Drugs and recurrent ocular herpes.
There are two types of ocular herpes simplex virus (HSV), type 1 and type 2, and infections can be primary or recurrent. This paper reviews characteristics of herpes infections, the prevalence of the disease, virus latency and reactivation, types of ocular involvement, and current concepts for the management of ocular HSV. Various exogenous factors associated with recurrent herpes of the eye are covered with an emphasis placed on corticosteroids, epinephrine, and medroxyprogesterone. Mechanisms of drug action, and reactivation/exacerbation of ocular herpes are discussed. Clinical guidelines for potential drug contraindications are discussed.


Superoxide Radical Photogenerator with Amplification Effect: Surmounting the Achilles' Heels of Photodynamic Oncotherapy.
Strong oxygen dependence, poor tumor targeting, and limited treatment depth have been considered as the "Achilles' heels" facing the clinical usage of photodynamic therapy (PDT). Different from common approaches, here, we propose an innovative tactic by using photon-initiated dyad cationic superoxide radical (O2-•) generator (ENBOS) featuring "0 + 1 > 1" amplification effect to simultaneously overcome these drawbacks. In particular, by taking advantage of the Förster resonance energy transfer theory, the energy donor successfully endows ENBOS with significantly enhanced NIR absorbance and photon utility, which in turn lead to ENBOS more easily activated and generating more O2-• in deep tissues, that thus dramatically intensifies the type I PDT against hypoxic deep tumors. Moreover, benefiting from the dyad cationic feature, ENBOS achieves superior "structure-inherent targeting" abilities with the signal-to-background ratio as high as 25.2 at 48 h post intravenous injection, offering opportunities for accurate imaging-guided tumor treatment. Meanwhile, the intratumoral accumulation and retention performance are also markedly improved (>120 h). On the basis of these unique merits, ENBOS selectively inhibits the deep-seated hypoxic tumor proliferation at a low light-dose irradiation. Therefore, this delicate design may open new horizons and cause a paradigm change for PDT in future cancer therapy.


HAF mediates the evasive resistance of anti-angiogenesis TKI through disrupting HIF-1α and HIF-2α balance in renal cell carcinoma.
Anti-angiogenesis has emerged as a standard of care for metastatic renal cell carcinoma. However, long-lasting efficacy is seldom reached, and evasive resistance eventually occurs under anti-angiogenic tyrosine kinase inhibitor (TKI) therapy. To establish new therapeutic strategies, investigating the molecular mechanism of resistance is critically important. In our study, human umbilical vascular endothelial cells (HUVECs) were incubated with TKI treatment in conditioned medium derived from renal cancer cells (RCCs) to demonstrate cell viability. Quantitative real time PCR or Western blotting analysis detected the fluctuation of transcriptional factors HIF-1α and HIF-2α in RCCs under TKI treatment. We demonstrated the alteration of a specific cytokine produced from RCCs under normoxia or hypoxia incubation by utilizing a cytokine RT-PCR primer array. We found that the anti-angiogenic TKI sunitinib disrupted the balance between HIF-1α and HIF-2α in RCCs and led to a protective effect on HUVECs against sunitinib treatment when cultured with conditioned medium. Mechanistically, RCCs treated with sunitinib resulted in down-regulation of HIF-1α, but not HIF-2α, through reduction of both mRNA and protein levels. The down-regulation of HIF-1α by sunitinib occurred via hypoxia associated factor (HAF), which also enhanced HIF-2α transactivation activity to increase the production of pro-angiogenic factors and cytokines and promote HUVEC proliferation. This phenomenon was observed in ACHN and A498 cells, which express both HIF-1α and HIF-2α, but was not observed in 786-O cells, which express only HIF-2α. Our results illustrated that targeting both angiogenesis and hypoxia pathways might provide a resolution to dealing with the devastating effects of anti-angiogenesis resistance.


Rapid screening for pesticides using automated online sample preparation with a high-resolution benchtop Orbitrap mass spectrometer.
For pesticide analysis in food products a common approach is to develop a fast multi-residue method that is capable of identifying and quantifying a large number of analytes in various matrices. This study demonstrates rapid screening and accurate mass confirmation of 116 pesticides in oranges and hazelnuts using an automated online sample preparation method with turbulent-flow chromatography technology coupled to a high-resolution benchtop Orbitrap™ mass spectrometer. The limits of quantification (LOQs) for the majority of analytes are well below the maximum residue limit (MRL) set by the European Union and the Japanese government. The recoveries were in the range of 70-120% for over 75% of analytes in both matrices. The present methodology is suitable for routine pesticides analysis in food safety laboratories.


Comparative decorporation efficacy of 3,4,3-LIHOPO, 4,4,4-LIHOPO and DTPA after contamination of rats with soluble forms of 238Pu and 233U.
The aim of this study was to compare the efficacies of DTPA, 3,4,3-LIHOPO and a newly synthesised molecule, 4,4,4-LIHOPO, in removing 233U and 238Pu after internal contamination by soluble forms of those nuclides. For this purpose, intravenous injections of DTPA (30 micromol kg(-1)) or 3,4,3-LIHOPO or 4,4,4-LIHOPO at dosages of 0.3 or 30 micromol kg(-1) were performed 1, 6 and 24 h after contamination of rats by intravenously injected 238Pu citrate and 1 h after intravenous injection of 233U nitrate. Actinide content in the main retention organs and cumulated excretion were measured 48 h after contamination. These experiments show similar decorporation efficacies of 4,4,4-LIHOPO and 3,4,3-LIHOPO for Pu, which are much higher than that of DTPA. At a dosage of 0.3 micromol kg(-1), the two LIHOPO analogues were as efficient as DTPA at a dosage of 30 micromol kg(-1). After U contamination, a 20% decorporation efficacy was obtained for either 3,4,3-LIHOPO or 4,4,4-LIHOPO at a dosage of 30 micromol kg(-1).


Symposium on surgical techniques in small animal practice. Cryosurgery in the treatment of perianal fistulae.
The advantages of cryosurgery over resection techniques in treating perianal fistulae include low recurrence rate, low incidence of incontinence, ease of performance, the relatively short amount of time required for the procedure, and minimal blood loss. If the disease is diagnosed and treated early in its course, complete resolution may be expected after one cryosurgical procedure. However several months and more than one surgical procedure are sometimes required in severe cases. The prognosis is good to excellent, depending on the stage and severity of the disease.


Conversion of antimalarial drug artemisinin to a new series of tricyclic 1,2,4-trioxanes1.
A highly efficient route for the conversion of the antimalarial drug artemisinin to a novel hydroxy-functionalized tricyclic 1,2,4-trioxane 6 is reported. Neither the trioxane 6 nor its derivatives 14-16, all of which lack the hydrolytically unstable acetal-lactone linkage, show antimalarial activity comparable with that of artemisinin.


Sugars, energy metabolism, and body weight control.
Obesity represents a major threat to health and quality of life. Although obesity has strong genetic determinants, it is generally accepted that it results from an imbalance between food intake and daily physical activity. Health guidelines have been focused on 3 particular lifestyle factors: increased levels of physical activity and reductions in the intakes of fat and sugars. The dietary guidelines, especially, are under debate. This review covers evidence from carefully controlled laboratory studies, clinical trials, studies in populations at high risk of developing obesity, and epidemiologic studies on the role of sugars, particularly sucrose, in the development of obesity. Although many environmental factors promote a positive energy balance, it is clear that the consumption of a low-carbohydrate, high-fat diet increases the likelihood of weight gain. The evidence related to carbohydrate, particularly sugars, and the type of food (solid or liquid) is less clear because the number of long-term ad libitum dietary intervention trials is very small. Data on sucrose intake in relation to metabolism and weight gain do not associate high consumption of sucrose with the prevalence of obesity. The evidence supports the current dietary guidelines for reducing fat intake. However, the effect of the carbohydrate source and class and of the form in which carbohydrate is consumed (solid or liquid) on body weight control requires further consideration.


Familial Becker's nevus.
The authors describe 4 patients with Becker's nevus (BN) in two families. Another 4 patients of the german literature are also presented. Together with the first two published cases of BN, familial BN is now known in 10 patients. All three clinical types of BN could be noticed.


Foraging behaviour of larval cod (Gadus morhua) at low light intensities.
The ability to forage at low light intensities can be of great importance for the survival of fish larvae in a pelagic environment. Three-dimensional silhouette imaging was used to observe larval cod foraging and swimming behaviour at three light intensities (dusk ~1.36 × 10-3 W/m2, night ~1.38 × 10-4 W/m2 and darkness ~3.67 × 10-6 W/m2) at 4 different ages from 6 to 53 days post-hatch (dph). At 6 dph, active pursuit of prey was only observed under dusk conditions. Attacks, and frequent orientations, were observed from 26 dph under night conditions. This was consistent with swimming behaviour which suggested that turn angles were the same under dusk and night conditions, but lower in darkness. Cod at 53 dph attacked prey in darkness and turn angles were not different from those under other light conditions. This suggests that larvae are still able to feed at light intensities of 3.67 × 10-6 W/m2. We conclude that larval cod can maintain foraging behaviour under light intensities that correspond to night-time at depths at which they are observed in the field, at least if they encounter high-density patches of prey such as those that they would encounter at thin layers or fronts.


The influence of methodological differences on the outcome of body size estimation studies in anorexia nervosa.
A major problem that has dogged research into body image disturbance in anorexia nervosa concerns the diversity of measurement procedures employed in studies of body size estimation. Many researchers believe that results obtained with different procedures cannot meaningfully be compared with each other, because the methods used measure different aspects of the body image. A meta-analysis of 33 body size estimation studies was conducted to investigate whether methodological differences do indeed influence outcome. This analysis revealed a general overestimation of body size among anorexia patients. Although a difference in mean effect size was found between studies using Body Part and Whole Body methods, this difference was absent when only the most commonly used Body Part method, the visual size estimation procedure, was considered. Among Whole Body methods, silhouette methods could not be distinguished from the rest in terms of effect size. It was concluded that Whole Body methods and the visual size estimation procedure assess correlated aspects of the body image.


