Tumor regression and modulation of gene expression via tumor-targeted tocotrienol niosomes.
To develop 6-O-palmitoyl-ascorbic acid-based niosomes targeted to transferrin receptor for intravenous administration of tocotrienols (T3) in breast cancer. Niosomes were prepared using film hydration and ultrasonication methods. Transferrin was coupled to the surface of niosomes via chemical linker. Nanovesicles were characterized for size, zeta potential, morphology, stability and biological efficacy. When evaluated in MDA-MB-231 cells, entrapment of T3 in niosomes caused 1.5-fold reduction in IC50 value compared with nonformulated T3. In vivo, the average tumor volume of mice treated with tumor-targeted niosomes was 12-fold lower than that of untreated group, accompanied by marked downregulation of three genes involved in metastasis. Findings suggested that tumor-targeted niosomes served as promising delivery system for T3 in cancer therapy.


Identification of melatonin in Trichoderma spp. and detection of melatonin content under controlled-stress growth conditions from T. asperellum.
T. koningii, T. harzianum, T. asperellum, T. longibrachiatum, and T. viride were analyzed using liquid chromatography-tandem mass spectrometry to determine whether melatonin is present. Results showed that there were abundant amounts of endogenous melatonin in five Trichoderma species, but no melatonin was found in any of the culture filtrates. T. asperellum had the highest amount of melatonin (27.588 ± 0.326 μg g(-1) dry mass), followed by T. koningii, T. harzianum, T. longibrachiatum, and T. viride. The endogenous melatonin content of T. asperellum in controlled-stress growth conditions was also detected. The data showed that chemical stressors (CdCl2 , CuSO4 , and H2 O2 ) provoked an increase in endogenous melatonin levels. CdCl2 had the highest stimulatory effect on melatonin production, as the product reached reaching up to three times the melatonin content of the control. NaCl stimulated a decrease of melatonin. Acidic conditions (pH 3 and pH 5) as well as slightly alkaline conditions (pH 9) resulted in an increase in the melatonin content, whereas pH11 resulted in a significant decrease in the melatonin content, only 12.276 ± 0.205 μg g(-1) dry mass. The current study is first to report melatonin content and the change of melatonin content under different stress situations in Trichoderma spp.


Diagnosis of suspected intracranial metastases. Role of direct tissue examination.
Accurate histologic diagnosis is often critical to the appropriate choice of treatment of patients suspected of harboring brain metastases. In most cases, frame based stereotactic biopsy can provide an accurate histologic diagnosis with minimal risk of morbidity. In addition, newer modalities allow for efficient coupling of stereotactic biopsy with treatment in a single session. These include frameless stereotactic systems that facilitate the combination of open biopsy and resection as well as biopsy procedures that are combined with focal interstitial or external beam irradiation. These techniques provide increasingly convenient and effective means of achieving both diagnosis and treatment of cerebral metastases.


Transparent surfaces defined by implicit X junctions.
An X junction is known to be a strong cue for transparency whereas a T junction typically indicates occlusion by an opaque surface. In this article, however, we will demonstrate two cases in which special T junctions (implicit X) can support the perception of a transparent surface. The T junction is perceived as having an additional illusory contour rendering it as an implicit X junction. There is physically realizable condition in which transparency can produce a T junction and the existence of this special case may explain why T junctions are not necessarily taken as cues for opaque surface. The similar processing for X junctions and implicit Xs to form transparent surfaces is suggested.


Pre-operative synovial hyperaemia in haemophilia patients undergoing total knee replacement and the effects of genicular artery embolization: A retrospective cohort study.
Haemophilia is characterized by recurrent joint bleeding caused by a lack of clotting factor VIII or IX. Due to repeated joint bleeding, end-stage arthropathy occurs in relatively young patients. A total knee replacement (TKR) can be a solution. However, TKR may be complicated by perioperative and postoperative bleeds despite clotting factor therapy. The aim of this study was to evaluate the prevalence of pre-operative synovial hyperaemia and the effects of Genicular Artery Embolization on synovial hyperaemia and 3-month postoperative joint bleeding. In this retrospective cohort study, all patients with haemophilia who underwent periarticular catheter angiography between 2009 and 2020 were evaluated after written informed consent. Synovial hyperaemia on angiography was scored by an interventional radiologist. Thirty-three angiography procedures in 24 patients were evaluated. Median age was 54.4 years (IQR 48.4-65.9). Preoperative synovial hyperaemia was observed in 21/33 joints (64%). Moderate and severe synovial hyperaemia was observed in 10/33 joints (30%). Synovial hyperaemia decreased in 13/15 (87%) joints after embolization. Three-month postoperative joint bleeding occurred in 5/32 joints: in 2/18 joints (11%) without synovial hyperaemia and in 3/14 joints (21%) with mild synovial hypertrophy. Non-embolized and embolized joints did not differ regarding 3-month postoperative bleeding (P = .425). No complications were observed after embolization. One-third of patients with haemophilia requiring a TKR had moderate or severe synovial hyperaemia which can be reduced safely by Genicular Artery Embolization prior to TKR. Three-month postoperative bleeding appears to occur independently of the presence of residual mild synovial hyperaemia.


Prenatal exposure to ethanol alters the postnatal development and transformation of radial glia to astrocytes in the cortex.
Postmitotic neurons migrate from a zone(s) near the ventricles to the neocortex. During this migration, neurons associate with radial glia. After serving their role as guides for neuronal migration, the radial glia transform into astrocytes. Prenatal exposure to ethanol causes abnormal neuronal migration. We examined the effects of gestational exposure to ethanol on radial glia and astrocytes. Radial glia were stained immunohistochemically with the antibody RAT-401, and astrocytes were labeled with an antibody directed against glial fibrillary acidic protein (GFAP). The subjects were the offspring of rats fed an ethanol-containing liquid diet (Et), pair-fed a liquid control diet (Ct), or fed chow and water (Ch). During the first postnatal week, radial glial fibers (in Et-treated rats and controls) stretched from the ventricular surface through the developing cerebral wall to the pial surface. In the Et-treated rats, the radial processes were less dense and more poorly fasciculated than they were in the Ch- and Ct-treated rats. Moreover, by postnatal day (P) 5, there was a significant reduction in RAT-401 immunostaining in the Et-treated rats, particularly in the superficial cortex. A similar reduction in control rats did not begin until P10. In all three treatment groups, GFAP-immunoreactive astrocytes were in the cortex throughout the period from P1 to P45. In neonates, GFAP-positive cells were distributed in the marginal zone (layer I) and the intermediate zone (the white matter). The number of GFAP-positive cells in the cortical plate increased steadily with time so that, by P26, GFAP-immunoreactive astrocytes were distributed evenly through all cortical laminae. Interestingly, between P5 and P12, the number of astrocytes was significantly greater in Et-treated rats than in controls. Thus prenatal exposure to ethanol induces the premature loss of RAT-401-positive processes and the precocious increase in GFAP immunostaining. These ethanol-induced changes in glial development indicate that ethanol accelerates the transformation of radial glia into astrocytes. Moreover, the ethanol-induced premature degradation of the network of radial glial fibers may underlie the migration of late-generated neurons to ectopic sites.


Regioselective synthesis of 3-alkylindoles mediated by zinc triflate.
Zinc triflate was found to be an effective reagent for the C3-alkylation of indoles by alkyl halides in the presence of Hünig's base and tetrabutylammonium iodide. This new method for indole alkylation proceeds by a S(N)1-like pathway, and is general for allylic, benzylic, and tertiary halides.


Phage bacteriolysis, protistan bacterivory potential, and bacterial production in a freshwater reservoir: coupling with temperature.
Phage abundance and infection of bacterioplankton were studied from March to November 2003 in the Sep Reservoir (Massif Central, France), together with temperature, chlorophyll, bacteria (abundance and production), and heterotrophic nanoflagellates (abundance and potential bacterivory). Virus abundance (VA) ranged from 0.6 to 13 x 10(10) viruses l(-1), exceeding bacterial abundance (BA) approximately sixfold on average. In terms of carbon, viruses corresponded to up to 25% of bacterial biomass. A multiple regression model indicated that BA was the best predictor for VA (R(2) = 0.75). The frequency of infected bacteria (estimated from the percentage of visibly infected cells) varied from 1% to 32% and was best explained by a combination of temperature (R(2) = 0.20) and bacterial production (R(2) = 0.25). Viruses and flagellates contributed about equally to bacterial mortality. Both factors destroyed 55% of bacterial production, with a shift from phage bacteriolysis in early spring to protistan bacterivory in late summer. The vertical differences in most of the biological variables were not significant, contrasting with the seasonal differences (i.e., spring vs. summer-autumn). All biological variables under study were indeed significantly coupled to temperature. We regarded this to be the consequence of the enhanced discharge of the reservoir in 2003 (compared to previous years). This substantially weakened the stability and the thermal inertia of the water column, thereby establishing temperature as a stronger forcing factor in setting the conditions for optimal metabolic activity of microbial communities.


Proteases of the nematode Caenorhabditis elegans.
Crude homogenates of the soil nematode Caenorhabditis elegans exhibit strong proteolytic activity at acid pH. Several kinds of enzyme account for much of this activity: cathepsin D, a carboxyl protease which is inhibited by pepstatin and optimally active toward hemoglobin at pH 3; at least two isoelectrically distinct thiol proteases (cathepsins Ce1 and Ce2) which are inhibited by leupeptin and optimally active toward Z-Phe-Arg-7-amino-4-methylcoumarin amide at pH 5; and a thiol-independent leupeptin-insensitive protease (cathepsin Ce3) with optimal activity toward casein at pH 5.5. Cathepsin D is quantitatively most significant for digestion of macromolecular substrates in vitro, since proteolysis is inhibited greater than 95% by pepstatin. Cathepsin D and the leupeptin-sensitive proteases act synergistically, but the relative contribution of the leupeptin-sensitive proteases depends upon the protein substrate.


