultures were positive for Mycobacterium peregrinum, twice. He was given a diagnosis of pulmonary mycobacteriosis caused by M. peregrinum and treated with clarithromycin, levofloxacin, and ethambutol. His symptoms and the infiltrates improved, and further sputum cultures were negative for mycobacteria. M. peregrinum is a species included in the M. fortuitum group, of rapidly-growing non-tuberculous mycobacteria. To the best of our knowledge, only 2 cases with lung infection caused by M. peregrinum have been previously reported, both of which occurred in patients in their 60s with underlying diseases, including low immunity due to immunosuppressants for polymyositis, or bronchiectasia. We describe a rare case of pulmonary mycobacteriosis due to M. peregrinum in a healthy man without any underlying diseases.


Mortality in a cohort with high fish consumption.
Our aim was to assess the mortality of fishermen and fishermen's wives in Finland, presuming that the mortality reflects their high consumption of contaminated fish. All Finnish fishermen, registered since 1980, were identified from the Professional Fishermen Register (N = 6410), and the fishermen's wives from the national population register (N = 4260). The cohorts were individually linked with cause-of-death data until 2005 at Statistics Finland. The follow-up started in the year after the first registration as a fisherman and at marriage (if later) for the wives. The standardized mortality ratios (SMRs) were calculated based on the national mortality rates. In addition, blood samples and food frequency questionnaire data were collected from a volunteer sample. The average fish consumption and serum concentrations of fish-derived fatty acids and environmental contaminants were higher among the fishermen and their wives than among the general population from the same region. The fishermen and their wives had lower mortality from all causes (SMR 0.78, 95% confidence interval (CI) 0.73-0.82, and 0.84, 0.76-0.93, respectively), and ischaemic heart diseases (0.73, 0.65-0.81, and 0.65, 0.50-0.83) than the general population. Mortality from cerebrovascular diseases and malignant neoplasms was decreased among the fishermen (0.67, 0.52-0.85, and 0.90, 0.80-1.01), but not among the wives. In addition, the fishermen's mortality from water transport accidents was extremely high (8.31, 5.65-11.79). The fishermen and their wives had lower mortality from many natural causes. The high intakes of environmental contaminants in fish were not seen as excess mortality.


Malignant pilomatricoma.
An 86-year-old man had a tumor in the right posterior cervical region. The lesion showed histopathologic features of pilomatricoma but differed from that lesion by the presence of cytologically atypical cells and focal squamoid differentiation. The term "malignant pilomatricoma" is suggested for this tumor.


Development and validation of a simple and fast HPLC method for determination of lovastatin, pravastatin and simvastatin.
Statins are effective and often-prescribed drugs for the treatment of hypercholesterolemia. This study shows a simple and fast method validation by reversed-phase high-performance liquid chromatography in the linear range 28 to 52 µg/mL to quantify lovastatin, pravastatin sodium or simvastatin in bulk drug or dosage forms. Statins were determined using a C8 endcapped column (250 × 4 mm, 5 µm), isocratic mobile phase of acetonitrile and 0.1% phosphoric acid (65:35), 30°C, ultraviolet-diode array detection at λ 238 nm and 1.5 mL/min flow for lovastatin and simvastatin and 1.0 mL/min for pravastatin sodium. The developed method is fast, simple, reliable and shows appropriate linearity (r > 0.999), accuracy (98.8-101.6%), precision (relative standard deviation <2%) and selectivity toward placebo and/or degradation products in very similar chromatographic conditions for all statins.


Electrocatalytic H2 Generation from Water Relying on Cooperative Ligand Electron Transfer in "PN3 P" Pincer-Supported NiII Complexes.
Water is the most sustainable source for H2 production, and the efficient electrocatalytic production of H2 from mixed water/acetonitrile solutions by using two new air-stable nickel(II) pincer complexes, [Ni(κ3 -2,6-{Ph2 PNR}2 (NC5 H3 )Br2 ] (R=H I, Me II) is reported. Hydrogen generation from H2 O/CH3 CN solutions is initiated at -2 V against Fc+/0 , and bulk electrocatalysis studies showed that the catalyst functions with an excellent Faradaic efficiency and a turnover frequency of 160 s-1 . A DFT computational investigation of the reduction behavior of I and II revealed a correlation of H2 formation with charge donation from electrons originating in a reduced ligand-localized orbital. As a result, these catalysts are proposed to proceed by a novel mechanism involving electron/proton transfer between a Ni0I species bonded to an anionic PN3 P ligand ("L- /Ni0I ") and a NiI -hydride ("Ni-H"). Furthermore, these catalysts are able to reduce phenol and acetic acid, more active proton sources, at lower potentials that correlate with the substrate pKa .


The specificity of the histochemical NADPH diaphorase reaction for nitric oxide synthase-1 in skeletal muscles is increased in the presence of urea.
Nitric oxide synthase-1 (NOS-1) can be demonstrated in the sarcolemma region of myofibers in rodent skeletal muscles with the use of NADPH diaphorase histochemistry. Since other, especially intrafibrar enzymes also exhibit NADPH diaphorase activity, we tried to increase the specificity of the histochemical reaction for NOS-1. A qualitative and quantitative analysis was performed on cryostat sections of fast-twitch oxidative myofiber-rich tongue and fast-twitch glycolytic myofibers-rich tibialis anterior muscle derived from C57 mice and NOS-1 deficient knockout mice. All myofibers of both C57 mice and NOS-1 knockout mice contained significant intrafibrar NADPH diaphorase activity which was inhibited to almost background levels when 2 M urea was added to the incubation medium. On the other hand, myofibers of C57 mice but not of NOS-1-deficient knockout mice exhibited NADPH diaphorase activity in their sarcolemma region which was only weakly reduced in the presence of 2 M urea as was demonstrated by image analysis. Quantitative data on the activity of NADPH diaphorase(s) were obtained in situ by photometric analysis of formazan extracted from cryostat sections. The catalytic activity in tongue and tibialis anterior muscle was reduced in presence of 2 M urea to approximately 27% in C57 mice and to 7-17% in NOS-1 knockout mice, respectively. An in vitro NADPH diaphorase assay performed on homogenates of skeletal muscles also revealed an inhibitory effect of 2 M urea in both mouse strains and, additionally, indicated an upregulation of NADPH diaphorase activity in NOS-1 knockout mice. Finally, an immunodepletion analysis demonstrated that NOS-1 comprises 38% of the total NADPH diaphorase activity in tongue and approximately 59% in tibialis anterior muscle in C57 mice. In conclusion, we recommend the addition of 2 M urea to the incubation medium to increase the specificity of the NADPH diaphorase reaction to localise NOS-1 with the use of catalytic histochemistry.


Suicide intent among parasuicide patients in Nicaragua: a surveillance and follow-up study.
This study examines suicide intent among parasuicide patients in a low-income country, Nicaragua, with special reference to gender patterns and future suicidal behavior. Using the Suicide Intent Scale (SIS), suicide intent was assessed in 204 persons presenting to hospital after parasuicide. Repetition was checked after a mean follow-up period of three years. The total SIS scores did not differ between women and men. However, a higher SIS score among women was significantly associated with older age, having children and use of pesticide as the parasuicide method. The overall method of suicide intent was low in Nicaragua compared to other countries, as was the nonfatal repetition rate (4.8% after three years). Subsequent suicides were found only in three men. Factor structures within the SIS disclosed supported the cross-cultural validity of the instrument. The level of suicide intent at the index attempt did not show any association with future suicidal behavior.


