Remodeling of Mitochondrial Flashes in Muscular Development and Dystrophy in Zebrafish.
Mitochondrial flash (mitoflash) is a highly-conserved, universal, and physiological mitochondrial activity in isolated mitochondria, intact cells, and live organisms. Here we investigated developmental and disease-related remodeling of mitoflash activity in zebrafish skeletal muscles. In transgenic zebrafish expressing the mitoflash reporter cpYFP, in vivo imaging revealed that mitoflash frequency and unitary properties underwent multiphasic and muscle type-specific changes, accompanying mitochondrial morphogenesis from 2 to 14 dpf. In particular, short (S)-type mitoflashes predominated in early muscle formation, then S-, transitory (T)- and regular (R)-type mitoflashes coexisted during muscle maturation, followed by a switch to R-type mitoflashes in mature skeletal muscles. In early development of muscular dystrophy, we found accelerated S- to R-type mitoflash transition and reduced mitochondrial NAD(P)H amidst a remarkable cell-to-cell heterogeneity. This study not only unravels a profound functional and morphological remodeling of mitochondria in developing and diseased skeletal muscles, but also underscores mitoflashes as a useful reporter of mitochondrial function in milieu of live animals under physiological and pathophysiological conditions.


High Visceral Fat is Associated with a Worse Survival after Liver Resection for Intrahepatic Cholangiocarcinoma.
The impact of body composition (BC) on the prognosis of resected intrahepatic cholangiocarcinoma (ICC) has been poorly studied. Aims: i) to evaluate the prevalence of low muscle mass (MM) in patients; ii) to assess the impact of BC on patient overall survival (OS) and disease-free survival (DFS), and iii) on the incidence of postoperative complications. All consecutive patients who underwent liver resection for ICC between 2004 and 2016 and who had preoperative CT scans were included. Ninety-three patients were included. Sixty percent (55/91) had low total MM. On multivariable analysis, high visceral fat (HR 2.48, CI95% [1.63; 3.77], p < 0.0001), nodules >1 (HR 3.15 [1.67; 5.93], p = 0.0004), involvement adjacent organ (HR 6.67 [1.88; 23.69], p = 0.003), and postoperative sepsis (HR 3.04 [1.54; 5.99], p = 0.0013) were independently associated with OS. High visceral fat (HR 2.10 [1.31; 3.38], p = 0.002], nodules >1 (HR 3.01, [1.49; 6.10], p = 0.002), postoperative sepsis (HR 5.16 [2.24; 11.89], p = 0.0001), ASA score (p = 0.02) and perineural invasion (HR 3.30 [1.62; 6.76], p = 0.001) were independently associated with lower DFS. Conclusion: 60% of ICC patients had low MM before surgery. High visceral fat, but not muscle mass, was an independent prognostic factor for poor OS and DFS in European patients with resected ICC.


Inherited thrombocytopenias: molecular mechanisms.
Each megakaryocyte forms 10(3) platelets and 10(11) platelets are replenished daily. The unique and amazing mechanisms that allow megakaryocytes to become giant and polyploid and to release such a large number of platelets are still poorly understood. The study of inherited thrombocytopenias offers the possibility to gain new information on these processes because several different forms, deriving from defective megakaryocytic commitment, differentiation, maturation, or platelet formation, have been identified. Moreover, in the presence of some genetic defects, megakaryocytes produce platelets with a shortened life span. In this review, we summarize what we have learned about inherited thrombocytopenias in the last few years.


Clonal growth of colorectal-carcinoma cell lines transplanted to nude mice.
It is generally assumed that tumor progression is a microevolutionary process in which increasingly aggressive clones, generated through genetic instability, emerge in an initially monoclonal lesion. The present study was undertaken to determine how rapidly a dominant clone will emerge from an initial polyclonal situation, and whether dominance of these clones is a prerequisite for the onset of metastasis. To this end, colon-carcinoma cells were infected in culture with an amphotropic retroviral vector containing the neomycin-phosphotransferase gene, which makes cells resistant to neomycin. A heterogeneous population of neomycin-resistant cells carrying random retroviral integrations was xenografted to the subcutis and to the cecum of nude mice. The xenografts obtained, as well as the available metastases, were analyzed as to viral integrations by Southern blotting. The results show that, (i) clonal selection already takes place during growth of the primary tumor; (ii) dominant clones also generate metastases. The retroviral integration pattern of metastases turned out to be identical to that found in the primary xenografts. This pattern remained unchanged in tumors obtained after serial transplantations of cells cultured from metastases.


Massive cardiac involvement of adult T-cell leukemia/lymphoma. An autopsy case.
We describe an unusual autopsy case of adult T-cell leukemia/lymphoma with massive cardiac involvement. The patient was admitted to the hospital with symptoms of fever and cervical lymph node enlargement, which improved following treatment with vincristine sulfate, cyclophosphamide (Endoxan), prednisolone sodium succinate, and doxorubicin hydrochloride (Adriamycin). He was then followed up in the outpatient clinic, but was readmitted to the hospital with palpitations and dyspnea. Cardiomegaly developed rapidly, and the patient died of congestive heart failure 3 months after readmission. The heart was massively enlarged at autopsy. The heart, including adhered surrounding tissue, weighed 1600 g. The myocardium was found to be replaced by massive infiltration of atypical lymphoid cells. Cardiac involvement by adult T-cell leukemia/lymphoma may result from extension or retrograde flow through cardiac lymphatics from the destroyed mediastinal lymphatic system.


Most probable numbers of organisms: revised tables for the multiple tube method.
Estimation of numbers of organisms is often made using dilution series, for example when examining water samples for coliform organisms. In this paper the most probable numbers (MPNs) are calculated for a 15-tube series consisting of five replicates at three consecutive tenfold dilutions. Exact conditional probabilities are computed to replace previous approximations. When growth is observed in several of the tubes it is not realistic to select a single MPN. Instead a most probable range (MPR) should be reported. But using an MPR creates problems when comparison has to be made with a legislated, single-valued Standard. It is suggested that the wording of the Standards should be expressed differently when the multiple tube method is used.


Homology modeling of anti-parathion antibody and its interaction with organophosphorous pesticides and analogues.
The mechanism of specific recognition in pesticide immunochemistry was investigated by computer-based strategy, and a rapid method for the identification of antibody specificity was developed. Based on the previously produced anti-parathion monoclonal antibody (mAb), the DNA sequence was analyzed by polymerase chain reaction (PCR). From the translated amino acid sequences, a three-dimensional structure of the antibody was constructed by homology modeling method, and then it was coordinated by 1 ns molecular dynamics under the explicit solvent condition. The stereochemical property and folding quality were further assessed by Procheck and Profile-3D. The self-compatibility score for the antibody model was 98.7, which was greater than the low score 46.2 and close to the top score 102.6. In addition, parathion and several structural analogues were docked to the constructed antibody structure. The docking results showed that the interaction energy (-40.54 kcal/mol) of antibody-parathion complex was the lowest among all the tested pesticides, which accounted for the high specificity of the antibody to parathion and perfectly matched with the experimental data. Moreover, three residues, Phe165, Asp107 and Thr100 were recognized as the most important residues for antibody reacting with parathion. The interaction energy negatively correlated with the antibody specificity.


[Intravenous immunoglobulin treatment in idiopathic inflammatory myopathy].
Idiopathic inflammatory myopathies are chronic, systemic autoimmune diseases, characterized by symmetric and progressive weakness of proximal muscles in the upper and lower extremities. Treatment of the disease presents a complex challenge and it needs practical knowledge. In this review the authors summarize current treatment options, and discuss intravenous immunoglobulin treatment in therapy-unresponsive cases. Relevant data from the international literature is collected, too. Benefits and side effects of this treatment are also disclosed.


Health Care and Education Access of Transnational Children in Mexico.
Between 2001 and 2018, more than 5.5 million Mexican migrants were removed from the United States or returned to Mexico with their families as immigration enforcement escalated. Learning how this transition affected their children-also referred to as "the invisibles"-is a policy-relevant topic for both the United States and Mexico. Using representative data on 7.6 million Mexican- and U.S.-born children from the 2015 Mexican Intercensal Survey, we provide evidence of the gaps in access to education and health care between these two groups and of the factors potentially responsible for the existing barriers. Relative to children born in Mexico, U.S.-born children are at a considerable disadvantage in terms of health care access, but less so in terms of education. Lack of a Mexican-issued birth certificate is among the persistent factors responsible for the gaps in services. Policies aimed at changing the approach to immigration enforcement in the United States, lessening paperwork requirements in Mexico, and easing access to documentation in both countries could improve transnational children's access to basic services, as well as their present and long-term well-being.


Tight Junction Disruption Induced by Type 3 Secretion System Effectors Injected by Enteropathogenic and Enterohemorrhagic Escherichia coli.
The intestinal epithelium consists of a single cell layer, which is a critical selectively permeable barrier to both absorb nutrients and avoid the entry of potentially harmful entities, including microorganisms. Epithelial cells are held together by the apical junctional complexes, consisting of adherens junctions, and tight junctions (TJs), and by underlying desmosomes. TJs lay in the apical domain of epithelial cells and are mainly composed by transmembrane proteins such as occludin, claudins, JAMs, and tricellulin, that are associated with the cytoplasmic plaque formed by proteins from the MAGUK family, such as ZO-1/2/3, connecting TJ to the actin cytoskeleton, and cingulin and paracingulin connecting TJ to the microtubule network. Extracellular bacteria such as EPEC and EHEC living in the intestinal lumen inject effectors proteins directly from the bacterial cytoplasm to the host cell cytoplasm, where they play a relevant role in the manipulation of the eukaryotic cell functions by modifying or blocking cell signaling pathways. TJ integrity depends on various cell functions such as actin cytoskeleton, microtubule network for vesicular trafficking, membrane integrity, inflammation, and cell survival. EPEC and EHEC effectors target most of these functions. Effectors encoded inside or outside of locus of enterocyte effacement (LEE) disrupt the TJ strands. EPEC and EHEC exploit the TJ dynamics to open this structure, for causing diarrhea. EPEC and EHEC secrete effectors that mimic host proteins to manipulate the signaling pathways, including those related to TJ dynamics. In this review, we focus on the known mechanisms exploited by EPEC and EHEC effectors for causing TJ disruption.