Murine and human leukemias.
Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).


Where do we stand with radioimmunotherapy for acute myeloid leukemia?
Despite the approval of several new drugs, deaths from acute myeloid leukemia (AML) remain common. Because of well-defined cell surface antigens, easy accessibility, and radiosensitivity of leukemia cells, there is long-standing interest in radiolabeled antibodies (radioimmunotherapy [RIT]) to complement or replace existing treatments and improve outcomes in AML. Targeting primarily CD33, CD45, or CD66, early RIT efforts have focused on β-emitters, including iodine-131 (131I) and yttrium-90, mostly to intensify conditioning therapy before allogeneic hematopoietic cell transplantation (HCT). An 131I-labeled CD45 antibody (Iomab-B [apamistamab-I131]) is currently studied in the registration-type phase 3 SIERRA trial (NCT02665065) for this purpose. Of growing interest as therapeutic payloads are α-particle emitting radionuclides such as actinium-225 (225Ac) or astatine-211 (211At) since they deliver substantially higher decay energies over a much shorter distance than β-emitters, rendering them more suitable for precise, potent, and efficient target cell killing while minimizing toxicity to surrounding bystander cells, possibly allowing use outside of HCT. Clinical efforts with 211At-labeled CD45 antibodies and 225Ac-labeled CD33 antibodies (e.g. 225Ac-lintuzumab [Actimab-A]) are ongoing. A first anti-AML RIT may soon become available. This might propel further work to develop RIT-based treatments for AML, with many such efforts already ongoing.


Biochemical and molecular characterization of the mitochondrial peroxiredoxin PsPrxII F from Pisum sativum.
The pea peroxiredoxin homologue PsPrxII F of the Arabidopsis thaliana mitochondrial AtPrxII F was isolated as cDNA and genomic DNA, and characterized in respect to its biochemical and molecular properties. The deduced amino acid sequence contains an N-terminal targeting address for mitochondrial import. Mitochondrial location of PsPrxII F was confirmed by immunocytochemistry. The mature enzyme, without the transit peptide, has a molecular mass of 18.75 kDa, and, at positions 59 and 84, carries the two catalytic cysteinyl residues which are characteristic for this particular Prx subgroup. Activity of site-directed mutagenized C84S-variant lacking the so-called resolving Cys dropped to about 12% of WT Prx while C59S lost its peroxidatic activity completely. Likewise, WT PsPrxII F and C84S-variant but not C59S protected plasmid DNA against strand breakage in a mixed function oxidation assay. WT PrxII F and the variant proteins aggregated to high mass oligomers not yet described for type II Prx. Upon oxidation with hydrogen peroxide PsPrxII F focussed in a series of spots of distinct pI but similar molecular masses in two-dimensional gels indicating different oxidation states of the protein. Using this technique, partial oxidation was also detected in leaf extracts and isolated mitochondria. PsPrxII F mRNA and protein accumulated in cold and heavy metals treated pea plants suggesting a particular function under stress.


Differential induction of IL-1beta and TNF by CD40 ligand or cellular contact with stimulated T cells depends on the maturation stage of human monocytes.
Cellular contact with stimulated T cells potently induces cytokine production in monocytes, a mechanism that is likely to be relevant to chronic inflammation. Although the identity of surface molecules involved in this process remains elusive, CD40 and its ligand, CD40L, are thought to be implicated, considering that they are expressed at the inflammatory site. To ascertain the involvement of CD40L, we compared the activation of three different types of human monocytic cells, i.e., freshly isolated monocytes, monocytes primed with IFN-gamma (IFN-gamma-macrophages), and THP-1 cells. These cells were activated by either membranes isolated from stimulated T cells (HUT-78 or T lymphocytes) to mimic cellular contact, soluble extracts from isolated membranes, or CD40L trimer (CD40LT). The production of TNF and IL-1beta was induced by membranes of stimulated T cells in the three types of target cells, whereas CD40LT induced TNF production in IFN-gamma-macrophages only. Similar results were obtained with soluble extracts of T cell membranes, demonstrating that the difference between membranes and CD40LT was not due to the particulate form of membranes. CD40LT induced neither transcript nor protein of cytokines in monocytes, whereas in IFN-gamma-macrophages, IL-1beta and TNF mRNA were observed, but only TNF was measured in cell supernatants. Finally, anti-CD40L Abs failed to inhibit TNF and IL-1beta production induced in IFN-gamma-macrophages by solubilized membranes, whereas TNF production induced by CD40LT was inhibited. These results demonstrate that CD40L is not required in monocyte activation by direct cellular contact with stimulated T cells, although soluble CD40LT induces the production of TNF in IFN-gamma-macrophages.


Factors Associated With Mental Health Status Among Older Primary Caregivers in Japan.
This study aimed to elucidate factors affecting the mental health status of older primary caregivers. Participants comprised 81 pairs of home care recipients aged ≥65 years and primary caregivers aged ≥65 years who were caring for the recipients. We used an individual interview method, which covered basic attributes, activities of daily living by Barthel Index, mental health status by Center for Epidemiologic Studies Depression Scale (CES-D), sense of coherence (SOC), and sense of care burden by Japanese version of the Zarit Burden Interview (J-ZBI). The score for the comprehensibility subscale of the SOC was significantly higher for the old-old caregivers compared with the young-old caregivers (P < .01). A significant positive correlation between the number of years of caregiving and the score for the SOC meaningfulness subscale was seen for the young-old caregivers (P < .05). For the old-old caregivers alone, negative correlations were seen between the CES-D score and the scores for all the SOC items. Multiple linear regression analysis using CES-D as the dependent variable showed a significant positive relationship to J-ZBI in all caregivers (P < .01). In contrast, a significant negative relationship was seen with meaningfulness, an SOC subscale only for the old-old caregivers. Meaningfulness as well as J-ZBI was extracted as a factor affecting the mental health status of the old-old caregivers, suggesting that higher SOC relates to lower stress levels with a remarkable decline in physical condition. Meaningfulness, an SOC subscale, is an important factor for improving the mental health of old-old caregivers.


Characterization, drug loading and antibacterial activity of nanohydroxyapatite/polycaprolactone (nHA/PCL) electrospun membrane.
Considering the important factor of bioactive nanohydoxyapatite (nHA) to enhance osteoconductivity or bone-bonding capacity, nHA was incorporated into an electrospun polycaprolactone (PCL) membrane using electrospinning techniques. The viscosity of the PCL and nHA/PCL with different concentrations of nHA was measured and the morphology of the electrospun membranes was compared using a field emission scanning electron microscopy. The water contact angle of the nanofiber determined the wettability of the membranes of different concentrations. The surface roughness of the electrospun nanofibers fabricated from pure PCL and nHA/PCL was determined and compared using atomic force microscopy. Attenuated total reflectance Fourier transform infrared spectroscopy was used to study the chemical bonding of the composite electrospun nanofibers. Beadless nanofibers were achieved after the incorporation of nHA with a diameter of 200-700 nm. Results showed that the fiber diameter and the surface roughness of electrospun nanofibers were significantly increased after the incorporation of nHA. In contrast, the water contact angle (132° ± 3.5°) was reduced for PCL membrane after addition of 10% (w/w) nHA (112° ± 3.0°). Ultimate tensile strengths of PCL membrane and 10% (w/w) nHA/PCL membrane were 25.02 ± 2.3 and 18.5 ± 4.4 MPa. A model drug tetracycline hydrochloride was successfully loaded in the membrane and the membrane demonstrated good antibacterial effects against the growth of bacteria by showing inhibition zone for E. coli (2.53 ± 0.06 cm) and B. cereus (2.87 ± 0.06 cm).


Oxygen toxicity in recreational and technical diving.
It is increasingly common for recreational scuba divers to use breathing mixtures enriched with additional oxygen ('nitrox' or 'enriched air nitrogen') and for technical divers to be exposed to elevated partial pressures of oxygen for prolonged periods of time. The National Oceanic and Atmospheric Administration oxygen exposure limits have traditionally been used by the recreational diving industry and technical diving communities. Review of the original research into oxygen toxicity brings into question the validity of these limits and would suggest revised limits with a maximum partial pressure of oxygen of 162 kPa (1.6 Ata) and 142 kPa (1.4 Ata) at depth and the use of the repetitive air excursion (REPEX) limits for single and repetitive exposures. Suitable conservatism in case of the need for recompression therapy is recommended.


Targeted activation in deterministic and stochastic systems.
Metastable escape is ubiquitous in many physical systems and is becoming a concern in engineering design as these designs (e.g., swarms of vehicles, coupled building energetics, nanoengineering, etc.) become more inspired by dynamics of biological, molecular and other natural systems. In light of this, we study a chain of coupled bistable oscillators which has two global conformations and we investigate how specialized or targeted disturbance is funneled in an inverse energy cascade and ultimately influences the transition process between the conformations. We derive a multiphase averaged approximation to these dynamics which illustrates the influence of actions in modal coordinates on the coarse behavior of this process. An activation condition that predicts how the disturbance influences the rate of transition is then derived. The prediction tools are derived for deterministic dynamics and we also present analogous behavior in the stochastic setting and show a divergence from Kramers activation behavior under targeted activation conditions.


The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway.
Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener) or pinacidil (Pin, a non-selective KATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker) or glibenclamide (Gli, a non-selective KATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.


Implementation of an evidence-based feeding protocol and aspiration risk reduction algorithm.
Aspiration pneumonia is a serious complication of mechanical ventilation and enteral tube feedings. It results in increased patient mortality, increased length of hospital stay, and increased healthcare costs. This article describes an evidence-based practice approach to the creation of an enteral feeding protocol and an aspiration risk reduction algorithm. These tools were piloted in a Medical Intensive Care Unit at a Midwest tertiary care center. Chart audits show an increase in the percentage of patients who reach their goal rate for enteral feedings from 78% to 85%. Reported aspiration pneumonias decreased from an average count of 4.8 patients per month to 4.3 per month and ventilator-associated pneumonia rates decreased from 6.8 to 3.2 per 1000 patient days.


