Effect of oxidized low-density lipoprotein concentration polarization on human smooth muscle cells' proliferation, cycle, apoptosis and oxidized low-density lipoprotein uptake.
To clarify the effect of concentration polarization of oxidative modification of low-density lipoproteins (ox-LDLs) on human smooth muscle cells (SMCs), the proliferation, ox-LDL uptake and apoptosis with SMCs cultured on permeable (the permeable group) or non-permeable membranes (the non-permeable group) were analysed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, spectrofluorometry and flow cytometry using a parallel-plate flow chamber technique. The concentration polarization of ox-LDLs at the surface of the cultured cell monolayer was assessed by confocal laser microscopy. The results showed that concentration polarization of ox-LDLs could indeed occur at the cultured cell monolayer surface of the permeable group, leading to an enhanced wall concentration of ox-LDLs that was over 15 per cent higher than the bulk concentration of the perfusion solution at a pressure of 100 mmHg. When concentration of ox-LDLs in the perfusion solution was less than or equal to 100 µg ml(-1), SMCs' proliferation was induced, while cell apoptosis was induced when its concentration was above 150 µg ml(-1). The uptake of ox-LDLs by the cultured cells was significantly higher for the permeable group than for the non-permeable group. In addition, the ox-LDL-induced cell death and apoptosis were much more severe in the permeable group than that in the non-permeable group. Therefore, the experimental study suggests that concentration polarization of ox-LDLs plays an adverse role in the vascular system owing to its toxicity to vascular cells, in turn enhance ox-LDL infiltration into the arterial wall and accelerate SMC apoptosis.


Are We Doing Enough to Address the Cancer Care Needs of the LGBT Community?
The 2011 film titled Gen Silent (http://gensilent.com) focuses on the needs and issues of six aging lesbian, gay, bisexual, and transgender (LGBT) people, at least two of whom had cancer. One of the issues made apparent in the film was the lack of trust in the healthcare system and the discrimination these individuals faced at a time when their needs were growing and they were increasingly vulnerable. It was sad and caused us to reflect on what we, as oncology nurses, are doing to meet the needs of LGBT individuals faced with a cancer diagnosis. .


Generation and functional analyses for base-substitution mutants of the adenovirus 2 major late promoter.
The function of guanosine residues surrounding the TATA box of the adenovirus 2 major late promoter (MLP) in promoting efficient transcription initiation and in selecting a specific transcription start site in vitro has been examined. Multiple and single base substitutions (G----A) were generated in this region (from -63 to +25 relative to the cap site, +1) of the MLP. The promoter activities of the wild type and 21 mutants were assayed in an in vitro transcription system using whole cell extract (WCE) prepared from HeLa cells. The results suggest that the strings of G residues immediately adjacent to the TATA box are not required for full promoter activity in vitro. These G residues also appear not to be involved in the selection of a specific transcription start site by RNA polymerase II in vitro, since the identical cap site was used by wild-type and mutated MLP's. However, two G residues (-55 and -57) were identified as part of an upstream promoter element: a G----A transition at either -55 or -57 resulted in a 2.6 fold reduction in promoter activity. However, neither single nor double G----A transitions at -62 and -63 had an effect on promoter activity.


Modeling of the thermoregulation system in the skunk cabbage: Symplocarpus foetidus.
This paper presents a model of the thermoregulation system of the spadix of skunk cabbage Symplocarpus foetidus which regulates its internal temperature at around 20 degrees C during flowering even when the ambient air temperature drops below freezing. From the temperature responses of the spadix to changing ambient air temperature, we assumed that the thermoregulation system of the spadix is probably one of negative feedback control. The feedback signals are based on the rate of temperature change of the spadix over time. A signal is factored into the biochemical energy generator, and becomes biochemical energy, some of which becomes heat. Comparing our proposed model temperature responses and those of the living spadix, we found good agreement. In the process of engineering the model, the existence of two regulatory pathways in the thermoregulation system was simulated, and our proposed model appears to provide the necessary elements to explain the fundamental mechanism of the thermoregulation system of S. foetidus.


Symptomatic Acute Toxoplasmosis in Returning Travelers.
We report a family who acquired acute toxoplasmosis after a trip to Central America. One member developed severe clinical manifestations including bilateral chorioretinitis, hepatitis, and myocarditis requiring therapy. Symptomatic acute toxoplasmosis is unusual and possesses a diagnostic challenge. We discuss the clinical and epidemiological implications, laboratory diagnosis, and treatment plan.


European Board for Accreditation in Cardiology (EBAC) 2015 CME/CPD Survey Summary.
In the spring of 2015, the European Board for Accreditation in Cardiology (EBAC) collaborated with International CME/CPD Consulting to design and administer a survey to approximately 1,171 professionals active in the field of European CME/CPD, with a focus on cardiology. With a nearly 5% response rate, the results herewith are non-representative, but do express current behaviours and attitudes of those active in European accredited CME/CPD.


Comparative reactivity of ferric-superoxo and ferryl-oxo species in heme and non-heme complexes.
Ferryl-oxo species have been recognized as a key oxidant in many heme and non-heme enzymes. Recently, less-characterized ferric-superoxo species have been found or suggested to be another electrophilic oxidant. Reactivity of several vital ferryl-oxo and ferric-superoxo model complexes was examined by DFT calculations. Reactivity is found to correlate well with thermodynamic driving force and can increase with higher electrophilicity of the oxidant. Reactivity of the ferric-superoxo oxidants generally is not "superior" to the ferryl-oxo ones. Compared to the high-spin non-heme ferric-superoxo, the lower reactivity of low-spin heme ferric-superoxo, seldom utilized in nature, can be attributed to lower electrophilicity and more pronounced quenching of anti-ferromagnetic coupling between the ferric and superoxo parts. The present comparison should shed some light on mechanistic strategies in heme and non-heme enzymes and provide clues to rational design of ferric-superoxo oxidants.


[Effects of different fertilization measures on N2O emission in oil sunflower field in irrigation area of upper Yellow River].
Agricultural soil has become the largest anthropogenic source of atmospheric nitrous oxide (N20). To estimate the impacts of long-term combined application of organic and inorganic fertilizers on N20 emission in a typical winter wheat-oil sunflower cropping system in the Ningxia irrigation area, we measured N20 fluxes using the static opaque chamber-gas chromatograph method and monitored the seasonal dynamics of related factors. Our results showed that nitrogen addition in the previous crop field significantly stimulated N2O emissions during the following oil-sunflower cultivation, and the mean fluxes of N300-OM, N240-OM1/2, N300 and N240 were (34.16 ± 9.72), (39.69 ±10.70), (27.75 ±9.57) and (26.30 ± 8.52) µg . m-2 . h-1, respectively, which were 4.09, 4.75, 3.32 and 3.15 times of the control groups. The total cumulative N2O emissions of fertilizer treatments in growing season was as high as 796.7 to 1242.5 g . hm-2, which was 2.99 to 4.67 times of the control groups. During the growing season, the rates of N2O emission in each month organic and inorganic fertlizers combined treatments were similar at high levels. N2O emission in chemical fertilizer treatments gradually decreased, and the main period of N2O emission occurred at the beginning of growing season. Taking July for example, N2O emission accounted for 41.3% to 41. 8% of total cumulative amount. The amounts of N20 emission under organic and inorganic fertilizers combined treatments were significantly higher than under chemical fertilizer treatments. The N2O emissions were not significantly different between conventional and optimized applications of nitrogen fertilizer under the same fertilizing method, either between N300-OM and N240-OM1/2, or between N300 and N240. On account of the drought, N2O emission in each treatment was mainly affected by soil moisture. N2O emission had a significant positive correlation with soil ammonium nitrogen content under combined applications of organic and inorganic fertilizers, but was not correlated with soil nitrate nitrogen content under all treatments. This showed that adding organic fertilizer could stimulate the NO2 production via increasing the soil ammonium nitrogen content.


Antineutrophil cytoplasmic antibody-associated vasculitides and respiratory disease.
Vasculitides associated with serum positivity for antineutrophil cytoplasmic antibodies (ANCAs) are a well-established subgroup affecting small- to medium-sized vessels that are commonly recognized as ANCA-associated vasculitis, which includes necrotizing granulomatous vasculitis (NGV) [formerly Wegener granulomatosis], microscopic polyangiitis (MPA), and Churg-Strauss syndrome. NGV usually starts as a granulomatous disease of the respiratory tract and progresses to systemic disease with proteinase 3 (PR3)-ANCA-associated vasculitis, suggesting an aberrant cell-mediated immune response to exogenous or endogenous antigens in the respiratory tract and resulting in granuloma formation. In NGV, granulomata may represent lymphoid structures ultimately responsible for PR3-ANCA production. In both NGV and MPA, necrotizing glomerulonephritis and necrotizing pulmonary capillaritis may well result from an injury orchestrated by ANCA. Untreated NGV and MPA normally are rapidly progressive and fatal. Pulmonary capillaritis with alveolar hemorrhage is a severe complication in patients with MPA and NGV. Because plasma exchange removes circulating ANCAs and other proteins from the blood, its use has been advocated in critical situations of severe renal and pulmonary involvement. However, no studies of plasma exchange in ANCA-associated vasculitis focused on pulmonary involvement have been reported. Dissecting the mechanisms of inflammation may identify molecular targets for future therapies in ANCA-associated vasculitis. Thus, biological agents are emerging as potential therapies in refractory cases. Notably, rituximab and infliximab have been trialed with apparent initial clinical success.


Effects of reversible inactivation of the medial septum on rat exploratory behavior in the elevated plus-maze using a test-retest paradigm.
The effect of intraseptal injections of lidocaine before a first or a second session in the elevated plus-maze, in a test-retest paradigm, was investigated. In addition to gross session analyses, a minute-by-minute analysis of the sessions was used to evaluate both anxiety and memory. Lidocaine injections before the test session produced increases in the frequency of entries, time spent and distance run in the open arms without affecting activity occurring in the closed arms. During the retest session, saline- and lidocaine-treated rats exhibited increased indices of anxiety and lidocaine-treated rats exhibited decreased closed-arm entries. The minute-by-minute analysis showed a faster decrease in anxiety-related behaviors during the test session by saline- than by lidocaine-treated rats and a significant decrease in closed-arm exploration by saline-treated rats, but not by lidocaine-treated ones. Lidocaine injection before the retest session produced increases in the frequency of entries, time spent and distance run in the open arms in the second session when compared with saline-treated rats. Minute-by-minute analysis showed an increase in the time spent in the open arms by lidocaine animals at the beginning of the retest session in comparison to saline animals and a significant decrease in closed-arm exploration by both groups. These results suggest that inactivation of the medial septum by lidocaine affects the expression of unconditioned and conditioned forms of anxiety in the elevated plus-maze and, in a lesser way, the acquisition and retention of spatial information.