Sequential hemodynamic change in hepatocellular carcinoma and dysplastic nodules: CT angiography and pathologic correlation.
The purpose of this study was to clarify the hemodynamic changes associated with hepatocarcinogenesis using CT angiography. Eighty-six hepatocellular lesions were confirmed at pathology in 49 patients who underwent CT with both hepatic arteriography and arterioportography. These images were compared with lesion-to-liver vascular ratios of cumulative arteries, preexisting hepatic arteries, and portal veins in resected specimens. Lesions were classified in five groups according to intranodular hemodynamics determined by CT hepatic arteriography and CT during arterioportography: group 1, isoattenuating on both procedures; group 2, hypoattenuating on CT hepatic arteriography and isoattenuating on CT during arterioportography; group 3, hypoattenuating on both procedures; group 4, isoattenuating on CT hepatic arteriography and hypoattenuating on CT during arterioportography; and group 5, hyperattenuating on CT hepatic arteriography and hypoattenuating on CT during arterioportography. Among 86 lesions, we identified seven low-grade dysplastic nodules, eight high-grade dysplastic nodules, 14 well-differentiated hepatocellular carcinomas, 45 moderately differentiated hepatocellular carcinomas, and 12 poorly differentiated hepatocellular carcinomas. The lesions were classified as group 1 (n = 5), group 2 (n = 13), group 3 (n = 6), group 4 (n = 2), or group 5 (n = 60). Intranodular hemodynamics was significantly correlated with pathologic grading (p < 0.001). For correlations between combinations of the groups and pathologic gradings, the order "groups 1-2-3-4-5" was the most significant (p < 0.001). During hepatocarcinogenesis, most hepatocellular nodules show deterioration of arterial blood flow before loss of portal blood flow. Vascular imaging of hepatic nodules may predict malignant abnormality via the early loss of hepatic arterial flow seen before portal flow changes.


Strain-tuned magnetism and half-metal to metal transition in defective BCN monolayer.
Recently, two-dimensional (2D) BCN, an in-plane heterostructure formed by graphene and hexagonal boron nitride, has been successfully synthesized experimentally and exhibits diverse electronic properties. Unfortunately, it has been slow on the application of 2D BCN for spintronics due to the lack of the magnetic ordering. Here, using density functional theory calculations, we explored the effect of vacancy defect and biaxial strain on the electronic and magnetic properties of BCN monolayer. It is demonstrated that BCN monolayer can be converted from nonmagnetic semiconductor to magnetic half-metal/metal by introducing C or B vacancies. The half-metal/metal behavior can be remained under the different vacancy concentrations in defective BCN monolayer. In addition, BCN monolayer with C and B vacancies can be converted between half-metal and metal by applying biaxial strain. Moreover, the magnetic properties of defective BCN monolayer can also be efficiently modulated under the biaxial strain by regulating the spin polarization of the C/N/B 2porbitals. Our findings not only provide an effective way to achieve half-metal/metal transition, but also can induce and manipulate the magnetism of BCN monolayer, which may be utilized for the development of 2D BCN spintronic nanodevices.


[Towards immuno-modulation through the molecular mechanism of lymphocyte activation].
Recognition of the antigen/MHC complex by the T cell receptor (TCR)-CD3 complex in T cells triggers early activation events such as tyrosine phosphorylation, phosphatidylinositol turnover, intracellular Ca2+ mobilization or activation of protein kinases, and finally exhibits effector functions such as lymphokine secretion by helper T cells or cytotoxicity by killer T cells as late activation events. Several key molecules have been shown to engage in these signaling cascades. In addition to the TCR-CD3 molecules, other surface molecules such as CD28 or LFA-1 contribute to the regulation of T cell activation as a co-stimulator. Growing knowledge about the downstream of antigen recognition is promoting the attempt to modulate the signal transduction by specific drugs, mAbs, altered peptides or cytokines. Further investigations on the molecular mechanism of T cell activation will provide clinical successes to control immune responses.


How to assess the nose for rhinoplasty.
Rhinoplasty is one of the most demanding of all cosmetic procedures. The surgeon has to have a knowledge of facial and nasal esthetics and must work within the framework of the structure of the nose at hand. The total preoperative evaluation of the patient is discussed including the process of consultation and recognition of risk factors. The guidelines that we use to structure our esthetically pleasing nose are discussed.


The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis.
Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40-75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but no difference between duloxetine and placebo (P>0.05) was observed. In the per protocol analysis, NRS pain was reduced for pregabalin (P<0.0001) and duloxetine (P=0.029) compared to placebo. We conclude that centrally acting analgesics improve pain outcomes in people with hand arthritis, offering new treatment paradigms for OA pain.


Variable interactions between sucrose non-fermented 1-related protein kinases and regulatory proteins in higher plants.
WPK4 is a sucrose non-fermented 1 (SNF1)-related wheat protein kinase, and was previously reported to interact with 14-3-3 proteins. We identified four Arabidopsis thaliana WPK4-like genes, and designated them AtWL1 through AtWL4. Yeast two-hybrid analysis, however, indicated that none of the AtWLs interacted with any of A. thaliana 14-3-3 (At14-3-3) proteins, although WPK4 itself interacted with six of them. Structurally, AtWLs were classified into a subfamiliy of AtCIPK, which generally interacts with calucineurin B-like proteins (CBL). This was also the case for AtWL1 and AtWL2, showing an efficient interaction with AtCBL2. In contrast, WPK4 interacted with none of the CBLs. In addition, to ascertain the possible interaction in vivo, expression of those genes was examined with a promoter-GUS assay. These results suggested that the interacting partner of SNF1-related protein kinases varies among plant species, and that, in the case of A. thaliana, it was CBLs, some of which were predicted to broadly regulate multiple CIPKs.


Induction of Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury in Mice.
Acute myocardial infarction is a common cardiovascular disease with high mortality. Myocardial reperfusion injury can counteract the beneficial effects of heart reflow and induce secondary myocardial injury. A simple and reproducible model of myocardial infarction and myocardial ischemia-reperfusion injury is a good tool for researchers. Here, a customizable method to create a myocardial infarction (MI) model and MIRI by precision ligation of the left anterior descending coronary artery (LAD) through micromanipulation is described. Accurate and reproducible ligature positioning of the LAD helps obtain consistent results for heart injury. ST-segment changes can help to identify model accuracy. The serum level of cardiac troponin T (cTnT) is used to assess the myocardial injury, cardiac ultrasound is employed to evaluate the myocardial systolic function, and Evans-Blue/triphenyl tetrazolium chloride staining is used to measure infarct size. In general, this protocol reduces procedure duration, ensures controllable infarct size, and improves mouse survival.


Laser-induced corneal cross-linking upon photorefractive ablation with riboflavin.
To estimate the biomechanical effect of the laser-induced cross-linking resulting from photorefractive ablation of the cornea with riboflavin. Excimer laser ablation studies were performed ex vivo (32 eyes of 16 rabbits) by phototherapeutic keratectomy (PTK) and in vivo (24 eyes of 12 rabbits) by transepithelial photorefractive keratectomy (TransPRK), with and without riboflavin saturation of the stroma. Then, we performed corneal optical coherence tomography on 36 eyes of 18 patients with varying degrees of myopia at different times after the TransPRK was performed with riboflavin saturation of the stroma. Biomechanical testing of corneal samples saturated with riboflavin revealed cross-linking effect accompanied by the increase in tensile strength and maximum strength. PTK showed increase in tensile strength from 5.1±1.4 to 7.2±1.6 MPa (P=0.001), while Trans-PRK showed increase in tensile strength from 8.8±0.9 to 12.8±1.3 MPa (P=0.0004). Maximum strength increased from 8.7±2.5 to 12.0±2.8 N (P=0.005) in PTK and from 12.8±1.6 to 18.3±1.2 N (P=0.0004) in TransPRK. Clinical optical coherence tomography studies of the biomicroscopic transparent cornea at different times after TransPRK showed increased density in the surface layers of the stroma and membrane-like structure beneath the epithelium. Photorefractive ablation of the preliminary corneal stroma saturation with riboflavin causes the effect of laser-induced cross-linking, which is attended with an increase in corneal tensile strength, maximum strength, increased density in the surface layers of the stroma, and formation of a membrane-like structure beneath the epithelium after TransPRK.


Bioprinting Au Natural: The Biologics of Bioinks.
The development of appropriate bioinks is a complex task, dependent on the mechanical and biochemical requirements of the final construct and the type of printer used for fabrication. The two most common tissue printers are micro-extrusion and digital light projection printers. Here we briefly discuss the required characteristics of a bioink for each of these printing processes. However, physical printing is only a short window in the lifespan of a printed construct-the system must support and facilitate cellular development after it is printed. To that end, we provide a broad overview of some of the biological molecules currently used as bioinks. Each molecule has advantages for specific tissues/cells, and potential disadvantages are discussed, along with examples of their current use in the field. Notably, it is stressed that active researchers are trending towards the use of composite bioinks. Utilizing the strengths from multiple materials is highlighted as a key component of bioink development.