Image-Guided Peri-Tumoral Radiofrequency Hyperthermia-Enhanced Direct Chemo-Destruction of Hepatic Tumor Margins.
To validate the feasibility of using peri-tumoral radiofrequency hyperthermia (RFH)-enhanced chemotherapy to obliterate hepatic tumor margins. This study included in vitro experiments with VX2 tumor cells and in vivo validation experiments using rabbit models of liver VX2 tumors. Both in vitro and in vivo experiments received different treatments in four groups (n=6/group): (i) RFH-enhanced chemotherapy consisting of peri-tumoral injection of doxorubicin plus RFH at 42°C; (ii) RFH alone; (iii) doxorubicin alone; and (iv) saline. Therapeutic effect on cells was evaluated using different laboratory examinations. For in vivo experiments, orthotopic hepatic VX2 tumors in 24 rabbits were treated by using a multipolar radiofrequency ablation electrode, enabling simultaneous delivery of both doxorubicin and RFH within the tumor margins. Ultrasound imaging was used to follow tumor growth overtime, correlated with subsequent histopathological analysis. In in vitro experiments, MTS assay demonstrated the lowest cell proliferation, and apoptosis analysis showed the highest apoptotic index with RFH-enhanced chemotherapy, compared with the other three groups (p<0.01). In in vivo experiments, ultrasound imaging detected the smallest relative tumor volume with RFH-enhanced chemotherapy (p<0.01). The TUNEL assay further confirmed the significantly increased apoptotic index and decreased cell proliferation in the RFH-enhanced therapy group (p<0.01). This study demonstrates that peri-tumoral RFH can specifically enhance the destruction of tumor margins in combination with peri-tumoral injection of a chemotherapeutic agent. This new interventional oncology technique may address the critical clinical problem of frequent marginal tumor recurrence/persistence following thermal ablation of large (>3 cm) hepatic cancers.


[Epidemiology and pathophysiology of primary varicose veins].
Epidemiological investigations in German-speaking countries have covered over 14,000 people. Chronic venous insufficiency (edema, dermal alteration) was found in 13% and extensive varicosis in 15%. Thus, nearly 30% must be regarded as afflicted with varicose veins. The major pathophysiology, the absence of a directed blood flow due to venous dilatation and valve incompetence, becomes relevant hemodynamically and clinically if the proximal valves of the saphenous veins and/or perforating veins are also incompetent. Chronic venous insufficiency develops.


Recent developments in nanofabrication using ion projection lithography.
Ion projection lithography (IPL) is an emerging technology and a major candidate for the next-generation lithography (NGL) designed to complement and supplement current optical lithographic techniques for future chip manufacturing. In this Review, the recent developments of IPL technology are examined with an emphasis on its ability to fabricate a wide variety of nanostructures for the semiconductor industry. Following an introduction of the uniqueness and strength of the technology, the basics of ion-source development and ion-target interactions with and without chemical enhancement are presented. The developments in equipment systems, masks, and resists are subsequently studied. The resolution of printed nanostructures and the corresponding throughput of the current system are assessed for NGL. Finally, concluding remarks are presented to summarize the strengths and weaknesses of the current technology and to suggest the scope for future improvement.


The role of computerized tomography of the pelvis in the presurgical staging of carcinoma of the cervix and of the ovary.
Computerized Tomography (CT) has largely contributed to the diagnosis of the pathology of the female pelvis. After setting up a technique to outline the different viscera the authors have employed this method in the staging of neoplastic pathology of the cervix and ovary. They describe the successes obtained and the main cause of error in the interpretation of the images of CT.


[Expression and function of interleukin-18 in mouse dextran sulfate sodium colitis].
Interleukin-18 (IL-18) is a proinflammatory cytokine that induces Th1 cytokines production and may play a role in the pathogenesis of inflammatory bowel diseases. This study was aimed at detecting the expression and role of IL-18 in colonic mucosa of dextran sulfate sodium (DSS) colitic mice. Expression of IL-18 in colon of DSS colitis was determined by immunohistochemistry. Extract and supernatant of intestinal epithelial cells (IEC) from colon of DSS colitis mice were used to stimulate splenic mononuclear cells (SMC); IFN-gamma and IL-2 concentrations in supernatant of SMC were measured by ELISA. The levels of expression of IL-18 in extract or supernatant of IEC were examined by Western blot. Colon epithelial cells and part of lamina propria mononuclear cells were stained positive for IL-18 antibody. Stimulation assay and Western blot indicated that IL-18 positive proteins were present in both IEC extract and supernatant. Colon epithelial cells in mice with DSS colitis express and secret pro IL-18 and active IL-18.


Effect of Low-Dose Dexmedetomidine on the Anesthetic and Recovery Profile of Sevoflurane-Based Anesthesia in Patients Presenting for Supratentorial Neurosurgeries: A Randomized Double-Blind Placebo-Controlled Trial.
Background Dexmedetomidine could be a suitable adjuvant in neuroanesthesia due to its analgesic and anesthetic-sparing properties with the added advantage of facilitating intraoperative neuromonitoring. However, its recovery profile is still debated upon, as in neuroanesthesia, a prompt recovery is essential for postoperative neurologic assessment. We designed this study to evaluate the effect of dexmedetomidine on the anesthetic and recovery profile of patients presenting for supratentorial neurosurgeries. Materials and Methods Forty adult patients undergoing supratentorial surgeries were recruited in this prospective, randomized, double-blinded study and were divided into two groups: group S and group SD. Both groups received sevoflurane and fentanyl for maintenance, whereas group SD alone received a low dose of dexmedetomidine infusion. Recovery parameters, opioid consumption, Richmond Agitation-Sedation Scale (RASS) and visual analogue scale (VAS) scores, incidence of nausea and vomiting, and intraoperative hemodynamics were analyzed. Results There were no statistically significant differences between the groups S and SD in case of recovery parameters-time taken (in minutes, presented as median with interquartile range [IQR]) for (1) eye-opening to command: 9.5 (8-18) versus 22.5 (5-47.5) ( p = 0.414); 2) following verbal command: 10.5 (8.25-29.5) versus 25 (10-28.75) ( p = 0.512); (3) extubation: 11 (9.25-22) versus 25 (10-30) ( p = 0.277); and (4) getting oriented to place, time, and date: 23 (20-52.75) versus 27.5 (25-36.5) ( p = 0.121). Fentanyl consumption was significantly less in group SD (451 ± 39.3) versus group S (524.3 ± 144.1) ( p = 0.034). The median RASS score with IQR and the median VAS scores with IQR were comparable between the groups at all time points. Of the 20 patients in group S, 5 had complaints of nausea and vomiting compared with none in the group SD, although it was not statistically significant. The hemodynamic parameters did not show a significant difference between the groups except for a surge in mean arterial pressure at 30 minutes in group S. Conclusion Low-dose dexmedetomidine as an adjuvant to sevoflurane- and fentanyl-based anesthesia could provide stable hemodynamics and lesser anesthetics and opioid consumption, without adversely affecting the recovery profile in patients undergoing supratentorial neurosurgical procedures.


The living interface between synthetic biology and biomaterial design.
Recent far-reaching advances in synthetic biology have yielded exciting tools for the creation of new materials. Conversely, advances in the fundamental understanding of soft-condensed matter, polymers and biomaterials offer new avenues to extend the reach of synthetic biology. The broad and exciting range of possible applications have substantial implications to address grand challenges in health, biotechnology and sustainability. Despite the potentially transformative impact that lies at the interface of synthetic biology and biomaterials, the two fields have, so far, progressed mostly separately. This Perspective provides a review of recent key advances in these two fields, and a roadmap for collaboration at the interface between the two communities. We highlight the near-term applications of this interface to the development of hierarchically structured biomaterials, from bioinspired building blocks to 'living' materials that sense and respond based on the reciprocal interactions between materials and embedded cells.


Ultrasound Signs in the Diagnosis and Staging of Small Bowel Obstruction.
Ultrasound (US) is highly accurate in the diagnosis of small bowel obstruction (SBO). Because the indications for and timing of surgical intervention for SBO have changed over the past several decades, there is a widespread assumption that the majority of patients with simple SBO may be conservatively managed; in this scenario, staging SBO is crucial. This study evaluated the association between morphological and functional US signs in the diagnosis and staging (simple, decompensated and complicated), and the associations and prevalence of US signs correlated with clinical or surgical outcome. The US signs were divided into diagnostic (dilated bowel loops and altered kinesis) and staging criteria (extraluminal free fluid, parietal and villi alterations). We performed a retrospective, single-center cohort, observational study examining the prevalence of morphologic and functional US signs in the staging of simple, decompensated and complicated SBO. The most significant US signs were dilated bowel loops (100%), hypokinesis (90.46%), thickened walls (82.54%) and free fluid (74.60%). By linear regression, free fluid was positively correlated to US staging in both univariate and multivariate analysis; that is, the more advanced the stage of SBO, the more probable the presence of free fluid between the bowel loops. In univariate analysis only, we found a positive correlation between US staging/thickened walls and the prominence of valvulae conniventes. Additionally, the multivariate analysis indicated that parietal stratification and bowel jump kinesis were negative predictors for US staging in comparison to other US signs. In addition, we found significant associations between conservative treatment or surgery and hypokinesis (p = 0.0326), akinesis (p = 0.0326), free fluid (p = 0.0013) and prominence of valvulae conniventes (p = 0.011). Free fluid in particular was significantly less present in patients that were conservatively treated (p = 0.040). We conclude that the US staging of SBO may be crucial, with a valuable role in the initial diagnosis and staging of the pathology, saving time and reducing total radiation exposure to the patient.