A three dimensional parabolic equation method for sound propagation in moving inhomogeneous media.
In this paper, a formulation of the Helmholtz equation for three dimensional sound propagation in a moving inhomogeneous medium in cylindrical coordinates is derived. Based on this formulation, a three dimensional parabolic equation (PE) is constructed. This PE can be used to model sound propagation in an inhomogeneous arbitrary moving medium. The method is used here to simulate three dimensional outdoor sound propagation above a rigid flat ground surface. The numerical results for two simple wind cases are presented and compared with analytical results to validate the methodology. Examples of propagation problems with more complicated wind are then included to demonstrate the importance of including the wind velocity directly in the PE method.


Neem oil (Azadirachta indica) nanoemulsion--a potent larvicidal agent against Culex quinquefasciatus.
Nanoemulsion composed of neem oil and non-ionic surfactant Tween 20, with a mean droplet size ranging from 31.03 to 251.43 nm, was formulated for various concentrations of the oil and surfactant. The larvicidal effect of the formulated neem oil nanoemulsion was checked against Culex quinquefasciatus. O/W emulsion was prepared using neem oil, Tween 20 and water. Nanoemulsion of 31.03 nm size was obtained at a 1:3 ratio of oil and surfactant, and it was found to be stable. The larger droplet size (251.43 nm) shifted to a smaller size of 31.03 nm with increase in the concentration of Tween 20. The viscosity of the nanoemulsion increased with increasing concentration of Tween 20. The lethal concentration (LC50) of the nanoemulsion against Cx. quinquefasciatus was checked for 1:0.30, 1:1.5 and 1:3 ratios of oil and surfactant respectively. The LC50 decreased with droplet size. The LC50 for the ratio 1:3 nanoemulsions was 11.75 mg L(-1). The formulated nanoemulsion of 31.03 nm size was found to be an effective larvicidal agent. This is the first time that a neem oil nanoemulsion of this droplet size has been reported. It may be a good choice as a potent and selective larvicide for Cx. quinquefasciatus.


Revolutionising the AIDS response.
Individual behaviour change interventions and technological approaches to HIV prevention can only be effective over time if the broader social environment in which health-related decisions are made facilitate their uptake. People need to be not only willing but also able to take up and maintain preventive behaviours, seek testing, treatment and care for HIV. This paper presents findings and recommendations of the Social Drivers Working Group of the aids2031 initiative, which focus on how to ensure that efforts to address the root causes of HIV vulnerability are integrated into AIDS responses at the national level. Specific guidance is given on how to operationalise a structural approach.


Age differences in religious participation among black adults.
Age differences in level of religious participation were examined using data from the National Survey of Black Americans (N = 2107). Seven indicators of organizational, nonorganizational, and attitudinal forms of religious involvement were examined. For women, age was positively associated with each of the religiosity measures; among men, requests for prayer from others was the only indicator for which age was not a significant predictor. The findings are discussed in relation to previous work on age and religious participation.


Simple view on fingering instability of debonding soft elastic adhesives.
We study the crack-front fingering instability of an elastic adhesive tape that is peeled off a solid substrate. Our analysis is based on an energy approach using fracture mechanics and scaling laws and provides simple physical explanations for (i) the fact that the wavelength depends only on the thickness of the adhesive film and (ii) the threshold of the instability, and (iii) additionally estimates the characteristic size of the fingers. The scaling laws for these three observables are in agreement with existing experimental data.


Antifungal active triterpene glycosides from sea cucumber Holothuria scabra.
To study the new antifungal active triterpene glycosides of sea cucumber Holothuria scabra. Triterpene glycosides from Holothuria scabra were separated and purified by silica gel chromatography, reversed-phase silica gel chromatography and RP-HPLC. Their structures were elucidated on the basis of spectral data and chemical evidence. Three triterpene glycosides were identified as scabraside A (1), echinoidea A (2) and holothurin A1 (3). Scabraside A (1) is a new triterpene glycoside, and compounds 2 and 3 were isolated from Holothuria scabra for the first time. They showed antifungal activities (1 < or = MIC80 < or = 16 microg mL(-1)).


The Danish cancer pathway for patients with serious non-specific symptoms and signs of cancer-a cross-sectional study of patient characteristics and cancer probability.
A Danish cancer pathway has been implemented for patients with serious non-specific symptoms and signs of cancer (NSSC-CPP). The initiative is one of several to improve the long diagnostic interval and the poor survival of Danish cancer patients. However, little is known about the patients investigated under this pathway. We aim to describe the characteristics of patients referred from general practice to the NSSC-CPP and to estimate the cancer probability and distribution in this population. A cross-sectional study was performed, including all patients referred to the NSSC-CPP at the hospitals in Aarhus or Silkeborg in the Central Denmark Region between March 2012 and March 2013. Data were based on a questionnaire completed by the patient's general practitioner (GP) combined with nationwide registers. Cancer probability was the percentage of new cancers per investigated patient. Associations between patient characteristics and cancer diagnosis were estimated with prevalence rate ratios (PRRs) from a generalised linear model. The mean age of all 1278 included patients was 65.9 years, and 47.5 % were men. In total, 16.2 % of all patients had a cancer diagnosis after six months; the most common types were lung cancer (17.9 %), colorectal cancer (12.6 %), hematopoietic tissue cancer (10.1 %) and pancreatic cancer (9.2 %). All patients in combination had more than 80 different symptoms and 51 different clinical findings at referral. Most symptoms were non-specific and vague; weight loss and fatigue were present in more than half of all cases. The three most common clinical findings were 'affected general condition' (35.8 %), 'GP's gut feeling' (22.5 %) and 'findings from the abdomen' (13.0 %). A strong association was found between GP-estimated cancer risk at referral and probability of cancer. In total, 16.2 % of the patients referred through the NSSC-CPP had cancer. They constituted a heterogeneous group with many different symptoms and clinical findings. The GP's gut feeling was a common reason for referral which proved to be a strong predictor of cancer. The GP's overall estimation of the patient's risk of cancer at referral was associated with the probability of finding cancer.


Voluntary exercise improves murine dermal connective tissue status in high-fat diet-induced obesity.
Obesity is a risk factor for several cardiovascular and metabolic diseases. Its influence on the skin is less obvious, yet certain negative effects of adipose tissue inflammation on the dermis have been suggested. Excess weight is closely associated with sedentary behavior, so any increase in physical activity is considered beneficial against obesity. To investigate the effects of obesity and physical exercise on the skin, we established a mouse model in which mice were kept either on a high-fat diet or received standard chow. After the two groups achieved a significant weight difference, physical exercise was introduced to both. Animals were given the opportunity to perform voluntary exercise for 40 min daily in a hamster wheel for a period of 8 weeks. We evaluated the status of the dermis at the beginning and at the end of the exercise period by in vivo nonlinear microscopy. Obese mice kept on high-fat diet lost weight steadily after they started to exercise. In the high-fat diet group, we could detect significantly larger adipocytes and a thicker layer of subcutaneous tissue; both changes started to normalize after exercise. Nonlinear microscopy revealed an impaired collagen structure in obese mice that improved considerably after physical activity was introduced. With the ability to detect damage on collagen structure, we set out to address the question whether this process is reversible. With the use of a novel imaging method, we were able to show the reversibility of connective tissue deterioration as a benefit of physical exercise.


Ultrastructural study of motoneurons in Werdnig-Hoffmann disease.
Ultrastructural studies of the lumbar spinal cord in three children with Werdnig-Hoffmann (W-H) disease type Ia revealed numerous small neurons which appeared both atrophic and immature. We compared these motoneurons with anterior horn cells of a 3-month-old child, a 27-week and a 16-week human fetus, and found (1) that the motoneurons were much smaller in W-H disease, and (2) the Nissl substance was peripherally located and less developed. Signs of motoneuron immaturity as well as secondary degenerative changes suggest that in W-H disease neurons die either because they fail to make adequate peripheral contact or because the neurons are genetically intrinsically defective.


Transcutaneous carbon dioxide application accelerates muscle injury repair in rat models.
Skeletal muscle injuries are commonly observed in sports and traumatology medicine. Previously, we demonstrated that transcutaneous application of carbon dioxide (CO2) to lower limbs increased the number of muscle mitochondria and promoted muscle endurance. Therefore, we aimed to investigate whether transcutaneous CO2 application could enhance recovery from muscle injury. Tibialis anterior muscle damage was induced in 27 Sprague Dawley rats via intramuscular injection of bupivacaine. After muscle injury, rats were randomly assigned to transcutaneous CO2-treated or -untreated groups. From each group, three rats were sacrificed at weeks one, two, four and six. At each time point, histology and immunofluorescence analyses were performed, and changes in muscle weight, muscle weight/body weight ratio, muscle fibre circumference, gene expression levels and capillary density were measured. Injured muscle fibres were completely repaired at week six in the CO2-treated group but only partially repaired in the untreated group. The repair of basement and plasma membranes did not differ significantly between groups. However, expression levels of genes and proteins related to muscle protein synthesis were significantly higher in the CO2-treated group and significantly more capillaries four weeks after injury. Transcutaneous CO2 application can accelerate recovery after muscle injury in rats.