Facile Solvothermal Preparation of Mn2CuO4 Microspheres: Excellent Electrocatalyst for Real-Time Detection of H2O2 Released from Live Cells.
Hydrogen peroxide (H2O2) is an eminent biomarker in pathogenesis; a selective, highly sensitive real-time detection of H2O2 released from live cells has drawn a significant research interest in bioanalytical chemistry. Binary transition-metal oxides (BTMOs) displayed a recognizable benefit in enhancing the sensitivity of H2O2 detection; although the reported BTMO-based H2O2 sensor's detection limit is still insufficient, it is not appropriate for in situ profiling of trace amounts of cellular H2O2. In this paper, we describe an efficient, reliable electrochemical biosensor based on Mn2CuO4 (MCO) microspheres to assay cellular H2O2. The Mn2CuO4 microspheres were prepared through a superficial solvothermal method. It is obvious from impedance studies, introduction of manganese into copper oxide lattice significantly improved the ionic conductivity, which is beneficial for the electrochemical sensing process. Thanks to the distinct microsphere structure and excellent synergy, MCO-modified electrode exhibited excellent nonenzymatic electrochemical behavior toward H2O2 sensing. The MCO-modified electrode delivered a broad working range (36 nM to 9.3 mM) and an appreciable detection limit (13 nM), with high selectivity toward H2O2. To prove its practicality, the developed sensor was applied in the detection of cellular H2O2 released by RAW 264.7 cells in presence of CHAPS. These results label the possible appliance of the sensor in clinical analysis and pathophysiology. Thus, BTMOs are evolving as a promising candidate in designing catalytic matrices for biosensor applications.


Fabry-Perot cavity based on silica tube for strain sensing at high temperatures.
In this work, a Fabry-Perot cavity based on a new silica tube design is proposed. The tube presents a cladding with a thickness of ~14 μm and a hollow core. The presence of four small rods, of ~20 μm diameter each, placed in diametrically opposite positions ensure the mechanical stability of the tube. The cavity, formed by splicing a section of the silica tube between two sections of single mode fiber, is characterized in strain and temperature (from room temperature to 900 °C). When the sensor is exposed to high temperatures, there is a change in the response to strain. The influence of the thermal annealing is investigated in order to improve the sensing head performance.


[Changes of dystrophin and desmin in rat gastrocnemius under micro-damage induced by hypoxia].
To explore the changes and regulation mechanism of dystropin and desmin under muscle injury without mechanic stress, 40 male Sprague-Dawley rats were randomly divided into 5 groups, which included normoxia control and hypoxia groups for 1, 2, 4 and 7 d with 10% O2. Two rats from each group were examined for sarcolemma integrity using Evans blue dye (EBD) and EBD-positive fiber typing by metachromatic dye-ATPase method. The rest six rats from each group were analyzed for the changes of protein content and gene expression using Western blot, RT-PCR and fluorescence assays. The results showed that the EBD-positive muscle fibers, mainly type IIA and type IIB, appeared at 1 d after hypoxia exposure. Both the ratio of EBD-positive cell and the mean fluorescence density were significantly higher in hypoxia groups than those in control group (P<0.05). The contents of dystrophin and desmin fluctuated after hypoxia exposure, increased at 1 d, decreased at 2 d, increased dramatically again at 4 d, and returned to a normal level at 7 d. Consistently, the gene expression began to increase significantly after 2 d. The total activity of calpain was significantly higher in hypoxia groups at 1, 4 and 7 d. Significantly higher levels of HSP70 and HSP90 were also observed at 4 and 7 d, respectively (P<0.05). These results suggest that the mechanical stress is not the only cause of damage of sarcolemma membrane integrity. In contrast to eccentric contraction, hypoxia-induced muscle damage is not accompanied by the loss of dystrophin and desmin. The types of muscle fibers recruited by motor units and the activities of calpain may be important in hypoxia-induced damage of sarcolemma membrane integrity.


Adaptation and validation of the Advanced Practice Nursing Competency Assessment Instrument.
To adapt and validate the content of the Advanced Practice Nursing Competency Assessment Instrument (APNCAI) to Brazilian culture. This is a methodological study that followed the stages of translation, synthesis, back translation, evaluation by a committee of five specialists, pre-test with 31 nurses, and evaluation by the author of the original instrument. The Content Validity Index (minimum 0.90) and the modified Kappa (minimum 0.74) were calculated to evaluate the content. In the first round of content evaluation, 18 items had to be altered because they did not reach the minimum values established. Three items have not reached a consensus in the second round and had to be sent to the author of the original version. In the pre-test, 13 items were returned to the specialists because they suffered content changes. The Advanced Practice Nursing Competency Assessment Instrument (APNCAI) - Brazilian version was cross-culturally adapted, and its content was validated.


Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid transformation.
Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a recently described entity in the World Health Organization (WHO) 2004 classification and has a relatively indolent behavior. Sarcomatoid differentiation has been well documented in most histologic variants of renal cell carcinoma and its presence is known to have a worse prognosis. Its occurrence in an otherwise benign MTSCC is extremely rare. Here, we report a unique case of MTSCC in a 64-year-old patient with multiple areas of high-grade spindle cells and large areas of necrosis in it. The patient had a rapidly fatal clinical outcome.


Interdisciplinary Management of Minimally Displaced Orbital Roof Fractures: Delayed Pulsatile Exophthalmos and Orbital Encephalocele.
Traumatic orbital roof fractures are rare and are managed nonoperatively in most cases. They are typically associated with severe mechanisms of injury and may be associated with significant neurologic or ophthalmologic compromise including traumatic brain injury and vision loss. Rarely, traumatic encephalocele or pulsatile exophthalmos may be present at the time of injury or develop in delayed fashion, necessitating close observation of these patients. In this article, we describe two patients with minimally displaced blow-in type orbital roof fractures that were later complicated by orbital encephalocele and pulsatile exophthalmos, prompting urgent surgical intervention. We also suggest a management algorithm for adult patients with orbital roof fractures, emphasizing careful observation and interdisciplinary management involving plastic surgery, neurosurgery, and ophthalmology.


Prevention and management of complications of regional orbital anesthesia.
The majority of ophthalmic procedures are performed under regional anesthesia, but the proximity of important structures such as the blood vessels, optic nerve and the brainstem lead to increased risks associated with these blocks. The most serious of these complications is brainstem anesthesia. As the number of outpatient freestanding surgical centers increase, the significance of these potential complications is expected to increase from orbital blocks for ocular surgical procedures such as cataract removal and vitrectomy. An understanding of these complications, which may sometimes be life-threatening, are thus vital to the anesthesia practitioner. Procedural improvements include a close evaluation of the precise anatomy of the region, with particular attention to injection sites, depth of injection, position of the globe, and techniques to avoid nerve damage and accidental injection into surrounding structures, including blood vessels, globe and cerebrospinal fluid. This literature review emphasizes the importance of the prevention, recognition and management of these complications, which includes the extremely serious complication of brainstem anesthesia.


Differences in Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for the Treatment of Focal Articular Cartilage Defects.
Articular cartilage pathology can result from a spectrum of origins, including trauma, osteochondritis dissecans, avascular necrosis, or degenerative joint disease. To compare the differences in clinical and patient-reported outcomes after autologous chondrocyte implantation (ACI) versus osteochondral allograft transplantation (OCA) in patients with focal articular cartilage defects without underlying bone loss. Cohort study; Level of evidence, 3. A retrospective review identified patients who underwent ACI or OCA between 2008 and 2016 for isolated grades 3 and 4 articular cartilage defects without underlying bone loss. Outcome measures included the Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), International Knee Documentation Committee (IKDC) evaluation, and 12-Item Short Form Health Survey-Physical Component (SF-12-P) scores. Defect location, size, complications, and rate of subsequent surgery were determined. Overall, 148 patients were included: 82 (55%) underwent ACI and 66 (45%) underwent OCA. The mean age at the time of surgery was 31.2 years within the ACI cohort and 37.7 years within the OCA cohort (P < .001); the mean follow-up for both cohorts was 6.7 years (P = .902). Within the ACI group, 28 (34%) patients had multifocal defects, 21 (26%) had defects confined to the femoral condyles, and 33 (40%) had defects in the patellofemoral region. Within the OCA group, 23 (35%) patients had multifocal defects, 30 (46%) had confined femoral condyle lesions, and 13 (20%) had patellofemoral defects. When comparing by lesion location, there were no significant differences in KOOS JR, and IKDC scores between the ACI and OCA cohorts (P < .05). There was, however, a significant difference for SF-12-P scores for FDD trochlear lesions. In both cohorts, traumatic patellofemoral pathology demonstrated lower patient-reported outcomes and higher failure rates than degenerative lesions. The overall rate of failure, defined as graft failure with revision surgery and/or conversion to arthroplasty, was significantly greater in the OCA group (21% vs 4%; P = .002). Study results indicated that ACI provides similar outcomes to OCA with or without concomitant procedures for the treatment of symptomatic articular cartilage defects in all lesion locations and may have a lower revision rate for multifocal and condylar lesions.


The TORC1-Sch9-Rim15 signaling pathway represses yeast-to-hypha transition in response to glycerol availability in the oleaginous yeast Yarrowia lipolytica.
The yeast-to-hypha dimorphic transition is important for survival under nutrient starvation in fungi. The oleaginous yeast Yarrowia lipolytica grows in the oval-shaped yeast form in glycerol media whereas it adopts a filamentous form in glucose media. It is not clear why this yeast responds differently to glycerol and glucose. Here, we show that glycerol blocks dimorphic transition even in the presence of glucose whereas glycerol depletion induces filamentous growth, suggesting that dimorphic transition is repressed in response to glycerol availability. We show that the repression of dimorphic transition in glycerol media is mediated by the TORC1-Sch9 signaling pathway as both TORC1 inhibition and the loss of YlSch9 cause hyperfilamentation. TORC1-Sch9 signaling inhibits the nuclear translocation of YlRim15, a protein kinase that positively regulates filamentous growth, preventing it from entering the nucleus to activate the transcription of genes implicated in filamentous growth. Interestingly, TORC1-Sch9 signaling appears not to inhibit YlRim15 in glucose media, which could explain why Y. lipolytica responds differently to glycerol and glucose. We identified MHY1, a transcription factor-encoding gene known to be critical for filamentous growth, as one target regulated by the TORC1-Sch9-Rim15 signaling pathway. Our results provide new insights in the regulation of dimorphic transition in yeast.