In silico mining and characterization of bifidobacterial lipoprotein with CHAP domain secreted in an aggregated form.
Bifidobacterium breve C50 secretes a lipoprotein associated with glucose, acting in an aggregating form (>600kDa) as an agonist of TLR2/6. Similar lipoproteins were sought for in bifidobacteria. In silico, the closest homology was shown with a Bifidobacterium longum protein containing CHAP and lipobox domains. Two strains secreted aggregates whose peptides sequences aligned with the mined protein. C16:0 and C18:0 fatty acids detected in the aggregates further supported a lipoprotein structure. Glucose and mannose detected by gas chromatography were likely ligands of the lipoprotein. The binding of aggregates to galectin-1 indicated that hexosamines and galactose surrounded them. However, unlike B. breve C50, aggregate secreted by B. longum CBi0703 was unable to bind TLR2/6 likely because of a more hydrophobic structure. In gnotobiotic mice, the intake of B. longum aggregate induced, in splenic dendritic cells, the expression of genes involved in antigen presentation. A positive correlation between the number of dendritic cells and CD4(+)CD25(+) cells was observed in mice receiving these aggregates. In conclusion, B. longum secretes a lipoprotein forming aggregates which may influence dendritic and CD4(+)CD25(+) cell interactions independently of the TLR2/6 pathway.


Left ventricular pseudoaneurysm and rupture after limited myocardial infarction.
A 50-year-old man had a large lateral left ventricular wall pseudoaneurysm with rupture after a limited myocardial infarction. This was diagnosed by the combination of flow in and out of the aneurysm and pulsatile flow in the pericardial cavity using color flow and continuous wave Doppler ultrasound. This report describes the case management, the use of echocardiography in this setting, and the implications of pseudoaneurysm formation.


Qualitative changes in carboxylesterase-2 phenotypes of tetraploid loaches (Misgurnus fossilis L.).
We have shown in our previous work that in the tetraploid loach Misgurnus fossilis carboxylesterase-2 (E-2) phenotypes of embryos and early larvae are controlled by the alleles of the Est-2 locus. In the present work it has been established that the somatic tissues of many adult fish homozygous for one of the Est-2 alleles, unlike the tissues of embryos and larvae, reveal an additional fraction of E-2 with electrophoretic mobility corresponding to that of the second allozyme. The activity of this additional fraction of E-2 varies with the tissue and depends on the age of fish and maintenance conditions. Phenotypes of the same individual homozygous for one of the Est-2 alleles can be manifested as homozygous or heterozygous according to the activity of the additional E-2 fraction. The results obtained are consistent with the assumption that in the tetraploid species Misgurnus fossilis there are two E-2 loci with common alleles of identical electrophoretic mobility.


A critical review of advances in reproductive toxicity of common nanomaterials to Caenorhabditis elegans and influencing factors.
In recent decades, nanotechnology has rapidly developed. Therefore, there is growing concern about the potential environmental risks of nanoparticles (NPs). Caenorhabditis elegans (C. elegans) has been used as a powerful tool for studying the potential ecotoxicological impacts of nanomaterials from the whole animal level to single cell level, especially in the area of reproduction. In this review, we discuss the reproductive toxicity of common nanomaterials in C. elegans, such as metal-based nanomaterial (silver nanoparticles (NPs), gold NPs, zinc oxide NPs, copper oxide NPs), carbon-based nanomaterial (graphene oxide, multi-walled carbon nanotubes, fullerene nanoparticles), polymeric NPs, silica NPs, quantum dots, and the potential mechanisms involved. This insights into the toxic effects of existing nanomaterials on the human reproductive system. In addition, we summarize how the physicochemical properties (e.g., size, charge, surface modification, shape) of nanomaterials influence their reproductive toxicity. Overall, using C. elegans as a platform to develop rapid detection techniques and prediction methods for nanomaterial reproductive toxicity is expected to reduce the gap between biosafety evaluation of nanomaterials and their application.


Relationship of bovine herpesvirus 1 immediate-early, early, and late gene expression to host cellular gene transcription.
Bovine herpesvirus 1 (BHV-1) gene expression was examined by RNA blot hybridization using clones representing immediate-early, early, and late genes. An immediate-early protein gene probe hybridized with two transcripts, 3.4 and 5.8 kb, expressed by infected cells in the presence of cycloheximide (CH). During infection of cells without metabolic inhibitors these transcripts were detected as early as 2 hr postinfection (p.i.) and accumulated to 8 hr p.i. The early gene probe, thymidine kinase, hybridized with a 4.3-kb RNA that was detected in the presence of phosphonoacetic acid (PAA), but not in the presence of CH. The late gene probe, glycoprotein III, (gIII) hybridized with a 1.6-kb transcript that was not expressed by infected cells treated with CH and only in very reduced amounts by infected cells treated with PAA. The gIII RNA was not detected until 4 hr p.i. in total cell RNA. Transcripts for the bovine actin and beta-galactosyltransferase genes did not decrease in BHV-1-infected cells until 6 hr p.i., coincident with the increase of BHV-1 DNA and RNA synthesis. Consequently, shutoff of host cell transcription by BHV-1 may be different than what has been described for herpes simplex virus.


Differential effects of ocular BDNF-injections onto the development of tectal cells characterized by calcium-binding proteins in pigeons.
The optic tectum of vertebrates bears a set of visual neurons which can be differentiated by the expression of distinct calcium-binding proteins (CaBPs). Using immunohistochemistry, we mapped the distribution of the CaBPs calbindin (CB) and parvalbumin (PV) in the pigeon's optic tectum and examined if their differentiation is affected by retinal brain-derived neurotrophic factor (BDNF)-injections. CB-immunoreactive (ir) and PV-ir cells displayed a lamination pattern which differed from other birds. While PV-ir cells were present in several retinorecipient tectal laminae, CB-ir cells were confined to layer 3 and 5 and - as a specialization of pigeons - were also detected in a subpopulation of layer 13 neurons. Comparison of saline- and BDNF-injected animals revealed that this general expression pattern was not affected by ocular BDNF-injections. In contrast, the size of tectal cells was differentially modulated. While CB-ir cells in layers 3 and 13 were unaffected by retinal BDNF, cells in layer 5 developed enlarged cell bodies. The PV-ir cells displayed smaller soma sizes within both tectal hemispheres suggesting also an indirect effect of retinal BDNF. These data indicate a differential sensitivity of tectal cell types to retinal BDNF, which might be one mechanism by which retinal input modulates tectal circuitries.


Modern aridity in the Altai-Sayan mountain range derived from multiple millennial proxies.
Temperature and precipitation changes are crucial for larch trees growing at high-elevation sites covered by permafrost in the Altai-Sayan mountain range (ASMR). To contextualize the amplitude of recent climate fluctuations, we have to look into the past by analyzing millennial paleoclimatic archives recording both temperature and precipitation. We developed annually resolved 1500-year tree-ring cellulose chronologies (δ13Ccell, δ18Ocell), and used these new records to reconstruct the variability in local summer precipitation and air temperature. We combined our new local reconstructions with existing paleoclimatic archives available for the Altai. The data show a strong decreasing trend by ca. 49% in regional summer precipitation, along with a regional summer temperature increase towards the twenty-first century, relative to the preceding 1500 years. Modern dry conditions (1966-2016 CE) in the ASMR are the result of simultaneous summer warming and decreased precipitation. Our new reconstructions also demonstrate that climate change in the ASMR is much stronger compared to the global average.


Herpes Zoster Presentation, Management, and Prevention: A Modern Case-Based Review.
Herpes zoster (HZ) is a common cutaneous entity with protean clinical presentations, management options, complication rates, and prevention strategies, all of which are rife with dogma. During an inpatient consultation for HZ, have you ever been approached by a frantic staff or family member, worried that a pregnant, elderly, or infant contact will be 'infected' if they get too close? Have your patients ever asked you about their risk of having HZ twice, or claimed that they have frequent 'recurrences'? In what timeline should antiviral therapy be employed? Is there evidence for prednisone or gabapentin in acute HZ treatment? Who should be vaccinated against HZ and what are the benefits and risks? In case-based form, these and other complex but common scenarios will be examined using clinical and viral mechanistic clues, along with updated treatment and prevention guidelines, to provide a modern HZ case management compendium, comprehensive of the diverse age and health populations now presenting with this condition.


Red Wine, but not port wine, protects rat hippocampal dentate gyrus against ethanol-induced neuronal damage--relevance of the sugar content.
Chronic ethanol consumption leads to oxidative damage in the central nervous system inducing neuronal degeneration and impairment of brain functions. Nevertheless, it has been reported that grape polyphenols might prevent the alluded ethanol effects. We have reported that prolonged red wine intake improves hippocampal formation oxidative status, a finding not replicated using Port wine. Thus, we thought of interest to compare the effects of chronic ingestion of these wines in the morphology of dentate gyrus (DG) neurons that are particularly vulnerable to alcohol effects. Six-month-old Wistar rats were fed either with red wine or Port wine (both with 20% ethanol content, v/v), and the results were compared with 20% (v/v) ethanol-treated, ethanol/glucose and pair-fed control groups. After 6 months of treatment, the layer volumes of the DG and the total number of granule and hilar neurons were estimated. The dendritic trees of granule cells were also studied in Golgi-impregnated material. The number of granule cells and the DG layer volumes were similar among all groups. However, the number of hilar neurons was reduced in Port wine, ethanol-treated and ethanol/glucose animals. Furthermore, the granule cells from these groups showed a decrease in the total dendritic length. Although the Port wine and red wine have similar amounts of flavanols with identical ability to protect against oxidative stress, the differences observed are probably related to the very dissimilar processes of wine production, leading in Port wine to a high content of sugars, which are known to have potent pro-oxidant effects.


Old-age lifestyles: Patterns of participation in leisure activities and their associations with different forms of capital.
As an important dimension of lifestyle, participation in leisure activities can enhance people's quality of life. Thus, pursuing an engaged lifestyle has become an assumed requirement of ageing successfully. People's opportunities to pursue an engaged lifestyle are influenced by their social positions, which are defined by their access to economic, cultural, and social capital. However, lifestyles in very old age and the significance of these forms of capital have not been sufficiently investigated. Against this background, we examined the questions of what lifestyles people pursue in very old age, and how these lifestyles are associated with their access to different forms of capital. Representative data from the NRW80+ study in North Rhine-Westphalia, Germany, were used. The sample comprised 1863 respondents aged 80 and older, and was carried out in 2017. First, the respondents' patterns of participation in leisure activities, which were used to measure their lifestyles, were identified by applying latent class analysis. Second, the associations between lifestyles and indicators of economic, cultural, and social capital were analysed separately for community- and institutional-dwelling very old adults using logistic regression. Three patterns of leisure activity participation were identified: a digital (16.5%), a sociable (41.0%), and a withdrawn (42.4%) lifestyle. For community-dwelling very old adults with low or medium education and those with low occupational prestige in their last job, the odds of having a withdrawn lifestyle were increased. For both community- and institutional-dwelling individuals, larger social networks were associated with decreased odds of pursuing a withdrawn lifestyle. We conclude that the different forms of capital continue to be related to the lifestyle opportunities of very old adults, but lose their importance for institutional-dwelling individuals. A life course perspective on social inequalities in lifestyle is therefore needed.