Expression of T-follicular helper markers in sequential biopsies of progressive mycosis fungoides and other primary cutaneous T-cell lymphomas.
T-follicular helper (Tfh) lymphocytes represent the neoplastic cells of angioimmunoblastic T-cell lymphoma and have been observed also in several cutaneous T-cell lymphomas (CTCLs) and extracutaneous T-cell lymphomas, including peripheral T-cell lymphoma, not otherwise specified, mycosis fungoides (MF), cutaneous CD4 small/medium T-cell lymphoma (CD4SMTCL), and Sezary syndrome. We studied a large number of different types of primary CTCL for expression of Tfh markers, including 36 biopsies from 21 patients with MF (with sequential biopsies from patch stage and tumor stage of 15 patients), 13 patients with CD4SMTCL, 9 with lymphomatoid papulosis, 11 with cutaneous anaplastic large cell lymphoma (cALCL), 2 with cutaneous γ/δ T-cell lymphoma, 8 with subcutaneous panniculitis-like T-cell lymphoma, 3 with cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma, 6 with cutaneous peripheral T-cell lymphoma, not otherwise specified, and 1 with Sezary syndrome. Expression of at least 3 of 5 markers (PD-1, CXCL-13, ICOS, Bcl-6, and CD10) in >10% of tumor cells was observed in 33 biopsies (MF = 20; CD4SMTCL = 11; 1 each cutaneous anaplastic large cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma, respectively). Our study shows that a Tfh phenotype is very common in MF and CD4SMTCL but can be observed rarely also in other types of CTCL. Expression of Tfh markers should not be used for classification of any entity of CTCL and may only integrate other immunohistochemical stainings for a more accurate characterization of these disorders. Precise distinction of Tfh-positive CTCLs from secondary skin manifestations of angioimmunoblastic T-cell lymphoma cannot rest on demonstration of a Tfh phenotype alone and should be achieved by a synthesis of clinical, histological, and phenotypic features.


Trauma of the Frontal Region Is Influenced by the Volume of Frontal Sinuses. A Finite Element Study.
Anatomy of frontal sinuses varies individually, from differences in volume and shape to a rare case when the sinuses are absent. However, there are scarce data related to influence of these variations on impact generated fracture pattern. Therefore, the aim of this study was to analyse the influence of frontal sinus volume on the stress distribution and fracture pattern in the frontal region. The study included four representative Finite Element models of the skull. Reference model was built on the basis of computed tomography scans of a human head with normally developed frontal sinuses. By modifying the reference model, three additional models were generated: a model without sinuses, with hypoplasic, and with hyperplasic sinuses. A 7.7 kN force was applied perpendicularly to the forehead of each model, in order to simulate a frontal impact. The results demonstrated that the distribution of impact stress in frontal region depends on the frontal sinus volume. The anterior sinus wall showed the highest fragility in case with hyperplasic sinuses, whereas posterior wall/inner plate showed more fragility in cases with hypoplasic and undeveloped sinuses. Well-developed frontal sinuses might, through absorption of the impact energy by anterior wall, protect the posterior wall and intracranial contents.


Dynamical instabilities of quasistatic crack propagation under thermal stress.
We address the theory of quasistatic crack propagation in a strip of glass that is pulled from a hot oven towards a cold bath. This problem had been carefully studied in a number of experiments that offer a wealth of data to challenge the theory. We improve upon previous theoretical treatments in a number of ways. First, we offer a technical improvement of the discussion of the instability towards the creation of a straight crack. This improvement consists in employing Padé approximants to solve the relevant Wiener-Hopf factorization problem that is associated with this transition. Next we improve the discussion of the onset of oscillatory instability towards an undulating crack. We offer a way of considering the problem as a sum of solutions of a finite strip without a crack and an infinite medium with a crack. This allows us to present a closed form solution of the stress intensity factors in the vicinity of the oscillatory instability. Most importantly we develop a dynamical description of the actual trajectory in the regime of oscillatory crack. This theory is based on the dynamical law for crack propagation proposed by Hodgdon and Sethna. We show that this dynamical law results in a solution of the actual crack trajectory in post-critical conditions; we can compute from first principles the critical value of the control parameters, and the characteristics of the solution such as the wavelength of the oscillations. We present detailed comparison with experimental measurements without any free parameters. The comparison appears quite excellent. Finally we show that the dynamical law can be translated to an equation for the amplitude of the oscillatory crack; this equation predicts correctly the scaling exponents observed in experiments.


Spontaneous formation of stringlike clusters and smectic sheets for colloidal rods confined in thin wedgelike gaps.
Monodispersed colloidal rods of β-FeOOH with sizes ranging from 270 to 580 nm in length and 50 to 80 nm in width were synthesized. Narrow wedgelike gaps (0 to 700 nm in height) were formed around the inner bottom edge of the suspension glass cells. Optical microscopic observations revealed the formation of stringlike clusters of the rods and smectic sheets (by spontaneous side-by-side clustering of the strings) in the isotropic phase of the rod suspensions confined in narrow gaps; the electrolyte (HCl) concentrations of the suspensions are 5-40 mM, at which inter-rod interactions are attractive. The strings exhibit different colors that were used to investigate the structures of the strings with the help of interference color theory for thin films. The results are as follows. (1) The rods, lying flat on the gap bottom, are connected side-by-side and stacked upward to form stringlike clusters with different thicknesses depending on the gap height. (2) The stacking numbers (N(sr)) of the rods are estimated to be 1-5. With N(sr) increasing from 2 to 5, the volume fractions (ϕ) of the rods in the strings increased typically from 0.25-0.3 to 0.35-0.42 to reach limiting values (close to the ϕ values of the rods in the bulk smectic phase). (3) Unexpected low-ϕ strings are found in regions with an intermediate height in the gaps. These behaviors of ϕ may be caused by thermal fluctuations of the strings.


[Hypereosinophilic syndrome. Clinical case].
We report the case of a 16 years old girl with hypereosinophilic syndrome, presenting with fever, abdominal pain, skin lesions and peripheral neuropathy, which responded successfully to treatment with prednisone.


Outcomes valued by people living with dementia and their care partners: protocol for a qualitative systematic review and synthesis.
Growing numbers of interventions are being developed to support people and families living with dementia, but the extent to which they address the areas of most importance to the intended recipients is unclear. This qualitative review will synthesise outcomes identified as important from the perspectives of people living with dementia and their care partners, both for themselves and each other. The review will employ thematic synthesis methodology. Studies from 1990 or later will be eligible if they include qualitative data on the views of people living with dementia or their care partners on valued outcomes or the lived experience of dementia. Databases to be searched include MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and Social Sciences Premium Collection, in addition to systematically gathered grey literature. Rayyan QCRI software will be used to manage the screening processes, and NVivo software will be used to manage data extraction and analysis. The review will also critically evaluate the extent to which international recommendations address the areas of importance to people living with dementia and their families. The findings will be of relevance to researchers, policy makers and providers and commissioners of dementia services. The protocol is written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. As the methodology of this study consists of collecting data from publicly available articles, it does not require ethical approval. We will share the results through conference presentations and an open-access publication in a peer-reviewed journal. Our mixed stakeholder involvement group will advise on dissemination to non-academic audiences. CRD42020219274.


The expression level of frog relaxin mRNA (fRLX), in the testis of Rana esculenta, is influenced by testosterone.
Frog relaxin (fRLX) belongs to the relaxin/insulin gene family present in the testis of Rana esculenta and is specifically expressed by Leydig cells. Since the expression of fRLX transcript changes during the reproductive cycle and is more abundant when circulating levels of androgens are relatively high, we investigated the effect(s) of testosterone and its antagonist (cyproterone acetate, CPA) on its expression pattern, in the testis of the frog Rana esculenta. Results from in vivo and in vitro experiments demonstrate that testosterone strongly induces a significant increase of fRLX mRNA expression in frog testes and, this effect is counteracted by CPA, supporting the existence of intratesticular (autocrine/paracrine) mechanisms of action. Interestingly, in both the control and testosterone-treated testes, fRLX mRNA expression was markedly decreased 24 h post-treatment, as compared to that measured at 2 h and 8 h post-treatment, suggesting that factor(s), other than testosterone, may act(s) in controlling its expression. In addition, RT-PCR analysis and in situ hybridization performed on frog testis injected with CPA for 15 days, on alternate days, showed a strong decrease of fRLX expression, suggesting that CPA counteracts the effect of testosterone on fRLX expression. Taken together our results strongly indicate that changes in the production, by the Leydig cells, of both testosterone and fRLX may represent a marker for the study of Leydig cell activity in the testis of the frog Rana esculenta.


Antimycobacterial activity of 3'- and 4'-fluorothiobenzanilides.
On the basis of a preliminary study of the antimycobacterial activity of thiobenzanilides, a group of 3'-fluoro- and 4'-fluorothiobenzanilides has been synthesized and tested against Mycobacterium tuberculosis, M. kansasii, M. avium and M. fortuitum. The results of this study demonstrate that electron withdrawing groups increase the activity of thiobenzanilides and fluoro benzothioanilides against atypical strains which is higher then that of INH.


Van der Woude syndrome.
Van der Woude syndrome (VWS) is an autosomal dominant craniofacial syndrome with variable expression characterised by congenital pits and sinuses in the lower lip together with cleft lip, or palate, or both. We report a case of VWS, which occurred as a new mutation, and review previous reports.