Ultrasonographic evaluation of incidence of diaphragmatic paralysis following different volumes of supraclavicular brachial plexus block- A prospective randomized double blinded study.
Ipsilateral diaphragmatic paralysis occurs following supraclavicular blocks such as interscalene blocks, supposedly attributable to the backward diffusion of the local anesthetic (LA) inside the neural sheath. Hence, we have made an attempt to assess diaphragmatic paralysis with ultrasonogram (US) following different volumes of supraclavicular brachial plexus blocks (SCB). To compare the incidence of diaphragmatic paralysis with different volumes of supraclavicular brachial plexus block using ultrasonogram. Sixty patients with American Society of Anesthesiologists (ASA) Physical Status I and II were randomized to receive 20, 25, or 30 mL of 0.375% bupivacaine in a double-blinded fashion, and supraclavicular block was performed using ultrasound guidance in an in-plane technique. Diaphragmatic excursion and velocity were studied using a curvilinear 3.5 MHz transducer before and 20 min after giving the block. The incidence of reduction in diaphragmatic excursion and velocity in the group receiving 30 mL was 45% and 45%, respectively, which was higher, whereas it was 47.5% and 32.5% in the 25 mL group and 40% and 25% in the 20 mL group, respectively, which were still lower. Pre- and post-block data were studied using T-test, Kruskal-Wallis test, and Mann-Whitney U test. The probability of reduction in diaphragmatic excursion and velocity in each group was <0.05, which was statistically significant. Our results suggest that there is a greater risk of inadvertent phrenic nerve blockade even in supraclavicular brachial plexus block. The resulting hemidiaphragmatic paralysis is volume dependent, and the overall incidence is higher at greater volumes. Hence, caution is required against compromised perioperative lung function in patients with preexisting cardiorespiratory dysfunction.


Infrared optical sensor for measuring internal interfacial wave motions.
The absorption of infrared energy is used to infer internal interfacial displacements. The probe consists of an infrared emitting diode, operated in a pulsed mode, which projects a collimated beam of radiation across a fluid interface onto a silicon photodiode detector. The output of the diode feeds an amplifier and a sample-and-hold circuit. Through multiplexing, the electronics are capable of handling up to eight probes. The infrared sensor has a sensitivity of about 1 V/cm, and it may easily be used to resolve wave motions as small as 0.01 mm.


The Presence of Cough and Tuberculosis: Active Case Finding Outcomes in the Philippines.
The results of a tuberculosis (TB) active case finding (ACF) program, implemented by International Care Ministries (ICM) in the Philippines, were examined to understand how the presence of physical symptoms might influence ACF outcomes among extreme low-income Filipinos. ICM health staff implemented symptom screening in villages and suspected cases were referred to the closest rural health unit (RHU) for TB testing. ACF was carried out in Mindanao and the Visayas, across 16 different provinces. All participants were interviewed pre/postprogram, and screening outcomes were collected. A multilevel regression model was constructed to explore the effect of factors on the likelihood of getting tested. A total of 4635 individuals were screened; 1290 (27.8%) were symptom positive and referred. From those referred, 336 (7.2%) were tested for TB and 53 (1.1%) were TB positive. "Cough for more than two weeks" was associated with a 1.09 (95% CI 1.01, 1.15) times increase in likelihood of getting tested. The finding that the presence of cough is associated with higher rate of testing suggests that individuals in these settings might not know or believe that the lack of cough does not equate to lack of TB infection. While technologies and screening algorithms give us the ability to refine the 'supply' side of the TB screening, addressing the knowledge gap should improve 'demand'.


Prediction tests for recurrent hypertensive disease in pregnancy, a systematic review.
To summarize reported evidence on the performance and clinical usefulness of prediction tests for recurrent hypertensive disease in pregnancy. A literature search was conducted in MEDLINE/PubMed and EMBASE. Test characteristics were extracted for relevant reports. Thirty-three of 4,311 articles found met the inclusion criteria. Twenty-four potential predictors were identified. Pre-pregnant plasma volume, uterine-artery blood flow velocity profiles, and combined longitudinal patterns of in-pregnancy laboratory variables had reasonable predictive capacity, but also some practical shortcomings. Confidence intervals were often wide. Although evidence points to promising predictive accuracy of some tests, immediate applicability is hampered by statistical imprecision and clinical drawbacks.


Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy.
Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4+ T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes.


Mechanisms, Diagnosis and Treatment of Bone Metastases.
Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, well-tolerated and more successful treatments for a significant improvement of patients' quality of life and disease outcome. In this review, we provide comparative mechanistic insights into the bone metastatic process of various solid tumors, including pediatric cancers. We also highlight current and innovative approaches to biologically targeted therapy and immunotherapy. In particular, we discuss the role of the bone marrow microenvironment in the attraction, homing, dormancy and outgrowth of metastatic tumor cells and the ensuing therapeutic implications. Multiple signaling pathways have been described to contribute to metastatic spread to the bone of specific cancer entities, with most knowledge derived from the study of breast and prostate cancer. However, it is likely that similar mechanisms are involved in different types of cancer, including multiple myeloma, primary bone sarcomas and neuroblastoma. The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.


Antiplatelet and Anticoagulant Activities of Angelica shikokiana Extract and Its Isolated Compounds.
Angelica shikokiana is a Japanese medicinal plant that is used traditionally in several ailments of cardiovascular diseases. However, there is no report regarding its anticoagulant or antiplatelet activities. So this study was designed to screen for such activities (anticoagulant by prothrombin time [PT], activated partial thromboplastin time, and thrombin time assays and antiplatelet activities against adenosine 5'-diphosphate [ADP] and arachidonic acid-induced platelet aggregations) for the methanol extract of the aerial part (Angelica methanol extract [AME]), its isolated coumarins, flavonoids, and flavonoid metabolites. The AME had potent anticoagulant and antiplatelet activities, and the flavonoid compounds were evidenced to be responsible for such activities. Among coumarins compounds, hyuganin C showed significant prolongation of only PT, while other coumarins were inactive. Similarly, hyuganin C and bergapten were the only active coumarins against ADP-induced platelet aggregation. Compared to the parent compounds, colonic metabolites of the flavonoids had similar anticoagulant and antiplatelet activities, while glucuronides showed sharp decreases in all studied activities. This is the first report showing that the medicinal plant A shikokiana has potent antiplatelet and anticoagulant activities.


[A Case of Surgical Resection of Hepatic Leiomyosarcoma].
A 72-year-old woman was referred to our hospital due to an abdominal mass. Ultrasound sonography and computed tomography revealed liver tumors in liver segments 2 and 3. The preoperative diagnosis was hepatocellular carcinoma. The patient underwent an extended left lobectomy. Histological examination of resected specimens revealed that the tumors were hepatic leiomyosarcoma. We report our experience of this hepatic leiomyosarcoma, along with the literature on this tumor type.


Depressed systolic function after a prolonged and strenuous exercise.
Prolonged and strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Although a consensus exists regarding the decrease in diastolic function, the existence of a decrease in systolic function by a PSE remains controversial, probably due to the transient tachycardia and changes in loading conditions observed upon the completion of exercise. Therefore, the objective was to evaluate LV systolic function before and after a PSE using two-dimensional speckle tracking echocardiography not only at rest but also during incremental tests to adjust heart rates (HR). Sixteen healthy young men (23 ± 3 yr old) performed a 3-h period of intensity-controlled upright cycling. LV strain (S), systolic strain rate (SR), rotation, and systolic rotational rate were evaluated by two-dimensional speckle tracking echocardiography before and after a 3-h period of PSE at rest and during incremental tests. Posttest evaluation was performed once the HR had returned to the pretest value. Under resting conditions, parameters of systolic function were either unchanged or increased after the PSE. However, during the incremental test, all LV systolic SR and apical rotational rates were decreased after PSE (radial SR at workload 3 (W3): 2.21 ± 0.12.s(-1) vs 1.87 ± 0.10.s(-1), P < 0.01 and apical rotational rate at W3: 128 ± 28 deg.s(-1) vs 105 ± 26 deg.s(-1), P < 0.05). Regression analyses between LV systolic SR and HR showed lower y-intercepts without differences in slopes, suggesting a decrease of both global and regional systolic functions irrespective of HR after the PSE. Our findings based on LV S and SR data during incremental tests demonstrate that the 3-h period of PSE induces LV systolic dysfunction.


New class of benzothiophene morpholine analogues with high selectivity and affinity were designed and evaluated for anti-drug addiction.
To probe the mechanism of dopamine receptors in drug addiction and look for potential new methods for treating this disease, we have designed and synthesized benzothiophene morpholine analogues that were considered as dopamine D3 receptor-selective ligands. Radioligand binding assay was used to determine the binding affinity of target compounds. Members of this class have great selectivity and binding affinity in D3 receptor. In addition, the ability of these compounds to mitigate the symptoms of addiction from opioids was investigated in animal behavior patterns, and we have found that two compounds (18a and 18d) have good affinity in the D3R and exhibit the efficacy of anti-drug addiction in morphine-dependent mice induced by naloxone.