In silico testing of flavonoids as potential inhibitors of protease and helicase domains of dengue and Zika viruses.
Dengue and Zika are two major vector-borne diseases. Dengue causes up to 25,000 deaths and nearly a 100 million cases worldwide per year, while the incidence of Zika has increased in recent years. Although Zika has been associated to fetal microcephaly and Guillain-Barré syndrome both it and dengue have common clinical symptoms such as severe headache, retroocular pain, muscle and join pain, nausea, vomiting, and rash. Currently, vaccines have been designed and antivirals have been identified for these diseases but there still need for more options for treatment. Our group previously obtained some fractions from medicinal plants that blocked dengue virus (DENV) infection in vitro. In the present work, we explored the possible targets by molecular docking a group of molecules contained in the plant fractions against DENV and Zika virus (ZIKV) NS3-helicase (NS3-hel) and NS3-protease (NS3-pro) structures. Finally, the best ligands were evaluated by molecular dynamic simulations. To establish if these molecules could act as wide spectrum inhibitors, we used structures from four DENV serotypes and from ZIKV. ADFR 1.2 rc1 software was used for docking analysis; subsequently molecular dynamics analysis was carried out using AMBER20. Docking suggested that 3,5-dicaffeoylquinic acid (DCA01), quercetin 3-rutinoside (QNR05) and quercetin 3,7-diglucoside (QND10) can tightly bind to both NS3-hel and NS3-pro. However, after a molecular dynamics analysis, tight binding was not maintained for NS3-hel. In contrast, NS3-pro from two dengue serotypes, DENV3 and DENV4, retained both QNR05 and QND10 which converged near the catalytic site. After the molecular dynamics analysis, both ligands presented a stable trajectory over time, in contrast to DCA01. These findings allowed us to work on the design of a molecule called MOD10, using the QND10 skeleton to improve the interaction in the active site of the NS3-pro domain, which was verified through molecular dynamics simulation, turning out to be better than QNR05 and QND10, both in interaction and in the trajectory. Our results suggests that NS3-hel RNA empty binding site is not a good target for drug design as the binding site located through docking is too big. However, our results indicate that QNR05 and QND10 could block NS3-pro activity in DENV and ZIKV. In the interaction with these molecules, the sub-pocket-2 remained unoccupied in NS3-pro, leaving opportunity for improvement and drug design using the quercetin scaffold. The analysis of the NS3-pro in complex with MOD10 show a molecule that exerts contact with sub-pockets S1, S1', S2 and S3, increasing its affinity and apparent stability on NS3-pro.


The L-arginine/nitric oxide/cyclic-GMP pathway apparently mediates the peripheral antihyperalgesic action of fentanyl in rats.
There are only a few studies on the molecular mechanisms underlying the peripheral antihyperalgesic effect of opioids. The aim of this study was to investigate the molecular bases of the peripheral antihyperalgesic effect of fentanyl in a model of prostaglandin-induced chemical hyperalgesia. Prostaglandin E2 (1.4 nmol) injected into one hind paw of male Wistar rats (200-250 g, N = 6 in each experimental or control group) pretreated with indomethacin (2.5 mg/kg) potentiated the nocifensive response to formalin (1%) injection made 60 min later. Drugs applied locally 30 min after prostaglandin E2 induced the following effects: fentanyl (0.1-1.0 nmol) caused a dose-dependent reversal of the hyperalgesic state, naloxone (2 nmol) co-injected with fentanyl (1 nmol) completely reversed the antihyperalgesic effect, Nomega-nitro-L-arginine (NOARG, 0.05-0.2 mol) in combination with fentanyl (1.0 nmol) caused a dose-dependent inhibition of the antihyperalgesic effect of fentanyl, co-administration of L-arginine (0.5 mol) with NOARG (0.2 mol) plus fentanyl (1.0 nmol) fully restored the antihyperalgesic effect, and the cyclic-GMP phosphodiesterase inhibitor UK-114,542-27 (5-[2-ethoxy-5-(morpholinylacetyl) phenyl]-1,6-dihydro-1-methyl-3-propyl-7H-pyrazolo [4,3-d]-pyrimidin-7-one methanesulfonate monohydrate; 0.5-2.0 mol) potentiated a subeffective dose of fentanyl (0.1 nmol) in a dose-dependent manner. However, UK-114,542-27 (2.0 mol) injected alone did not produce this antihyperalgesic effect. Systemically administered fentanyl (1.0 nmol, sc) did not cause antinociception. Taken together, these results support the view that fentanyl reverses prostaglandin E2-induced hyperalgesia, probably by activating an opioid receptor at the periphery, and furthermore the L-arginine/nitric oxide/cyclic-GMP pathway may mediate this peripheral effect of fentanyl.


The immunity-diet-microbiota axis in the development of metabolic syndrome.
Recent evidence demonstrates that the gut-microbiota can be considered as one of the major factors causing metabolic and cardiovascular diseases. Pattern recognition receptors as well as antimicrobial peptides are a key factor in controlling the intestinal microbiota composition. Deficiencies in these genes lead to changes in the composition of the gut-microbiota, causing leakage of endotoxins into the circulation, and the development of low-grade chronic inflammation and insulin resistance. Dietary composition can also affect the microbiota: a diet rich in saturated fats allows the expansion of pathobionts that damage the intestinal epithelial cell layer and compromise its barrier function. In contrast, a diet high in fiber supports the microbiota to produce short-chain fatty acids, thereby promoting energy expenditure and protecting against inflammation and insulin resistance. The interactions between the microbiota, innate immunity, and diet play an important role in controlling metabolic homeostasis. A properly functioning innate immune system, combined with a low-fat and high-fiber diet, is important in preventing dysbiosis and reducing the susceptibility to developing the metabolic syndrome and its associated cardiovascular diseases.


[A study on the application of intraoral camera in the identification of oral anatomical landmarks].
To preliminarily explore the applicable scenarios of an intraoral camera to assist oral anatomical landmarks recognition, so as to improve the clinical diagnosis and treatment mode, cultivate the concept of caring for patients, strengthen doctor-patient communication, assist experts to teach, and improve the clinical diagnosis and efficacy rate. A new type of an intraoral camera was applied in the recognition of oral anatomy landmarks and four application scenarios were developed, namely: (1) clinical diagnosis and treatment scenarios, in which doctors used intraoral camera to conduct a comprehensive examination of patients in the mouth and take videos and photos; (2) doctor-patient communication scenarios, when the doctor told the patient about the treatment plan, the video or photo taken by the intraoral camera was displayed to the patient; (3) expert teaching scenarios, when the expert used an intraoral camera to teach in the patient's mouth, and the young doctor learned oral anatomical signs on the projection screen, with the study of theoretical lessons; (4) difficult case recording scenarios, in the process of clinical diagnosis and treatment, when encountering difficult cases, you could use intraoral camera to record and take photos for young doctors to discuss, and experts to comment and guide. The application of intraoral camera could: (1) improve the clinical diagnosis and treatment mode and raise the clinical diagnosis and efficacy rate; (2) stimulate young doctors' interest in learning, use intraoral camera in assessments, and skillfully combine theoretical knowledge of anatomical landmarks with clinical practice, so as to improve the teaching effect; (3) cultivate, through self or mutual use, the concept of caring for patients and reinforce the importance of gentle operation; (4) strengthen doctor-patient communication. Doctors could communicate with patients more visually, so that the patients could better understand their own situation, and strengthen the patients' trust in the doctors. Intraoral camera can assist oral clinical diagnosis and treatment, such as the recognition of oral anatomical landmarks. It plays a certain role in promoting the improvement of clinical diagnosis and treatment mode, stimulating learning interest, cultivating the concept of caring for patients, and enhancing doctor-patient communication.


Purification and characterization of a highly thermostable chitinase from the stomach of the red scorpionfish Scorpaena scrofa with bioinsecticidal activity toward cowpea weevil Callosobruchus maculatus (Coleoptera: Bruchidae).
This present study is the first attempt to report on the purification and characterization of a chitinase from the stomach of the red scorpionfish Scorpaena scrofa. A 50-kDa chitinase (SsChi50) was purified to homogeneity, and matrix assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) analysis showed that SsChi50 was a monomer with a molecular mass of 50,103 Da. The 25 N-terminal residues of SsChi50 displayed high homology with family-18 chitinases. Optimal activity was obtained at pH 5.0 at 80 °C. SsChi50 was stable at pH and temperature ranges of 3.0 to 7.0 and 70 to 90 °C for 48 and 4 h respectively. Among the inhibitors and metals tested, p-chloromercuribenzoic acid, N-ethylmaleimide, Hg(2+), and Hg(+) completely inhibited enzyme activity. Chitinase activity was high on colloidal chitin, glycol chitin, glycol chitosane, chitotriose, and chitooligosaccharide. Chitinase activity towards synthetic substrates in the order of p-NP-(GlcNAc)(n) (n = 2-4) was p-NP-(GlcNAc)(2) > p-NP-(GlcNAc)(4) > p-NP-(GlcNAc)(3). Our results suggest that the SsChi50 enzyme preferentially hydrolyzed the second glycosidic link from the non-reducing end of (GlcNAc)(n). This enzyme obeyed Michaelis-Menten kinetics, the K(m) and k(cat) values being 0.412 mg, colloidal chitin mL(-1) and 5.33 s(-1) respectively. An in vivo bioinsecticidal assay was developed for SsChi50 against Callosobruchus maculatus adults. The enzyme showed bioinsecticidal activity toward Callosobruchus maculatus, indicating the possibility of using it in biotechnological strategies for insect management for stored cowpea seeds.


The pharmacology of ageing in Drosophila.
Recent research indicates that aging is affected by many genes and thus many biochemical pathways. This has led to a failure to find pharmaceuticals that significantly ameliorate the human aging process. Progress in evolutionary and genetic research, however, suggests the possibility of combining experimental evolution, genomic analysis, and mass screening of pharmaceuticals and botanicals to produce effective therapeutics for human aging. The starting point for this strategy is model systems that have outbred populations with substantially increased lifespan. These are easily produced by tuning the force of natural selection in the laboratory. Such biological material is then a good candidate for genomic analysis, leading to the identification of numerous biochemical pathways involved in increased lifespan, in the model system. These biochemical pathways would then be available for pharmaceutical development, first in fruit flies, then in rodents, and eventually in a clinical human population. We include a discussion of the pharmacological methods appropriate to this strategy of drug discovery.