Persistence of viral HLA-DR- CD4 T-cell reservoir during prolonged treatment of HIV-1 infection with a five-drug regimen.
During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication-competent HIV-1 can still be recovered from resting memory CD4 T cells. In an attempt to accelerate the clearance of this pool of infected CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were treated with a five-drug regimen. While plasma HIV-1 RNA levels generally remained below the level of detection (< 5 copies/ml), replication competent HIV-1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions throughout treatment. Decay slopes of infected CD4 T cells ranged from -0.061/week (half-life=2.6 months) to +0.003/week (half-life = infinite). Virus was still detectable at the last time point analysed (80-173 weeks) in all patients. Although more intensive treatment results in improved suppression of plasma viraemia compared with standard drug regimens, it does not result in clearance of the viral reservoir in this timeframe. Strategies other than treatment with a combination of five of the currently available drugs need to be pursued in order to achieve eradication of HIV-1 from this cellular reservoir.


Emerging role of the pediatric nurse practitioner in acute care.
The pediatric nurse practitioner role in the tertiary setting is one of several emerging roles gaining recognition in the various groups of advanced practice nursing programs today. The advanced practice nurse (APN) who is a pediatric nurse practitioner (PNP) in an acute care setting helps to provide cost-effective, quality patient care for critically and chronically ill children who are in these settings. The foundation of advanced practice nursing in this role incorporates the general role expectations of advanced nursing preparation, including case management, clinical pathway development, consultation and education, research, and collaboration, with the specific knowledge and skills of the pediatric nurse practitioner to function effectively with sick children in the acute care areas.


Cost-effectiveness of biological treatment of ulcerative colitis - a systematic review.
The aim of this systematic review was to collect and summarise all current data on the cost-effectiveness of biological treatment in ulcerative colitis. A literature search was conducted using the Medline, Embase, Centre for Reviews and Dissemination databases and included all cost-effectiveness analyses comparing biological treatment with any comparator. We identified 277 records of which 10 were included in this review. Eighty percent of identified analyses used quality-adjusted life years (QALY) as a measure of outcome. The most commonly assessed biological agent was infliximab. Half of the eight economic analyses, with QALY as an outcome, showed the cost-effectiveness of biological treatment against the comparator. Incremental cost-effectiveness ratios (ICER) ranged from 15,748 euro to 450,791 euro. The highest ICER values were observed when biologicals were compared with standard care alone. This systematic review revealed that in some cases the biological treatment, despite its clinical effectiveness, is too expensive and exceeds the national threshold value.


[Challenges for developing a comparative analytical model for health services].
This paper presents different models that describe health determinants, services, and systems. It highlights the important model developed by Contandriopoulos, proposing a separation between the health status and health care circuits. The article is intended as a contribution to the field of comparative analysis with a new theoretical, methodological, and evaluative approach. Problems were identified in the development of a new model. Decentralization and access are introduced as categories, suggesting that they may take part in such new model.


Inequality in the distribution of health resources and health services in China: hospitals versus primary care institutions.
Equity is one of the major goals of China's recent health system reform. This study aimed to evaluate the equality of the distribution of health resources and health services between hospitals and primary care institutions. Data of this study were drawn from the China Health Statistical Year Books. We calculated Gini coefficients based on population size and geographic size, respectively, for the indicators: number of institutions, number of health workers and number of beds; and the concentration index (CI) for the indicators: per capita outpatient visits and annual hospitalization rates. The Gini coefficients against population size ranged between 0.17 and 0.44 in the hospital sector, indicating a relatively good equality. The primary care sector showed a slightly higher level of Gini coefficients (around 0.45) in the number of health workers. However, inequality was evident in the geographic distribution of health resources. The Gini coefficients exceeded 0.7 in the geographic distribution of institutions, health workers and beds in both the hospital and the primary care sectors, indicating high levels of inequality. The CI values of hospital inpatient care and outpatient visits to primary care institutions were small (ranging from -0.02 to 0.02), indicating good wealth-related equality. The CI values of outpatient visits to hospitals ranged from 0.16 to 0.21, indicating a concentration of services towards the richer populations. By contrast, the CI values of inpatient care in primary care institutions ranged from -0.24 to -0.22, indicating a concentration of services towards the poorer populations. The eastern developed region also had a high internal inequality compared with the other less developed regions. Significant inequality in the geographic distribution of health resources is evident, despite a more equitable per capita distribution of resources. Richer people are more likely to use well-resourced hospitals for outpatient care. By contrast, poorer people are more likely to use poorly-resourced primary care institutions for inpatient care. There is a risk of the emergence of a two-tiered health care delivery system.


[Effects of CCN5 overexpression on the expression of alpha-SMA and collagen I in hepatic stellate cells and its mechanism].
To investigate the relationship between connective tissue growth factor (CCN5) and hepatic stellate cell (HSC) activation as well as the mechanism of action. As the research object, LX-2 cells were stimulated with transforming growth factor-beta1 ( TGF-(beta1), and the protein expression levels of CCN5 and CCN2 were determined by Western blot; Hepatocyte high expression system of CCN5 was constructed and transfected hepatic stellate cells (HSC) to make CCN5 overexpression; The expression levels of alpha-smooth muscle actin (alpha-SMA) and collagen I were determined by RT-PCR and Western blot. To further study its mechanism of action, Smad2 and phosphorylation level of Smad2 were determined by RT-PCR and Western blot. Under normal circumstances, CCN2 expression levels were much higher than CCN5 in LX-2 cells, while CCN2 expression was significantly higher than CCN5 if LX-2 cells were stimulated by TGF-beta1. However, there was no change for CCN5. Compared with the control group and the vector group, CCN5 was successfully overexpressed in the transfection group, and mRNA and protein levels of alpha-SMA and collagen I were significantly decreased (P < 0.01). Meanwhile, phosphorylation level of Smad2 was also significantly decreased (P < 0.01). CCN5, which has the function that inhibits HSC activation, has the opposite role compared with CCN2, therefore, a new idea was proposed for the prevention and treatment of liver fibrosis.


Modifications of recognition memory processes in preterm children: an event-related potential study.
Prematurity may cause hippocampal compromise. Therefore, hippocampus-dependent memory processes (recollection-based retrieval) may be more impaired than hippocampus-independent processes (familiarity-based retrieval). The memory of 18 children born preterm with reduced hippocampal volumes, without neonatal complications (weeks of gestation < 34, weight < 1,600 g), and 15 controls (8-10 years) was tested using an item recognition task. While groups were equal in memory performance, dissociation was found: The event-related potential (ERP) correlate of familiarity was intact in the preterm group, whereas the correlate of recollection was attenuated. A follow-up experiment ruled out that this was due to general cognitive deficits. Furthermore, gestational age correlated with the ERP index of recollection. Thus, recognition memory in preterm children may be characterized by a compensation of attenuated recollection by familiarity.


Receptor binding and cellular uptake studies of macrophage migration inhibitory factor (MIF): use of biologically active labeled MIF derivatives.
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine for which a receptor has not been identified. That MIF has intracellular functions has been suggested by its enzymatic activity and constitutive expression profile. The discovery of functional MIF-c-Jun activation domain binding protein 1 (JAB1) binding has confirmed this notion and indicated that nonreceptor-based signaling mechanisms are important for MIF function. Here, we have generated and tested several biologically active labeled MIF derivatives to further define target protein binding by MIF and its cellular uptake characteristics. (35)S-MIF, biotinylated MIF, and fluoresceinated MIF were demonstrated to exhibit full biologic activity. Neither by applying a standard iodinated MIF preparation nor by using the biologically active (35)S-MIF derivative in receptor-binding studies were we able to measure any receptor-binding activity on numerous cells, confirming that uptake of MIF into target cells and MIF signaling can occur by receptor-independent pathways. When MIF derivatives were applied in cellular uptake studies, MIF was found to be endocytosed into both immune and nonimmune cells and targeted to the cytosol and lysosomes. The entry of MIF was temperature and energy dependent and was inhibited by monodansylcadaverine but not by ouabain. Endocytosed biotin-MIF bound JAB1 not only in macrophages, as shown previously, but also in nonimmune cells. A tagged MIF construct, MIF-enhanced green fluorescent protein (EGFP), was shown to be a valuable tool, as EGFP constructs of critical MIF cysteine mutants exhibited identical cellular localization properties to those of wild-type MIF (wtMIF). Our results indicate that MIF membrane receptors are not widely expressed, if at all, and suggest that the cellular uptake of MIF occurs by nonreceptor-mediated endocytosis rather than penetration. All the derivatives investigated, except for iodinated MIF, represent valuable tools for further MIF target protein and cellular studies.


How good are US dermatologists at discriminating skin cancers? A number-needed-to-treat analysis.
Identification of skin cancer requires discrimination of malignant lesions from benign lesions. The number of biopsies performed to yield one cancer diagnosis can be presented as a number needed to treat (NNT), and provides an assessment of the efficiency of skin cancer detection. To assess the clinical accuracy of US dermatologists screening for skin cancer, the NNT for both melanoma and non-melanoma skin cancer was examined. Pathology reports from 2021 biopsies performed at the Wake Forest University Department of Dermatology were reviewed, including the physician's differential diagnosis and final pathological diagnosis. The NNT was calculated for melanoma, non-melanoma skin cancer, and all skin cancer diagnosed. Of 1240 biopsies suspicious for skin cancer, 559 cancers were diagnosed, yielding a NNT of 2.22 for any cancer. The NNT specifically for non-melanoma skin cancer was 1.6, while the NNT for melanoma was 15. Patient age, anatomical location, sex and physician all significantly impacted on NNT values. The NNT for melanoma in our study was lower compared to recently published values obtained from general practitioners in Australian skin cancer clinics (NNT of 30). Variability amongst institutions, practice settings and physicians supports the need to establish a benchmark NNT.