Structure and Yielding of Colloidal Silica Gels Varying the Range of Interparticle Interactions.
The relationship between interaction range, structure, fluid-gel transition, and viscoelastic properties of silica dispersions at intermediate volume fraction, Φv ≈ 0.1 and in alkaline conditions, pH = 9 was investigated. For this purpose, rheological, physicochemical, and structural (synchrotron-SAXS) analyses were combined. The range of interaction and the aggregation state of the dispersions were tuned by adding either divalent counterions (Ca(2+)) or polycounterions (PDDA). With increasing calcium chloride concentration, a progressive aggregation was observed which precludes a fluid-gel transition at above 75 mM of calcium chloride. In this case, the aggregation mechanism is driven by short-range ion-ion correlations. Upon addition of PDDA, a fluid-gel transition, at a much lower concentration, followed by a reentrant gel-fluid transition was observed. The gel formation with PDDA was induced by charge neutralization and longer range polymer bridging interactions. The refluidification at high PDDA concentrations was explained by the overcompensation of the charge of the silica particles and by the steric repulsions induced by the polycation chains. Rheological measurements on the so-obtained gels reveal broad yielding transition with two steps when the size of the silica particle clusters exceeds ≈0.5 μm.


An active lifestyle induces positive antioxidant enzyme modulation in peripheral blood mononuclear cells of overweight/obese postmenopausal women.
The aim of this study was to investigate the effects of an active lifestyle on mitochondrial functioning, viability, bioenergetics, and redox status markers in peripheral blood mononuclear cells (PBMC) of overweight/ obese postmenopausal women. We performed a cross-sectional study with postmenopausal women aged 45–64 years and body mass index N 25 kg/m2, divided into physically active (n = 23) and sedentary (n = 12) groups. Mitochondria functioning and viability, bioenergetics and redox status parameters were assessed in PBMC with spectrophotometric and fluorometric assays. No differences were found in the enzyme activity of complexes I and II of the electron transport chain (ETC), mitochondrial superoxide dismutase (MnSOD) activity, methyl-tetrazolium reduction levels and reduced glutathione and oxidized glutathione levels between the groups. However, the physically active group presented higher levels of reactive oxygen species (ROS) (P= 0.04) and increased catalase (CAT) (P= 0.029), total (P= 0.011) and cytosolic SOD (CuZnSOD) (P= 0.009) activities. An active lifestyle that includes aerobic exercise for at least 30 min, three times per week may improve antioxidant enzyme activities in PBMC in overweight/obese postmenopausal women, without changes in the activity of the ETC enzymes. However, this low intensity physical activity is not able to induce relevant mitochondrial adaptations.


Endless Journey of Adenosine Signaling in Cardioprotective Mechanism of Conditioning Techniques: Clinical Evidences.
Myocardial ischemic injury is a primary cause of death among various cardiovascular disorders. The condition occurs due to interrupted blood supply and vital nutrients (necessary for normal cellular activities and viability) to the myocardium, eventually leading to damage. Restoration of blood supply to ischemic tissue is noted to cause even more lethal reperfusion injury. Various strategies, including some conditioning techniques like preconditioning & postconditioning have been developed to check detrimental effects of reperfusion injury. Many endogenous substances have been proposed to act as initiator, mediators and end effectors of these conditioning techniques. Substances like adenosine, bradykinin, acetylcholine, angiotensin, norepinephrine, opioids, etc., have been reported to mediate cardioprotective activity. Among these agents, adenosine has been widely studied and suggested to have the most pronounced cardioprotective effects. The current review article highlights the role of adenosine signaling in the cardioprotective mechanism of conditioning techniques. The article also provides an insight into various clinical studies that substantiate the applicability of adenosine as a cardioprotective agent in myocardial-reperfusion injury.


Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity.
Retroviruses package two complete RNA genomes into a viral particle but generate only one provirus after each infection. This pseudodiploid replication strategy facilitates frequent recombination, which occurs during DNA synthesis when reverse transcriptase switches templates between two copackaged RNA genomes, generating chimeric DNA. Recombination has played an important role in shaping the current HIV-1 pandemic; however, whether recombination is required for HIV-1 replication is currently unknown. In this report, we examined viral replication when recombination was blocked in defined regions of the HIV-1 genome. We found that blocking recombination reduced viral titers. Furthermore, a significant proportion of the resulting proviruses contained large deletions. Analyses of the deletion junctions indicated that these deletions were the direct consequence of blocking recombination. Thus, our findings illustrate that recombination is a major mechanism to maintain HIV-1 genome integrity. Our study also shows that both obligatory and nonobligatory crossovers occur during reverse transcription, thereby supporting both the forced and dynamic copy-choice models of retroviral recombination. Taken together, our results demonstrate that, in most viruses, both packaged RNA genomes contribute to the genetic information in the DNA form. Furthermore, recombination allows generation of the intact HIV-1 DNA genome and is required for efficient viral replication.


Mechanisms of Strain-Induced Interfacial Strengthening of Wet-Spun Filaments.
We investigate the mechanism of binding of dopamine-conjugated carboxymethyl cellulose (DA-CMC) with carbon nanotubes (CNTs) and the strain-induced interfacial strengthening that takes place upon wet drawing and stretching filaments produced by wet-spinning. The filaments are known for their tensile strength (as high as 972 MPa and Young modulus of 84 GPa) and electrical conductivity (241 S cm-1). The role of axial orientation in the development of interfacial interactions and structural changes, enabling shear load bearing, is studied by molecular dynamics simulation, which further reveals the elasto-plasticity of the system. We propose that the reversible torsion of vicinal molecules and DA-CMC wrapping around CNTs are the main contributions to the interfacial strengthening of the filaments. Such effects play important roles in impacting the properties of filaments, including those related to electrothermal heating and sensing. Our findings contribute to a better understanding of high aspect nanoparticle assembly and alignment to achieve high-performance filaments.


Evolving pathway-driven biomarkers in breast cancer.
Detection and initiation of the most appropriate therapy at an early stage of breast cancer are two major determinants of a successful anticancer therapy. In this context, it is important to continue to identify novel biologic endpoints (commonly known as biomarkers) which also facilitate therapeutic decisions. Here we briefly review the following pathways from the perspective of biomarkers through works from Dr Kumar's lab: i) estrogen receptor alpha (ER) signaling; ii) nuclear receptor coregulators in ER-directed therapies; iii) p21-activated kinase-1 in ER action; iv) cytoskeleton components in breast cancer cell progression; v) emerging molecules as biomarkers. We believe that the potential usefulness of the cytoplasmic kinases, coregulators, and cytoskeleton molecules is likely to accelerate the development of the next generation of biomarkers for the surveillance, prognosis and therapeutic decisions for cancer.


Using Six Sigma to make a difference in health care quality.
For years, the health care industry has borrowed ideas and initiatives from other industries to promote and enhance quality. The most recent idea to capture the interest of many in the health care field has been Six Sigma, which has been used and refined during the past two decades by top corporations. This issue looks at how five organizations are using the Six Sigma management process--with its reliance on data, statistical analysis, and change--to enhance quality.