Structure, optical properties, and magnetism of the full Zn(1-x)Cu(x)WO4 (0 ≤ x ≤ 1) composition range.
Microcrystalline and submicrometer powders of Zn(1-x)Cu(x)WO(4) (0 ≤ x ≤ 1) have been prepared by a solid-state synthesis from stoichiometric quantities of the constituent d-block metal oxide and tungsten oxide as well as from a Pechini sol-gel synthesis starting from the d-block metal nitrate and ammonium metatungstate. The stoichiometry of the product is confirmed by inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. X-ray diffraction shows that for the entire range of compositions, a single-phase product crystallizes in the wolframite structure, with a symmetry-lowering transition from P2/c to P1[overline] at x = 0.20, concomitant with the first-order Jahn-Teller distortion of Cu(2+). Far-IR spectroscopy corroborates that symmetry lowering is directly related to the tetragonal distortion within the CuO(6) octahedra, with the Zn-O A(u) symmetry mode at 320 cm(-1) (x = 0) splitting into two stretches at 295 and 338 cm(-1) (x = 0.3). UV-vis-NIR spectroscopy shows an optical absorption edge characteristic of an indirect band gap that linearly decreases in energy from 3.0 eV (x = 0) to 2.25 eV (x = 1). SQUID magnetometry shows that Zn(1-x)Cu(x)WO(4) (0.1 ≤ x ≤ 1) has an effective moment of 2.30 ± 0.19 μ(B) per mol copper, typical of Cu(2+) in extended solids. For high concentrations of copper (x ≥ 0.8), two transitions are observed: one at high-temperature, 82 K (x = 1.0) that decreases to 59 K (x = 0.8), and the Néel temperature, 23.5 K (x = 1.0) that decreases to 5.5 K (x = 0.8). For x < 0.8, no long-range order is observed. A physical 1:1 mixture of both CuWO(4):ZnWO(4) shows magnetic ordering identical to that of CuWO(4).


The Role of HSP90 in Preserving the Integrity of Genomes Against Transposons Is Evolutionarily Conserved.
The HSP90 protein is a molecular chaperone intensively studied for its role in numerous cellular processes both under physiological and stress conditions. This protein acts on a wide range of substrates with a well-established role in cancer and neurological disorders. In this review, we focused on the involvement of HSP90 in the silencing of transposable elements and in the genomic integrity maintenance. The common feature of transposable elements is the potential jumping in new genomic positions, causing chromosome structure rearrangements, gene mutations, and influencing gene expression levels. The role of HSP90 in the control of these elements is evolutionarily conserved and opens new perspectives in the HSP90-related mechanisms underlying human disorders. Here, we discuss the hypothesis that its role in the piRNA pathway regulating transposons may be implicated in the onset of neurological diseases.


Impact of anaemia on outcome in burn patients.
Currently, most critical care physicians maintain a patient's haemoglobin levels at 7 to 8 g dL-1. However, little data have been available on haemoglobin-related outcomes in burn patients. The purpose of this study was to evaluate inpatients with greater than 20% total body surface area burns and the effects of haemoglobin below 8 g dL-1 on clinical outcomes. This study included 70 patients with burns amounting to greater than 20% of total body surface area. Data were retrospectively evaluated and included age, gender, adult respiratory distress syndrome presence, length of intensive care unit stay, length of mechanical ventilation, days requiring vasopressors, renal insufficiency, positive cultures/infections, cardiovascular complications, number of operations, inhalation injury, and mortality. Logistic regression analyses that were adjusted for age, sex, and percent total body surface area were used to assess the relationships between haemoglobin and multiple clinical outcomes. Odds ratios (OR) were estimated with 99% confidence intervals (99% CI). Haemoglobin below 8 g dL-1 was associated with a need for vasopressors (OR = 2.17; 99% CI = 1.03-8.22). Furthermore, haemoglobin below 8 g dL-1 was associated with higher positive wound (OR = 2.86; 99% CI = 1.00-34.40), urine (OR = 4.63; 99% CI = 1.15-67.00), and lung cultures (OR = 2.24; 99% CI = 1.06-5.47). These associations largely remained after controlling for blood transfusions. Contrary to most other patient groups, burn patients with burns amounting to greater than 20% of total body surface area and low haemoglobin levels were more likely to develop positive cultures in urine, wounds, and the lung and require vasopressor treatment.


Contribution of natural food sources to reproductive behaviour, fecundity and longevity of Ceratitis cosyra, C. fasciventris and C. capitata (Diptera: Tephritidae).
The influence of food sources comprising the natural diet on the reproductive behaviour, fecundity and longevity of three African fruit flies Ceratitis cosyra (Walker), C. fasciventris (Bezzi) and C. capitata (Wiedemann) was investigated. Three natural food sources, varying in protein and sugar content, were evaluated. These included bird droppings (farm chicken), aphid honeydew and guava (Psidium guajava L.) juice. For C. fasciventris and C. capitata, flies fed on a protein-rich diet displayed higher frequency of calling, mating and oviposition than flies fed on a protein-poor diet, whilst for C. cosyra, quality of diet significantly influenced the mating behaviour of the flies, but not the calling and oviposition behaviour. Net fecundity rates were lowest for C. fasciventris and C. capitata when fed only on guava juice (0.1, 2.6 eggs per female, respectively), and higher for those on a diet of honeydew only (9.5, 33.8 eggs per female, respectively) and a combined diet of guava, honeydew and chicken faeces (11.8, 25.8 eggs per female, respectively). For C. cosyra, due to low numbers of eggs collected, no significant differences in fecundity between diets could be detected. All species fed only on a diet of chicken faeces since emergence died within the first three days of adult life without laying eggs, but when carbohydrates were provided by addition of guava juice and honeydew, the longevity of the flies was sustained for more than four weeks after adult emergence. The practical implications of these findings for control purposes are discussed.


The effect of varying the amplitude-frequency response on the masked speech-reception threshold of sentences for hearing-impaired listeners.
In an evaluation of frequency-dependent automatic gain-control systems in hearing aids, the effect of varying the amplitude-frequency response on the speech-reception threshold (SRT) for sentences in noise is studied for 20 hearing-impaired listeners. The noise has a spectrum identical to the long-term average spectrum of the sentences. Speech and noise are shaped by the same amplitude-frequency response; their spectra are varied relative to the bisector of the individual's dynamic range. In four experimental conditions, the effect of a steady-state amplitude-frequency response is studied. Steepening the negative spectral slope of speech and noise appears to cause an increase of masked SRT, possibly due to increased effect of upward spread of masking. The effect of a single transition of the amplitude-frequency response between 10 and -10 dB/oct halfway through the sentence seems to be related to the effect for the fixed -10-dB/oct condition. Two transition times are tested. For a transition time of 0.25 s, the SRT is only a little higher than for 1 s. The results suggest that the amplitude-frequency response may be varied in time without having a detrimental effect on the masked SRT of sentences for hearing-impaired listeners as long as strongly negatively sloping spectra are avoided.


Differential amplification and expression of c-myb oncogene in Zajdela ascitic hepatoma.
Organisation and expression of c-myb protooncogene have been studied in a heterogeneous tumour the Zajdela ascitic hepatoma (ZAH). The myb gene is selectively amplified in the more tumorigenic subpopulation of the tumour while the non-lethal subpopulation does not show any change. Analysis of transcripts of the myb gene in tumorigenic versus nontumorigenic cells shows that the level of amplification of the gene does not correspond to the level of its transcription. Results have been discussed in the light of existing evidence regarding the role of c-myb gene expression during cell cycle.


["We must relate to ourselves". Substance, causality, and narrative text].
Since Aristotle the concept of "substance" has described those features of an object which remain constant over time despite varying additional stochastic factors (coincidences). "Causality" places several or more chronological events into a direct relationship. The change of stochastic factors on a substance always has a causal justification. Based on these metaphysical considerations the present contemplations will apply the concept of substance to people. The causal explanation for changes during the lifetime is achieved by narrative sentences. These are, therefore, decisive for the maintenance of the identity of individuals and collectives despite all time-linked changes. The conclusion is reached that speech and thought processes based on speech patterns are essential for humans.


Electronic and vibrational structure of one-dimensional conductors and superconductors.
An attempt is made to treat molecular wires by quantum chemical methods. What is the electronic difference between systems (molecules, stacks of molecules, or polymers) that conducting and almost identical systems that are insulating? At 50% band filling a one-dimensional crystal undergoes a Peierls transition and becomes an insulator (without doping). In the case of 75% band filling, on the other hand, two phases are possible: charge density wave (CDW) and spin-density wave (SDW). The transition between these two insulating phases should be connected to a high conductivity. If CDW and SDW are energetically possible at zero T, vibrational coupling leads to stabilization of a superconducting (SC) ground state and the formation of an energy gap. This hypothesis is exemplified on (SN)x and (TMTSF)2X (X = ClO4, PF6).


Production of enterotoxin a.
A method for production of enterotoxin A in multiple liter lots is described. The medium contained 4% N-Z Amine NAK supplemented with 0.001% niacin and 0.00005% thiamine, and was adjusted to pH 6. The inoculated medium in lots of 400 to 600 ml, in 2-liter Erlenmeyer flasks, was incubated at 37 C for 24 hr on a gyrotory shaker at 280 rev/min. Production of 4 to 6 mug of enterotoxin A per ml occurred.


Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.
In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions.


The association of pityriasis rosea with cytomegalovirus, Epstein-Barr virus and parvovirus B19 infections - a prospective case control study by polymerase chain reaction and serology.
A viral aetiology is suspected for pityriasis rosea (PR). The objective was to investigate the association of PR with cytomegalovirus (CMV), Epstein Barr virus (EBV) and parvovirus B19 infections. Patients with PR were recruited in a primary care setting over 18 months. Blood was collected at initial presentation and four weeks later. Controls were the next age-and-sex-matched patients requiring blood collection for non-dermatological disease. Polymerase chain reaction was performed for EBV and parvovirus B19 DNA. Serology was done for CMV, EBV and parvovirus B19. 12 patients with PR and 12 control subjects were recruited. No patient had viral DNA or significant antibody rise against any of the viruses investigated. The seroprevalence of all three viruses and Ab titres in the patients with PR were insignificantly different from those of control subjects. Two patients had IgM detectable against CMV and EBV respectively. Based on other investigation results, we believe that both IgM results were caused by cross reactivity. PR is not associated with CMV, EBV or parvovirus B19 infections.


Timing delivery of the growth-restricted fetus.
Intrauterine growth restriction (IUGR) is commonly defined as an estimated fetal weight of less than the 10th percentile. While 70% of these are small for normal reasons and not at risk, 30% are pathologically small at risk for numerous complications including fetal death. In the late preterm IUGR fetus (>34 weeks), prematurity risks less and the risk of fetal demise becomes the primary concern. Pulsed-wave Doppler interrogation of the umbilical and middle cerebral artery is useful in reducing perinatal mortality, however, Doppler changes in these vessels of the IUGR fetus may not occur after 34 weeks gestation. There are no randomized trials addressing the timing of delivery of the IUGR fetus in the late preterm or early-term period. However, retrospective reports show an increase risk of fetal demise. While timing the delivery of the late preterm/early-term IUGR fetus requires consideration of multiple factors (e.g. degree of growth restriction, etiology, amniotic fluid volume, and biophysical and Doppler testing), available data suggests that delivery should occur by 37 to 38 weeks for singleton IUGR fetuses. In twin pregnancies with a co-twin IUGR fetus, chorionicity also impacts timing of delivery, but delivery should occur by 34-36 weeks.