Detection of Chlamydia trachomatis deoxyribonucleic acid in women with tubal infertility.
To determine the presence of Chlamydia trachomatis by in situ hybridization in fallopian tube tissues of women with distal tubal occlusion. Subjects were selected from a Seattle-based study of infertility in women with distally occluded fallopian tubes undergoing reconstructive surgery. For comparison, six specimens were obtained from women undergoing surgery for noninfertility-related conditions who had normal appearing tubes. Tissue specimens from 16 of these patients were selected for analysis by in situ hybridization and immunoperoxidase (IP) staining. C. trachomatis was detected in 9 of 16 women by either in situ hybridization or IP. Six of the nine were seropositive with titers ranging from 1:16 to 1:64. Tissue from 6 women with normal appearing fallopian tubes were negative by in situ hybridization. The demonstration of C. trachomatis deoxyribonucleic acid and/or antigens in fallopian tube tissue from infertile women with distal tubal disease suggests that C. trachomatis can persist in these tissues in an uncultivable state.


Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia.
Camptocormia is known as "bent spine syndrome" and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. The relationship between the DBS and camptocormia is discussed in this unique condition.


Flow microcalorimetry as a tool for an improved analysis of antibiotic activity: the different stages of chloramphenicol action.
Flow microcalorimetry in combination with photometric mass determination of staphylococci in suspension was used to reveal alterations in the intensity, extent and efficiency of bacterial metabolism during inhibition of protein synthesis by chloramphenicol. It could be demonstrated that these three parameters of metabolic activity were distinctly affected by this drug, and that the method described promises to be a more reliable tool for assaying the degree and the mode of bacteriostatic inhibition than the conventional determination of the minimum inhibitory concentration.


High tyrosine kinase activity in normal nonproliferating cells.
Protein phosphorylation at serine and threonine residues has been implicated in the regulation of many cellular processes. More recently, tyrosine residue phosphorylation has been shown to be associated with stimulation of cell proliferation, including viral transformation and stimulation by epidermal growth factors (EGF), platelet-derived growth factor (PDGF) and other compounds related to cellular growth such as insulin and dimethyl sulphoxide. To compare protein kinases and phosphoproteins of normal and leukaemic human haematopoietic cells in vivo and in vitro, we first have investigated the percentages of phosphoserine, phosphothreonine and phosphotyrosine obtained after hydrolysis of proteins from different blood cell fractions phosphorylated in vitro. We report here that phosphotyrosine formed less than 1% of the soluble fractions from polymorphonuclear cells, mononuclear cells (80% circulating lymphocytes, 20% monocytes), blood platelets and red blood cells (not shown). Surprisingly, high percentages of phosphorylated tyrosine were found only in the particulate fractions from non-proliferating anuclear cells, platelets and red blood cells.


Diagnostic Value of Pepsin Measurements in Dysphonia Attributed to Laryngopharyngeal Reflux Disease.
To investigate the diagnostic value of pepsin test in detecting laryngopharyngeal reflux (LPR) in patients with suspected LPR-induced dysphonia. Dysphonic and non-dysphonic patients with LPR at the 24-hour hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) were recruited from January 2019 to November 2022. Patients collected saliva/sputum samples to measure pepsin concentrations. Symptoms and findings were studied through reflux symptom score (RSS) and reflux sign assessment (RSA). Voice quality was assessed with maximum phonation time, GRBAS, voice handicap index (VHI), and acoustic parameters at baseline and 3-month post-treatment. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin tests for dysphonia-related to LPR were calculated at ≥16 ng/mL cutoff. The relationship between HEMII-pH, clinical features, voice quality outcomes, and pepsin measurement was investigated. Sixty-seven patients with LPR at the HEMII-pH completed the evaluations accounting for 30 patients consulting for dysphonia. Dysphonic patients reported higher RSS than non-dysphonic patients. RSS, RSA, laryngeal findings, VHI, and grade of dysphonia significantly improved from baseline to 3-month posttreatment. Pepsin test detected LPR in 73% of dysphonic cases. The pepsin test was 73.3 sensitive and 18.9 specific when considering the highest pepsin level of morning, postlunch, and postdinner sputum collections. Sensitivity, specificity, PPV, and NPV varied regarding the time of sputum collections. There was a strong significant association between the concentration of the morning pepsin test and the severity of laryngeal RSA score (P = 0.018). The morning pepsin saliva test concentration was predictive of the 3-month otolaryngological RSS (P = 0.014). Pepsin test is a sensitive but poorly specific diagnostic approach for patients with dysphonia attributed to LPR. Multiple pepsin measurements may increase the sensitivity and predictive value of pepsin test. Future large-cohort studies are needed to investigate the accuracy of pepsin test in this population.


Adolescent immunization rates and the effect of socio-demographic factors on immunization in a cosmopolitan city (ERZURUM) in the eastern Turkey.
Pediatric vaccinations have decreased the incidence and mortality from infectious diseases in children, but adolescents continue to be adversely affected by vaccine preventable disease. The present study was performed to determine the status of adolescents immunization and to investigate the effect of several socio-demographic factors on immunization. Using the cluster-sampling method, 817 adolescents were selected in 24 high schools (15,000 students) in central district of Erzurum (Turkey). Adolescents were categorized as completely vaccinated, incompletely vaccinated, unvaccinated or vaccination status unknown. Of the 817 adolescents, 6.9% were completely vaccinated, 24.4% were incompletely vaccinated and 64.1% were unvaccinated. The vaccination status of 4.6% of adolescents was unknown. A significantly correlation was seen between the number of siblings, the level of mother and father education, the level of parent's socio-economics status, health insurance and immunization status. Our findings indicated a small percentage of adolescents receive all of the recommended vaccine. In immunization programs in Turkey, priority should be given to increase adolescent immunization rate with a middle school and/or adolescents, vaccination.


Perineural invasion and perineural spread in periocular squamous cell carcinoma.
Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) of the periocular region is a prognostic marker of adverse tumour outcomes. PNI carries a well-established risk of tumour recurrence, regional metastasis and higher likelihood of mortality. This review will explore and stratify the risks conferred by histological PNI parameters. The radiological features of perineural spread (PNS) and the imaging sequences that delineate these findings will also be highlighted. Surgical excision with en face margin control is the preferred technique for achieving histological clearance. Adjuvant radiotherapy improves treatment outcomes in the setting of concomitant high-risk features. For locally advanced or metastatic cutaneous SCC, immunotherapy represents a novel treatment alternative. This review will provide an algorithm for the diagnosis and management of periocular SCC with PNI and PNS.


Exploring the temporal dimension in cancer patients' experiences of nonbiomedical therapeutics.
To date, research on complementary and alternative medicine (CAM) use by cancer patients has tended to provide a "snapshot" of experience, with little attention given to the evolution of experience over time. Drawing on data from solicited diaries, this article examines individual cancer patients' temporal experiences of CAM. Our findings suggest that experiences of CAM are variable over time and space, and furthermore, that the everyday act of "doing CAM" is considerably more problematic than is often reported in face-to-face interview or survey studies. This is explored in relation to the tension between the perceived need for restrictive self-discipline alongside a sense of the emancipatory potential of CAM; the role of CAM therapists in reconceptualizing disease; and the complex interplay between CAM-derived notions of self-healing and acceptance of individual mortality. We argue that an emphasis on the temporality of cancer patients' CAM engagement is necessary to access a more nuanced understanding of the lived experiences of cancer patients.


Distribution and ontogeny of B cells in the garden lizard, Calotes versicolor.
Surface immunoglobulin bearing (sIg+) cells were identified in the lizard Calotes versicolor by immunofluorescence using a polyvalent antiserum to lizard immunoglobulins and class-specific antibodies to lizard IgM and IgY. 53.3 +/- 1.6% of spleen cells, 23.6 +/- 0.8% of peripheral blood mononuclear cells, 21.5 +/- 1.8% of bone marrow mononuclear cells and less than 1% of thymus cells were found to bear immunoglobulin (Ig) on their surface. A similar proportion of cells in each tissue was stained with rabbit anti-lizard mu (specific for IgM) whereas only a small proportion of cells were stained with rabbit anti-lizard (specific for IgY). Adult thymectomy significantly increased the proportion of sIgM+ cells in spleen and blood whereas high dose cyclophosphamide (300mg/kg body weight) decreased the proportion of sIgM+ cells thus suggesting that sIg+ cells in the lizard are of B cell lineage as in higher vertebrates. Ontogenetic studies indicate that embryonic liver is an organ enriched for sIgM+ cells at certain stages of development and thus suggest liver to be a site for differentiation of sIg+ cells in lizard embryos.


Prevalence and type distribution of high-risk human papillomavirus infections among women in Wufeng County, China.
The aim of this survey was to assess the prevalence and type distribution of oncogenic human papillomavirus (HPV) infections among women in Wufeng County of Hubei province, where the cervical cancer mortality rate is the highest in China Cervical. DNA samples were collected from 1,100 women, then screened and quantified by a multi-fluorescent, quantitative real-time PCR assay. The cervical DNA samples were then re-typed by real-time PCR using seven-pair primers of high-risk (HR) HPVs designed to detect types 16, 31, 18/45, 33, 52, 58, and 67. The overall prevalence of HR HPVs was 11.14 % (95 % CI, 9.74-13.72 %) in Wufeng County, which was not statistically different between Tu (12.17 %; 95 % CI, 10.03-12.34 %) and Han nationality (8.95 %; 95 % CI, 3.55-14.35 %). Among different types of HPV, HPV 16 was the most frequently detected genotype, followed by HPV 52, 58, 18/45, and 31. The most prevalent types of HR HPV in Tu nationality were HPV 16, 52, and 58, and the most prevalent types of HR HPV in Han nationality were HPV 16, 33, and 18/45. The overall prevalence of HPV was highest in the 20-24 year age group (21.43 %; 95 % CI, 17.56-25.30 %) and the prevalence of HR HPV was associated with education. HPV 16, 52, and 58 are common genotypes in Wufeng County, and support the hypothesis that second-generation HPV prophylactic vaccines, including HPV 52 and 58, may offer higher protection for women in China and other areas of Asia. The findings of this study contribute to preventive and screening measures in clinical practice.