Diabetes mellitus in Nigeria: The past, present and future.
Diabetes mellitus (DM) is a diverse group of metabolic disorders that is often associated with a high disease burden in developing countries such as Nigeria. In the early nineties, not much was known about DM in Nigeria and traditionally, people related DM to "curses" or "hexes" and diagnosis was made based on blood or urinary tests for glucose. Currently, oral hypoglycaemic agents but not insulin are readily accessible and acceptable to persons with DM. The cost of diabetes care is borne in most instances by individuals and often payment is "out of pocket"-this being a sequel of a poorly functional national health insurance scheme. An insulin requiring individual on a minimum wage would spend 29% of his monthly income on insulin. Complementary and alternative medicines are widely used by persons with DM and form an integral component of DM care. Towards reducing the burden of DM in Nigeria, we suggest that there be concerted efforts by healthcare professionals and stakeholders in the health industry to put in place preventative measures, a better functioning health insurance scheme and a structured DM program.


[Ewing's sarcoma: therapeutic experience (author's transl)].
Since 1978, four patients with Ewing's sarcoma have been on a treatment-regimen based on the T-6 and T-2 Protocols according to Rosen. Preoperative chemotherapy produced tumor regression and thus enabled surgical resection in three cases. In the first case, radiation therapy was felt necessary because the surgical resection was performed after the first course of the T-6 Protocol and cells suspected to be malignant were found on histological examination of the resected tumor. The experience prompted us to refrain from using radiation therapy in the next two cases but to conduct the surgical resection after two cycles of T-6 Protocol. Here, histological examinations of the resected tumors showed no evidence of malignant cells. The fourth patient had a pathologic fracture in addition to the tumor. In this case, it was possible, by means of chemotherapy to heal the fracture and also to produce a regression of the tumor. Because of the radiation morbidity, we believe that it is a notable progress in the treatment of Ewing's sarcoma if radiation therapy can be avoided.


Trans-cricoid thyroid injection of local anaesthesia: a serious complication.
Transcricothyroid membrane (CTM) injection of local anaesthesia is widely used during bronchoscopic procedures. It is an effective way of delivering topical anaesthesia, and has been shown to reduce patient discomfort, improve clinician satisfaction and reduce overall sedation requirements. Risks from this procedure are uncommon and usually minor. Localisation of the CTM is usually performed clinically by palpation of anatomical landmarks and can vary depending on clinician skillset and experience. Clinical identification may be less accurate compared with ultrasound guidance in identifying puncture site, however, ultrasound is not always readily available and seldom used for this purpose. This case describes a rare complication following attempted local anaesthetic infiltration into the cricothyroid space, after clinical identification of puncture site. An obstructive fluid-filled mass formed around the site of injection on the right vocal cord; resulting in airway compromise, abandonment of procedure and subsequent intubation.


[Addiction therapy. Limits, problems, perspectives].
In health care, tending is a process, which offers for the patients a continuous watching on, a control, a treatment, and the prevention of worsening of their medical status as well as the reduction of their complaints. In the article, some fundamental segments of tending in addictology are reviewed, particularly paying attention to whom, how, where and how long to take care. On the basis of literature, the author stresses whatever method is used to treat addict patients it is more beneficial to society than the avoidance of any intervention due to the negligence of the problem. Addictology has lost a lot from its power in Hungary. The author recommends the introduction of the methods of health quality assurance to decrease the effect of negative trends seen in addictology. The paper also deals with special patient groups including homeless clients, adolescents, elderly and pregnant patients as well as health care professionals. The author critically mentions the double communication of society, the dual-face character of politics and has the opinion that competences are not clear making the situation confused. As a mistake of the point of view is it regarded that the addictological problems are classified as to belonging to the authority of psychiatry. It is emphasized that multidisciplinary approach is needed to understand the problem and to treat the client. General screening for addictological diseases does not seem possible in the light of low capacity of the system, but the screening of adolescents and pregnant women is definitely recommended. And finally, a financial support for medicines to prevent craving, a moratorium for the continuous changing of rules and law, the sponsoring of harm reduction programs as well as a better utilization of opportunities offered by local drug coordinating boards are proposed.


Fibrodysplasia ossificans progressiva: a case report.
Fibrodysplasia Ossificans Progressiva is a rare debilitating disorder of the musculoskeletal system affecting one in two million individuals. It is characterized by progressive extraskeletal ossification of soft tissues resulting in the original skeleton being encased in unyielding new bone leading to disability and ultimately death from cardiorespiratory failure. The present case brings to light the delays and potential pitfalls in diagnosis as a result of the rarity of the condition.


Uptake of mercury by thiol-grafted chitosan gel beads.
This study describes the synthesis and characterization of thiol-grafted chitosan beads for use as mercury (Hg) adsorbents. Chitosan flakes were dissolved and formed into spherical beads using a phase inversion technique, then crosslinked to improve their porosity and chemical stability. Cysteine was grafted onto the beads in order to improve the adsorption affinity of Hg to the beads. The beads possessed an average diameter of 3.2 mm, porosity of 0.9, specific surface area of approximately 100 m2/g, average pore size of approximately 120 angstroms, and specific gravity of 2.0. Equilibrium and kinetic uptake experiments were conducted to study the uptake of Hg by the beads. The adsorption capacity was approximately 8.0 mmol-Hg/g-dry beads at pH 7, and decreased with decreasing pH. Hg adsorption kinetics was modeled as radial pore diffusion into a spherical bead with nonlinear adsorption. Use of the nonlinear Freundlich isotherm in the diffusion equation allowed modeling of the uptake kinetics with a single tortuosity factor of 1.5 +/- 0.3 as the fitting parameter for all initial Hg concentrations, chitosan loadings, and agitation rates. At agitation rates of 50 and 75 rpm, where uptake rate was reduced significantly due to the boundary layer effect, the mass transfer coefficient at the outside boundary was also used as a fitting parameter to model the kinetic data. At agitation rates higher than 150 rpm, pore diffusion was the rate-limiting step. The beads exhibited a high initial uptake rate followed by a slower uptake rate suggesting pore diffusion as the rate-determining step especially at high agitation rates. Higher uptake rates observed in this study compared to those in a previous study of chitosan-based crab shells indicate that dissolution and gel formation increase the porosity and pore accessibility of chitosan.


Clinical significance of 1-year treatment with raloxifene on bone and lipid metabolism in Japanese postmenopausal women with osteoporosis.
It has been well established that raloxifene (RLX) has beneficial effects on bone primarily in Caucasian women. However, to date, there is a dearth of data for Japanese postmenopausal women. In this study, we prospectively evaluated the effects of RLX on bone and lipid metabolism in fifty Japanese postmenopausal patients with untreated osteoporosis. We measured bone mineral density (BMD) by dual-energy X-ray absorptiometry at 7 sites including the lumbar spine, femoral neck, and distal radius. BMD was significantly increased at the lumbar spine both at 6 months and at 12 months compared with at baseline (p<0.01 for both), although the possibility could not be completely excluded that this increase may be partly explained by an apparent increase induced by degenerative changes in lumbar vertebrae since we had no control subjects to compare and be more certain of the findings in this study. Both bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) significantly decreased both at 6 months (p<0.01 for both) and at 12 months (p<0.01 for both) compared with at baseline, but not below the lower limit of the reference value. Total cholesterol and low-density lipoprotein cholesterol were significantly improved while triglycerides and high-density lipoprotein cholesterol were unaltered. Although longer and larger studies with fracture endpoints are needed to draw definite conclusions, our findings suggest the favorable effects of RLX on bone and lipid metabolism in Japanese postmenopausal women with osteoporosis as in Caucasian women.


Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF.
Recent evidence suggests that autophagy may favor fibrosis through enhanced differentiation of fibroblasts in myofibroblasts. Here, we sought to characterize the mediators and signaling pathways implicated in autophagy-induced myofibroblast differentiation. Fibroblasts, serum starved for up to 4 d, showed increased LC3-II/-I ratios and decreased SQSTM1/p62 levels. Autophagy was associated with acquisition of markers of myofibroblast differentiation including increased protein levels of ACTA2/αSMA (actin, α 2, smooth muscle, aorta), enhanced gene and protein levels of COL1A1 (collagen, type I, α 1) and COL3A1, and the formation of stress fibers. Inhibiting autophagy with 3 different class I phosphoinositide 3-kinase and class III phosphatidylinositol 3-kinase (PtdIns3K) inhibitors or through ATG7 silencing prevented myofibroblast differentiation. Autophagic fibroblasts showed increased expression and secretion of CTGF (connective tissue growth factor), and CTGF silencing prevented myofibroblast differentiation. Phosphorylation of the MTORC1 target RPS6KB1/p70S6K kinase was abolished in starved fibroblasts. Phosphorylation of AKT at Ser473, a MTORC2 target, was reduced after initiation of starvation but was followed by spontaneous rephosphorylation after 2 d of starvation, suggesting the reactivation of MTORC2 with sustained autophagy. Inhibiting MTORC2 activation with long-term exposure to rapamycin or by silencing RICTOR, a central component of the MTORC2 complex abolished AKT rephosphorylation. Both RICTOR silencing and rapamycin treatment prevented CTGF and ACTA2 upregulation, demonstrating the central role of MTORC2 activation in CTGF induction and myofibroblast differentiation. Finally, inhibition of autophagy with PtdIns3K inhibitors or ATG7 silencing blocked AKT rephosphorylation. Collectively, these results identify autophagy as a novel activator of MTORC2 signaling leading to CTGF induction and myofibroblast differentiation.


Single-Channel Recording of Ligand-Gated Ion Channels.
Single-channel recordings reveal the microscopic properties of individual ligand-gated ion channels. Such recordings contain much more information than measurements of ensemble behavior and can yield structural and functional information about the receptors that participate in fast synaptic transmission in the brain. With a little care, a standard patch-clamp electrophysiology setup can be adapted for single-channel recording in a matter of hours. Thenceforth, it is a realistic aim to record single-molecule activity with microsecond resolution from arbitrary cell types, including cell lines and neurons.


Identification of an isoform of the estrogen receptor messenger RNA lacking exon four and present in the brain.
An isoform of the estrogen receptor messenger RNA (ER-mRNA) was identified in RNA from the brain of lizards and rats. Poly(A)+ RNA from brain and uteri was reverse transcribed using gene-specific primer for the ER. The resulting complementary DNA was amplified in a polymerase chain reaction followed by cloning and sequencing of the amplified products. This isoform lacks exon four and is designated delta 4 ER-mRNA. Although several isoforms of the ER have been described from cancerous cells, to our knowledge, none has been identified previously in the brain. Furthermore, the delta 4 isoform is the only isoform detected in normal tissue. The delta 4 isoform appeared most abundant in RNA from brain tissue, whereas uterine RNA contained only trace amounts of the isoform. Apparently, tissue-specific alternative splicing accounts for these differences in abundance. Because exon four encodes a part of the steroid-binding domain, we predict that the corresponding protein encoded by the isoform will not bind estradiol and may therefore belong to a growing subclass of the steroid/thyroid/vitamin superfamily known as orphan receptors. We predict that the putative delta 4 protein may function as a ligand-independent transcription factor that acts on the same DNA response elements as the conventional ER. The abundance of this isoform in the brain relative to the uterus raises fundamental questions regarding the regulation of estrogen-responsive genes in different tissues.


Malignant hyperthermia in Brazil: analysis of hotline activity in 2009.
Malignant hyperthermia (MH) is a pharmacogenetic disease that causes abnormal hypermetabolic reaction to halogenated anesthetics and/or depolarizing muscle relaxants. In Brazil, there is a hotline telephone service for MH since 1991, available 24 hours a day in São Paulo. This article analyzes the activity of the Brazilian hotline service for MH in 2009. Prospective analysis of all phone calls made to the Brazilian hotline service for MH from January to December 2009. Twenty-two phone calls were received: 21 from the South/Southeast region of Brazil and one from the North region. Fifteen calls were requests for general information about MH. Seven were about suspected MH acute episodes, two of which were not considered as MH. In five episodes compatible with MH, all patients received halogenated volatile anesthetics (2, isoflurane; 3, sevoflurane) and one also used succinylcholine; there were four men and one woman, with a mean age of 18 years (2-27). The problems described in the five MH episodes were tachycardia (5), increased expired carbon dioxide (4), hyperthermia (3), acidemia (1), rhabdomyolysis (1), and myoglobinuria (1). One patient received dantrolene. All five patients with MH episodes were follow-up in the intensive care unit and recovered without sequelae. Susceptibility to MH was later confirmed in two patients by in vitro muscle contracture test. The number of calls per year in the Brazilian hotline service for MH is still low. The characteristics of MH episode were similar to those reported in other countries. The knowledge of MH in Brazil needs to be increased.


URI1 suppresses irradiation-induced reactive oxygen species (ROS) by activating autophagy in hepatocellular carcinoma cells.
Radiotherapy has been extensively applied in cancer treatment. However, this treatment is ineffective in Hepatocellular carcinoma (HCC) due to lack of radiosensitivity. Unconventional prefoldin RPB5 interactor 1 (URI1) exhibits characteristics similar to those oncoproteins, which promotes survival of cancer cells. As a consequence of the irradiation, the levels of endogenous reactive oxygen species (ROS) rise. In the current study, we analyzed the role of URI1 in the control of ROS levels in HepG2 cells. Upon URI1 overexpression, HepG2 cells significantly suppressed irradiation-induced ROS, which may help cells escape from oxidative toxicity. And our data demonstrated that overexpression of URI1 not only resulted in an increase of autophagic flux, but also resulted in an further increased capacity of autophagy to eliminate ROS. It indicated that URI1 suppressed irradiation-induced ROS through activating autophagy. Moreover, URI1 activated autophagy by promoting the activities of AMP-activated protein kinase (AMPK). Results showed that overexpression of URI1 increased the phosphorylation of AMPKα at the Thr172 residue and the activated-AMPK promoted the phosphorylation of forkhead box O3 (FOXO3) at the Ser253 residue, which significantly induced autophagy. Taken together, our findings provide a mechanism that URI1 suppresses irradiation-induced ROS by activating autophagy through AMPK/FOXO3 signaling pathway. These new molecular insights will provide an important contribution to our better understanding about irradiation insensitivity of HCC.


Neuroblastoma cell-adapted yellow fever 17D virus: characterization of a viral variant associated with persistent infection and decreased virus spread.
Serial passage of yellow fever 17D virus (YF5.2iv, derived from an infectious molecular clone) on mouse neuroblastoma (NB41A3) cells established a persistent noncytopathic infection associated with a variant virus. This virus (NB15a) was dramatically reduced in plaque formation and exhibited impaired replication kinetics on all cell lines examined compared to the parental virus. Nucleotide sequence analysis of NB15a revealed a substitution in domain III of the envelope (E) protein at residue 360, where an aspartic acid residue was replaced by glycine. Single mutations were also found within the NS2A and NS3 proteins. Engineering of YF5.2iv virus to contain the E(360) substitution yielded a virus (G360 mutant) whose plaque size and growth efficiency in cell culture resembled those of NB15a. Compared with YF5.2iv, both NB15a and G360 were markedly restricted for spread through Vero cell monolayers and mildly restricted in C6/36 cells. On NB41A3 cells, spread of the viruses was similar, but all three were generally inefficient compared with spread in other cell lines. Compared to YF5.2iv virus, NB15a was uniformly impaired in its ability to penetrate different cell lines, but a difference in cell surface binding was detected only on NB41A3 cells, where NB15a appeared less efficient. Despite its small plaque size, impaired growth, and decreased penetration efficiency, NB15a did not differ from YF5.2iv in mouse neurovirulence testing, based on mortality rates and average survival times after intracerebral inoculation of young adult mice. The data indicate that persistence of yellow fever virus in NB41A3 cells is associated with a mutation in the receptor binding domain of the E protein that impairs the virus entry process in cell culture. However, the phenotypic changes which occur in the virus as a result of the persistent infection in vitro do not correlate with attenuation during pathogenesis in the mouse central nervous system.