MiRNA-142-3p increases radiosensitivity in human umbilical cord blood mononuclear cells by inhibiting the expression of CD133.
This study is to explore the molecular regulation mechanism of CD133 which is associated with malignancy and poor prognosis of blood system diseases. CD133+HUCB-MNC (human umbilical cord blood mononuclear cells) and CD133-HUCB-MNC were isolated and amplificated from umbilical cord blood, and then were exposed to different doses of radiation and subjected to a clonogenic assay. CCK-8 kit was used to detect cell viability, Annexin V-FITC/PI cell apoptosis detection kit was used for the detection of apoptotic cells and the BrdU assay was performed by flow cytometry. The expression of protein was analyzed by western blots. The profile of miRNA expression in response to radiation was examined and validated by RT-PCR. miR-142-3p inhibited the expression of CD133 in umbilical cord blood mononuclear cells to increase radiosensitivity. CD133+HUCB-MNC cells were more radioresistant compared with CD133-HUCB-MNC cells. CD133+HUCB-MNC cells showed higher p-AKT and p-ERK levels after radiation. And miR-142-3p acted on 3'UTR of CD133 mRNA to inhibit CD133 expression. Moreover, miRNA-142-3p mimic increased radiosensitivity in CD133+HUCB-MNC cells. Our results elucidated a novel regulation pathway in hematopoietic stem cells and suggested a potential therapeutic approach for blood system diseases therapy.


Turnip rape and oilseed rape are new potential food allergens in children with atopic dermatitis.
When skin prick testing (SPT) young children with atopic dermatitis (AD) for suspected food allergy, we frequently found positive reactions with turnip rape (Brassica rapa) and oilseed rape (Brassica napus). We performed food challenge to examine whether these children react clinically to turnip rape. A total of 1887 children were screened with SPTs for sensitization to turnip rape and oilseed rape. Twenty-eight children with clearly positive SPT (> or =5 mm) were first subjected to labial challenge with turnip rape seeds followed, if negative, by open oral challenge for up to 7 days. Twenty-five children with AD but negative SPT to turnip rape and oilseed rape served as controls. Two-hundred and six (10.9%) children had positive SPT to turnip rape and/or oilseed rape. Twenty-five (89%) of 28 children showed a positive challenge reaction to turnip rape. Seventeen reacted with labial whealing, and eight in oral challenge with facial urticaria, flare-up of AD or abdominal symptoms. All 25 control children remained negative in the labial challenge. Turnip rape and oilseed rape seem to be new important food allergens in young children with AD. The modes of exposure to these allergens and the possible routes of sensitization remain to be established.


Colorectal cancer liver metastases - understanding the differences in the management of synchronous and metachronous disease.
Metastatic disease to the liver in colorectal cancer is a common entity that may present synchronously or metachronously. While increasing surgical experience has improved survival outcomes, some evidence suggest that synchronous lesions should be managed differently. This review aims to update current literature on differences between the outcomes and management of synchronous and metachronous disease. Systematic review of MEDLINE database up till November 2008. Discrete differences in tumour biology have been identified in separate studies. Twenty-one articles comparing outcomes were reviewed. Definitions of metachronicity varied from anytime after primary tumour evaluation to 1 year after surgery for primary tumour. Most studies reported that synchronous lesions were associated with poorer survival rates (8% to 16% reduction over 5 years). Sixteen articles comparing combined vs staged resections for synchronous tumour showed comparable morbidity and mortality. Benefits over staged resections included shorter hospital stays and earlier initiation of chemotherapy. Suitability for combined resection depended on patient age and constitution, primary tumour characteristics, size and the number of liver metastases, and the extent of liver involvement. Surgery remains the only treatment option that offers a chance of long-term survival for patients amenable to curative resection. Synchronicity suggests more aggressive disease although a unifying theory for biological differences explaining the disparity in tumour behaviour has not been found. Combined resection of primary tumour and synchronous metastases is a viable option pending careful patient selection and institutional experience. Given the current evidence, management of synchronous and metachronous colorectal liver metastases needs to be individualised to the needs of each patient.


Fungi-Induced Upper and Lower Respiratory Tract Allergic Diseases: One Entity.
Introduction:Aspergillus can cause different allergic diseases including allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS). ABPA is allergic pulmonary disease against Aspergillus antigens. AFRS is a type of chronic rhinosinusitis (CRS) presented as hypersensitivity reactions to the fungal presence in sinuses. The aim of the present study was to clarify if ABPA and AFRS could be considered as a common disease entity. Methodology: The prospective cohort study included 75 patients with ABPA. Patients were divided into two groups and compared with each other: (i) patients with CT confirmation of rhinosinusitis and presence of fungi in sinuses (ABPA+AFRS group) and (ii) patients without CT or without mycological evidence of AFRS (ABPA group). Results: Findings of this study were: (i) AFRS was confirmed in 80% of patients with ABPA; (ii) all ABPA+AFRS patients had allergic mucin while fungal hyphae were present in 60% sinonasal aspirate; (iii) ABPA+AFRS patients had more often complicated CRS with (nasal polyps) NP (p < 0.001) and more severe forms of CRS; (iv) culture of sinonasal aspirate revealed fungal presence in 97% patients with ABPA+AFRS; (v) patients with ABPA+AFRS had more common positive skin prick test (SPT) for A. fumigatus (p = 0.037), while patients without AFRS had more common positive SPT for Alternaria alternata and Penicillium notatum (p = 0.04 and p = 0.03, respectively); (vi) 67% of ABPA patients had Aspergillus induced AFRS; (vii) larger number of fungi was isolated from the air-samples obtained from homes of patients with ABPA+AFRS than from the homes of patients without AFRS, while the most predominant species were A. fumigatus and A. niger isolated from almost 50% of the air-samples. Conclusion: The pathogenesis of ABPA and AFRS is similar, and AFRS can be considered as the upper airway counterpart of ABPA. Fungi-induced upper and lower respiratory tract allergic diseases present common entity. Next studies should clarify the mechanism by which fungi turn from "normal flora" into trigger of immunological reactions, resulting in ABPA or AFRS as well as to find new approaches for its' diagnosis and treatment.


An assessment of the diagnosis and management of dementia in nursing homes.
The purpose of this study was to evaluate the diagnosis and management of dementia in the nursing home setting through use of the Mini-Mental State Examination (MMSE) and monitoring of acetylcholinesterase-inhibitor (ACHEI) therapy. Longitudinal cross-sectional study. Long-term care facilities in Indiana. Residents in long-term care facilities were included. The number of residents with MMSE scores indicative of dementia, the presence of a dementia diagnosis, and receipt of ACHEI therapy. Data were collected on 782 residents. An MMSE score was available within the past 12 months in 456 (58.3%) of residents. The median MMSE score was 17 and ranged from 0 to 30 points. Out of the total population, ACHEI therapy was prescribed in 165 (21.1%) residents. Seventy-five (29.2%) of the residents with mild-moderate dementia (MMSE = 10-26) were prescribed ACHEI therapy. The most frequently prescribed ACHEI was donepezil 10 mg/day prescribed in 98 (59.4%) of the residents receiving ACHEI therapy. Average length of ACHEI therapy was 9.0 months. MMSE scores were not available in a large proportion of this nursing home population (41.7%). Of those residents with an available MMSE score, a significant number of them had scores indicative of dementia. Despite having scores indicative of dementia, 182 (70.8%) residents were not receiving AChEI therapy. An assessment to determine why residents were not receiving therapy is needed. Opportunities exist to improve the screening, diagnosis, and treatment of dementia in the nursing home setting.


CD9 and CD81 Interactions and Their Structural Modelling in Sperm Prior to Fertilization.
Proteins CD9 and CD81 are members of the tetraspanin superfamily and were detected in mammalian sperm, where they are suspected to form an active tetraspanin web and to participate in sperm⁻egg membrane fusion. The importance of these two proteins during the early stages of fertilization is supported by the complete sterility of CD9/CD81 double null female mice. In this study, the putative mechanism of CD9/CD81 involvement in tetraspanin web formation in sperm and its activity prior to fertilization was addressed. Confocal microscopy and colocalization assay was used to determine a mutual CD9/CD81 localization visualised in detail by super-resolution microscopy, and their interaction was address by co-immunoprecipitation. The species-specific traits in CD9 and CD81 distribution during sperm maturation were compared between mice and humans. A mutual position of CD9/CD81 is shown in human spermatozoa in the acrosomal cap, however in mice, CD9 and CD81 occupy a distinct area. During the acrosome reaction in human sperm, only CD9 is relocated, compared to the relocation of both proteins in mice. The structural modelling of CD9 and CD81 homologous and possibly heterologous network formation was used to propose their lateral Cis as well as Trans interactions within the sperm membrane and during sperm⁻egg membrane fusion.


Stakeholders' Understandings of Human Papillomavirus (HPV) Vaccination in Sub-Saharan Africa: A Rapid Qualitative Systematic Review.
Cervical cancer rates in Sub-Saharan Africa (SSA) are amongst the highest worldwide. All three of the Human Papillomavirus (HPV) vaccines (9-valent, quadrivalent and bivalent HPV vaccine) provide primary protection against the most common cancer-causing strains of HPV (types 16 and 18) that are known to cause 70% of cervical cancers. Over the last five years, there has been an increase in Sub-Saharan African countries that have introduced the HPV vaccine. The majority of research has been conducted on supply-side barriers and facilitators to HPV vaccination uptake in SSA, yet little research has been conducted on demand-side or end-user perspectives of, and decisions around, HPV vaccination. In order to complement existing research, and inform current and future HPV vaccination implementation approaches, this qualitative systematic review explored Stakeholders' understandings of HPV vaccination in SSA. This review searched the following databases: Embase (via Scopus), Scopus, MEDLINE (via PubMed), PubMed, EBSCOhost, Academic Search Premier, Africa-Wide Information, CINAHL, PsycARTICLES, PsycINFO, SocINDEX, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) and found a total of 259 articles. Thirty-one studies were found eligible for inclusion and were analyzed thematically using Braun and Clarke's methods for conducting a thematic analysis. The quality of included studies was assessed using the Critical Appraisal Skills Programme (CASP) checklist. Three major themes emerged from this analysis; knowledge of HPV vaccination and cervical cancer is intertwined with misinformation; fear has shaped contradictory perceptions about HPV vaccination and gender dynamics are relevant in how stakeholders understand HPV vaccination in SSA.