Screening for Lung Cancer: CHEST Guideline and Expert Panel Report.
Low-dose chest CT screening for lung cancer has become a standard of care in the United States in the past few years, in large part due to the results of the National Lung Screening Trial. The benefit and harms of low-dose chest CT screening differ in both frequency and magnitude. The translation of a favorable balance of benefit and harms into practice can be difficult. Here, we update the evidence base for the benefit, harms, and implementation of low radiation dose chest CT screening. We use the updated evidence base to provide recommendations where the evidence allows, and statements based on experience and expert consensus where it does not. Approved panelists developed key questions using the PICO (population, intervention, comparator, and outcome) format to address the benefit and harms of low-dose CT screening, as well as key areas of program implementation. A systematic literature review was conducted by using MEDLINE via PubMed, Embase, and the Cochrane Library. Reference lists from relevant retrievals were searched, and additional papers were added. The quality of the evidence was assessed for each critical or important outcome of interest using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Important clinical questions were addressed based on the evidence developed from the systematic literature review. Graded recommendations and ungraded statements were drafted, voted on, and revised until consensus was reached. The systematic literature review identified 59 studies that informed the response to the 12 PICO questions that were developed. Key clinical questions were addressed resulting in six graded recommendations and nine ungraded consensus based statements. Evidence suggests that low-dose CT screening for lung cancer results in a favorable but tenuous balance of benefit and harms. The selection of screen-eligible patients, the quality of imaging and image interpretation, the management of screen-detected findings, and the effectiveness of smoking cessation interventions can affect this balance. Additional research is needed to optimize the approach to low-dose CT screening.


Economic Analysis for Commingling Effects of Insect Activity in the Elevator Boot Area.
Boot areas in commercial grain elevators and feed mills contribute to commingling of insects with grain that moves through the elevator leg. A partial budget and stochastic dominance model were developed to improve pest management decision-making and risk analysis assessment from commingling effects of insect activity in the boot area. Modified pilot-scale bucket elevator legs, containing residual wheat or corn, were infested with varying insect pest densities prior to clean grain transfers. Appropriate grain discounts were applied to grain samples obtained from clean grain transfers over either: 1) insect-free and untreated boots, 2) infested and untreated boots, or 3) infested and chemical-treated (β-cyfluthrin) boots. The insect-free boots simulated performing clean-out of the boot area. Partial budget analysis and stochastic dominance modeling indicated that boot sanitation (cleanout) about every 30 d, avoiding costly grain discounts from insect commingling, is the preferred choice. Although chemical spray treatments of the empty boot may reduce insect populations of some boot residual grains, boot cleanout always had lower and usually zero insect pest populations in the boot residual grain, providing higher facility operational net income without the use of chemicals.


Acute care hospitalization of Aboriginal children and youth.
Research that has examined Aboriginal children's hospitalization rates at the national level has been limited to analyses of areas with large percentages of Aboriginal residents, rather than of Aboriginal individuals. This study uses linked census and administrative data to describe hospitalization patterns among children and youth aged 0 to 19, by Aboriginal identity, for all provinces and territories except Quebec. The 2006 Census was linked to the 2006/2007-to-2008/2009 Discharge Abstract Database, which contains hospital records from all acute care facilities (except Quebec). Hospital records were examined by Aboriginal identity, as reported to the census, according to International Classification of Diseases chapters based on "the most responsible diagnosis." Age-standardized hospitalization rates (ASHRs) were calculated per 100,000 population, and age-standardized rate ratios (RRs) were calculated for Aboriginal groups relative to non-Aboriginal people. ASHRs were consistently higher among Aboriginal children and youth relative to their non-Aboriginal counterparts; rates for children aged 0 to 9 were 1.4 to 1.8 times higher; for youth aged 10 to 19, 2.0 to 3.8 times higher. For all children aged 0 to 9, the leading cause of hospitalization was "diseases of the respiratory system," but RRs for Aboriginal children ranged from 1.7 to 2.5, compared with non-Aboriginal children. Disparities between Aboriginal and non-Aboriginal 10- to 19-year-olds were pronounced for injuries due to assaults (RRs from 4.8 to 10.0), self-inflicted injuries (RRs from 2.7 to 14.2), and pregnancy, childbirth and the puerperium (RRs from 4.1 to 9.8). Additional research is needed to examine reasons for the disparities in hospitalization rates between Aboriginal and non-Aboriginal children and youth.


Inhibition of angiogenesis and invasion by DMBT is mediated by downregulation of VEGF and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells.
Invasion, either directly or via metastasis formation, is the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. In order to obtain more potent inhibitors, a series of brartemicin analogs were synthesized and evaluated for their inhibitory activity against invasion. Among the synthetic analogs tested, DMBT, 6,6'-bis (2,3-dimethoxybenzoyl)-a,a-D-trehalose, was found to be the most potent anti-invasive agent. But the effects of DMBT on breast cancer cells were not known. In this study, the effects of DMBT on invasion and metastasis in MDA-MB-231 cells were investigated. MTT assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found. DMBT could inhibit invasion, migration and tube formation of HUVECs. Gelatin zymography showed that DMBT inhibited secretion and activity of MMP-9. Western blotting demonstrated that DMBT effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and p-Akt. These results suggested that DMBT could inhibit invasion and angiogenesis by downregulation of VEGF and MMP-9, resulting from the inhibition of Akt pathway. DMBT might be a promising lead molecule for the anti-metastasis and serve as a therapeutic agent to inhibit breast cancer cell invasion and metastasis.


Vascular consideration in raising the pectoralis major flap.
Several types of musculocutaneous flaps, including that the pectoralis major, have been used for reconstruction following resection of malignant tumors in the head and neck region. Although several clinical studies have investigated the vascularity of such musculocutaneous flaps, the findings have been inconsistent. The present study examined the distribution of arteries in the pectoralis major muscle and surrounding subcutaneous tissue by macroscopic dissection and angiography. Based on the results of this examination, muscle layer and surrounding subcutaneous tissue appear to be supplied by different arteries and show different distribution patterns. However, evidence of penetrating branches from the muscle layer to the subcutaneous tissue layer suggests the existence of blood flow from the muscle layer to the subcutaneous tissue layer. Such arterial branches should be considered when raising the pectoralis major flap in order to prevent necrosis and improve the viability of the flap.


Heat conduction and reversed thermal diode: the interface effect.
The important role of interface collisions on the thermal-diode effect, of the two-segment lattices is studied. In the high-average temperature region, it is found that the thermal-diode effect may be significantly weaken and even annihilated. In the low-temperature region, where the thermal diode is inhibited in the collisionless case, an interesting reversed thermal diode is achieved. These behaviors are interpreted in terms of phonon-band mixing induced by interface collisions. The regime where a reversed thermal diode can be observed by resorting to the dependence of the heat current on the average temperature, and a critical temperature exists. The results proposed in this paper reveal that thermal-diode effect can be qualitatively influenced if the interface collisions could not be neglected.


Contrast-enhanced Ultrasonography Features for Diagnosing Pseudoprogression of Hepatocellular Carcinoma with Immunotherapy: A Case Report of the Response after Pseudoprogression.
A male patient in his 70s with recurrent hepatocellular carcinoma (HCC) after surgery received atezolizumab plus bevacizumab (Atezo+Bev) therapy. Initial computed tomography (CT) revealed tumor growth along with an increase in tumor markers, and contrast-enhanced ultrasonography (CEUS) showed multiple round avascular areas within the nodules with an appearance similar to a slice of Swiss cheese. Continuation of immunotherapy with consideration of the potential for pseudoprogression produced a dramatic response. Although it is difficult to distinguish between true progression and pseudoprogression, the Swiss cheese-like appearance on CEUS may be important for the early diagnosis of pseudoprogression.


Mechanical measures of spasticity in stroke.
Mechanical measurements of stretch reflexes show promise for the quantification of spasticity after stroke. Mechanical measurements can increase the objectivity, repeatability, and precision of spasticity quantification and provide additional insight into the neuropathology that is not available with current clinical measurements. Several techniques are reviewed and the advantages and disadvantages of quantification of spasticity using mechanical measurements are considered. Although mechanical measures of spasticity offer many advantages, much research needs to be done to establish a standard measurement of spasticity that can be easily implemented in the clinic.


18F-AV-1451 PET Imaging in Three Patients with Probable Cerebral Amyloid Angiopathy.
Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo. Three patients with probable CAA underwent 11C-Pittsburgh Compound B (PiB) PET or 18F-florbetaben PET to evaluate amyloid burden, and 18F-AV-1451 PET to evaluate paired helical filament tau burden. Regions that had cerebral microbleeds or cortical superficial siderosis largely overlapped with those showing increased 18F-AV-1451. Our preliminary study raised the possibility that lobar cerebral microbleeds, and cortical superficial siderosis, which are characteristic markers of vascular amyloid, may be associated with local production of paired helical filament tau.


Lipid excess affects chaperone-mediated autophagy in hypothalamus.
Obesity is a major health problem worldwide. Overweight and obesity directly affect health-related quality of life and also have an important economic impact on healthcare systems. In experimental models, obesity leads to hypothalamic inflammation and loss of metabolic homeostasis. It is known that macroautophagy is decreased in the hypothalamus of obese mice but the role of chaperone-mediated autophagy is still unknown. In this study, we aimed to investigate the role of hypothalamic chaperone-mediated autophagy in response to high-fat diet and also the direct effect of palmitate on hypothalamic neurons. Mice received chow or high-fat diet for 3 days or 1 week. At the end of the experimental protocol, chaperone-mediated autophagy in hypothalamus was investigated, as well as cytokines expression. In other set of experiments, neuronal cell lines were treated with palmitic acid, a saturated fatty acid. We show that chaperone-mediated autophagy is differently regulated in response to high-fat diet intake for 3 days or 1 week. Also, when hypothalamic neurons are directly exposed to palmitate there is activation of chaperone-mediated autophagy. High-fat diet causes hypothalamic inflammation concomitantly to changes in the content of chaperone-mediated autophagy machinery. It remains to be studied the direct role of inflammation and lipids itself on the activation of chaperone-mediated autophagy in the hypothalamus in vivo and also the neuronal implications of chaperone-mediated autophagy inhibition in response to obesity.