[Comparative clinical study of efficacy of three multi-tufted short top toothbrushes with different bristle bed designs].
Three multi-tufted short-head toothbrushes were compared on 15 test persons, with respect to their efficiency in removing the plaque from margo gingivae and from the interdentium. With a different design of the bristle bed, all three brushes evidenced very little difference in the cleaning effect which, on the basis of the deliberately prescribed short cleaning time at the gingival margin, can be considered as good in respect of all teeth sections and as satisfactory in the approximal area. In individual cases, a slanted bristle bed can lead to better cleaning of the side teeth area.


Depletion of alloreactive donor T cells using immunomagnetic cell selection.
Donor T cells support both engraftment and immune reconstitution after allogeneic BMT. Moreover, they may exert potent anti-tumor effects (graft-versus-leukemia, GVL), which are used for adoptive immunotherapy. On the other hand, infusion of allogeneic T cells is frequently associated with the manifestation of immune reactions against healthy tissue, which may lead to life-threatening graft-versus-host disease (GVHD). To overcome this problem, we developed a new strategy for the exclusive depletion of alloreactive cells from donor leukocytes. We activated donor T cells by co-cultivation with a stroma layer of recipient cells and analyzed activation kinetics of CD3+, CD4+ and CD8+ T cells. Based on these data, activated cells were then depleted based on expression of activation-induced antigens using magnetic cell sorting (MACS). Alloreactivity of donor T cells was remarkably decreased after depletion of cells expressing either CD25 or CD69, as was shown in suitable in vitro assays. The lowest level of alloreactivity was found when both CD25- and CD69-positive cells were depleted. Importantly, depleted cell fractions preserved reactivity against third-party cells. In summary, we found that MACS-based ex vivo depletion of alloreactive cells may be a suitable way to prevent GVHD and therefore improve allogeneic BMT and adoptive immunotherapy.


[24-hour fluctuations of the values of certain components of the saliva and dental plaque in school children].
24-hours changes were studied in the saliva and dental plaque of the concentrations of total fluorine, inorganic phosphate and protein, and of pH value. The study was carried out in two groups of school children: I--control, II--subjected to contact fluoridation. The obtained results showed that circadian changes occurred in controls and in children subjected to fluoridation.


Acute cerebral infarction of posterior circulation in a patient with vertebral artery fenestration deformity: A case report.
Cerebrovascular fenestration malformation is a rare congenital vascular variation. Cerebrovascular fenestration malformation rarely directly leads to cerebral infarction, and the mechanism of cerebral infarction is not clear. Cases of young patients with vertebral artery fenestration malformation who suffered from acute cerebral infarction of posterior circulation are rare and have not been reported widely. A 36-year-old male patient, who had been in good health and without a family history of stroke, was admitted to our hospital with a 6-h history of dizziness and unstable walking. Brain MR examination showed multiple irregular high signal lesions in the left thalamus, left occipital lobe and left cerebellum. Brain MR enhancement examination confirmed multiple cerebral infarction in left thalamus, left occipital lobe and left cerebellum. CT angiography of head and neck showed fenestration deformity of V2-V3 segment of left vertebral artery. Considering that the patient was suffering from acute cerebral infarction of posterior circulation, he was treated with antiplatelet, lipid-lowering and plaque stabilization, etc. After receiving our treatment, the patient's symptoms were relieved. At 3 and 6 months after discharge, there was no dizziness, unstable walking, no acute cerebral infarction, which meant that the patient recovered well. In the absence of traditional risk factors and other evidence of cryptogenic stroke, the cerebral infarction in the blood supply area of fenestration malformation should be considered to be related to fenestration malformation, but its pathogenesis is not clear. Antiplatelet therapy, lipid-lowering and plaque stabilization, etc. are effective in prevention of new infarction for such patients.


Rheological properties of wood/bacterial cellulose and chitin nano-hydrogels as a function of concentration and their nano-films properties.
In this study, rheological properties of the Wood Cellulose NanoFibers (WCNF), Bacterial Cellulose NanoFibers (BCNF), and Chitin NanoFibers (ChNF) as well as physical properties of films prepared from each nano-hydrogel were investigated. Each nano-hydrogel was prepared in 2 concentrations of 0.5 and 1 wt% for rheological study. Rheological properties were measured using a rotational rheometer. The flow behaviour data were fitted with rheological models. Apparent viscosity was higher in higher concentrations of nano-hydrogels. Herschel-Bulkley model was the best model for flow behaviour data fitting. BCNF nano-hydrogels had the highest hysteresis loop while WCNF nano-hydrogels had the best structure recovery and lowest hysteresis loop. At LVE (Linear Viscoelastic Region), G' (storage modulus) and G″ (loss modulus) had a constant value, but as strain increased their values decreased. Storage modulus was found to be greater than loss modulus in all samples during frequency sweep test. BCNF nano-hydrogel showed the lowest frequency dependency. Chitin nanofilms had the highest elongation and stress value.


Focal granulomatous (Crohn's) colitis: radiologic-pathologic correlation.
In patients with Crohn's disease, early or localized lesions of the colon, termed 'focal granulomatous colitis', may give rise to small and often relatively inconspicuous nodular or tumor-like contour defects in conventional barium enema studies. This radiologic sign, first illustrated by Ettinger [7], has received scant attention in the literature. The present communication is intended to re-emphasize the radiologic appearances of focal granulomatous (Crohn's) colitis in conventional barium enema examinations, provide pathologic correlation, and illustrate by selected case reports the clinical significance of recognizing this particular radiologic abnormality.


Breast cancer screening among Chamorro women in California.
This study evaluated breast cancer-related knowledge, attitudes and behaviors among Chamorros in San Diego, California and compared mammogram use between those affiliated with the military and others. A survey was administered to 110 self-reported Chamorro women. Inclusion criteria included being self-reported Chamorro woman >40 years with no history of breast cancer. Approximately equal proportions of participants with (52%) and without (48%) military affiliation were recruited to test the assumption that use of mammography differed between the two groups. Descriptive statistics and bivarate analyses were conducted. Of the 110 respondents, 42% had at least some college education, 41% had household incomes of at least $50,000, and 87% reported having health insurance. Approximately 93% reporting ever having a mammogram and 75% reported having it within the past 2 years. The difference between mammography use among women with and without military affiliation was not significant (85% versus 72%; p=0.11). However, women with military insurance (95%) were more likely than others (74%) to have had a mammogram within that time frame (p=.05). Other factors associated with higher mammography use included reporting better access to medical care (p=.03), receiving a recommendation for mammography from a health care provider (p=.002), and knowledge that cancer can be cured if detected early (p=.01) and that women should get a mammogram yearly (p=.01). Chamorro women in San Diego have relatively high rates of mammography use. This finding may be due, in part, to the relatively high rates of health insurance coverage (particularly military insurance) among these women.


A new plate-hanging method for biofilm quantification and its application to evaluate the role of surface hydrophobicity.
A novel procedure for the quantitative analysis of biofilm formation by bacteria and yeasts, the Plate-hanging method, was developed. In this system, various polymer disks were hung from the lid of a 6-well plate, immersed in a cell suspension, and moderately shaken (70 rpm). In order to verify the validity of the procedure, the effects of the solid surface hydrophobicity of the test disks and the cell surface hydrophobicities of microorganisms on biofilm formation were investigated. Biofilm formation of bacteria and yeasts on the solid surface strongly depended on hydrophobic interactions between the solid surface and the cell surface. A positive correlation between the hydrophobic properties of substratum and cell surfaces was observed. On the other hand, hydrophilic yeasts preferentially adsorbed onto relatively hydrophilic surfaces. Moreover, the plate-hanging method coupled with the periodic exchange of the liquid medium enabled the quantification of long-term biofilm growth.


Detection of IL-2 receptor gene expression in peripheral blood from renal transplant patients.
Cytokine monitoring is a potentially useful tool in the management of transplant patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy volunteers and patients who underwent laparotomy or renal transplantation. In the patients who underwent laparotomy, IL-1 and TNF expression was detected postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL-2 receptor gene expression was detected in all the renal transplant patients, including those with signs of rejection. No cytokine gene expression was detected preoperatively, pretransplant, or in the healthy volunteers. We were able to discriminate transplantation from laparotomy by the cytokine profile. These results indicate that our method may be a useful tool for the immunological monitoring of transplant patients.


Molecular pathogen detection in biosolids with a focus on quantitative PCR using propidium monoazide for viable cell enumeration.
Sewage sludge is the solid, organic material remaining after wastewater is treated and discharged from a wastewater treatment plant. Sludge is treated to stabilize the organic matter and reduce the amount of human pathogens. Once government regulations are met, including material quality standards (e.g., E. coli levels and heavy metal content) sludge is termed "biosolids", which may be disposed of by land application according to regulations. Live-culture techniques have traditionally been used to enumerate select pathogens and/or indicator organisms to demonstrate compliance with regulatory requirements. However, these methods may result in underestimates of viable microorganisms due to several problems, including their inability to detect viable but non-culturable (VBNC) cells. Real-time quantitative polymerase chain reaction (qPCR) is currently under investigation as a fast, sensitive, and specific molecular tool for enumeration of pathogens in biosolids. Its main limitation is that it amplifies all target DNAs, including that from non-viable cells. This can be overcome by coupling qPCR with propidium monoazide (PMA), a microbial membrane-impermeant dye that binds to extracellular DNA and DNA in dead or membrane-compromised cells, inhibiting its amplification. PMA has successfully been used to monitor the presence of viable pathogens in several different matrices. In this review the use of PMA-qPCR is discussed as a suitable approach for viable microbial enumeration in biosolids. Recommendations for optimization of the method are made, with a focus on DNA extraction, dilution of sample turbidity, reagent concentration, and light exposure time.