Synthesis of CaTiO3 Nanofibers with Controllable Drug-Release Kinetics.
Calcium titanate (CaTiO3) nanofibers with controlled microstructure were fabricated by a combination of sol-gel and electrospinning approaches. The fiber morphology has been found to rely significantly on the precursor composition. Altering the volume ratio of ethanol to acetic acid from 3.5 to 1.25 enables the morphology of the CaTiO3 nanofibers to be transformed from fibers with a circular cross section to curved ribbon-like structures. Ibuprofen (IBU) was used as a model drug to investigate the drug-loading capacity and drug-release profile of the nanofibers. It was found that the BET surface area and the pore volume decrease markedly with the utilization of F127 surfactant. The nanofibers synthesized without F127 surfactant present the highest drug-loading capacity and the most sustained release kinetics. This study suggests that calcium titanate nanofibers can offer a promising platform for localized drug delivery.


Adherence to hydroxychloroquine improves long-term survival of patients with systemic lupus erythematosus.
HCQ, which is known to decrease SLE activity, may have a protective effect on survival, but this has not been proven in Asia. This study aimed to determine whether HCQ treatment is associated with increased survival in patients with SLE. We designed this prospective SLE cohort study using data from the Taiwan National Health Insurance Research Database. The participants were divided into HCQ and control groups according to whether HCQ was prescribed during the first year after an SLE diagnosis. The primary outcome was mortality 1 year after inclusion. In the subgroup analysis, these participants were divided based on medication possession ratio (MPR) in the first year into non-users, MPR <40%, 40% ⩽ MPR < 80% and MPR ⩾80% subgroups to explore the relationship between survival and HCQ adherence. A total of 12 443 patients were eligible for the analysis. After propensity score matching, we included 2287 patients in each group. During a mean follow-up of 7.6 years, there were 169 events in the HCQ group (7.4%) and 248 events in the control group (10.8%). The risk of mortality in the HCQ group was lower than that in the control group (hazard ratio = 0.68; 95% CI: 0.56, 0.82). The subgroup analysis revealed that the survival protective effect was associated with HCQ adherence. Patients with SLE who received HCQ had lower mortality rates due to any cause than those who did not. The survival benefit could be augmented by HCQ adherence.


Peripheral eosinophilia in bullous pemphigoid: prevalence and influence on the clinical manifestation.
Peripheral eosinophilia has been reported in 50-60% of patients with bullous pemphigoid (BP) and correlated positively with disease severity. To establish an association of peripheral eosinophilia with the different morphological characteristics of BP. The study was designed as a case-control study. Diagnosis of BP was grounded on well-established immunopathological criteria. Five age-, sex- and ethnicity-matched controls were randomly selected for each patient with BP. Overall, 225 patients with BP and 1125 control participants were enrolled. A total of 113 (50·2%) patients with BP and 49 (4·4%) controls had pathological peripheral eosinophilia (P < 0·001). An independent association between eosinophil count and the diagnosis of BP was observed [odds ratio 59·9 (per 1000 eosinophil μL-1 increase); P < 0·001]. Patients with BP with eosinophilia were significantly older at presentation (P = 0·003) and had increased palmoplantar involvement (P = 0·005), whereas patients with normal eosinophil counts had greater involvement of mucosal surfaces (P = 0·002) and the head and neck (P = 0·047). Patients with BP with extensive disease had significantly higher eosinophil counts than patients with mild-to-moderate disease (996·5 ± 1052·5 vs. 696·1 ± 962·6 cells μL-1 ; P < 0·001). Patients with BP with serum eosinophilia were significantly older and had higher palmoplantar involvement. Patients with BP with a normal eosinophil count were younger and presented more frequently with atypical clinical manifestations.


CT anatomy of the lingular segmental bronchi.
Thin-section CT scans were performed in 40 patients to demonstrate the normal appearance of the lingular division (LD) bronchus and its segmental and subsegmental bronchi and to search out the possible anatomical landmark dividing the anterior segment and LD of the left upper lobe. The LD bronchus was identified in all patients. The complete branching pattern of the lingular segmental and subsegmental bronchi could be traced in 19 (47.5%) patients. Since the lower branch of the draining vein of the anterior segment of the left upper lobe (V3b) runs horizontally between the anterior segment and the LD of the left upper lobe, it is a good landmark dividing the anterior segment and LD of the left upper lobe. Familiarity with thin-section CT anatomy of the lingular segmental and subsegmental bronchi and surrounding vascular structures is helpful in identifying the lingular bronchial tree precisely and localizing a lesion in the left upper lobe correctly.


Circulation of Toxocara spp. in suburban and rural ecosystems in the Slovak Republic.
Toxocara spp., the common roundworms of domestic and wild animals, are the causative agents of larval toxocarosis in humans. The migration of Toxocara larvae in men causes clinical syndrome, called larva migrans visceralis or larva migrans ocularis. The objective of the present work was to investigate the prevalence of toxocarosis in dogs, red foxes (Vulpes vulpes), and small mammals in the Slovak Republic. T. canis infection was diagnosed in 16.6% out of 145 dogs examined. Young animals showed significantly higher positivity (50.0%) than adults (12.4%). Coprological investigation of 310 red foxes showed 8.1% prevalence of T. canis, with higher occurrence in animals from rural conditions (8.6%) than from suburban environment (5.6%). Out of 710 small mammals examined, anti-Toxocara antibodies were detected in 7.7% of the animals. The most frequently seropositive species was Apodemus agrarius (15.9%). Seropositivity of small mammals from suburban localities was higher (10%) compared with rural areas (5.8%), with adult animals exhibiting higher seropositivity (8.0%) than subadults (6.8%). Our results have confirmed the importance of dogs, red foxes and small mammals in circulation of this serious helminthozoonosis in suburban and rural ecosystems.


The forensic use of behavioral genetics in criminal proceedings: Case of the MAOA-L genotype.
The role of behavioral genetic evidence in excusing and mitigating criminal behavior is unclear. Research has suggested that a low activity genotype of the enzyme monoamine oxidase (MAOA-L) may increase the risk for aggressive and antisocial behavior. By examining criminal proceedings in which MAOA-L genotype evidence was introduced, we explored the forensic uses of behavioral genetic science. Westlaw and LexisNexis legal databases were electronically searched for cases from 1995 to 2016 to identify court documents from cases involving the MAOA-L genotype. Evidence of the MAOA-L genotype was included in records from 11 criminal cases (9 U.S. and 2 Italian). In the guilt phase, genotype evidence was ruled admissible in one of two cases, and may have contributed to a conviction on a lesser charge. In the sentencing phase, genotype evidence was admissible in four of five cases, one of which ended with a lesser sentence. Five cases used genotype evidence for post-conviction appeals, two of which resulted in sentence reductions. Even when charges or sentences are reduced it is difficult to gauge the effect of evidence of the MAOA-L genotype. Genotype evidence may lack persuasive effect because the impact of the allele on a particular accused is difficult to establish.


Removal of Amoxicillin from Aqueous Media by Fenton-like Sonolysis/H2O2 Process Using Zero-Valent Iron Nanoparticles.
High concentrations of antibiotics have been identified in aqueous media, which has diminished the quality of water resources. These compounds are usually highly toxic and have low biodegradability, and there have been reports about their mutagenic or carcinogenic effects. The aim of this study was to apply zero-valent iron-oxide nanoparticles in the presence of hydrogen peroxide and the sonolysis process for the removal of the amoxicillin antibiotic from aqueous media. In this study, zero-valent iron nanoparticles were prepared by an iron chloride reduction method in the presence of sodium borohydride (NaBH4), and the obtained nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and vibrating-sample magnetometry (VSM). Then, using a Fenton-like process, synthetic wastewater containing 100 to 500 mg/L amoxicillin antibiotic was investigated, and the effects of different parameters, such as the frequency (1 and 2 kHz), contact time (15 to 120 min), the concentration of hydrogen peroxide (0.3%, 0.5%, and 6%), the dose of zero-valent iron nanoparticles (0.05, 0.1, 0.5 g/L), and pH (3, 5, 10) were thoroughly studied. A pH of 3, hydrogen peroxide concentration of 3%, ultrasonic-wave frequency of 130 kHz, zero-valent iron nanoparticles of 0.5 g/L, and contaminant concentration of 100 mg/L were obtained as the optimal conditions of the combined US/H2O2/nZVI process. Under the optimal conditions of the combined process of zero-valent iron nanoparticles and hydrogen peroxide in the presence of ultrasonic waves, a 99.7% removal efficiency of amoxicillin was achieved in 120 min. The results show that the combined US/H2O2/nZVI process could be successfully used to remove environmental contaminants, including antibiotics such as amoxicillin, with a high removal percentage.


Capacitive-Type Pressure-Mapping Sensor for Measuring Bite Force.
Bite force is an important indicator of masticatory performance. However, existing methods for measuring bite force are either ineffective or expensive. Hence, we developed a novel capacitive-type pressure-mapping sensor that converts mechanical forces into changes in capacitance and calculates bite force. A portable device was fabricated based on this sensor sheet, and the accuracy of the bite-force measurements provided by the device was evaluated. The sensor has a thickness of 1.6 mm and has 63 measurement points. It was inserted into a dental model, where the output value was measured and compared with that of a universal testing machine (AG-IS 100 kN). A regression equation to estimate the bite force was obtained based on the relationship between the output of the capacitive-type pressure-mapping sensor and that of the load cell of the universal testing machine. The estimated bite force from the sensor and the quadratic regression equation closely resembled the known load applied by the compression tester (R2 = 0.992). We therefore conclude that the developed sensor can measure bite force accurately and effectively. A device with a built-in capacitive-type pressure-mapping sensor can potentially be a user-friendly tool for bite-force measurements in both clinical and epidemiological settings.