Neuroimaging Features of San Luis Valley Syndrome.
A 14-month-old Hispanic female with a history of double-outlet right ventricle and developmental delay in the setting of recombinant chromosome 8 syndrome was referred for neurologic imaging. Brain MR revealed multiple abnormalities primarily affecting midline structures, including commissural dysgenesis, vermian and brainstem hypoplasia/dysplasia, an interhypothalamic adhesion, and an epidermoid between the frontal lobes that enlarged over time. Spine MR demonstrated hypoplastic C1 and C2 posterior elements, scoliosis, and a borderline low conus medullaris position. Presented herein is the first illustration of neuroimaging findings from a patient with San Luis Valley syndrome.


Outcomes of modified FOLFOX-6 as first line treatment in patients with advanced gastric cancer in a single institution; retrospective analysis.
Treatment options for patients with advanced gastric cancer remain limited. Few studies have investigated the efficacy and tolerability of the combination regimen of oxaliplatin and 5-fluorouracil with leucovorin for patients with advanced gastric cancer. The goal of this study was to examine the efficacy and toxicity of a modified FOLFOX-6 (mFOLFOX-6) regimen as a first-line chemotherapy regimen for patients with advanced gastric cancer. From March, 2006, to December, 2007, 82 patients with advanced gastric cancer received 100 mg/m² oxaliplatin and 100 mg/m² leucovorin on the first day of treatment, followed by 2,400 mg/m² of 5-fluorouracil on the first and second days of treatment every 2 weeks as a first-line treatment. The median age of the enrolled patients was 62 years (range; 30~75). Out of 82 patients, 34 cases (41.5%) were recurrent cases after curative resection, and the other 48 cases were unresectable or non-curative resectable cases. Their response was evaluated every 6 weeks. The overall response rate was 40.2%, with 2 (2.4%) complete response and 31 (37.8%) partial responses. The median time to progression (TTP) and overall survival (OS) time were 6.0 months (95% confidence interval [CI]: 4.69~7.31) and 13.0 months (7.99~18.0), respectively. The grade 3~4 hematologic toxicities observed included neutropenia (34.1%), thrombocytopenia (7.3%), and anemia (1.2%). The gastrointestinal toxicities observed included grade 3~4 nausea (9.8%) and vomiting (7.3%). Six patients (7.3%) experienced grade 3 neuropathy. No treatment-related deaths were recorded. The modified FOLFOX-6 regimen is effective and well tolerated as a first-line chemotherapy regimen for patients with advanced gastric cancer.


Plant Fe status affects the composition of siderophore-secreting microbes in the rhizosphere.
Soil microbes have been demonstrated to play an important role in favouring plant iron (Fe) uptake under Fe-limiting conditions. However, the mechanisms involved are still unclear. This present study reported the effects of plant Fe status on the composition of siderophore-secreting microbes in the rhizosphere, and their potential function in improving plant Fe nutrition. An Fe-efficient plant, red clover (Trifolium pratense 'Kenland') was cultured in a calcareous soil to obtain rhizosphere soils with (Fe-sufficient) or without (Fe-stressed) foliar FeEDTA spraying. The siderophore-producing ability of rhizospheric microbes was measured. The bioavailability of the siderophore-solubilized Fe from iron oxides/hydroxides was tested in hydroponic culture. In rhizosphere soil, the number of microbes that secreted siderophores quickly was more in the Fe-stressed treatment than in the Fe-sufficient one, while the number of microbes that did not secret siderophores was the opposite. A significantly higher concentration of phenolics was detected in the rhizosphere soil of Fe-stressed plants. Moreover, after the soil was incubated with phenolic root exudates, the composition of the siderophore-secreting microbial community was similar with that of the rhizosphere of Fe-stressed plant. Additionally, the siderophores produced by a rhizospheric microbe isolated from the Fe-stressed treatment can well solubilize iron oxides/hydroxides, and the utilization of the siderophore-solubilized Fe by plant was even more efficient than EDTA-Fe. Iron-deficiency stress of red clover would alter the composition of siderophore-secreting microbes in the rhizosphere, which is probably due to the phenolics secretion of the root, and may in turn help to improve the solubility of Fe in soils and plant Fe nutrition via elevated microbial siderophore secretion.


The role of capsule endoscopy in small bowel pathology: a review of 122 cases.
Small bowel capsule endoscopy (CE) has been introduced in New Zealand (NZ) in all of the tertiary and some secondary centres over the last few years. We describe our experience with CE from a single centre in NZ. In this 2-year, retrospective, study of 122 consecutive patients, data was collected on multiple variables from the patient clinical, laboratory, and radiology records. Pillcam of Given Imaging Diagnostic System (Given Imaging Ltd, Yogneam, Israel) was used to image the small bowel. Descriptive statistics were used to analyse the data. Good preparation was noted in 69% of the cases. The most common indication for referral was obscure GI bleeding (70%). The overall diagnostic yield for relevant findings was 52%, with angioectasia as the most common specific finding (37%). The diagnostic yield in those with overt bleeds improved with inpatient status (74%). Incomplete examinations were noted in 12% and were significantly more common in the male gender. Preliminary imaging (barium, CT/MR) was noted to have a lower diagnostic yield. Enteroscopies were considered in 25% of the patients post CE procedure. Apart from a lower diagnostic yield in patients with overt bleeds, our data is consistent with that reported in literature and support the role of CE as the minimally invasive gold standard investigation for small bowel imaging.


Do we need to create geriatric hospitals?
During a single illness episode, the sickest, frailest older patients are often treated in multiple distinct sites, including the emergency room, the intensive care unit, a general medical floor, and a skilled nursing facility. Such frequent transfers involve changes in physician, changes in nursing care, the rewriting of orders, and physical dislocation, all of which can adversely affect outcomes. This system, although efficient, increases the chance of medical errors, promotes delirium, and undermines the doctor-patient relationship. Partial solutions include a team approach to care, an electronic medical record, and substitution of home for hospital care. A more comprehensive solution is to create a geriatric hospital for treatment of the most common medical and surgical problems and for provision of rehabilitative or skilled nursing care. Designing new institutions for geriatric care will require new legislation and a new set of regulations but should be considered for the oldest and frailest patients.


The biological revolution: understanding the impact of SNPs on diet-cancer interrelationships.
Evidence is accumulating that individual risk of neoplasia depends on complex interactions among genetic inheritance, a range of exposures both in utero and in postnatal life, and the play of chance. Knowledge of the portfolio of genetic variants that confer susceptibility or resistance to cancer is limited, and there is potential for genome-wide scans and hypothesis-driven studies to reveal novel polymorphisms and haplotypes that modify risk. There is only fragmentary evidence of the scale and nature of diet-gene interactions that modulate risk of neoplasia, but it seems probable that such interactions will play a significant role as they do in other complex diseases including cardiovascular disease and type 2 diabetes. All existing evidence about diet-gene interactions and cancer risk comes from observational studies, and it will be necessary to undertake intervention studies to test the hypotheses generated by epidemiologic investigations. Because it is very unlikely that primary cancer will be an endpoint in dietary intervention studies in the foreseeable future, development of robust surrogate endpoints is a high priority. Emerging biological science using epigenomics, proteomics, and other molecular technologies appears to offer novel approaches to the discovery and validation of surrogate endpoints.


Metal Insertion in a Methylamine-Functionalized Zirconium Metal-Organic Framework for Enhanced Carbon Dioxide Capture.
The reaction of ZrCl4 with 2',3',5',6'-tetramethylamino-p-terphenyl-4,4″-dicarboxylic acid (H2tpdc-4CH2NH2·3HCl) in the presence of NaF affords Zr6O4(OH)2.1F1.9(tpdc-4CH2NH2·3HCl)6 (1), which is a new member of the Zr6O4(OH)4(dicarboxylate linker)12 or UiO-68 family, and exhibits high porosity with BET and Langmuir surface areas of 1910 m2/g and 2220 m2/g, respectively. Remarkably, fluoride ion incorporation in the zirconium clusters results in increased thermal stability, marking the first example of enhancement in the stability of a UiO framework by this defect-restoration approach. Although material 1 features four alkylamine groups on each organic linker, the framework does not exhibit the high CO2 uptake that would be expected for reaction between CO2 and the amine groups to form carbamic acid or ammonium carbamate species. The absence of strong CO2 adsorption can likely be attributed to protonation at some of the amine sites and the presence of counterions. Indeed, exposure of material 1 to acetonitrile solutions of the organic bases 1,8-bis(dimethylamino)naphthalene (DMAN) or trimethylamine, affords a partially deprotonated material, which exhibits enhanced CO2 uptake. Exposure of basic amine sites also facilitates the postsynthetic chelation of copper(I) ([Cu(MeCN)4]·CF3SO3) to yield material 2 with an enhanced CO2 uptake of 4 wt % at 0.15 bar, which is double that of the parent framework 1.