Optimization of the diameter of a radial irradiation device for photodynamic therapy in the esophagus.
Photodynamic therapy (PDT) is a local therapeutic technique based on the photosensitization of lesions using a dye prior to light-induced tissue destruction. PDT of intraepithelial neoplasia in Barrett's esophagus, or of early squamous-cell carcinoma of the esophagus, requires light application devices that allow homogeneous and well-defined illumination of the tissue surface. Such devices must be large enough to induce complete unfolding of the esophagus in spite of esophageal motility and elasticity. The aim of this study was therefore to determine the optimal diameter of a cylindrical illumination device for PDT in this organ. The study included nine patients (aged 49-72 years) who underwent panendoscopy. Flexible transparent hollow tubes with diameters ranging from 13 to 19 mm were successively introduced into the esophagus, and the esophageal wall was viewed from the inside through the tube using a flexible small-diameter endoscope. The number of folds was counted. Observations of the upper, middle, and lower thirds of the esophagus were recorded. The radial location of the folds was also recorded, and defined as follows: anterior wall (up), posterior wall (down), side walls (right, left). No significant difference in the number of folds between the lower and middle parts of the esophagus was noticed. However, the upper third had significantly fewer folds (about 30 %) than the other two parts. For diameters above 17 mm, this difference was less dramatic. The number of such folds was shown to decrease with the increasing diameter of the device. It appears that 18 mm or more is the optimal diameter for a fixed-geometry cylindrical photodynamic therapy irradiating device for the patient category considered in this study. It was also observed that most folds were located on the side walls of the esophagus.


A survey of television meteorologists about their sources for and understanding of pollen counts.
Pollen counts are widely used by television stations in news programming but little is known about the sources for and quality of this information. The purpose of this investigation was to survey television meteorologists about their sources for pollen counts and to assess their general understanding of these data. Sixty-seven meteorologists employed by television stations in the nation's 20 largest Designated Market Areas (DMAs) were contacted by telephone. A brief survey was administered verbally and their responses were recorded. Thirty-seven meteorologists indicated that their station used pollen counts in news programming. Most were aware of their station's source for this information and reported that viewers contacted them about the pollen count. Few meteorologists, however, knew the type of instrument that was used to obtain pollen samples they aired and only 10 selected the correct definition of a pollen count from a list of three choices. Pollen counts are an important element in television news programming that are poorly understood by the meteorologists who present them to the public. Allergists are encouraged to better educate the personnel at stations to which they supply pollen counts.


Liver cell adenoma associated with oral contraceptive hormone therapy.
A patient receiving oral contraceptive hormone therapy developed a hepatic adenoma. Widespread haemorrhages, which were apparently unrelated to trauma, developed in the adenoma. Attention is drawn to the increasing incidence of Pill-associated hepatic tumours, and to the possibility of a fatal haemorrhage.


Interaction of antibodies with Entamoeba histolytica trophozoites from experimental amebic liver abscess: an immunocytochemical study.
Using immunocytochemical techniques, we studied the interaction of antibodies with Entamoeba histolytica trophozoites present during the development of amebic liver abscess. Hamsters were intrahepatically inoculated with HM1-IMSS axenic amebas and sacrificed at different days post-inoculation. IgG of rabbit anti-E. histolytica and IgG of rabbit anti-IgG of hamster were used, both labeled with peroxidase. With the rabbit anti-E. histolytica, all trophozoites present in hepatic lesions from 1-7 days post-inoculation were highly labeled. The IgG of rabbit anti-IgG of hamster intensively stained only those trophozoites present in lesions from 1-2 days post-inoculation. From day 3, the intensity and number of labeled trophozoites decreased progressively. The results suggest that the interaction between the amebas and the IgG of hamster is non-specific during the first 2 days. The absence of labeling in the chronic stages could be due to changes in the membrane antigens of the parasite or to alterations in the bloodstream around necrosis. Also, the anti-E. histolytica antibodies produced in the serum during the development of the hepatic disease are apparently incapable of reaching and interacting with the trophozoites present on the liver abscess. This can explain in part why antibodies do not have an important role in the defense of the host.


Biological and molecular characterization of ArkGA: A novel Arkansas serotype vaccine that is highly attenuated, efficacious, and protective against homologous challenge.
Almost all commercial poultry are vaccinated against avian coronavirus infectious bronchitis virus (IBV) using live attenuated vaccines mass administered by spray at day of hatch. Although many different types of IBV vaccines are used successfully, the ArkDPI serotype vaccine, when applied by spray, does not infect and replicate sufficiently to provide protection against homologous challenge. In this study, we examined a different Ark vaccine strain (Ark99), which is no longer used commercially due to its reactivity in one day old chicks, to determine if it could be further attenuated by passage in embryonated eggs but still provide adequate protection. Further attenuation of the Ark99 vaccine was achieved by passage in embryonated eggs but ArkGA P1, P20, and P40 (designated ArkGA after P1) were still too reactive to be suitable vaccine candidates. However, ArkGA P60 when given by spray had little or no vaccine reaction in one day old broiler chicks, and it induced protection from clinical signs and ciliostasis following homologous challenge. In addition, vaccinated and challenged birds had significantly less challenge virus, an important measure of protection, compared to non-vaccinated and challenged controls. The full-length genomes of viruses from egg passages 1, 20, 40, and 60 were sequenced using the Illumina platform and the data showed single nucleotide polymorphisms (SNPs) had accumulated in regions of the genome associated with viral replication, pathogenicity, and cell tropism. ArkGA P60 accumulated the most SNPs in key genes associated with pathogenicity (polyprotein gene 1ab) and cell tropism (spike gene), compared to previous passages, which likely resulted in its more attenuated phenotype. These results indicate that the ArkGA P60 vaccine is safe for spray vaccination of broiler chicks and induces suitable protection against challenge with pathogenic Ark-type virus.


Unusual coordination mode for 1,3-diphosphete ligands towards a Cr-Cr quintuple bond complex.
The reaction of LCr5̲CrL (L = N2C25H29, 1) with the phosphaalkynes R-C≡P (R = tBu, Me, Ad) yields the neutral dimerisation compounds [L2Cr2(μ,η1:η1:η2:η2-P2C2R2)] (R = tBu (2), Me (3)) and the tetrahedrane complex [L2Cr2(μ,η2:η2-PCAd)] (4). The 1,3-diphosphete ligands in complexes 2 and 3 are the first to possess this structural feature spanned over a metal-metal multiple bond, while the slightly bigger adamantyl phosphaalkyne remains a monomer in 4 with a side-on coordination mode.


Enhancement of tributyltin degradation under natural light by N-doped TiO2 photocatalyst.
Photo-degradation of tributyltin (TBT) has been enhanced by TiO(2) nanoparticles doped with nitrogen (N-doped TiO(2)). The N-doped catalyst was prepared by a sol-gel reaction of titanium (IV) tetraisopropoxide with 25% ammonia solution and calcined at various temperatures from 300 to 600°C. X-ray diffraction results showed that N-doped TiO(2) remained amorphous at 300°C. At 400°C the anatase phase occurred then transformed to the rutile phase at 600°C. The crystallite size calculated from Scherrer's equation was in the range of 16-51 nm which depended on the calcination temperature. N-doped TiO(2) calcined at 400°C which contained 0.054% nitrogen, demonstrated the highest photocatalytic degradation of TBT at 28% in 3h under natural light when compared with undoped TiO(2) and commercial photocatalyst, P25-TiO(2) which gave 14.8 and 18% conversion, respectively.


Oral contraceptives and cervical carcinoma.
In a case-control study, 689 consecutive patients with cervical carcinoma were studied for their use of oral contraceptives. The control patients were matched for age, ethnic origin, age at first pregnancy, age at first coitus, and socioeconomic status. There was no significant difference between case and control subjects in the duration or oral contraceptive use, the type of estrogen used, or the years in which oral contraceptives were used. The mean duration of oral contraceptive use was 30.9 months by the case subjects and 30.2 months by the control subjects.


Significance of white-coat hypertension in older persons with isolated systolic hypertension: a meta-analysis using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes population.
The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes database who had daytime ambulatory blood pressure (BP; ABP) and conventional BP (CBP) measurements. After excluding persons with diastolic hypertension by CBP (≥90 mm Hg) or by daytime ABP (≥85 mm Hg), a history of cardiovascular disease, and persons <18 years of age, the present analysis totaled 7295 persons, of whom 1593 had isolated systolic hypertension. During a median follow-up of 10.6 years, there was a total of 655 fatal and nonfatal cardiovascular events. The analyses were stratified by treatment status. In untreated subjects, those with white-coat hypertension (CBP ≥140/<90 mm Hg and ABP <135/<85 mm Hg) and subjects with normal BP (CBP <140/<90 mm Hg and ABP <135/<85 mm Hg) were at similar risk (adjusted hazard rate: 1.17 [95% CI: 0.87-1.57]; P=0.29). Furthermore, in treated subjects with isolated systolic hypertension, the cardiovascular risk was similar in elevated conventional and normal daytime systolic BP as compared with those with normal conventional and normal daytime BPs (adjusted hazard rate: 1.10 [95% CI: 0.79-1.53]; P=0.57). However, both treated isolated systolic hypertension subjects with white-coat hypertension (adjusted hazard rate: 2.00; [95% CI: 1.43-2.79]; P<0.0001) and treated subjects with normal BP (adjusted hazard rate: 1.98 [95% CI: 1.49-2.62]; P<0.0001) were at higher risk as compared with untreated normotensive subjects. In conclusion, subjects with sustained hypertension who have their ABP normalized on antihypertensive therapy but with residual white-coat effect by CBP measurement have an entity that we have termed, "treated normalized hypertension." Therefore, one should be cautious in applying the term "white-coat hypertension" to persons receiving antihypertensive treatment.


On the relationship of arousal and attentional distraction by emotional novel sounds.
Unexpected and task-irrelevant sounds can impair performance in a task. It has been shown that highly arousing emotional distractor sounds impaired performance less compared to moderately arousing neutral distractor sounds. The present study tests whether these differential emotion-related distraction effects are directly related to an enhancement of arousal evoked by processing of emotional distractor sounds. We disentangled costs of orienting of attention and benefits of increased arousal levels during the presentation of highly arousing emotional and moderately arousing neutral novel sounds that were embedded in a sequence of repeated standard sounds. We used sound-related pupil dilation responses as a marker of arousal and RTs as a marker of distraction in a visual categorization task in 57 healthy young adults. Multilevel analyses revealed increased RT and increased pupil dilation in response to novel vs. standard sounds. Emotional novel sounds reduced distraction effects on the behavioral level and increased pupil dilation responses compared to neutral novel sounds. Bayes Factors revealed strong evidence against an inverse proportional relationship between behavioral distraction effects and sound-related pupil dilation responses for emotional sounds. Given that the activity of the locus coeruleus has been linked to both changes in pupil diameter and arousal, it may embody an indirect relationship as a common antecedent by the release of norepinephrine into brain networks involved in attention control and control of the pupil. The present study provides new insights into the relation of changes in arousal and attentional distraction during the processing of emotional task-irrelevant novel sounds.