Computational Studies of Molecular Permeation through Connexin26 Channels.
A signal property of connexin channels is the ability to mediate selective diffusive movement of molecules through plasma membrane(s), but the energetics and determinants of molecular movement through these channels have yet to be understood. Different connexin channels have distinct molecular selectivities that cannot be explained simply on the basis of size or charge of the permeants. To gain insight into the forces and interactions that underlie selective molecular permeation, we investigated the energetics of two uncharged derivatized sugars, one permeable and one impermeable, through a validated connexin26 (Cx26) channel structural model, using molecular dynamics and associated analytic tools. The system is a Cx26 channel equilibrated in explicit membrane/solvent, shown by Brownian dynamics to reproduce key conductance characteristics of the native channel. The results are consistent with the known difference in permeability to each molecule. The energetic barriers extend through most of the pore length, rather than being highly localized as in ion-specific channels. There is little evidence for binding within the pore. Force decomposition reveals how, for each tested molecule, interactions with water and the Cx26 protein vary over the length of the pore and reveals a significant contribution from hydrogen bonding and interaction with K(+). The flexibility of the pore width varies along its length, and the tested molecules have differential effects on pore width as they pass through. Potential sites of interaction within the pore are defined for each molecule. The results suggest that for the tested molecules, differences in hydrogen bonding and entropic factors arising from permeant flexibility substantially contribute to the energetics of permeation. This work highlights factors involved in selective molecular permeation that differ from those that define selectivity among atomic ions.


Image-Guided Percutaneous Omental and Mesenteric Biopsy: Assessment of Technical Success Rate and Diagnostic Yield.
To assess biopsy technique, technical success rate, and diagnostic yield of image-guided percutaneous biopsy of omental and mesenteric lesions. This retrospective study included 186 patients (89 men, 97 women; mean [SD] age, 63 [13.8] y) who underwent percutaneous image-guided biopsy of omentum and mesentery between March 2007 and August 2015. Biopsies were performed with computed tomography (CT) (n = 172) or ultrasound (US) (n = 14) guidance using coaxial technique yielding core and fine-needle aspiration (FNA) specimens. Biopsy results were classified as diagnostic (neoplastic or nonneoplastic) or nondiagnostic based on histopathology and cytology. Technical success rate and diagnostic yield of omental and mesenteric lesions were calculated. There were 186 image-guided percutaneous biopsies of omental (n = 95) and mesenteric (n = 91) lesions performed. Technical success rate was 99.5% for all biopsies, 100% for omental biopsies, and 98.9% for mesenteric biopsies. Overall sensitivity was 95.5%, specificity was 100%, negative predictive value was 78.3%, and positive predictive value was 100%, which was comparable for omental and mesenteric biopsies. Core biopsies had higher diagnostic yields compared with FNA: 98.4% versus 84% overall, 99% versus 88% for omental biopsies, and 97.7% versus 80% for mesenteric biopsies. Spearman rank correlation showed no correlation between lesion size and diagnostic yield (P = .14) and lesion depth and diagnostic yield (P = .29) for both groups. There were 5 complications. Image-guided percutaneous omental and mesenteric biopsies have high technical success rates and diagnostic yield regardless of lesion size or depth from the skin for both omental and mesenteric specimens.


Rapid healing of sickle cell leg ulcers treated with collagen dressing.
Chronic leg ulcers in sickle cell anemia occur mainly around the ankles. The prevalence is up to 75% in adults. These ulcers are painful and debilitating, yet medical treatment is unsuccessful. Surgical treatment consists of repeated skin grafting procedures, which eventually deplete the patient's available donor sites. Thus, in vitro generation of human epidermal autograft for potential treatment of leg ulcers in sickle cell anemia was initiated. However, because epidermal cells need a supporting matrix in order to be applied to the ulcer, the authors decided to assess the independent effect of a collagen matrix alone in promoting healing of sickle cell leg ulcers. Collistat (Hellistex, Inc) dressing was applied directly to the ulcers. The ulcers were reviewed every 2 weeks, and the dressing reapplied every 4 weeks. Collagen matrix caused the chronic ulcers to heal completely in fewer than 3 months. This encouraging performance of collagen alone should be greatly enhanced by the in vitro epidermal autograft.


Diffential diagnosis of the caloric nystagmus.
Diagnostic considerations based upon the nystagmogram are limited. Quantitative assessment of horizontal canal sensitivity is available through the use of culmination frequency or culmination slow phase velocity. Qualitative characteristics of nystagmometry have been sought but with no satisfactory results. Three distinctive features of the caloric nystagmus were evaluated and were found to be suggestive or outrightly pathognomonic for retrolabyrinthine or central nervous system abnormalities. These are: (1) Vestibular decruitment. The disproportionate caloric responsiveness when a weak stimulus elicits a more intense nystagmic reaction than a strong stimulus is capable of creating. (2) Hyperactive vestibular responsiveness (3) Ocular fixation reversal phenomenon. Contrary to the normal behaviour, the elimination of fixation decreases the nystagmus intensity instead of facilitating the evoked nystagmus. The assessment of these qualitative features of the caloric nystagmus in addition to the quantitative measurements widens the scope of our diagnostic capabilities.


Diarrheagenic Escherichia coli isolated from stools of sporadic cases of diarrheal illness in Osaka City, Japan between 1997 and 2000: prevalence of enteroaggregative E. coli heat-stable enterotoxin 1 gene-possessing E. coli.
Diarrheagenic Escherichia coli (DEC) represents an elusive target, since they are not easily distinguished from fecal coliforms. To clarify if DEC are prevalent among sporadic cases of diarrheal illness in Osaka City, Japan, diarrheal specimens were examined for E. coli that were enterohemorrhagic (EHEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), or enteroaggregative (EAggEC). EAST1EC, a strain of E. coli that does not possess any diarrheagenic characteristics except the EAggEC heat-stable toxin 1 (EAST1) gene, was also included as a possible DEC. A total of 924 specimens were examined between July 1997 and March 2000. DEC and Salmonella were isolated from 7.3% (67/924) and 6.8% (63/924) of specimens, respectively. DEC was therefore as prevalent as Salmonella among sporadic cases. The 67 strains were composed of 17 EPEC (26%), 10 EHEC (15%), four ETEC (6%), 13 EAggEC (20%), and 23 EAST1EC (35%), including two strains of EAST1EC O166:H15. Although PCR and tissue culture adhesion tests were useful to detect DEC, the effectiveness of serotyping was limited: only 40 strains (17.5%) out of 229 isolates that had been assumed to be enterovirulent on the basis of their O antigen were recognized to be diarrheagenic. In conclusion, not only EHEC but also the other subgroups of DEC, including EAST1EC, seem to play an important role in causing sporadic diarrheal illnesses. Methods to detect and unified criteria to identify various kinds of DEC are strongly desired.


The utility of Thin Slice ratings for predicting language growth in children with autism spectrum disorder.
Literature on "Thin Slice" ratings indicates that a number of personality characteristics and behaviors can be accurately predicted by ratings of very short segments (<5 min) of behavior. This study examined the utility of Thin Slice ratings of young children with autism spectrum disorder for predicting developmental skills and language gains over time. A total of 22 preschool-aged children with autism spectrum disorder participated in a battery of developmental assessments and a video-taped therapist-child interaction at Time 1. They then participated in follow-up testing of language skills and a second therapist-child interaction 6 months later (Time 2). Groups of approximately 25 naïve undergraduate students provided impression ratings ("Thin Slice ratings") about each child's skills and behaviors during 2-min segments taken from the therapist-child interaction videos at each time point. Thin Slice ratings at Time 1 were highly correlated with child scores on several developmental assessments at Time 1. In addition, Thin Slice ratings at Time 1 predicted gain in parent-reported expressive vocabulary over the course of 6 months, over and above the predictive utility of Time 1 vocabulary size. These findings provide preliminary evidence for the concurrent and predictive validity of Thin Slice ratings in young children with autism spectrum disorder.


Effect of Mandatory Centers of Excellence Designation on Demographic Characteristics of Patients Who Undergo Bariatric Surgery.
From February 21, 2006, through September 24, 2013, the Centers for Medicare & Medicaid Services (CMS) required, via the National Coverage Determination manual, that bariatric surgery be performed only in hospitals that had been designated as a Center of Excellence (COE). The effect of this certification requirement on access to bariatric surgery has been reported only anecdotally. To investigate whether the COE certification requirement proved to be a barrier to patients' access to bariatric surgical procedures. Using the National Inpatient Sample, we retrospectively identified patients who underwent bariatric surgery from January 1, 2006, through December 31, 2011. Bariatric surgery. Logistic regression and χ² tests were used to examine differences in patients' sociodemographic characteristics over time. A total of 134,227 bariatric surgical patients were identified. The proportion of the population who were older than 64 years increased from 2.9% in 2006 to 7.0% in 2011 (P < .001) and there was a decrease in the proportion of patients who were 49 years and younger (P < .001). The percentage of female patients who underwent bariatric surgery decreased from 80.4% to 78.1% (P < .001) and the percentage of patients who were classified as black, Hispanic, or Asian or Pacific Islander increased from 12.3% to 15.1% (P < .001), 9.7% to 12.5% (P < .001), and 0.3% to 0.4% (P < .001), respectively. The proportion of patients with Medicare increased from 8.5% to 16.3% (P < .001) and those with Medicaid from 6.6% to 11.8% (P < .001). The percentage of patients with private insurance declined from 72.4% to 63.3% (P < .001). The proportion of patients in the lowest income quartile increased from 20.7% to 22.9% (P < .001) while those in the highest income quartile decreased from 25.8% to 23.9% (P < .001). The COE certification requirement by CMS did not appear to limit access to bariatric surgery. Future studies should determine whether CMS's recent (2013) change in policy (ie, removing the mandatory COE certification for bariatric surgical insurance coverage) might sacrifice patient safety without addressing the real cause of limited access to health care.


Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19.
Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results: IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions: Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.


"Just in Time": The Role of Cryo-Electron Microscopy in Combating Recent Pandemics.
Single-particle cryogenic electron microscopy (cryo-EM), whose full power was not realized until the advent of powerful detectors in 2012, has a unique position as a method of structure determination as it is capable of providing information about not only the structure but also the dynamical features of biomolecules. This information is of special importance in understanding virus-host interaction and explains the crucial role of cryo-EM in the efforts to find vaccinations and cures for pandemics the world has experienced in the past decade.