Effect of Enterprise Social Media on Employee Creativity: Social Exchange Theory Perspective.
This study applied an artifact-centric view to investigate the consequences of enterprise social media usage. It investigates how enterprise social media usage influences employee creativity. A moderated mediation model is developed based on social exchange theory. The empirical sample of 238 employees is used to test the proposed model. Results of the empirical analysis performed using PROCESS macro of SPSS indicate that enterprise social media usage positively impacts employee creativity via the mediating mechanisms (i.e., leader-member exchange and support for innovation). Furthermore, social media usage frequency negatively moderates this impact of enterprise social media usage on employee creativity via leader-member exchange. Interestingly, the empirical analysis reveals that the impact of enterprise social media usage frequency strengthens the indirect effect that enterprise social media usage has on employee creativity via perceived support for innovation.


Naloxone reduces decrease in ventilation induced by hypoxia in newborn infants.
The mechanism responsible for the decrease in ventilation during breathing of low fractional concentration of inspired O2 in the newborn infant is poorly understood. The present study tested the hypothesis that endogenous opiates account for this ventilatory decrease. Eleven healthy newborn infants breathed 15% O2, balance N2 for 5 min following an injection of saline and following an injection of naloxone. Neither injection caused a change in minute ventilation (VE) or ventilatory pattern when the infants were breathing room air. However, the decreased ventilation during hypoxia following naloxone was significantly less than that following saline. VE dropped about 14% following saline but only about 4% following naloxone. However, the adult ventilatory response to hypoxemia, i.e., a relatively sustained increase in VE, was not attained. Naloxone had no influence on the occurrence of periodic breathing during hypoxemia. Thus in the healthy full-term newborn infant, endogenous opiates account only for a part of the decreased ventilation during hypoxemia.


A prospective, randomized, controlled trial comparing radiographic and clinical outcomes between stand-alone lateral interbody lumbar fusion with either silicate calcium phosphate or rh-BMP2.
Iliac crest autograft has traditionally been considered the gold standard for lumbar spine fusion, though it is not without drawbacks related to harvesting site pain and other complications. Bone graft alternatives, such as recombinant human bone morphogenetic protein 2 (rh-BMP2), are now widely used but also have unique risk profiles and substantially increase costs. The purpose of the current study was to compare the efficacy of rh-BMP2 and synthetic silicate calcium phosphate (SiCaP) as bone graft substitutes on fusion rates and clinical outcomes in patients undergoing single-level lumbar stand-alone extreme lateral interbody fusion (XLIF). A prospective, randomized, controlled, clinical, and radiographic study was performed at a single institution. Thirty patients with L4-L5 degenerative disc disease (DDD) were enrolled. Patients were randomized into one of two groups, 15 underwent lumbar single-level stand-alone XLIF using SiCaP, and 15 using rh-BMP2. Clinical and radiographic results were compared between the study groups. Pain (visual analogue scale) and disability (Oswestry disability index) were assessed preoperatively and at postoperative weeks 1 and 6 and postoperative months 3, 6, 12, 24, and 36. Radiographic evaluations were performed at 6, 12, 24, and 36 months. Neurological examinations and adverse events were recorded at each visit. No intraoperative complications were observed in either treatment group, and clinical outcomes were similarly improved between bone graft substitutes from baseline to 36 months postoperative. Complications were transient hip flexion weakness (13%), insufficient indirect decompression (7%), subsidence (17%), excessive bone formation (4%), and adjacent segment disease (14%). Complication rates between the groups were similar, though with slightly more instances of subsidence in the SiCaP group and higher rates of excessive bone formation and adjacent segment disease in the rh-BMP2 group. Rates of fusion at different time points were different between the groups, with the SiCaP patients progressing more slowly toward solid fusion. However, at 36 months, 100% of patients undergoing XLIF achieved solid fusion. In stand-alone XLIF, SiCaP and rhBMP-2 bone graft substitutes both resulted in complete long-term fusion. rhBMP-2, however, seemed to result in more rapid early postoperative fusion, though with one instance of excessive bone formation in one patient that required subsequent surgical intervention.


Structure-activity study on antiviral 5-vinylpyrimidine nucleoside analogs using Wiener's topological index.
The relationship between Wiener's topological index and the antiviral activity of a series of 5-vinylpyrimidine nucleoside analogs has been investigated. Values for more than 100 compounds were computed, and an active range was identified. The predicted activity of each compound was compared with reported antiviral activity against herpes simplex virus type I. Due to significant correlation between antiviral activity and Wiener's topological index, it was possible to predict antiviral activity with an accuracy of approximately 83%.


Orthodontic extrusion of horizontally impacted mandibular molars.
To introduce and evaluate a novel approach in treating horizontally impacted mandibular second and third molars. An orthodontic technique was applied for treatment of horizontally impacted mandibular second and third molars, which included a push-type spring for rotation first, and then a cantilever for extrusion. There were 8 mandibular third molars (M3s) and 2 second molars (M2s) in this study. Tooth mobility, extraction time, the inclination and parallelism of the impacted tooth, alveolar bone height of the adjacent tooth, and the relationship of impacted M3 and the inferior alveolar nerve (IAN) were evaluated. Two horizontally impacted M2s could be upright in the arch and good occlusal relationships were obtained after treatment. All impacted M3s were successfully separated from the IAN, without any neurologic consequences. The average extraction time was 5 minutes. There was a significant change in the inclination and parallelism of the impacted tooth after treatment. A new bone apposition with the average height of 3.2 mm was noted distal to the adjacent tooth. This two-step orthodontic technique as presented here may be a safe and feasible alternative in management of severely horizontally impacted mandibular molars, which achieves a successful separation of M3s from the IAN and an excellent position for M2s.


A randomized controlled trial of nitrous oxide for intrauterine device insertion in nulliparous women.
To evaluate the effectiveness of inhaled nitrous oxide for pain management among nulliparous women undergoing intrauterine device (IUD) insertion. A double-blind, randomized controlled trial was conducted among nulliparous women aged 13-45years who underwent IUD insertion at a US center between October 1, 2013, and August 31, 2014. Using a computer-generated randomization sequence, participants were randomly assigned to inhale either oxygen (O2) or a mixture of 50% nitrous oxide and 50% oxygen (N2O/O2) through a nasal mask for 2minutes before insertion. Only the person administering the inhalation agent was aware of group assignment. The primary outcome was maximum pain assessed 2minutes after insertion via a 100-mm visual analog scale. Analyses were by intention to treat. Forty women were assigned to each group. Mean maximum pain score at the time of insertion was 54.3±24.8mm for the N2O/O2 group and 55.3±20.9mm for the O2 group (P=0.86). Adverse effects were reported for 6 (15%) women in the N2O/O2 group and 7 (18%) in the O2 group (P=0.32). N2O/O2 did not reduce the pain of IUD insertion among nulliparous women. ClinicalTrials.gov: NCT02391714.


A prevalence study of folate deficiency in a psychiatric in-patient population.
Controlled clinical trials in the UK have shown folate deficiency in psychiatric patients, and it has been suggested that such deficiency is most likely to occur among patients with affective disorders. Studies have led to the use of folate as an adjunct to therapy in such patients. The present paper describes a preliminary investigation into the red cell folate status of psychiatric patients in a general hospital unit compared with age- and sex-matched healthy controls, using up-to-date assays and strict entry criteria and overall improved methods on previous studies. The study showed that, although there is a trend for psychiatric patients to have lower serum folate levels than controls, there is no statistically significant difference in folate levels as measured by red cell folate, a more reliable measure of folate status, between healthy controls and psychiatric patients, and all but one of the patients had normal haematological indices.