Respiratory carbon fluxes in leaves.
Leaf respiration is a major metabolic process that drives energy production and growth. Earlier works in this field were focused on the measurement of respiration rates in relation to carbohydrate content, photosynthesis, enzymatic activities or nitrogen content. Recently, several studies have shed light on the mechanisms describing the regulation of respiration in the light and in the dark and on associated metabolic flux patterns. This review will highlight advances made into characterizing respiratory fluxes and provide a discussion of metabolic respiration dynamics in relation to important biological functions.


UV-vis absorption spectroscopy and multivariate analysis as a method to discriminate tequila.
Based on the UV-vis absorption spectra of commercially bottled tequilas, and with the aid of multivariate analysis, it is proved that different brands of white tequila can be identified from such spectra, and that 100% agave and mixed tequilas can be discriminated as well. Our study was done with 60 tequilas, 58 of them purchased at liquor stores in various Mexican cities, and two directly acquired from a distillery. All the tequilas were of the "white" type, that is, no aged spirits were considered. For the purposes of discrimination and quality control of tequilas, the spectroscopic method that we present here offers an attractive alternative to the traditional methods, like gas chromatography, which is expensive and time-consuming.


Effect of metformin on adiponectin in PCOS: A meta-analysis and a systematic review.
Conflicting results have been reported regarding the effect of metformin on adiponectin levels in women with polycystic ovary syndrome (PCOS). This meta-analysis reviewed all studies comparing adiponectin levels before and after metformin treatment in PCOS women. Additionally, changes in other indicators, including long-term complications associated with PCOS, such as inflammatory, metabolism factors and hormonal profile, were investigated following metformin treatment. We conducted subgroup analysis based on body mass index (BMI) stratification and appropriate pooling. We searched literature in PUBMED, EMBASE, the Cochrane Library, and CNKI databases. The main meta-analysis included 11 studies containing data on 353 subjects. Metformin treatment was associated with significantly increased serum adiponectin concentrations [10 studies, random-effects SMD (95% CI) -0.58 [-1.03, -0.13]; I2 = 86%; P = 0.01]. Additionally, the meta-analysis revealed that circulating tumor necrosis factor-α(TNF-α) and C-reactive protein (CRP) concentrations were significantly decreased after metformin treatment, with corresponding SMDs of 1.01 (95% CI: 0.74-1.28, P<0.00001) and 0.48(95% CI: 0.35-0.60, P<0.00001). Following metformin administration, serum adiponectin concentrations of PCOS women were found to be significantly increased, accompanied by a significant improvement in other indicators. Further investigation with a larger sample size should be conducted to validate optimal dose and duration of metformin.


A machine learning model for distinguishing Kawasaki disease from sepsis.
KD is an acute systemic vasculitis that most commonly affects children under 5 years old. Sepsis is a systemic inflammatory response syndrome caused by infection. The main clinical manifestations of both are fever, and laboratory tests include elevated WBC count, C-reactive protein, and procalcitonin. However, the two treatments are very different. Therefore, it is necessary to establish a dynamic nomogram based on clinical data to help clinicians make timely diagnoses and decision-making. In this study, we analyzed 299 KD patients and 309 sepsis patients. We collected patients' age, sex, height, weight, BMI, and 33 biological parameters of a routine blood test. After dividing the patients into a training set and validation set, the least absolute shrinkage and selection operator method, support vector machine and receiver operating characteristic curve were used to select significant factors and construct the nomogram. The performance of the nomogram was evaluated by discrimination and calibration. The decision curve analysis was used to assess the clinical usefulness of the nomogram. This nomogram shows that height, WBC, monocyte, eosinophil, lymphocyte to monocyte count ratio (LMR), PA, GGT and platelet are independent predictors of the KD diagnostic model. The c-index of the nomogram in the training set and validation is 0.926 and 0.878, which describes good discrimination. The nomogram is well calibrated. The decision curve analysis showed that the nomogram has better clinical application value and decision-making assistance ability. The nomogram has good performance of distinguishing KD from sepsis and is helpful for clinical pediatricians to make early clinical decisions.


[Identification of Sun-dried and Sulfur-fumigated Chuanxiong Rhizoma by FTIR].
To evaluate the sulfur-fumigation effects on the chemical constituents of Chuanxiong Rhizoma. Alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Chuanxiong Rhizoma samples were analyzed by FIIR. FTIR spectra were acquired and disposed by software Omnic 8. 0, second derivative IR spectra were analyzed by software OPUS 6. 5 through smoothing and differentiation treatment to FTIR spectra, and the absorption frequencies of alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Chuanxiong Rhizoma samples were assessed by using principal component analysis with software SPSS. There were significant differences between sun-dried and sulfur-fumigated Chuanxiong Rhizoma samples in the region ranging from 2 000 cm-1 to 750 cm-1. Some absorption peaks weakened or disappeared, and some newly emerged after the processing of sulfur-fumigation. The processing of sulfur-fumigation can influence the effective constituents of Chuanxiong Rhizoma. The established method of FTIR combined with second derivative and principal component analysis has been proved to be an effective, intuitional and rapid approach to distinguish sun-dried and sulfur-fumigated Chuanxiong Rhizoma.


Impact of BDNF -196 G>A and BDNF -270 C>T polymorphisms on stroke rehabilitation outcome: sex and age differences.
Genetic factors, including gene polymorphisms, are promising in determining stroke rehabilitation outcome. Brain-derived neurotrophic factor (BDNF) is one of the most attractive because of its role in neuroplasticity and brain repair. The aim of present study was to assess the role of BDNF -196 G≯A (val66met) and -270 C≯T on clinical parameters and functional outcome in patients with ischemic and hemorrhagic stroke. Additional analyses according to sex and age (≤55 and ≯55 years) were performed. Three hundred thirty-eight patients (287 with ischemic and 51 with hemorrhagic stroke) were evaluated in terms of neurological deficit (National Institute of Heath Stroke Scale [NIHSS]), activities of daily living (Barthel Index [BI]), and everyday functionality (Rankin score [RS]) before and after rehabilitation. BDNF polymorphism genotyping was performed by polymerase chain reaction restriction fragment length polymorphism analysis. In multivariative analysis, unfavorable outcome of stroke rehabilitation (RS ≥2) was associated with independent factors: ischemic stroke (odds ratio [OR], 2.59; 95% CI, 1.03-6.47), female gender (OR, 2.80; 95% CI, 1.39-5.64), depression (OR, 4.24; 95% CI, 1.45-12.35), falls (OR, 2.61; 95% CI, 1.16-5.87), and BDNF -196 GG polymorphism (OR, 2.18; 95% CI, 1.09-4.35). The differences of functional parameters measured with BI and RS on admission and at discharge are apparent only for comparisons between patients ≤55 and ≯55 years old carrying BDNF -196 GA+AA genotypes but not in those carrying -196 GG genotype; the differences were evident in women but not in men. BDNF -196 G≯A polymorphism might affect functional outcome of stroke rehabilitation, but this hypothesis needs further verification.


Blueberry muffin baby secondary to ganglioneuroblastoma.
We report the case of a neonate presenting with the clinical features of blueberry muffin syndrome caused by ganglioneuroblastoma, a rare variant of neuroblastoma. This syndrome may be the only visible manifestation of a neonatal tumor and highlights the importance of early recognition and initiation of therapy to reduce mortality.


Safety and immunogenicity of 17DD attenuated yellow fever vaccine in howler monkeys (Alouatta spp.).
Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP). Susceptible howler monkeys were immunized with three different concentrations of the human Brazilian commercial YF17DD vaccine. Post-vaccination viremia/RNAemia, immunogenicity, and safety were characterized. The vaccine did not produce YF clinical manifestations in any of the NHPs. After immunization, all animals seroconverted demonstrating the ability of the YF vaccine to induce humoral response in Alouatta species. The present work has demonstrated the safe and immunogenic profile of the existing YF 17DD vaccine in howler monkeys. This knowledge may support further studies with other susceptible monkey species and provide a possible solution for controlling epizootics and preventing the devastation of endangered species.


Cytosol estrogen and progesterone receptor levels measured in normal and pathological tissue of endometrium, endocervical mucosa and cervical vaginal portion.
The aim of this study was to compare cytosol estrogen (ER) and progesterone (PgR) receptor levels measured in normal and pathological tissue specimens (n = 395) of endometrium (ED), endocervical mucosa (EM) and cervical vaginal portion (VP) from 108 patients (age 27-79). The highest ER levels were found in ED which decreased to 25% in VP. The PgR decline was more pronounced in VP since the majority of samples were PgR-negative. In addition pathological tissue from ED exhibited marked differences in steroid receptor levels: The highest ER and PgR concentrations were detected in the proliferative phase, whereas the secretory phase exhibited significantly reduced ER and PgR levels. The lowest ER and PgR amounts were measured in atrophic and quiescent tissues; in proliferative tissue ER and PgR levels were comparable to hyperplastic tissue. Cervical ER and PgR concentrations were significantly lower as compared with ED (25-30%), and no cyclic variations were detectable. Also ER and PgR levels were different between EM and VP. 96% of ER were positive in the cervix, whereas 73% were PgR-negative in VP. Furthermore an inverse correlation between ER and progesterone was found in ED and a positive correlation between estradiol and PgR. These results suggest that the cytosol ER and PgR levels vary markedly in the uterine corpus and may explain in part the different response to endocrine therapy.