Developmental toxicity of clarified slurry oil, syntower bottoms, and distillate aromatic extract administered as a single oral dose to pregnant rats.
Clarified slurry oil (CSO), syntower bottoms (STB), and distillate aromatic extract (DAE) are refinery streams produced by processing crude oil. Each of these refinery streams is rich in both hydrocarbons having carbon numbers of C20 or greater and polycyclic aromatic compounds. Available data indicate that some refinery streams are developmentally toxic (manifested primarily as increased embryolethality and growth retardation) by the dermal route of exposure. However, there is no conclusive evidence for their being teratogenic. The present studies were designed to further explore the suspected teratogenic potency of refinery streams while at the same time limiting embryolethality. To profile teratogenic effects as a function of gestation day, pregnant rats received a single oral dose (2000 mg/kg) of CSO, STB, or DAE on one of gestation days (GD) 11-14; DAE and STB were also administered on GD 15. To profile effects as a dose response function, rats received a single oral dose of CSO, DAE, or STB on GD 12 at 125, 500, and 2000 mg/kg. Control animals were similarly treated but were administered tap water. On GD 20, dams were necropsied and the fetuses evaluated for normal development. In general, evidence of maternal toxicity (i.e., decreased body weight gain, decreased thymus weight) was observed at doses greater than or equal to 500 mg/kg. For each refinery stream tested, the incidence of resorption was greatest on GD 11. A common pattern of fetal malformations was observed for all of the refinery streams tested and included cleft palate, diaphragmatic hernia, and paw and tail defects. The incidence and type of malformation observed were influenced by the gestation day of exposure. The incidences of external and skeletal malformations were greatest on GD 11 and 12 for fetuses exposed to CSO; on GD 13 and 14, the incidence of malformation was comparable for CSO- and STB-exposed fetuses. The incidence of visceral anomalies was greatest on GD 11-13 for fetuses exposed to CSO and STB; on Gestation D 14, the incidence was comparable for each of the refinery streams tested. In general, the ability to produce adverse effects on development was greatest for CSO and least for DAE. Effects produced by STB were comparable to or less severe than those observed for CSO.


Copper-catalyzed gem-difluoroolefination of diazo compounds with TMSCF3 via C-F bond cleavage.
A novel Cu-catalyzed gem-difluoroolefination of diazo compounds is described. This transformation starts from readily available TMSCF3 and diazo compounds, via trifluoromethylation followed by C-F bond cleavage, to afford the desired 1,1-difluoroalkene products.


Mental health initiatives as peace initiatives in Sri Lankan schoolchildren affected by armed conflict.
The Health Reach Sri Lanka project (1993-96) is described. It was a school-based assessment of children's exposure to war-related events and the presence of psychological distress, undertaken in six communities in parts of Sri Lanka variously affected by armed conflict. Its objectives, methods and results are presented. The research project aimed to raise national awareness of the psychosocial effects of armed conflict on children, using a community-development approach to local capacity building, based on the 'health initiative as peace initiative' model. As a follow-up to the study, a locally run programme, based on creative play and trauma-healing, was established, initially for the children involved in the study. This was later extended to other children in the district affected by armed conflict.


Metalloprotease inhibitor blocks angiotensin II-induced migration through inhibition of epidermal growth factor receptor transactivation.
In vascular smooth muscle cells (VSMCs), angiotensin II (AngII) induces transactivation of the EGF receptor (EGFR) which involves a metalloprotease that stimulates processing of heparin-binding EGF from its precursor. However, the identity and pharmacological sensitivity of the metalloprotease remain unclear. Here, we screened the effects of several metalloprotease inhibitors on AngII-induced EGFR transactivation in VSMCs. We found that an N-phenylsulfonyl-hydroxamic acid derivative [2R-[(4-biphenylsulfonyl)amino]-N-hydroxy-3-phenylpropinamide] (BiPS), previously known as matrix metalloprotease (MMP)-2/9 inhibitor, markedly inhibited AngII-induced EGFR transactivation, whereas the MMP-2 or -9 inhibition by other MMP inhibitors failed to block the transactivation. BiPS markedly inhibited AngII-induced ERK activation and protein synthesis without affecting AngII-induced intracellular Ca2+ elevation. VSMC migration induced by AngII was also inhibited not only by an EGFR inhibitor but also by BiPS. Thus, BiPS is a specific candidate to block AngII-induced EGFR transactivation and subsequent growth and migration of VSMCs, suggesting its potency to prevent vascular remodeling.


Sepsis: a pro- and anti-inflammatory disequilibrium syndrome.
Severe sepsis and probably most prolonged critical illnesses reflect a paradox of combined increased activation and depression of the immune apparatus. The increased activation of the inflammatory response is evidenced from the increased levels of circulating proinflammatory cytokines in the blood, increased endothelial activation with increased expression of inducible nitric oxide synthase, and increased de novo CD11b expression on circulating immune effector cells, such as PMNs, monocytes and lymphocytes. However, coexisting with this proinflammatory process is a profound anti-inflammatory state characterized by increased circulating levels of anti-inflammatory species that both directly block the binding of proinflammatory stimuli to their cell surface receptors (IL-1ra, soluble TNF receptors) and also induce an anti-inflammatory state on their own (IL-10, TFG-beta). This humoral anti-inflammatory state is mirrored at the cellular levels by decreased monocyte ability to process antigen, characterized by a reduced HLA-DR expression and impaired PMN upregulation in response to clearly proinflammatory stimuli. Accordingly, severe sepsis reflects a combined pro- and anti-inflammatory state. Both the pro- and anti-inflammatory arms have protective and destructive aspects, making their modulation by treatment less predictable than if their actions were purely beneficial or detrimental.


Acne through the ages: case-based observations through childhood and adolescence.
Acne vulgaris is a common disorder that affects more than 17 million individuals in the United States. Knowledge of the disease is an important part of clinical practice, particularly for the pediatric practitioner. Contrary to common belief, acne is not a disease limited to adolescents and young adults but can occur at any stage of life. This article is a case-based review of acne during childhood and adolescence. Workup is based on age and concurrent physical findings, whereas therapy depends on the type of skin lesions along with patient characteristics and preferences.


Upside-down position leads to choroidal expansion and anterior chamber shallowing: OCT study.
To determine whether dynamic changes in choroidal thickness (CT) cause shallowing of the anterior chamber. 34 healthy volunteers were enrolled. The participants in our study adopted the upside-down position for 1.5 min, which was the model we used to study the dynamic changes in CT. Intraocular pressure (IOP) elevation, optical coherence tomography images of the choroid and anterior chamber were obtained at baseline, after being in an upside-down position in an inversion machine and after 15 min of rest. The changes in IOP, anterior chamber and choroidal blood flow between the baseline and the upside-down position were compared. Sixty-eight eyes from 34 subjects were analysed. After being in upside-down position for 1.5 min, there was a significant increase in CT from 226.39±52.44 µm to 238.34±54.84 µm (p<0.001). Choroidal flow index decreased from 0.3357±0.0251 to 0.3004±0.0190 in upside-down position, and there was a decrease in anterior chamber depth (3.21±0.22 mm to 3.13±0.21 mm, p<0.001) and angle opening distance at 500 µm from the scleral spur (0.65±0.24 mm to 0.58±0.20 mm, p=0.007). Pearson correlation analysis showed that the increase in CT was positively related with CT at baseline CT (p=0.001). When the body position changed from sitting to upside-down position, there was choroidal thickening, anterior chamber shallowing and IOP elevation with reduced choroidal blood flow. The data provide evidence about the relationship between choroid expansion and shallowing of the anterior chamber, which may be of relevance for the pathogenesis of angle closure.


Selection of top 10 quality indicators for nutrition therapy.
The identification of useful quality indicators for nutrition therapy (QINTs) is of great interest and a challenge. This study attempted to identify the 10 QINTs that best suit the practice of quality control in nutrition therapy (NT) by evaluating the opinion of experts in NT with the use of psychometric techniques and statistical tools. Thirty-six QINTs available for clinical application in Brazil were assessed in 2 distinct phases. In phase 1, 26 nutrition experts ranked QINTs by scoring 4 attributes (utility, simplicity, objectivity, low cost) to assess each QINT on a 5-point Likert scale. The top 10 QINTs were identified from the 10 best scores obtained, and the reliability of expert opinion for each indicator was assessed by Cronbach's α. In phase 2, experts provided feedback regarding the selected top 10 QINTs by answering 2 closed questions. The top 10 QINTs, in descending order, are the frequency of nutrition screening of hospitalized patients, diarrhea, involuntary withdrawal of enteral feeding tubes, feeding tube obstruction, fasting longer than 24 hours, glycemic dysfunction, estimated energy expenditure and protein needs, central venous catheter infection, compliance of NT indication, and frequency of application of subjective global assessment. Opinions were consistent among the interviewed experts. During feedback, 96% of experts were satisfied with the top 10 QINTs, and 100% had considered them in accordance with their previous opinion. The top 10 QINTs were identified according to their usefulness in clinical practice by obtaining adequate agreement and representativeness of opinion of nutrition experts.


Diradylglycerol formation in cholecystokinin-stimulated rabbit pancreatic acini. Assessment of precursor phospholipids by means of molecular species analysis.
The aim of the present study was to assess the origin of the 1,2-diradylglycerols produced during prolonged hormonal stimulation of rabbit pancreatic acini by comparison of their relative molecular species composition with that of the major acinar phospholipids. Both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) consisted of 1,2-diacyl as well as 1-alk-1-2-acyl species. In contrast, phosphatidylinositol (PtdIns), phosphatidylserine and phosphatidic acid existed only in the 1,2-diacyl form. Acinar cells did not contain detectable amounts of 1-alkyl-2-acyl phospholipids. Similarly, the acinar 1,2-diradylglycerol fraction consisted of 1,2-diacylglycerols and 1-alk-1-enyl-2-acylglycerols. Mass 1,2-diradylglycerol measurements revealed that prolonged stimulation with cholecystokinin resulted in a marked and sustained increase in acinar 1,2-diradylglycerol content. Based on the relative amounts of the 1,2-diacyl species present in both the 1,2-diradylglycerol fraction and the individual phospholipids, it is calculated that under control conditions 60% of the 1,2-diacylglycerols originate from PtdCho and 40% from PtdIns, whereas under stimulatory conditions 53% is calculated to be derived from PtdCho, 46% from PtdIns and 1% from PtdEtn. Likewise, it is calculated that in control as well as stimulated acini 100% of the 1-alk-l-enyl-2-acylglycerols originate from plasmenylcholine. Further evidence in favour of the idea that at least a considerable part of the 1,2-diacylglycerols produced during prolonged hormonal stimulation originate from inositolphospholipids is provided by the observation that labeling of phosphatidylinositol 4,5-bisphosphate with inorganic phosphate reached isotopic equilibrium markedly faster under stimulatory conditions as compared to the control situation, which is in agreement with an elevated turnover rate. The data presented support the idea that PtdCho and inositolphospholipids are the major precursors in basal and stimulated 1,2-diradylglycerol production in rabbit pancreatic acini.