[The implantation of Bonebridge in bilateral congenital malformation of external and middle ear].
Objective: To evaluate the auditory efficacy of Bonebridge implantation in patients with bilateral congenital malformation of external and middle ear. Methods: Eleven cases (6 males and 5 females) had unilateral Bonebridge implantation. The age ranged from 8 to 26 and the average age was 16.9. Seven to ten days after operation, the first fitting was undergone. In acoustic sound field, the average auditory thresholds were respectively measured for unaided ears and Bonebridge implanted ears by pure tone auditory (PTA, 0.25, 0.5, 1, 2 and 4 kHz). For the group over 12-year-old, MSTM was applied to evaluate speech discrimination score (SDS). For the other cases, MLNT was used as the test material. The auditory efficacy post Bonebridge implantation would be analyzed and evaluated by comparing the differences between unaided ears and Bonebridge implanted ears. Results: The bone conduction audibility threshold after Bonebridge implantation was as well as the preoperative. The auditory threshold with Bonebridge aided was improved to 25-35 dB HL, when compared to that of the unaided ears in the sound field. The SDS in the group over 12-year-old was improved about 50%; the efficacy was slightly limited for the other two cases (both less than 12 years old). Statistical analysis showed that there were significant differences between unaided ears and Bonebridge implanted ears in the sound field and SDS(P<0.05). Conclusions: The auditory efficacy of Bonebridge is significant and noticeable in patients with bilateral congenital malformation of external and middle ear. Bonebridge provides a new and effective way for patient with congenital malformation of external and middle ear to reconstruct hearing.


Intestinal obstruction caused by extraperitoneal cerebrospinal fluid collection.
External compression caused by a massive extraperitoneal cerebrospinal fluid collection lead to intestinal obstruction in a 3-year-old child who had previously had a ventriculoperitoneal shunt for treatment of hydrocephalus. Radiological findings and ways of preventing this situation are discussed. A useful diagnostic radiological sign, the "coiling sign', indicating shunt misplacement at the peritoneal level, is also described.


Tumor targeting properties of monoclonal antibodies with different affinity for target antigen CD44V6 in nude mice bearing head-and-neck cancer xenografts.
The CD44 protein family consists of isoforms with tissue-specific expression, which are encoded by standard exons and up to 9 alternatively spliced variant exons (v2-v10) of the same gene. The murine MAbs U36 and BIWA-1, directed against overlapping epitopes within the v6 region of CD44, have previously been shown to efficiently target HNSCC. We herein report on the construction of 1 chimeric (BIWA-2) and 2 humanized (BIWA-4 and BIWA-8) derivatives of BIWA-1. Together with U36 and BIWA-1, these new antibodies were evaluated for affinity to the antigen in vitro as well as for biodistribution and efficacy in RIT using nude mice bearing the HNSCC xenograft line HNX-OE. As determined by surface plasmon resonance, the MAbs bound to CD44v6 with an up to 46-fold difference in affinity (K(d) ranging from 1.1 x 10(-8) to 2.4 x 10(-10) M) with the following ranking: mMAb U36 < hMAb BIWA-4 < hMAb BIWA-8 < mMAb BIWA-1 approximately cMAb BIWA-2. To evaluate their in vivo tumor-targeting properties, 2 MAbs with identical murine or human isotype were labeled with either (131)I or (125)I and administered simultaneously (50 microg/10 microCi each) as pairs showing a stepwise decrease in the difference in affinity: U36 vs. BIWA-1 (35.0-fold difference), BIWA-4 vs. BIWA-2 (14.0-fold) and BIWA-4 vs. BIWA-8 (4.0-fold). Biodistribution was assessed at 1, 2, 3 or 4 and 7 days after injection. Remarkably, for all 3 MAb pairs tested, the lower-affinity MAb showed a higher degree and specificity of tumor localization. The difference in tumor localization was more pronounced when the difference in affinity was larger. For example, 3 days after injection, the lower-affinity mMAb U36 showed a 50% higher tumor uptake than the higher-affinity mMAb BIWA-1, while blood levels and uptake in organs were similar. After labeling with (186)Re (300 or 400 microCi), the same MAb pairs showed RIT efficacy consistent with the biodistribution data: (186)Re-U36 was more effective than (186)Re-BIWA-1, (186)Re-BIWA-4 was slightly more effective than (186)Re-BIWA-2 and (186)Re-BIWA-4 and (186)Re-BIWA-8 demonstrated similar efficacy. Based on these data, we conclude that antibodies with markedly lower affinity to a given target antigen (e.g., U36, BIWA-4) may show superior tumor targeting in comparison with higher-affinity versions of these antibodies.


Acetaldehyde-induced aneuploidy in cultured Chinese hamster cells.
In this paper we report the cytogenetic activity of ethanol (EA) and its main metabolic derivative, acetaldehyde (AA) in cultured Chinese hamster cells. AA induced an increase of aneuploidy and chromosome breaks and exchanges. EA only induced an increase of achromatic lesions (gaps). However, following treatment with AA, the most notable effect was an increase of hypodiploid cells and a parallel increase of multinucleated interphase cells, the frequency of hyperdiploid cells being considerably lower. A strong correlation (r = 0.93, P less than 0.01) has been found on comparing the frequency of hypodiploid cells to the frequency of hyperdiploid plus multinucleated interphase cells. We conclude that there exists a higher chance of hypodiploid cells reaching the second mitosis after treatment and that the main effect of AA is the induction of hypodiploidy rather than hyperdiploidy and chromosome aberrations.


Emerging trends in health and productivity management.
Many large U.S. employers have generally embraced a Health and Productivity Management (HPM) perspective to guide their multiple employee health management efforts. In looking ahead there are a number of emerging trends that are helping to shape these efforts. As health promotion professionals assess the implications of these trends on their respective role and function within the worksite, it may provide a very useful process for refining strategies for programming and professional development. The identified trends also have a variety of implications for health promotion vendors and the growth of the health management marketplace.


Amentoflavone inhibits hepatitis B virus infection via the suppression of preS1 binding to host cells.
Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapeutic drugs for chronic HBV infection use IFN and nucleos(t)ide analogs; however, their efficacy is limited. Thus, there is an urgent need to develop new antivirals for HBV therapy. In this study, we identified a plant-derived polyphenolic bioflavonoid, amentoflavone, as a new anti-HBV compound. Amentoflavone treatment dose-dependently inhibited HBV infection in HBV-susceptible cells with HepG2-hNTCP-C4 and primary human hepatocyte PXB-cells. A mode-of-action study showed that amentoflavone inhibits the viral entry step, but not the viral internalization and early replication processes. Attachment of HBV particles as well as HBV preS1 peptide to HepG2-hNTCP-C4 cells was inhibited by amentoflavone. The transporter assay revealed that amentoflavone partly inhibits uptake of sodium taurocholate cotransporting polypeptide (NTCP)-mediated bile acid. Furthermore, effect of various amentoflavone analogs on HBs and HBe production from HBV-infected HepG2-hNTCP-C4 cells was examined. Robustaflavone exhibited comparable anti-HBV activity to that of amentoflavone and an amentoflavone-7,4', 4‴-trimethyl ether derivative (sciadopitysin) with moderate anti-HBV activity. Cupressuflavone or the monomeric flavonoid apigenin did not exhibit the antiviral activity. Amentoflavone and its structurally related biflavonoids may provide a potential drug scaffold in the design of a new anti-HBV drug inhibitor targeting NTCP.


A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington's disease mice.
Huntington's disease (HD) is a neurodegenerative disorder whose major symptoms include progressive motor and cognitive dysfunction. Cognitive decline is a critical quality of life concern for HD patients and families. The enzyme histone deacetylase 3 (HDAC3) appears to be important in HD pathology by negatively regulating genes involved in cognitive functions. Furthermore, HDAC3 has been implicated in the aberrant transcriptional patterns that help cause disease symptoms in HD mice. HDAC3 also helps fuel CAG repeat expansions in human cells, suggesting that HDAC3 may power striatal expansions in the HTT gene thought to drive disease progression. This multifaceted role suggests that early HDAC3 inhibition offers an attractive mechanism to prevent HD cognitive decline and to suppress striatal expansions. This hypothesis was investigated by treating HdhQ111 knock-in mice with the HDAC3-selective inhibitor RGFP966. Chronic early treatment prevented long-term memory impairments and normalized specific memory-related gene expression in hippocampus. Additionally, RGFP966 prevented corticostriatal-dependent motor learning deficits, significantly suppressed striatal CAG repeat expansions, partially rescued striatal protein marker expression and reduced accumulation of mutant huntingtin oligomeric forms. These novel results highlight RGFP966 as an appealing multiple-benefit therapy in HD that concurrently prevents cognitive decline and suppresses striatal CAG repeat expansions.


Structure of the heterophilic interaction between the nectin-like 4 and nectin-like 1 molecules.
Nectin-like (Necl) molecules are Ca2+-independent Ig-like transmembrane cell adhesion molecules that participate in junctions between different cell types. The specific cell-cell adhesions mediated by Necl proteins are important in neural development and have been implicated in neurodegenerative diseases. Here, we present the crystal structure of the mouse Necl-4 full ectodomain and the structure of the heterophilic Necl ectodomain complex formed by the mNecl-4 and mNecl-1 ectodomains. We demonstrate that, while the ectodomain of mNecl-4 is monomeric, it forms a stable heterodimer with Ig1 of mNecl-1, with an affinity significantly higher than that observed for self-dimerization of the mNecl-1 ectodomain. We validated our structural characterizations by performing a surface plasmon resonance assay and an Fc fusion protein binding assay in mouse primary dorsal root ganglia neurites and Schwann cells and identified a selection of residues important for heterophilic interactions. Finally, we proposed a model of Necl binding specificity that involves an induced-fit conformational change at the dimerization interface.