Hemodynamic profiles at rest and during supine exercise after orthotopic cardiac transplantation.
To characterize the spectrum of hemodynamic findings after orthotopic cardiac transplantation, 20 healthy heart transplant recipients with no evidence of cardiac dysfunction by noninvasive testing were studied for 1 to 51 months (mean 15) following surgery. After routine endomyocardial biopsy, right-sided heart pressures and thermodilution cardiac outputs were measured at rest (supine) and during symptom-limited, graded supine exercise. In addition, the effect of respiration on right atrial pressures and waveforms was determined at rest (supine, legs down), and after passive leg raising (volume loading). During exercise, striking increases of pulmonary artery, pulmonary artery wedge and right atrial pressures were seen. The mean pulmonary artery pressure rose 45% during the first stage of exercise (p less than 0.001) and by peak exercise it had increased 87% above resting values. The pulmonary artery wedge pressure increased significantly with passive leg elevation (p less than 0.001) and during the first stage of exercise rose 61% above baseline values. By peak exercise the mean pulmonary artery wedge pressure was more than double the resting value. Similarly, the right atrial mean pressure increased significantly (p less than 0.001) with passive leg elevation and nearly tripled at peak exercise. All values promptly returned to near baseline after exercise. The cardiac output increased 98% during exercise. During early exercise, the rise in cardiac output was mediated primarily by an increase in stroke volume. At rest, there was an abnormal response in right atrial mean pressure during slow deep inspiration in 7 individuals with legs down and in 12 after passive leg elevation (volume loading), including 4 of 10 patients studied beyond 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)


Leiomyosarcoma of the broad ligament: a case report and literature review.
Primary leiomyosarcoma of the broad ligament is a very rare, rapidly progressive and highly malignant gynaecological tumor. There are only 11 cases reported so far in the literature. An 87-year-old Caucasian lady with leiomyosarcoma of the broad ligament is presented. Treatment consisted of resection and total abdominal hysterectomy with bilateral salpingo-oopphorectomy. Unusually, she developed large recurrent pelvic disease in the absence of disseminated metastasis following surgery. She died within 8 weeks of primary surgery. This highlights the unknown behavior of this tumor and the need for more research into management.


[Oral antidiabetic drugs. How to begin and combine without cardiovascular risk].
Diabetes is recognized to be a major cardiovascular risk factor, and cardiocerebrovascular disease is the main cause of death of diabetic patients. Over the past decade, randomized controlled trials in type 2 diabetes have failed to demonstrate a clear association between glycemic control and a reduction in cardiovascular events and mortality, and have actually suggested that reducing glycemia to near normal levels may be harmful in some patients, increasing overall mortality. A meta-analysis showed that one of the most promising drugs for the treatment of hyperglycemia in type 2 diabetics, namely rosiglitazone, increases the incidence of ischemic cardiovascular events, and this led to the drug's suspension in Europe and drastically restricted it's use in the US. Consequently, over the recent years, any new drug for the treatment of hyperglycemia is obliged to present pre-clinical studies that prove it's cardiovascular safety, besides its efficacy, in order to receive approval by the regulatory authorities. Hence, the issue of how to treat type 2 diabetes in a cardiovascular safe manner is a current and very relevant concern.


Panic disorder with or without concomitant depression 5 years after treatment: a prospective follow-up.
50 patients with panic disorder (30 without and 20 with concomitant depression) were enrolled in a controlled treatment study using either imipramine or doxepin in addition to supportive psychotherapy and were then studied under naturalistic treatment conditions over a 5-year period. While patients with concomitant depression scored higher in overall measures of illness severity (as measured by HAMA, HAMD and GAS), no differences were detected between the groups with regard to panic disorder symptoms and degree of impairment. Our data suggest that comorbidity of panic disorder and depression is no prerequisite for poorer long-term outcome compared with panic disorder without depression.


Erratum: Association between mid-upper arm circumference and body mass index in pregnant women to assess their nutritional status.
[This corrects the article on p. 3321 in vol. 9, PMID: 33102290.].


The extended deep inferior epigastric flap: a case report.
The extended deep inferior epigastric flap, described by Taylor et al. (1983), 1984), offers a versatile and reliable technique for covering defects in the lower limb. A case of shark bite is described in which extensive soft tissue loss in the thigh resulted in a denuded femoral shaft which was successfully treated using such a flap.


ART use and associated factors among HIV positive caregivers of orphans and vulnerable children in Tanzania.
Utilization of antiretroviral therapy (ART) is crucial for better health outcomes among people living with the human immunodeficiency virus (PLHIV). Nearly 30% of the 1.6 million PLHIV in Tanzania are not on treatment. Since HIV positive status is the only eligibility criterion for ART use, it is critical to understand the obstacles to ART access and uptake to reach universal coverage of ART among PLHIV. For the caregivers of orphans and vulnerable children (OVC) LHIV and not on ART, attempts to identify them and ensure that they initiate and continue using ART is critical for their wellbeing and their ability to care for their children. Data are from the community-based, United States Agency for International Development (USAID)-funded Kizazi Kipya project that aims at scaling up the uptake of HIV/AIDS and other health and social services by orphans and vulnerable children (OVC) and their caregivers. HIV positive caregivers of OVC who were enrolled in the USAID Kizazi Kipya project between January 2017 and June 2018 were included in this cross-sectional study. The caregivers were drawn from 11 regions: Arusha, Iringa, Katavi, Kigoma, Mara, Mbeya, Morogoro, Ruvuma, Simiyu, Singida, and Tanga. The outcome variable was ART status (either using or not), which was enquired of each OVC caregiver LHIV at enrollment. Data analysis involved multivariable analysis using random-effects logistic regression to identify correlates of ART use. In total, 74,999 caregivers living with HIV with mean age of 44.4 years were analyzed. Of these, 96.4% were currently on ART at enrollment. In the multivariable analysis, ART use was 30% lower in urban than in rural areas (adjusted odds ratio (OR) = 0.70, 95% confidence interval (CI) 0.61-0.81). Food security improved the odds of being on ART (OR = 1.29, 95% CI 1.15-1.45). Disabled caregivers were 42% less likely than non-disabled ones to be on ART (OR = 0.58, 95% CI 0.45-0.76). Male caregivers with health insurance were 43% more likely than uninsured male caregivers to be on ART (OR = 1.43, 95% CI 1.11-1.83). Caregivers aged 40-49 years had 18% higher likelihood of being on ART than the youngest ones. Primary education level was associated with 26% increased odds of being on ART than no education (OR = 1.26, 95% CI 1.13-1.41). Although nearly all the caregivers LHIV in the current study were on ART (96.4%), more efforts are needed to achieve universal coverage. The unreached segments of the population LHIV, even if small, may lead to worse health outcomes, and also spur further spread of the HIV epidemic due to unachieved viral suppression. Targeting caregivers in urban areas, food insecure households, who are uninsured, and those with mental or physical disability can improve ART coverage among caregivers LHIV.


Two-year outcomes between ST-elevation and non-ST-elevation myocardial infarction in patients with chronic kidney disease undergoing newer-generation drug-eluting stent implantation.
We evaluated the 2-year clinical outcomes of ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) in patients with chronic kidney disease (CKD) who received newer-generation drug-eluting stents (DES). Overall, 18,875 acute myocardial infarction patients were divided into two groups: CKD (STEMI, n = 1707; NSTEMI, n = 1648) and non-CKD (STEMI, n = 8660; NSTEMI, n = 6860). The occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), any repeat coronary revascularization, and definite or probable stent thrombosis (ST), was evaluated. After multivariable-adjusted analysis, in the CKD group, the MACE (adjusted hazard ratio [aHR]: 1.365, p = 0.004), all-cause death (aHR: 1.503, p = 0.004), noncardiac death (non-CD; aHR: 1.960, p = 0.004), and all-cause death or MI rates (aHR: 1.458, p = 0.002) were significantly higher in the NSTEMI group than in the STEMI group. In the non-CKD group, the non-CD rate (aHR: 1.78, p = 0.006) was also higher in the NSTEMI group. The CD, re-MI, any repeat revascularization, and ST rates were similar between groups. In the CKD group, from 6 months to 2 years after the index procedure, all-cause death, non-CD, and all-cause death or MI rates were significantly higher in the NSTEMI group than in the STEMI group. These results may be related to the higher non-CD rate in the NSTEMI group. In the era of contemporary newer-generation DES, NSTEMI showed a relatively higher non-CD rate than STEMI in both CKD and non-CKD groups.


Function of the M1 π-helix in endplate receptor activation and desensitization.
A conserved proline in M1 causes a kink between α and π helical segments. The kink is under greater tension in the resting versus active conformation. The kink and the agonist do not interact directly. The π-helix separates the gating functions of the extracellular and transmembrane domains. Mutations of the conserved proline and propofol increase desensitization. Nicotinic acetylcholine receptors (AChRs) switch on/off to generate transient membrane currents (C↔O; closed-open 'gating') and enter/recover from long-lived, refractory states (O↔D; 'desensitization'). The M1 transmembrane helix of the muscle endplate AChR is linked to a β-strand of the extracellular domain that extends to a neurotransmitter binding site. We used electrophysiology to measure the effects of mutations of amino acids that are located at a proline kink in M1 that separates π and α helices, in both α (N217, V218 and P221) and non-α subunits. In related receptors, the kink is straighter and more stable in O vs. C structures (gating is 'spring-loaded'). None of the AChR kink mutations had a measureable effect on agonist affinity but many influenced the allosteric gating constant substantially. Side chains in the M1 α-helix experience extraordinarily large energy differences between C and O structures, probably because of a ∼2 Å displacement and tilt of M2 relative to M1. There is a discrete break in the character of the gating transition state between αN217 and αV218, indicating that the π-helix is a border between extracellular- and transmembrane-domain function. Mutations of the conserved M1 proline, and the anaesthetic propofol, increase a rate constant for desensitization. The results suggest that straightening of the M1 proline kink triggers AChR desensitization.


A case of Vogt-Koyanagi-Harada syndrome in a patient affected by Hodgkin's disease.
The Vogt-Koyanagi-Harada (VKH) syndrome, a disease of unknown origin, characterized by inflammation of the uveal tract, retina and meninges, was observed in a patient with Hodgkin's disease (HD) who had been treated with chemotherapy and radiotherapy. Ten years later the patient developed a cluster of neurological symptoms and signs (fever, pain, bilateral hypoacousia, dizziness, uveitis and psychiatric disorder) which were initially interpreted as a relapse of HD. The diagnosis of VKH syndrome was thereafter suspected from the clinical findings, response to therapy and further evolution. During the follow-up (14 months) the patient showed a varying course; hypoacousia remained unaltered while uveitis recurred and only a partial improvement was obtained by immunosuppressive therapy.