Telediagnosis of Parkinson's disease using measurements of dysphonia.
Parkinson's disease (PD) is a neurological illness which impairs motor skills, speech, and other functions such as mood, behavior, thinking, and sensation. It causes vocal impairment for approximately 90% of the patients. As the symptoms of PD occur gradually and mostly targeting the elderly people for whom physical visits to the clinic are inconvenient and costly, telemonitoring of the disease using measurements of dysphonia (vocal features) has a vital role in its early diagnosis. Such dysphonia features extracted from the voice come in variety and most of them are interrelated. The purpose of this study is twofold: (1) to select a minimal subset of features with maximal joint relevance to the PD-score, a binary score indicating whether or not the sample belongs to a person with PD; and (2) to build a predictive model with minimal bias (i.e. to maximize the generalization of the predictions so as to perform well with unseen test examples). For these tasks, we apply the mutual information measure with the permutation test for assessing the relevance and the statistical significance of the relations between the features and the PD-score, rank the features according to the maximum-relevance-minimum-redundancy (mRMR) criterion, use a Support Vector Machine (SVM) for building a classification model and test it with a more suitable cross-validation scheme that we called leave-one-individual-out that fits with the dataset in hand better than the conventional bootstrapping or leave-one-out validation methods.


Implantation of intracerebral depth electrodes for monitoring seizures using the Pelorus stereotactic system guided by magnetic resonance imaging. Technical note.
The Pelorus stereotactic system guided by magnetic resonance imaging was used to implant intracerebral depth electrodes for monitoring seizure activity. This stereotactic system is frameless and does not require the use of a computer. It is based on the concept of a ball-and-socket type stereotactic arc director and uses the center-of-arc principle to establish a trajectory for electrode placement. The system not only allows the use of the orthogonal approach, but also provides ample working space and flexibility to choose different entry points and trajectory angles.


The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX) Version 2.0: Modelling in vitro electrical stimulation of brain tissue.
Neuronal circuits can be modelled in detail allowing us to predict the effects of stimulation on individual neurons. Electrical stimulation of neuronal circuits in vitro and in vivo excites a range of neurons within the tissue and measurements of neural activity, e.g the local field potential (LFP), are again an aggregate of a large pool of cells. The previous version of our Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX) allowed for the simulation of the LFP generated by a patch of brain tissue. Here, we extend VERTEX to simulate the effect of electrical stimulation through a focal electric field. We observe both direct changes in neural activity and changes in synaptic plasticity. Testing our software in a model of a rat neocortical slice, we determine the currents contributing to the LFP, the effects of paired pulse stimulation to induce short term plasticity (STP), and the effect of theta burst stimulation (TBS) to induce long term potentiation (LTP).


Immune Cell-Epithelial/Mesenchymal Interaction Contributing to Allergic Airway Inflammation Associated Pathology.
The primary function of the lung is efficient gas exchange between alveolar air and alveolar capillary blood. At the same time, the lung protects the host from continuous invasion of harmful viruses and bacteria by developing unique epithelial barrier systems. Thus, the lung has a complex architecture comprising a mixture of various types of cells including epithelial cells, mesenchymal cells, and immune cells. Recent studies have revealed that Interleukin (IL-)33, a member of the IL-1 family of cytokines, is a key environmental cytokine that is derived from epithelial cells and induces type 2 inflammation in the barrier organs, including the lung. IL-33 induces allergic diseases, such as asthma, through the activation of various immune cells that express an IL-33 receptor, ST2, including ST2+ memory (CD62LlowCD44hi) CD4+ T cells. ST2+ memory CD4+ T cells have the capacity to produce high levels of IL-5 and Amphiregulin and are involved in the pathology of asthma. ST2+ memory CD4+ T cells are maintained by IL-7- and IL-33-produced lymphatic endothelial cells within inducible bronchus-associated lymphoid tissue (iBALT) around the bronchioles during chronic lung inflammation. In this review, we will discuss the impact of these immune cells-epithelial/mesenchymal interaction on shaping the pathology of chronic allergic inflammation. A better understanding of pathogenic roles of the cellular and molecular interaction between immune cells and non-immune cells is crucial for the development of new therapeutic strategies for intractable allergic diseases.


Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus.
We recently demonstrated that children with type 1 diabetes mellitus (DM) have decreased lumbar spine bone mineral density (BMD) as early as four years after clinical diagnosis of the disease. In order to determine whether osteopenia is already present in patients very early on after diagnosis of clinical DM, we evaluated the bone mineral status of a group of newly diagnosed children (5.8 +/- 1.5 mo after diagnosis). We studied 23 prepubertal children (7 M, 16 F) with a mean chronological age of 9.5 +/- 2.2 yr and a mean glycosylated hemoglobin of 8.9 +/- 2.4%. Lumbar spine and femoral neck BMD were measured by dual X-ray absorptiometry, while bone turnover was assessed by the determination of the serum concentration of the carboxy-terminal propeptide of type I collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type I collagen (N-telopeptide). Results were compared to those of age, height, and pubertal status matched controls. Lumbar spine BMD Z-scores were decreased in patients compared to controls (Z-scores of -0.89 +/- 1.2, with 10 of 22 patients showing values >1 SD below the mean). When lumbar spine Z-scores were analyzed in those patients with <3 months or > or =3 months since diagnosis of DM a significant difference was noticed between groups (-0.648 +/- 1.12 vs -1.267 +/- 1.17; p <0.02). No significant differences were noted in femoral neck BMD and total BMD between groups. Serum PICP levels were decreased when compared to controls (233.6 +/- 39.3 vs 375.9 +/- 50.7 microg/l; p <0.002), while serum N-telopeptide concentrations, although increased, were not significantly different (9.3 +/- 1.3 vs 5.7 +/- 1.5 microg/l). In summary, early on after the diagnosis of type 1 DM, children present with decreased lumbar spine BMD and decreased bone formation markers.


[Survey of occupational dermatosis in 11 work centers].
The development of Occupational Dermatosis Control Programme and the need for the planning of dermatological treatment as well as the prevention of such diseases makes it necessary to obtain morbidity data in different work places so as to classify them as dangerous from the occupational point of view. Eleven work places comprising 1431 workers were investigated. The existing dermatological pathology was established. It reached 48,1% of the workers investigated. Occupational dermatosis was 3,9% which is about the international average. The cases of dermatosis were treated and the workers' health improved; with sanitary instruction the environment underwent satisfactory changes which brought about the decrease of occupational risks. These surveys are a great help since they provide information about dermatological pathologies and their agents in different work places and facilitate the application of preventive measures.


CytA enables CryIV endotoxins of Bacillus thuringiensis to overcome high levels of CryIV resistance in the mosquito, Culex quinquefasciatus.
Cry proteins produced by Bacillus thuringiensis are selective biodegradable insecticides used increasingly in bacterial insecticides and transgenic plants as alternatives to synthetic chemical insecticides. However, the potential for development of resistance and cross-resistance in target insect populations to Cry proteins used alone or in combination threatens the more widespread use of this novel pest control technology. Here we show that high levels of resistance to CryIV proteins in larvae of the mosquito, Culex quinquefasciatus, can be suppressed or reduced markedly by combining these proteins with sublethal quantities of CytA, a cytolytic endotoxin of B. thuringiensis. Resistance at the LC95 level of 127-fold for a combination of three CryIV toxins (CryIVA, B, and D), resulting from 60 generations of continuous selection, was completely suppressed by combining sporulated powders of CytA in a 1:3 ratio with sporulated powders of a CryIVA, CryIVB, and CryIVD strain. Combining the CytA strain with a CryIVA and CryIVB strain also completely suppressed mosquito resistance of 217-fold to the latter toxins at the LC95 level, whereas combination of CytA with CryIVD reduced resistance in a CryIVD-selected mosquito strain from greater than 1,000-fold to less than 8-fold. The CytA/CryIV model provides a potential molecular genetic strategy for engineering resistance management for Cry proteins directly into bacterial insecticides and transgenic plants.


Fabrication and catalytic tests of MCM-22/silicon carbide structured catalysts.
The structured catalyst of zeolite MCM-22/silicon carbide (SiC) was prepared for the first time through the in situ hydrothermal synthesis approach. The zeolite loading of the structured catalyst could be tuned by changing the synthesis time and applying alkali pre-treatment of SiC substrate. An additional silica layer formed on SiC substrate after the precalcination treatment facilitated the crystallization of MCM-22 zeolite on the SiC substrate. The MCM-22/SiC structured catalyst thus prepared exhibited good catalytic performance in the methane dehydroaromatization reaction.


Resection for adenocarcinoma of the body and tail of the pancreas.
Adenocarcinoma of the pancreatic body and tail often presents late and is widely regarded as incurable by surgical resection; long-term survivors are rare. Thirteen patients underwent left resection (n = 7) or total pancreatectomy (n = 6) in a consecutive series of 105 patients with carcinoma of the body or tail of the pancreas. Comparison was made with 17 patients with locally advanced or metastatic disease. Preoperative computed tomography predicted irresectable disease when a large perivascular lymph node mass was demonstrated. Preoperative angiography predicted irresectable disease when there was encasement or obliteration of the coeliac axis or its major branches, or of the superior mesenteric artery or vein. Splenic vessel involvement was sometimes compatible with resection. After resection, median survival was 13 (range 3-50) months, with a minimum follow-up of 2 years. Five patients survived more than 2 years, and three are still alive 30, 43 and 50 months after resection. Resection of carcinoma of the body or tail of the pancreas was possible in 12 per cent of patients and long-term survival was observed in some of these.