[Abnormal aortic origin of coronary arteries].
The anomalous aortic origin of the coronary arteries has an estimated prevalence of 0.02-5.7%. It can be associated with sudden death when it has an interarterial or intramural pathway or be damaged during interventions on the mitral, pulmonary and/or aortic annulus or percutaneous closure of an interatrial septal defect. To identify these patients by imaging techniques such as transthoracic color Doppler echocardiography (TTE), computed tomography (CT) multislice angiography or coronary angiography. The imaging techniques used for the detection of coronary anomalies were TTE, multislice coronary angiography or coronary angiography according to what is generally accepted. Fifteen patients were identified; in 12 of them the suspicion was due to TTE and in the remaining 3, CT multislice angiography was diagnostic. The circumflex artery was the coronary artery most involved, associated or not with another coronary anomaly (12/15 patients) and in the other three cases, the anomalous coronary artery had an interarterial course, with the right coronary arteries and the anterior descending coronary arteries being involved. The under diagnosis by TTE of coronary artery abnormalities may be due to the difficulty of visualization that is accentuated with age. Their detection is crucial because they can both, lead to sudden death associated with an intramural and/or interarterial pathway and complicate an interventional procedure on the interatrial septum or within the mitral, pulmonary and/or aortic rings.


Mitochondrial DNA in pediatric leukemia patients.
Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequences in tumor and normal tissue and at various stages of cancer treatment in the same patient. However, there is little data on acute lymphoblastic leukemia (ALL), the most common type of leukemia in children. In this study we compared mitochondrial sequence variation in the D-loop region and in 5 genes of mtDNA in bone marrow samples of 6 pediatric patients with ALL at various stages of therapy. We found several common polymorphisms and one variant at position 3688 whose level varied during leukemia treatment. Our results suggest that mitochondrial DNA mutations, whose levels change during patient treatment, could be potential biomarkers for monitoring treatment efficacy and disease progression.


Alternatives to transvenous lead placement in a patient undergoing surgical tricuspid valve repair.
Tricuspid regurgitation is a widely recognised phenomenon in patients with transvenous cardiac rhythm management (CRM) devices. If tricuspid valve repair or replacement is to be considered, what to do with the existing CRM system requires scrutiny with multidisciplinary input. We present a case of multifactorial tricuspid regurgitation in a 48-year-old female with giant cell myocarditis and a transvenous implantable cardioverter-defibrillator (ICD). Key considerations in management and alternative CRM options are discussed.


Institution-Level Evolution of Lung Cancer Resection Quality With Implementation of a Lymph Node Specimen Collection Kit.
Lung cancer surgery with a lymph node kit improves patient-level outcomes, but institution-level impact is unproven. Using an institutional stepped-wedge implementation study design, we compared lung cancer resection quality between institutions in preimplementation and postimplementation phases of kit deployment and, within implementing institutions, resections without versus with the kit. Benchmarks included rates of nonexamination of lymph nodes, nonexamination of mediastinal lymph nodes, and attainment of American College of Surgeons Operative Standard 5.8. We report institution-level adjusted ORs (aORs) for attaining quality benchmarks. From 2009 to 2020, three preimplementing hospitals had 953 resections; 11 implementing hospitals had 4013 resections, 58% without and 42% with the kit. Quality was better in implementing institutions and with kit cases. Compared with preimplementing institutions, the aOR for nonexamination of lymph nodes was 0.62 (0.49-0.8, p = 0.002), nonexamination of mediastinal lymph nodes was 0.56 (0.47-0.68, p < 0.0001), and attainment of Operative Standard 5.8 was 7.3 (5.6-9.4, p < 0.0001); aORs for kit cases were 0.01 (0.001-0.06), 0.08 (0.06-0.11), and 11.6 (9.9-13.7), respectively (p < 0.0001 for all). Surgical quality was persistently poor in preimplementing institutions but sequentially improved in implementing institutions in parallel with kit adoption. In implementing institutions, resections with the kit had a uniformly high level of quality, whereas nonkit cases had a low level of quality, approximating that of preimplementing institutions. Within implementing institutions, 5-year overall survival was 61% versus 51% after surgery with versus without the kit (p < 0.001). Surgery with a lymph node specimen collection kit improved institution-level quality of curative-intent lung cancer resection.


Resistance of Neisseria gonorrhoeae to neutrophils.
Infection with the human-specific bacterial pathogen Neisseria gonorrhoeae triggers a potent, local inflammatory response driven by polymorphonuclear leukocytes (neutrophils or PMNs). PMNs are terminally differentiated phagocytic cells that are a vital component of the host innate immune response and are the first responders to bacterial and fungal infections. PMNs possess a diverse arsenal of components to combat microorganisms, including the production of reactive oxygen species and release of degradative enzymes and antimicrobial peptides. Despite numerous PMNs at the site of gonococcal infection, N. gonorrhoeae can be cultured from the PMN-rich exudates of individuals with acute gonorrhea, indicating that some bacteria resist killing by neutrophils. The contribution of PMNs to gonorrheal pathogenesis has been modeled in vivo by human male urethral challenge and murine female genital inoculation and in vitro using isolated primary PMNs or PMN-derived cell lines. These systems reveal that some gonococci survive and replicate within PMNs and suggest that gonococci defend themselves against PMNs in two ways: they express virulence factors that defend against PMNs' oxidative and non-oxidative antimicrobial components, and they modulate the ability of PMNs to phagocytose gonococci and to release antimicrobial components. In this review, we will highlight the varied and complementary approaches used by N. gonorrhoeae to resist clearance by human PMNs, with an emphasis on gonococcal gene products that modulate bacterial-PMN interactions. Understanding how some gonococci survive exposure to PMNs will help guide future initiatives for combating gonorrheal disease.


Effect of vitamin E and beta-carotene on DNA strand breakage induced by tobacco-specific nitrosamines and stimulated human phagocytes.
The tobacco-specific nitrosamines (TSNAs), nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are metabolites of nicotine and are major carcinogens in cigarette smoke. Chronic inflammation may promote the carcinogenic effect of these nitrosamines through the generation of oxygen radicals. To evaluate the effect of oxygen radicals on TSNA-induced genetic damage, cultured human lung cells treated with NNN or NNK were exposed to stimulated human phagocytes and assayed for single-strand DNA breaks. TSNAs or stimulated phagocytes alone cause a significant increase in strand breakage which is augmented in an additive fashion when the two are combined. Pretreating the cells with vitamin E or beta carotene provided significant protection against the induction of DNA damage but vitamin E was significantly more effective than beta carotene. These data suggest a possible approach to the chemoprevention of tobacco-induced carcinogenesis.


DNA Origami Mask for Sub-Ten-Nanometer Lithography.
DNA nanotechnology is currently widely explored and especially shows promises for advanced lithography due to its ability to define nanometer scale features. We demonstrate a 9 × 14 nm(2) hole pattern transfer from DNA origami into an SiO2 layer with a sub-10-nm resolution using anhydrous HF vapor in a semiconductor etching machine. We show that the resulting SiO2 pattern inherits its shape from the DNA structure within a process time ranging from 30 to 60 s at an etching rate of 0.2 nm/s. At 600 s of etching, the SiO2 pattern meets corrosion and the overall etching reaction is blocked. These results, in addition to the entire surface coverage by magnesium occurring on the substrate at a density of 1.1 × 10(15) atom/cm(2), define a process window, fabrication rules, and limits for DNA-based lithography.


Proteome informatics II: bioinformatics for comparative proteomics.
The present review attempts to cover the most recent initiatives directed towards representing, storing, displaying and processing protein-related data suited to undertake "comparative proteomics" studies. Data interpretation is brought into focus. Efforts invested into analysing and interpreting experimental data increasingly express the need for adding meaning. This trend is perceptible in work dedicated to determining ontologies, modelling interaction networks, etc. In parallel, technical advances in computer science are spurred by the development of the Web and the growing need to channel and understand massive volumes of data. Biology benefits from these advances as an application of choice for many generic solutions. Some examples of bioinformatics solutions are discussed and directions for on-going and future work conclude the review.