[Rapid improvement of fluid retention with lenalidomide plus low-dose dexamethasone for POEMS syndrome relapsed after autologous peripheral blood stem cell transplantation].
We report a 53-year-old male with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome who relapsed after autologous peripheral stem cell transplantation (ASCT), but responded extremely well to lenalidomide (LEN) plus low dose dexamethasone (Ld) therapy. The patient had been diagnosed with POEMS syndrome in November 2006, and underwent ASCT in February 2007. In July 2011, he developed respiratory distress, generalized edema, and massive bilateral pleural effusion. Plasma vascular endothelial growth factor (VEGF) and M protein were increased, strongly indicating a relapse. Ld therapy was remarkably effective for these symptoms, resulting in complete remission with M-protein becoming undetectable by immunofixation. Since completing 11 courses of therapy with an every 4 weeks regimen, he has remained in clinical remission. The patient's activities of daily living have also markedly improved from total physical incapacity to being able to stand with slight assistance. LEN is associated with a lower incidence of peripheral neuropathy than other new drugs. Although LEN has occasionally been given to patients with POEMS syndrome in recent years, there are still few reports on its use for patients with recurrent disease after ASCT. Our successful management of this patient suggests that Ld therapy is not only relatively safe but also a promising option for POEMS syndrome relapsing after ASCT.


[Strongyloidiasis and its current treatment].
A case of strongyloidosis and giardiasis was observed in a women aged 62 years. The treatment included tinidazole, metronidazole and ercefuryl. Modern views on the epidemiology, clinical course and therapy of this parasitic infestation are discussed.


Repeated inhibition of sigma-1 receptor suppresses GABAA receptor expression and long-term depression in the nucleus accumbens leading to depressive-like behaviors.
Sigma-1 receptor (σ1R) downregulation in male mice is known to cause a depressive-like phenotype. The nucleus accumbens (NAc), a region associated with affective regulation, has high levels of σ1R. Here, we investigated the effect of repeated inhibition of σ1R in the NAc on depressive-like behaviors and synaptic plasticity by microinjecting σ1R antagonist NE-100 into NAc nuclei in mice (NE-100 mice); this was followed by behavioral tests and field potentials recordings. We first examined the effect of NE-100 administration on σ1R expression and found that cell surface levels of σ1R were significantly reduced in the NAc of NE-100 mice. Compared to control mice, NE-100 mice exhibited significantly prolonged immobility in forced swim test (FST) and tail suspension test (TST), impaired long-term depression (LTD) as well as multi-spike waveform field excitatory postsynaptic potential (fEPSP) with an extended duration and an increased paired-pulse ratio (PPR). Reduced levels of GABAA receptor (GABAAR)-α1, -α2, -β2, and -β3 subunits, membrane D2R, and PKC phosphorylation in the NAc were observed in NE-100 mice. Activation of GABAAR by muscimol corrected the extended fEPSP duration and increased PPR, restored LTD maintenance as well as alleviated depressive-like behaviors in NE-100 mice. The decline of PKC phosphorylation in the NAc of NE-100 mice was corrected by injecting NAc with quinpirole, a D2R agonist. Injections of quinpirole or PMA (a PKC activator) into NAc of NE-100 mice rescued the expression levels of GABAAR, and alleviated the increase in PPR and impairment in LTD; these effects were sensitive to GF109203X, a PKC inhibitor. Furthermore, injecting NAc with quinpirole or PMA relieved depressive-like behaviors in NE-100 mice. Collectively, these results indicate that repeated inhibition of σ1R in the NAc reduces D2R-mediated PKC phosphorylation and suppresses GABAAR expression, thus impairing LTD maintenance and leading to depressive-like behaviors.


Emphysematous pyelonephritis and cystitis: A case report and literature review.
This present case report describes a 64-year-old female patient with type 2 diabetes mellitus who also had emphysematous pyelonephritis (EPN) and emphysematous cystitis (EC). Computed tomography revealed well defined emphysematous pyelonephritis and cystitis. Broad-spectrum antibiotic and percutaneous drainage of the right kidney were used as part of a conservative management regimen. The patient achieved clinical recovery and was discharged 12 days after admission. Furthermore, 13 other cases of EPC and EC that were reported between 1962 and 2017 were reviewed and discussed. The overall mortality was 15.4% (two of 13 patients), compared with 25% for EPN alone or 7.4% for EC alone as reported in the literature. The primary pathogen identified in the 13 patients was Escherichia coli (53.8%). All 13 patients were treated with antibiotics.


Block-Stereoblock Copolymers of Poly(ϵ-Caprolactone) and Poly(Lactic Acid).
A magnesium complex of the type {ONNN}Mg-HMDS wherein {ONNN} is a sequential tetradentate monoanionic ligand is introduced. In the presence of an alcohol initiator this complex catalyzes the living and immortal homopolymerization of the lactide enantiomers and ϵ-caprolactone at room-temperature with exceptionally high activities, as well as the precise block copolymerization of these monomers in a one-pot synthesis by sequential monomer addition. Copolymers of unprecedented microstructures such as the PCL-b-PLLA-b-PDLA and PDLA-b-PLLA-b-PCL-b-PLLA-b-PDLA block-stereoblock microstructures that feature unique thermal properties are readily accessed.


Helioseismic Holography of Simulated Sunspots: dependence of the travel time on magnetic field strength and Wilson depression.
Improving methods for determining the subsurface structure of sunspots from their seismic signature requires a better understanding of the interaction of waves with magnetic field concentrations. We aim to quantify the impact of changes in the internal structure of sunspots on local helioseismic signals. We have numerically simulated the propagation of a stochastic wave field through sunspot models with different properties, accounting for changes in the Wilson depression between 250 and 550 km and in the photospheric umbral magnetic field between 1500 and 3500 G. The results show that travel-time shifts at frequencies above approximately 3.50 mHz (depending on the phase-speed filter) are insensitive to the magnetic field strength. The travel time of these waves is determined exclusively by the Wilson depression and sound-speed perturbation. The travel time of waves with lower frequencies is affected by the direct effect of the magnetic field, although photospheric field strengths below 1500 G do not leave a significant trace on the travel-time measurements. These results could potentially be used to develop simplified travel-time inversion methods.


Ten rice peroxidases redundantly respond to multiple stresses including infection with rice blast fungus.
Class III plant peroxidases are believed to function in diverse physiological processes including disease resistance and wound response, but predicted low substrate specificities and the presence of 70 or more isoforms have made it difficult to define a specific physiological function(s) for each gene. To select pathogen-responsive POX genes, we analyzed the expression profiles of 22 rice POX genes after infection with rice blast fungus. The expression of 10 POX genes among the 22 genes was induced after fungal inoculation in both compatible and incompatible hosts. Seven of the 10 POX genes were expressed at higher levels in the incompatible host than in the compatible host 6-24 h after inoculation by which time no fungus-induced lesions have appeared. Organ-specific expression and stress-induced expression by wounding and treatment with probenazole, an agrichemical against blast fungus, jasmonic acid, salicylic acid and 1-aminocyclopropane-1-carboxylate, a precursor of ethylene, indicated that rice POXs have individual characteristics and can be classified into several types. A comparison of the amino acid sequences of POXs showed that multiple isoforms with a high sequence similarity respond to stress in different or similar ways. Such redundant responses of POX genes may guarantee POX activities that are necessary for self-defense in plant tissues against environmental stresses including pathogen infection.


Distribution pattern of GPRC6A mRNA in mouse tissue by in situ hybridization.
To explore the distribution pattern of G protein-coupled receptor family C, group 6, subtype A (GPRC6A) mRNA in adult mice. The distribution of GPRC6A mRNA in paraffin embedded adult mouse tissues was determined by highly sensitive nonradioactive cRNA probe in situ hybridization (ISH). We compared ISH with and without addition of tyramide signal amplification (TSA). GPRC6A wild-type and littermate GPRC6A null mice tissue sections were investigated by ISH. TSA greatly increased the sensitivity of ISH to detect GPRC6A mRNA in wild type mouse tissues. There was no detection of GPRC6A mRNA in GPRC6A gene specific knockout tissue in paraffin embedded tissue section. The mRNA of GPRC6A was detectable in the digestive gland or accessory digestive gland including salivary gland and pancreas, as well as in the tissues including kidney, testis, brain, muscle, and fat. The mRNA distribution pattern of GPRC6A gene is compatible with the phenotype of GPRC6A knockout mice.


Characterization of a novel KRAS mutation identified in Noonan syndrome.
Noonan syndrome (NS) is the most common non-chromosomal syndrome seen in children and is characterized by short stature, dysmorphic facial features, chest deformity, a wide range of congenital heart defects and developmental delay of variable degree. Mutations in the Ras/mitogen-activated protein kinase (MAPK) signaling pathways cause about 70% of NS cases with a KRAS mutation present in about 2%. In a cohort of 65 clinically confirmed NS patients of Japanese origin, we screened for mutations in the RAS genes by direct sequencing. We found a novel mutation in KRAS with an amino acid substitution of asparagine to serine at codon 116 (N116S). We analyzed the biological activity of this mutant by ectopic expression of wild-type or mutant KRAS. NS-associated KRAS mutation resulted in Erk activation and active Ras-GTP levels, and exhibited mild cell proliferation. In addition, kras-targeted morpholino knocked-down zebrafish embryos caused heart and craniofacial malformations, while the expression of mutated kras resulted in maldevelopment of the heart. Our findings implicate that N116S change in KRAS is a hyperactive mutation which is a causative agent of NS through maldevelopment of the heart.


Comparison of conventional phototherapy and fiberoptic phototherapy in the very-low-body-weight infants.
Phototherapy is effectively employed for the treatment of neonatal hyperbilirubinemia, but it may influence the physiological hemodynamics of the infants, such as skin blood flow, insensible water loss and the redistribution of cardiac output. This is a retrospective chart review study involved totally 42 very low birth weight prematures(birth body weight less than 1500 gm, VLBW) who received conventional or fiberoptic phototherapy. Infants with congenital malformation, severe cardiorespiratory instability and the requirement of diuretics, inotropics or blood transfusion were excluded. The body weight loss, daily intake/output and bilirubin level during the initial four days of phototherapy were analyzed. The results showed the efficacy of both methods was the same, while the fiberoptic therapy group had significantly more urine output(p < 0.05), the body weight loss was not statistically significant. It is possible that the fiberoptic therapy group had less insensible water loss and less attenuation of the decrease of renal blood flow, this resulted in more urine output.