Women's strategies for living in a nursing home.
1. Elderly women who appear to be managing their own lives even as nursing home residents were found in this study to employ 10 specific strategies. 2. The study showed that the women wanted as much control as possible over their lives and their day-to-day decisions. 3. Remaining active and, in particular, engaging in activities that encouraged them to remain mentally alert was important to them. 4. Sociability, including interaction with family members on a regular basis, was a strategy used by all participants.


The porcine small intestinal submucosa (SIS) patch in foot and ankle reconstruction.
We undertook a retrospective cohort study of 54 patients who underwent foot and ankle soft tissue reconstructive surgery augmented with a porcine small intestinal submucosal (SIS) patch. The mean patient age was 44 (range 17 to 68) years, there were 21 (38.89%) males in the cohort, and the mean follow-up duration was 1080 (range 365 to 1943) days. Clinical outcomes were considered excellent in 46 (85.19%) patients, good/fair in 3 (5.56%) patients, and poor in 5 (9.26%) patients; and no adverse events attributable to the xenograft were observed. Direct SIS patch failure, resulting in stretching of the repair, re-tear, or tendon stenosis, occurred in 3 (5.56%) patients, and delayed incision healing occurred in 6 (11.11%) patients. Based on our observations, we concluded that the porcine SIS xenograft, when used to augment cellular and vascular in-growth, is a viable adjunct to musculoskeletal reconstructions of the foot and ankle.


Crystallization and preliminary X-ray analysis of the inducible lysine decarboxylase from Escherichia coli.
The decameric inducible lysine decarboxylase (LdcI) from Escherichia coli has been crystallized in space groups C2 and C222(1); the Ta6Br12(2+) cluster was used to derivatize the C2 crystals. The method of single isomorphous replacement with anomalous scattering (SIRAS) as implemented in SHELXD was used to solve the Ta6Br12(2+)-derivatized structure to 5 A resolution. Many of the Ta6Br12(2+)-binding sites had twofold and fivefold noncrystallographic symmetry. Taking advantage of this feature, phase modification was performed in DM. The electron-density map of LdcI displays many features in agreement with the low-resolution negative-stain electron-density map [Snider et al. (2006), J. Biol. Chem. 281, 1532-1546].


Principles of cancer screening: lessons from history and study design issues.
Early detection of cancer has held great promise and intuitive appeal in the medical community for well over a century. Its history developed in tandem with that of the periodic health examination, in which any deviations--subtle or glaring--from a clearly demarcated "normal" were to be rooted out, given the underlying hypothesis that diseases develop along progressive linear paths of increasing abnormalities. This model of disease development drove the logical deduction that early detection, by "breaking the chain" of cancer development, must be of benefit to affected individuals. In the latter half of the 20th century, researchers and guidelines organizations began to explicitly challenge the core assumptions underpinning many clinical practices. A move away from intuitive thinking began with the development of evidence-based medicine. One key method developed to explicitly quantify the overall risk-benefit profile of a given procedure was the analytic framework. The shift away from pure deductive reasoning and reliance on personal observation was driven, in part, by a rising awareness of critical biases in cancer screening that can mislead clinicians, including healthy volunteer bias, length-biased sampling, lead-time bias, and overdiagnosis. A new focus on the net balance of both benefits and harms when determining the overall worth of an intervention also arose: it was recognized that the potential downsides of early detection were frequently overlooked or discounted because screening is performed on basically healthy persons and initially involves relatively noninvasive methods. Although still inconsistently applied to early detection programs, policies, and belief systems in the United States, an evidence-based approach is essential to counteract the misleading--even potentially harmful--allure of intuition and individual observation.


Evaluating linguistic equivalence of patient-reported outcomes in a cancer clinical trial.
In order to make meaningful cross-cultural or cross-linguistic comparisons of health-related quality of life (HRQL) or to pool international research data, it is essential to create unbiased measures that can detect clinically important differences. When HRQL scores differ between cultural/linguistic groups, it is important to determine whether this reflects real group differences, or is the result of systematic measurement variability. To investigate the linguistic measurement equivalence of a cancer-specific HRQL questionnaire, and to conduct a sensitivity analysis of treatment differences in HRQL in a clinical trial. Patients with newly diagnosed chronic myelogenous leukemia (n = 1049) completed serial HRQL assessments in an international Phase III trial. Two types of differential item functioning (uniform and non-uniform) were evaluated using item response theory and classical test theory approaches. A sensitivity analysis was conducted to compare HRQL between treatment arms using items without evidence of differential functioning. Among 27 items, nine (33%) did not exhibit any evidence of differential functioning in both linguistic comparisons (English versus French, English versus German). Although 18 items functioned differently, there was no evidence of systematic bias. In a sensitivity analysis, adjustment for differential functioning affected the magnitude, but not the direction or interpretation of clinical trial treatment arm differences. Sufficient sample sizes were available for only three of the eight language groups. Identification of differential functioning in two-thirds of the items suggests that current psychometric methods may be too sensitive. Enhanced methodologies are needed to differentiate trivial from substantive differential item functioning. Systematic variability in HRQL across different groups can be evaluated for its effect upon clinical trial results; a practice recommended when data are pooled across cultural or linguistic groups to make conclusions about treatment effects.


Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates.
Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori, which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori-related diseases.


Antimicrobial activity of Inga fendleriana extracts and isolated flavonoids.
The EtOAc and n-BuOH extracts of Inga fendleriana inhibited Gram-positive, but not Gram-negative bacteria; a narrow spectrum of activity against Staphylococcus epidermidis was detected. The MIC values of the extracts ranged from 125 to 850 microg/mL. Quercetin 3-methylether, myricetin 3-O-rhamnoside and tricetin showed antibacterial activity against the same bacterial strains with MICs in the range from 31 to 250 microg/mL. In time-kill kinetic studies, the flavonoids showed bactericidal effects at the concentrations corresponding to four times the MICs.


Using social media to crowdsource collection of urine samples during a national pandemic.
The COVID-19 pandemic and subsequent lockdown had a substantial impact on normal research operations. Researchers needed to adapt their methods to engage at-home participants. One method is crowdsourcing, in which researchers use social media to recruit participants, gather data, and collect samples. We utilized this method to develop a diagnostic test for Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). Participants were recruited via posts on popular social-media platforms, and enrolled via a website. Participants received and returned a mail kit containing bladder symptom surveys and a urine sample cup containing room-temperature preservative. Using this method, we collected 1254 IC/BPS and control samples in 3 months from all 50 United States. Our data demonstrate that crowdsourcing is a viable alternative to traditional research, with the ability to reach a broad patient population rapidly. Crowdsourcing is a powerful tool for at-home participation in research, particularly during the lockdown caused by the COVID-19 pandemic.


The vascular smooth muscle cell: a therapeutic target in Type 2 diabetes?
The rising epidemic of T2DM (Type 2 diabetes mellitus) worldwide is of significant concern. The inherently silent nature of the disease in its early stages precludes early detection; hence cardiovascular disease is often established by the time diabetes is diagnosed. This increased cardiovascular risk leads to significant morbidity and mortality in these individuals. Progressive development of complications as a result of previous exposure to metabolic disturbances appears to leave a long-lasting impression on cells of the vasculature that is not easily reversed and is termed 'metabolic memory'. SMCs (smooth muscle cells) of blood vessel walls, through their inherent ability to switch between a contractile quiescent phenotype and an active secretory state, maintain vascular homoeostasis in health and development. This plasticity also confers SMCs with the essential capacity to adapt and remodel in pathological states. Emerging clinical and experimental studies propose that SMCs in diabetes may be functionally impaired and thus contribute to the increased incidence of macrovascular complications. Although this idea has general support, the underlying molecular mechanisms are currently unknown and hence are the subject of intense research. The aim of the present review is to explore and evaluate the current literature relating to the problem of vascular disease in T2DM and to discuss the critical role of SMCs in vascular remodelling. Possibilities for therapeutic strategies specifically at the level of T2DM SMCs, including recent novel advances in the areas of microRNAs and epigenetics, will be evaluated. Since restoring glucose control in diabetic patients has limited effect in ameliorating their cardiovascular risk, discovering alternative strategies that restrict or reverse disease progression is vital. Current research in this area will be discussed.


[Influence of nitric oxide on cerebral hemodynamics during endotoxemia in dogs].
The aim of this study is to clarify the influence of nitric oxide (NO) in cerebral circulation during endotoxemia. Two groups of 24 mongrel dogs (N = 12 each) received saline 1 ml.kg-1.h-1 or endotoxin (lipopolysaccharide, LPS) 500 ng.kg-1.h-1 for 3 hours. To determine changes of NO in the systemic and cerebral circulation, we measured NOx (NO2-/NO3-) in the femoral artery and superior sagittal sinus as metabolites of NO using the Griess method. We also measured the concentrations of cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), total hemoglobin (total Hb) and cytochrome aa3 (Cytaa3) using near-infrared laser spectroscopy. Changes in cerebral blood volume were evaluated from the total Hb. NOx in systemic and cerebral circulation increased significantly after infusion of LPS. Therefore, the increased production of NO in cerebral circulation was consistent with increase of cerebral blood volume. In conclusion, it seems reasonable to assume that increased cerebral blood volume may result from increased production of cerebral NO during endotoxemia.


Ticlopidine induced prolonged leucopenia in a patient with immunocytoma and chronic hepatitis C.
Ticlopidine is increasingly used in the secondary prophylaxis in patients with arterial occlusive diseases. Neutropenia is a well known side effect of this drug. We report a case of a 73 year old woman who was admitted because of severe prolonged ticlopidine induced leucopenia. The past medical history included an immunocytoma of the IgM-kappa type diagnosed seven years ago with less than 10% infiltration of the bone marrow and a chronic hepatitis C. On admission the white cell count was 1000/microL. Ticlopidine was stopped. The white cell count did not increase within one week, thus filgastrim was applied on two consecutive days. The leucocyte count promptly increased to 6000/microL but consecutively dropped within the next fortnight again to levels below 500/microL forcing daily filgastrim application for another 9 days. Four months after the initiation of the therapy with filgastrim the patient had a white cell count of 4300/microL. We therefore conclude that in patients with a history of potentially bone marrow suppressing diseases the use of ticlopidine has to be carefully weighed against possible myelosuppressive effects.