Glycomics@ExPASy: Bridging the Gap.
Glycomics@ExPASy (https://www.expasy.org/glycomics) is the glycomics tab of ExPASy, the server of SIB Swiss Institute of Bioinformatics. It was created in 2016 to centralize web-based glycoinformatics resources developed within an international network of glycoscientists. The hosted collection currently includes mainly databases and tools created and maintained at SIB but also links to a range of reference resources popular in the glycomics community. The philosophy of our toolbox is that it should be {glycoscientist AND protein scientist}-friendly with the aim of (1) popularizing the use of bioinformatics in glycobiology and (2) emphasizing the relationship between glycobiology and protein-oriented bioinformatics resources. The scarcity of data bridging these two disciplines led us to design tools as interactive as possible based on database connectivity to facilitate data exploration and support hypothesis building. Glycomics@ExPASy was designed, and is developed, with a long-term vision in close collaboration with glycoscientists to meet as closely as possible the growing needs of the community for glycoinformatics.


EEG-fMRI reciprocal functional neuroimaging.
Integration of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has been pursued in an effort to achieve greater spatio-temporal resolution of imaging dynamic brain activity. We report a data-driven approach to image spatio-temporal features of neural oscillatory activity and event-related activity from continuously recorded EEG and fMRI signals. This approach starts with using the independent component analysis (ICA) to decompose the spatio-temporal EEG data into a linear combination of scalp potential maps and time courses. The time course of each independent component (IC) is used to construct a regressor to fit the fMRI time series. The resultant fMRI map then feeds back as a spatial constraint to the estimation of the source distribution underlying the corresponding IC's scalp map. The estimated source distributions multiplied by the corresponding IC time courses are summed across all ICs, giving rise to the reconstructed spatio-temporal brain activity. Functional connectivity between cortical areas can be further revealed from the imaged source signals using phase synchrony measures. We tested the method using both simulated oscillatory activity and event-related neural activity at various cortical regions. We also used this method to study the alpha-band EEG modulations in an eyes-open-eyes-closed human experiment. In the simulation study, reliable reconstruction of the localization, time-frequency feature and cortical functional connection were achieved for the simulated oscillatory and event-related activities. In the experimental study, the alpha rhythmic modulation was localized mainly in the occipital visual area and the parieto-occipital sulcus. Within these regions, time-frequency analysis and phase-synchronization analysis indicated increased alpha power and alpha-band phase-synchronization in eyes-closed condition versus eyes-open condition. Our results suggest that the proposed approach is well suited to image continuously oscillatory activities and their functional connectivity. Such ability promises to facilitate the investigation of the long-term neural behaviors and large-scale cortical interactions involved in spontaneous brain activity and cognitive tasks.


Prostatic Abscess Secondary to Staphylococcus haemolyticus and Escherichia coli: A Case Report.
A prostate abscess is a rare clinical entity with an incidence of 0.2%-0.5% in males. No case reports exist of Staphylococcus haemolyticus as an etiologic bacterial agent. We report a 59-year-old man with a past medical history of poorly controlled diabetes mellitus and benign prostatic hyperplasia who was hospitalized due to urosepsis and obstruction. A prostatic abscess was discovered and initially treated with intravenous vancomycin and ertapenem. Clinical improvement was apparent within two days following transrectal prostatic abscess drainage. Four weeks of intravenous antibiotics followed. Prostatic abscess cultures grew Staphylococcus haemolyticus and Escherichia coli following tube deployment. To the best of our knowledge, this is the first case reporting Staphylococcus haemolyticus as an organism in a prostate abscess. We regard this as another example of the rising incidence of gram-positive organisms in prostatic abscesses in the post-antibiotic era.


Noninvasive measurement of conjunctival PCO2 with a fiberoptic sensor.
A miniaturized fiberoptic PCO2 probe permits direct measurement of tissue PCO2 on nonkeratinized tissue surfaces without the heating effects produced by transcutaneous PCO2 sensors. This study of anesthetized dogs compared PCO2 measured at the palpebral conjunctiva (PcjCO2) with PaCO2 and mixed venous (PVCO2) measurements during normovolemic normotension and hypovolemic hypotension. During the control period, the average PcjCO2 was 3 +/- 1 (SEM) torr greater than PaCO2 (r = 0.98) when the latter ranged from 20 to 80 torr. There was a close association (r = 0.94) between PcjCO2 and PaCO2 when the cardiac index (CI) was greater than 2.0 L/min X m2. However, as CI decreased below this value, PcjCO2 and PaCO2 were less well correlated (r = 0.69). PcjCO2 was closely associated with PVCO2 at all stages of the experiment, both above (r = 0.95) and below (r = 0.82) a CI of 2 L/min X m2. Fiberoptic conjunctival PCO2 monitoring seems promising as a noninvasive measure of physiologic status.


Lipoprotein binding preference of CD36 is altered by filipin treatment.
The class B scavenger receptor CD36 binds multiple ligands, including oxidized and native lipoprotein species. CD36 and the related receptor SR-B1 have been localized to caveolae, domains that participate in cell signaling, transcytosis, and regulation of cellular cholesterol homeostasis. Previous work has indicated that the ligand preference of CD36 may depend on the cell type in which it is expressed. To determine if the presence or absence of caveolae is the determining factor for lipoprotein preference, we treated CHO-CD36 and C32 cells with filipin. Filipin treatment rapidly increased the binding capacity of CD36 for the native lipoproteins HDL and LDL, but did not affect the binding capacity of CD36 for oxidized LDL. Filipin treatment affected the distribution of caveolin and CD36 suggesting that the presence caveolae may modulate the ligand preference of CD36. However, its molecular mechanism how CD36 and caveolin interaction in regulating lipoprotein transport remains to be further studied.


Health care services for adults with cerebral palsy.
Increasing numbers of young adults with cerebral palsy (CP) are transitioning to adult services from coordinated multidisciplinary paediatric hospital services. Limitations on provision of adult services include inadequate funding, lack of trained staff, and fragmented medical, surgical and allied health teams. This article summarises changes in treatments for children with CP over the past 2 decades and the implications for adult health care services. A multidisciplinary clinic for adults with CP at a tertiary adult teaching hospital in Sydney (New South Wales) is described. Over the past 2 decades, interventions such as botulinum toxin-A, intrathecal baclofen infusion, gastrostomy feeding and single event multilevel orthopaedic surgery have improved the lives of children with CP. These interventions are generally delivered within multidisciplinary rehabilitation programs in paediatric hospitals. As the most recent cohorts of children move into adulthood, they, and their carers, have expectations of similarly structured services in the adult health care sector. The Children's Hospital at Westmead and Westmead Hospital, together with The Spastic Centre of New South Wales, recognised this need and developed a multidisciplinary consultative clinic for adults with CP.


DnaK2 Mediates a Negative Feedback Regulation of the Heat Shock Responsive Hik2-Rre1 Two-component System in the Cyanobacterium Synechococcus elongatus PCC 7942.
The two-component system (TCS) is a conserved signal transduction module in bacteria. The Hik2-Rre1 system is responsible for transcriptional activation upon high-temperature shift as well as plastoquinone-related redox stress in the cyanobacterium Synechococcus elongatus PCC 7942. As heat-induced de novo protein synthesis was previously shown to be required to quench the heat-activated response, we investigated the underlying mechanism in this study. We found that the heat-inducible transcription activation was alleviated by the overexpression of dnaK2, which is an essential homolog of the highly conserved HSP70 chaperone and whose expression is induced under the control of the Hik2-Rre1 TCS. Phosphorylation of Rre1 correlated with transcription of the regulatory target hspA. The redox stress response was found to be similarly repressed by dnaK2 overexpression. Considered together with the previous information, we propose a negative feedback mechanism of the Hik2-Rre1-dependent stress response that maintains the cellular homeostasis mediated by DnaK2.


Detection of Circulating Tumor Cells in Non-Small Cell Lung Cancer.
Lung cancer is the most common cause of cancer-related deaths that frequently metastasizes prior to disease diagnosis. Circulating tumor cells (CTCs) are found in many different types of epithelial tumors and are of great clinical interest in terms of prognosis and therapy intervention. Here, we present and discuss epithelial cell adhesion molecule-dependent and -independent capture of CTCs in non-small cell lung cancer (NSCLC) and the clinical relevance of CTC detection and characterization. Taking blood samples and analyzing CTCs as "liquid biopsy" might be a far less invasive diagnostic strategy than biopsies of lung tumors or metastases. Moreover, sequential blood sampling allows to study the dynamic changes of tumor cells during therapy, in particular the development of resistant tumor cell clones.


Differences in fluorodeoxyglucose positron emission tomography/computed tomography findings between elderly onset rheumatoid arthritis and polymyalgia rheumatica.
To compare the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings in patients with elderly-onset rheumatoid arthritis (EORA) with those in patients with polymyalgia rheumatica (PMR), two conditions with similar clinical presentations. We retrospectively analyzed the FDG-PET/CT findings in 10 patients with EORA and 27 patients with PMR admitted to our department between 2006 and 2012. No significant difference was observed in the median patient ages at the time of FDG-PET/CT scans in the EORA and PMR groups (73.5 vs. 78.0 years, respectively). Significant differences in both FDG uptake scores and standardized uptake values were observed between the two groups in the ischial tuberosities, spinous processes, and wrists. No significant differences were detected in the shoulders and hips. However, specific uptake patterns were observed in each group: circular and linear uptake patterns were observed around the humeral head in the EORA group, whereas focal and non-linear uptake patterns were observed in the PMR group. Moreover, focal uptake in front of the hip joint, indicating iliopectineal bursitis, tended to be limited to the PMR group. High sensitivity (92.6%) and specificity (90%) were observed for PMR diagnoses when at least three of the following five items were satisfied: characteristic findings of shoulder and iliopectineal bursitis, FDG uptake in ischial tuberosities and spinal spinous processes, and lack of FDG uptake in the wrists. The differences in the degree of uptake at each lesion and in uptake patterns at the shoulders and hips are potentially useful for obtaining a definitive diagnosis.