[Code dark grey in hospitals: short hospital admission and high mortality due to COVID-19].
During the COVID-19 pandemic, we have experienced several waves in which the number of hospital beds occupied by patients with COVID-19 has varied greatly. In December 2022, hospitals were under a tremendous pressure, and were forced to upgrade their capacity to phase 2D ("Code Dark Grey"). This is the last phase prior to phase 3 ("Code Black"), in which we would be unable to treat all patients and would be forced to triage based on medical and non-medical characteristics of the patients. In this brief analysis, we demonstrate that phase 2D is characterized by a relatively short mean period of hospital admission and a higher hospital mortality.


Mechanism and adverse effects of multiple sclerosis drugs: a review article. Part 2.
Multiple Sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system (CNS) mostly affecting young adults. The exact mechanism and pathogenesis of MS remain still undiscovered but there have been useful treatments with different efficacy rates. Most of these therapies are divided into the first line, second line and third line, impact on the immune system and immune cells. These drugs are approved to be useful in MS, but like any other therapies, adverse effects (AE) are associated with these drugs. In this review, we continue the survey over mechanisms of actions and AEs of MS drugs. Physicians must be aware of such AEs and complications to choose the best drug for each patient.


[The colors produced by Fusarium Link ex Fr. 1821 (Deuteromycetes) species in various carbohydrate cultures. I. Fusarium equiseti (Corda) Sacc. 1886].
In this study, Fusarium equiseti (Corda) Sacc. 1886 fungus was inoculated in cultures containing glucose, maltose, galactose, mannitol, sucrose, fructose, lactose and starch and control media cultures and were observed at intervals of five days. In most of the cultures various tones of brown were observed. Our results showed a correlation when compared with literature in general no different results were observed. Three color catalogs were used for the identification of these colors.


I2/CHP mediated [1 + 1 + 1 + 1] cyclization of aromatic isocyanides with amines to construct 1,3-diazetidine-2,4-diimine derivatives.
An I2/CHP (cumene hydroperoxide) mediated [1 + 1 + 1 + 1] cyclization of aromatic isocyanides with readily accessible amines via the formation 4 new C-N bonds has been developed to construct unsymmetric 1,3-diazetidine-2,4-diimine derivatives under mild conditions.


Direct Measurement of Surface Dissolution Rates in Potential Nuclear Waste Forms: The Example of Pyrochlore.
The long-term stability of ceramic materials that are considered as potential nuclear waste forms is governed by heterogeneous surface reactivity. Thus, instead of a mean rate, the identification of one or more dominant contributors to the overall dissolution rate is the key to predict the stability of waste forms quantitatively. Direct surface measurements by vertical scanning interferometry (VSI) and their analysis via material flux maps and resulting dissolution rate spectra provide data about dominant rate contributors and their variability over time. Using pyrochlore (Nd2Zr2O7) pellet dissolution under acidic conditions as an example, we demonstrate the identification and quantification of dissolution rate contributors, based on VSI data and rate spectrum analysis. Heterogeneous surface alteration of pyrochlore varies by a factor of about 5 and additional material loss by chemo-mechanical grain pull-out within the uppermost grain layer. We identified four different rate contributors that are responsible for the observed dissolution rate range of single grains. Our new concept offers the opportunity to increase our mechanistic understanding and to predict quantitatively the alteration of ceramic waste forms.


Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin.
The mechanisms controlling growth and patterning along the proximal-distal axis of the vertebrate limb are yet to be understood. We show that restriction of expression of the homeobox gene Meis2 to proximal regions of the limb bud is essential for limb development, since ectopic Meis2 severely disrupts limb outgrowth. We also uncover an antagonistic relationship between the secreted factors Gremlin and BMPs required to maintain the Shh/FGF loop that regulates distal outgrowth. These proximal and distal factors have coordinated activities: Meis2 can repress distal genes, and Bmps and Hoxd genes restrict Meis2 expression to the proximal limb bud. Moreover, combinations of BMPs and AER factors are sufficient to distalize proximal limb cells. Our results unveil a novel set of proximal-distal regulatory interactions that establish and maintain outgrowth of the vertebrate limb.


Clinicopathological features of syphilitic gastritis in Korean patients.
Syphilitic gastritis is difficult to diagnose without a history of syphilis, because endoscopic and microscopic findings can simulate gastric cancer or lymphoma. Herein are reported two cases of syphilitic gastritis and analysis of the clinicopathological characteristics of 11 cases in Korean subjects, including nine previously reported ones. The two present patients were 25- and 32-year-old men with epigastric pain. The gastroduodenoscopy features were similar: multiple erosive or ulcerative lesions in whole gastric mucosa. Microscopically, gastric mucosa contained severe chronic active gastritis involving submucosa with crypt abscesses, venulitis and granulomas, suggesting unusual infectious gastritis. Numerous spirochetes were identified on silver staining, and serological tests for syphilis were reactive in both patients. They were treated with benzathin penicillin, and follow-up gastric biopsy specimens indicated non-specific chronic gastritis without evidence of syphilis. Of the 11 Korean patients with syphilitic gastritis, six were female and five were male (mean age, 31.7 years). The most common symptom was epigastric pain and all patients had diffuse erosive, ulcerative or infiltrative lesions on gastroduodenoscopy. Syphilitic gastritis should be considered in young patients with epigastric pain who have diffuse gastric involvement such as erosion or shallow ulcer on endoscopy and unusually extensive chronic active gastritis on microscopy, even if the history of syphilis is not clear.


Futility of medical treatment in current medical practice.
Intensive care provides support for acute reversible organ failure and most patients who receive intensive care recover from their illness. In some patients organ failure may become irreversible and in these patients further treatment or organ support may be considered futile. Emerging technologies and expertise can enable the medical profession to prolong life / death indefinitely without curing or controlling the underlying disease process. Introduction of ultramodern organ supports such as extracorporeal life-support systems, ventricular assist devices and organ transplantation surgeries have introduced some degree of ambiguity in defining futility of care. Furthermore medico legal implications of futility of care introduce further complexities in defining and instituting futile treatments. In this review we discuss the evolution of the concept of futility of care, review the various meanings of the term "futility of care", explore the complexities of management when care is considered futile, offer suggestions as to how such patients and their families could be managed. We also review the legal framework when consensus is not achieved.


Arthroscopy surgery versus shock wave therapy for chronic calcifying tendinitis of the shoulder.
There are several treatment modalities for calcifying tendinitis of the shoulder. If the pain becomes chronic after several months of conservative treatment, open or arthroscopic removal is usually recommended. Recently, extracorporeal shock wave therapy has shown encouraging results in treating calcific deposits. We report a retrospective study to compare the outcome after arthroscopic extirpation (group I, 22 cases) with the effect of low extracorporeal shock wave therapy (group II, 24 cases) in patients with a chronic homogeneous calcific deposit in the supraspinatus tendon. Patients included in the study had undergone unsuccessful conservative therapy in the previous six months with no evidence of subacromial impingement of the rotator cuff independent of the calcium deposit or rupture of the rotator cuff detected by sonography or magnetic resonance imaging. AP and LL radiographies were performed for all of the patients at least one week before the treatment and 24 months after the treatment. To keep the possibility of spontaneous resorption low, the deposit had to be sharply outlined and densely structured on the radiograph (types I and II in the Gärtner classification). In group II, the patients underwent an average of three treatment sessions of extracorporeal shock waves therapy with 1,500 impulses/session of 0.10-0.13 mJ/mm(2). Preoperative symptoms (P = 0.09), sex (P = 0.17), operated (P = 0.11) and dominant (P = 0.33) limbs, and age (P = 0.99) of the two groups did not show a significative difference between groups. According to the University of California Los Angeles (UCLA) rating system, the mean score in group I improved from 9.36 (+/-5.2) to 30.3 (+/-7.62) points after 24 months, with 81.81% reporting good or excellent results (P < 0.001). In group II the mean score after 24 months rose from 12.38 (+/-6.5) to 28.13 (+/-9.34) points, with 70.83% reporting good or excellent results (P < 0.001). Radiologically, after two years of follow up, there was no calcific deposit in 86.35% (P < 0.001) of the patients of group I and in 58.33 % (P < 0.001) of the patients of group II. According to the UCLA scores, there was no significant difference between the groups at two years of follow-up (P = 0.38). We conclude that shock wave therapy is equivalent to arthroscopy, and so shock wave therapy should be preferred because of its noninvasiveness.


Patent Ductus Arteriosus: A Contemporary Perspective for the Pediatric and Adult Cardiac Care Provider.
The burden of patent ductus arteriosus (PDA) continues to be significant. In view of marked differences in preterm infants versus more mature, term counterparts (viewed on a continuum with adolescent and adult patients), mechanisms regulating ductal patency, genetic contributions, clinical consequences, and diagnostic and treatment thresholds are discussed separately, when appropriate. Among both preterm infants and older children and adults, a range of hemodynamic profiles highlighting the markedly variable consequences of the PDA are provided. In most contemporary settings, transcatheter closure is preferable over surgical ligation, but data on longer-term outcomes, particularly among preterm infants, are lacking. The present review provides recommendations to identify gaps in PDA diagnosis, management, and treatment on which subsequent research can be developed. Ultimately, the combination of refined diagnostic thresholds and expanded treatment options provides the best opportunities to address the burden of PDA. Although fundamental gaps remain unanswered, the present review provides pediatric and adult cardiac care providers with a contemporary framework in PDA care to support the practice of evidence-based medicine.