Isoform- and cell type-specific structure of apolipoprotein E lipoparticles as revealed by a novel Forster resonance energy transfer assay.
Apolipoprotein E (apoE) has an important role in the pathogenesis of Alzheimer's disease with its three isoforms having distinct effects on disease risk. Here, we assessed the conformational differences between those isoforms using a novel flow cytometry-Forster resonance energy transfer (FRET) assay. We showed that the conformation of intracellular apoE within HEK cells and astrocytes adopts a directional pattern; in other words, E4 adopts the most closed conformation, E2 adopts the most open conformation, and E3 adopts an intermediate conformation. However, this pattern was not maintained upon secretion of apoE from astrocytes. Intermolecular interactions between apoE molecules were isoform-specific, indicating a great diversity in the structure of apoE lipoparticles. Finally, we showed that secreted E4 is the most lipidated isoform in astrocytes, suggesting that increased lipidation acts as a folding chaperone enabling E4 to adopt a closed conformation. In conclusion, this study gives insights into apoE biology and establishes a robust screening system to monitor apoE conformation.


[Acute pancreatitis: our experience in the light of natural history].
The Authors enumerate main steps of acute pancreatitis natural history. Then they discuss their last five years case-report. After having stated that clinical presentation depends on anatomo-pathological conditions, they consider aetiological causes and morphopathogenetic moments involved in the onset and development of this disease. They conclude stating how only proper diagnosis and treatment can prevent its potential evolution in multiorgan failure.


Single bone metastasis from adenocarcinoma of the lacrimal gland: a case report.
Malignant tumors of the lacrimal gland are rare, and single bone metastases from lacrimal gland carcinoma are an exceptional event. We present the case of a 71-year-old man with a history of lumbar pain and left exophthalmos. Surgical resection of the lacrimal lesion and a bone biopsy gave a final histopathological diagnosis of primary ductal adenocarcinoma of the lacrimal gland with bone metastasis. The pathological tissue from both procedures was positive for androgen receptor expression. The patient underwent embolization and radiotherapy in association with total androgen blockade. After 20 months, the patient is still asymptomatic and has maintained the partial response at L1 with no progression to other sites. Our patient would appear to have a better prognosis and the disease a more indolent clinical course than the other cases of ductal adenocarcinoma of the lacrimal gland reported in the literature.


Mental health day units: users' views.
This article describes clients' perspectives on psychiatric day care units in an area in the South of England. The results of a small-scale research project show that clients from different localities have similar perspectives and feelings about the units. It is demonstrated that, in the clients' view, the units achieve many of their aims and fulfil needs that supersede the initial purpose.


Transcatheter aortic valve replacement failure: a case report of the bicuspid aortic valve type 0 with a single coronary artery.
Transcatheter aortic valve replacement (TAVR) is the treatment of choice for aortic stenosis. However, its safety and efficacy in patients with the bicuspid aortic valve (BAV) remain controversial. Especially, whether the BAV phenotype affects outcomes following TAVR remains debated. Despite the higher ellipticity index and more calcifications of the aortic annulus in type 1 BAV, a high residual gradient was observed in type 0 anatomy. Moreover, severe calcification of the cusps rather than aortic annulus in type 0 is predisposed to asymmetrical under-expansion of the prosthesis at the edge of the native aortic cusp. We report the rare case of a patient with BAV stenosis type 0 and single coronary artery receiving TAVR, subsequently requiring surgical aortic valve replacement. The extensive non-coronary cusp calcification caused under-expansion of the prosthesis and was protruded into the left ventricular outflow tract, leading to an obstruction.


Complete genome analysis of the C4 subgenotype strains of enterovirus 71: predominant recombination C4 viruses persistently circulating in China for 14 years.
Genetic recombination is a well-known phenomenon for enteroviruses. To investigate the genetic characterization and the potential recombination of enterovirus 71 (EV71) circulating in China, we determined the 16 complete genome sequences of EV71 isolated from Hand Foot Mouth Disease (HFMD) patients during the large scale outbreak and non-outbreak years since 1998 in China. The full length genome sequences of 16 Chinese EV71 in present study were aligned with 186 genome sequences of EV71 available from GenBank, including 104 China mainland and 82 international sequences, covering the time period of 1970-2011. The oldest strains of each subgenotype of EV71 and prototype strains of HEV-A were included to do the phylogenetic and Simplot analysis. Phylogenetic analysis indicated that all Chinese strains were clustered into C4 subgenotype of EV71, except for HuB/CHN/2009 clustered into A and Xiamen/CHN/2009 clustered into B5 subgenotype. Most of C4 EV71 were clustered into 2 predominant evolutionary branches: C4b and C4a evolutionary brunches. Our comprehensive recombination analysis showed the evidence of genome recombination of subgenotype C4 (including C4a and C4b) sequences between structural genes from genotype C EV71 and non-structural genes from the prototype strains of CAV16, 14 and 4, but the evidence of intratypic recombination between C4 strains and B subgenotype was not enough strong. This intertypic recombination C4 viruses were first seen in 1998 and became the predominant endemic viruses circulating in China mainland for at least 14 years. A shift between C4a and C4b evolutionary brunches of C4 recombination viruses were observed, and C4a viruses have been associated with large scale nationwide HFMD outbreak with higher morbidity and mortality since 2007.


Anticancer agents and phytotherapy: Interactions that are often unrecognized.
Phytotherapy is the main complementary medicine for which patients afflicted with cancer have recourse but the associated consumption of phytotherapy products gives rise to a risk of interaction with anticancer agents. The aim of this prospective study was to measure the prevalence of the consumption of phytotherapy products as well as their interactions with anticancer agents in a cohort of patients from January 2018 to August 2019. Patients hospitalized in the conventional hematology unit and outpatients who had their prescriptions for oral anticancer agents filled at the hospital pharmacy were questioned about consumption of phytotherapy products by pharmacy externs trained in pharmaceutical interviews. Among the 110 hospitalized patients who answered the questionnaire, 40% (n = 44) used phytotherapy and 5 of them continued to consume it during the cycles of injectable chemotherapy. As a result, 10 interactions were found between the plants and the anticancer agents (prevalence of 27%). Among the 59 outpatients, 17% (n = 10) consumed phytotherapy. Eight interactions were identified (prevalence of 80%). The potential consequences were an increase or a decrease in the concentration of the anticancer agents and an increase in the risk of bleeding, hepatoxicity, and hypokalemia. The consumption of phytotherapy was unknown by a health professional for 44% of hospitalized patients and 60% of the outpatients. The risk of interactions between plants and anticancer agents is not negligible and professionals should be cognizant of this in their daily practice. The availability of tools for training and detection of interactions is indispensable for managing patients undergoing onco-hematology treatments.


Glutathione and ocular photobiology.
Glutathione is present in both the reduced and oxidized form in the cornea, aqueous humor, ocular lens and retina. In these tissues it serves a variety of functions including maintaining normal tissue hydration (in the cornea) detoxifying peroxides and electrophilic compounds via enzymatic pathways and acting as a free radical scavenger to protect against photoinduced damage. In the ocular lens, glutathione levels decrease with aging and cataract formation. Recent evidence which may account in part for this phenomenon suggests that glutathione is altered when subjected to UV radiation in the presence of H2O2. Analyses employing fluorescence, phosphorescence, UV absorption and proton mode NMR spectroscopy demonstrate that UV exposure does alter both the reduced and oxidized forms of glutathione, producing the same final products. Moreover, while H2O2 speeds up the process, it is not essential to the reaction.


The Transition From Spousal Caregiver to Widowhood: Quantitative Findings of a Mixed-Methods Study.
BACKGROUND: The number of persons diagnosed with dementia is projected to triple to 14 million by 2050. The significance of these projections is particularly relevant to older women (>65 years), who are more likely to provide dementia caregiving for a husband than vice versa. Research has identified consistent themes around the impact of caregiving during the caregiving experience, yet there is limited research exploring the ongoing impact during the transition to widowhood. Moreover, there is a paucity of research examining differences between rural and urban spousal dementia caregivers. AIMS: The aims were to compare differences between older rural and urban spousal caregivers on physical and mental health factors affecting the transition from caregiver to widow and to identify resources the women used during this transition over 12 months. METHOD: This mixed-methods longitudinal study recruited 13 urban and nine rural female spousal caregivers. Participants were interviewed three times over 12 months. The dependent variables were depression (measured using Center for Epidemiologic Studies Depression Scale), physical and mental functioning (measured using the 12-item Medical Outcomes Study-Short Form Health Survey Version 2). RESULTS: No statistically significant differences were detected between rural and urban female caregivers on the dependent variables. However, rural caregivers scored higher on depression and lower on both physical and mental functioning compared to their urban counterparts. CONCLUSIONS: The findings have clinical and research implications. Psychiatric nurses are well positioned to provide education related to dementia information deficits; implement interventions that facilitate bereavement, resilience, self-care, and identity; advocate for additional services; and conduct larger scale studies with a more diverse sample of female spousal caregivers.


Dopamine beta-hydroxylase release during hypertension from sympathetic nervous overactivity in man.
In subjects with cervical spinal cord transections, hypertension due to sympathetic nervous overactivity resulted in a rise in plasma dopamine beta-hydroxylase (DbetaH), the peak occurring 3 to 5 min after the peak blood pressure response. This indicates that DbetaH may be released from sympathetic nerve terminals during sympathetic activity in man, and emphasizes the importance of sample timing in acute studies on DbetaH.


Smoking: what has been addressed in Brazilian journals.
The topic of tobacco smoking, in its several aspects, has been receiving increasing attention among researchers over the past few years, which has been reflected in more data and more solid scientific literature on the subject in national journals. This article aims to review the studies that focused on smoking published between January 2010 and June 2012, in Arquivos Brasileiros de Cardiologia (Brazilian Archives of Cardiology), Brazilian Journal of Medical and Biological Research, Clinics (Sao Paulo), Jornal Brasileiro de Pneumologia (Brazilian Journal of Pulmonology), Revista da Associação Médica Brasileira (Journal of the Brazilian Medical Association) and Revista Brasileira de Cirurgia Cardiovascular (Brazilian Journal of Cardiovascular Surgery). During the aforementioned period 58 articles were published, 52 of which were original ones, addressing several aspects of smoking, such as effects on health, epidemiology, cessation and experimental studies.