Evaluating process-based and crew- centred approaches to procedure design in aviation: workload and performance changes in go-around manoeuvres.
In this article, we compare and evaluate two methods of procedure design using an aircraft go-around (GA) as a test scenario. We contrast the manufacturer specified, crew-centric procedure with a redesigned process-centred perspective. We test the claim that the process-centred design can take into account situational factors more effectively and generate less workload. We report a heuristic assessment of the new procedure against design guidelines and an evaluation in a full-flight simulator at the German Aerospace Centre (DLR) using qualified airline pilots to assess workload and performance. Both the manufacturer specified and new procedure were employed in three GA scenarios representative of increasing operational complexity. Results demonstrate an advantage for the new procedure design in the most complex scenario. The new, process-based procedure can reduce reported crew workload and improve response flexibility in more complex scenarios, improving rated performance. This study suggests that the process-based account in procedure design has advantages when compared to the flight crew-centric approach. These advantages include enhanced flexibility, robustness and improved crew performance during GA.


Was Mafeisan an Anesthetic in Ancient China?
According to the Chinese historical books, Records of the Three Kingdoms () and Book of the Later Han (), Hua Tuo (, 140 - 208), a Traditional Chinese medicine (TCM) physician invented Mafeisan, an oral herbal general anesthetic, more than 1800 years ago during Eastern Han Dynasty. However, no written record of ingredients of the original Mafeisan has been found anywhere so far although there have been several similar anesthetic prescriptions published in TCM books later. There has been controversy over the existence of Mafeisan and even Hua Tuo in Chinese literature. We did extensive literature search and analysis, and believe that there indeed was Mafeisan in Hua Tuo's time.


Helicobacter pylori inflammation, immunity, and vaccines.
Helicobacter pylori infects almost 50% of the world population and is the major cause of gastroduodenal diseases. H. pylori colonizes the gastric mucosa, activates Toll-like and Nod-like receptors, and usually elicits a T helper 1 (Th1) type of immune response, fully polarized in peptic ulcer patients. Among several bacterial factors, the neutrophil-activating protein represents a key factor driving Th1 inflammation. A complex and fascinating balance between H. pylori and host factors takes part in the gastric niche and allows the majority of infected individuals to be without any symptom during their entire life. Novel insights into the innate and adaptive responses against H. pylori, dealing with regulatory T cells and cytokines, CTLA-4 molecule, cholesterol glucosylation, and immune evasion have been elucidated during the past year and are discussed for the development of an effective vaccine.


Negative symptoms in Alzheimer's disease: a confirmatory factor analysis.
To examine different conceptual models of negative symptoms in Alzheimer's disease. Confirmatory factor analysis of cross-sectional data. Alzheimer patients (n=281) admitted to a psychogeriatric observation ward. Nurses' Behavioural observation scale for psychogeriatric inpatients (GIP). Global clinical ratings of severity of dementia and depression based on the Cambridge Examination for Mental Disorders of the Elderly-Dutch version (CAMDEX-N). A unidimensional model of dementia fitted the data poorly. Multidimensional models produced better results. In two- and three-factor models negative symptoms were separated from cognitive impairment and mood disturbances. The more severe the memory impairment, the more socially withdrawn patients were. In this sense negative symptoms may have been secondary to cognitive decline. However, no association was found between negative symptoms and mood disturbances. Negative symptoms are a prominent clinical feature of Alzheimer's disease and they are related to memory impairment but not to mood disturbances.


Benzene-1,2-diaminium bis-(4-methyl-benzene-1-sulfonate).
The structure of the title salt, C6H10N2 2+·2C7H7O3S-, consists of a unique benzene-1,2-diaminium dication charge balanced by a pair of crystallographically independent 4-methyl-benzene-1-sulfonate anions. The cations and anions are inter-linked by several N-H⋯O hydrogen bonds.


Molecularly Precise, Bright, Photostable, and Biocompatible Cyanine Nanodots as Alternatives to Quantum Dots for Biomedical Applications.
Fluorescent imaging with fluorophores has become a powerful way to explore complex biological systems and visualize nanoparticles for drug delivery. However, it is challenging to develop fluorophores with ideal physical and optical properties. We report a method to synthesize cyanine nanodots with a single-molecule structure, well-defined particle size, customizable fluorescent spectrum, and bright and stable fluorescence. These cyanine nanodots are acquired by the divergent synthesis of cyanine-dye-cored polylysine (PLL) dendrimers. We demonstrated the feasibility of the method by synthesizing cyanine 3 (Cy3), cyanine 5 (Cy5), or cyanine 7 (Cy7) cored single-molecule nanodots up to eight generations with a size of around 11 nm. We show that these cyanine nanodots are capable of multiple biomedical applications, including multicolor cellular tracing and cancer imaging. These cyanine nanodots possess many merits of organic dots and quantum dots that are promising for future application.


Barrett's esophagus: What do we need to know?
Barrett's esophagus (BE) is characterized by a change in the mucosal lining of the distal esophagus whereby the squamous epithelium of the esophagus is replaced by the metaplastic columnar epithelium. It is a pre-malignant lesion associated with esophageal adenocarcinoma. Patients with gastroesophageal reflux disease who have additional risk factors (Caucasian race, male gender, age > 50 years, tobacco use, and central obesity) should undergo an esophagogastroduodenoscopy to screen for Barrett's esophagus. Patients with Barrett's esophagus should undergo endoscopic surveillance every 3-5 years if no dysplasia is found. Patients with Barrett's esophagus who are found to have dysplasia should be treated endoscopically. We present a comprehensive review of the pathophysiology, diagnosis, surveillance and management of Barrett's esophagus.


Automatic column chromatographic analysis of saccharides and uronic acids.
Using n-proponal/water as the eluting solvent, a flow rate of 50 ml/h and a 90 degrees C column temperature, the separation of a complex mixture of 11 monosaccharides could be much improved over the procedure described by v. Wilm and Sordé using isopropanol/water, 70--100 ml/h flow rate and temperatures of 83--90 degrees C. With a small total error of 3%, the saccharide analysis lies in the region of reproducibility that has also been reached in amino acid analysis. The limit of detection for saccharides lies at 1 x 10(-9) mole/ml.


Diabetes-induced skeletal muscle fibrosis: Fibro-adipogenic precursors at work.
Skeletal muscle fibrosis is a complication of diabetes and insulin resistance. In this issue of Cell Metabolism, Farup et al. (2021) characterized fibro-adipogenic precursors (FAPs) in human skeletal muscle and showed that a CD34+CD90+ FAP subset is involved in diabetes-induced muscle fibrosis through PDGFRα signaling and activation of glycolysis.


Production of murine V-human Cr1 chimeric anti-TAG72 antibody using V region cDNA amplified by PCR.
A mouse/human chimeric B72.3-1-3 antibody was produced by construction of a novel expression vector mpSV2neo-EP1-V-Cr1. This vector contains the neo gene as a selection marker, the murine immunoglobulin heavy chain promoter and enhancer, the murine V region cDNA containing mRNA splicing joint sequences, amplified and cloned by the PCR technique directly from the B72.3 hybridoma RNA, and the human genomic Cr1 region. The expression vector containing the murine/human chimeric immunoglobulin heavy chain gene was transfected into heavy chain loss mutant cell line, B72.3Ml. Chimeric B72.3-1-3 antibody was produced at 2 micrograms/ml and retained full binding reactivity to TAG72 compared to the murine B72.3 parental antibody. Using this method, chimeric immunoglobulin molecules can be produced rapidly in comparison with the cDNA and genomic cloning techniques.


One-stage biotrickling filter for the removal of a mixture of volatile pollutants from air: performance and microbial community analysis.
The biodegradation of gas-phase mixtures of methanol, α-pinene and H2S was examined in a biotrickling filter (BTF), inoculated with a microbial consortium composed of an autotrophic H2S-degrading culture, and pure strains of Candida boidinii, Rhodococcus erythropolis, and Ophiostoma stenoceras. The inlet concentrations of methanol, α-pinene and H2S varied from 0.05 to 3.3 gm(-3), 0.05 to 2.7 gm(-3), and 0.01 to 1.4 gm(-3), respectively, at empty bed residence times (EBRT) of either 38 or 26s. The maximum elimination capacities (ECmax) of the BTF were 302, 175, and 191 gm(-3)h(-1), with 100%, 67%, and >99% removal of methanol, α-pinene and H2S, respectively. The presence of methanol showed an antagonistic removal pattern for α-pinene, but the opposite did not occur. For α-pinene, inlet loading rates (ILRs) >150 gα-pinenem(-3)h(-1) affected its own removal in the BTF. The presence of H2S did not show any declining effect on the removal of both methanol and α-pinene.


Estimating Lyme disease risk using pet dogs as sentinels.
The reported number of cases of Lyme disease, Borrelia burgdorferi sensu lato, is thought to have increased in the UK over the past decade, but consistent surveillance data are lacking. Here the prevalence of B. burgdorferi in ticks attached to pet dogs was examined - using them as sentinels for human disease risk. Dogs give a good indication of the exposure of their human owners to infected ticks, since they largely share the same environment and visit the same outdoor areas. PCR was used to test 739 tick samples collected from 3534 dogs selected at random as they visited veterinary practices over a period of six months. Overall, the prevalence of infected ticks on all dogs was 0.5% giving an estimated 481 infected ticks per 100,000 dogs. The data suggest that the prevalence of Borrelia in the UK tick population is considerably higher than most recent estimates indicate.


Icariin, a major constituent of flavonoids from Epimedium brevicornum, protects against cognitive deficits induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats.
Chronic cerebral hypoperfusion is considered to be a pivotal contributing factor of cognitive impairments that occur in vascular dementia and Alzheimer's disease, and ideal drug treatment for these diseases is unavailable. Hence, this study was designed to investigate the protective effects of icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum, on cognitive impairments and neuronal morphological damage induced by permanent occlusion of bilateral common carotid arteries (BCCAO) in rats, and further explore the potential mechanisms. This study found that BCCAO could induce cognitive deficits and neuronal morphological damage, along with deposition of beta-amyloid (Aβ) in rat hippocampus. However, oral administration of icariin twice per day for 23days might attenuate cognitive deficits and neuronal morphological damage induced by BCCAO. Subsequently, icariin decreased the level of Aβ in rat hippocampus subjected to BCCAO. Administration of icariin reduced the expressions of amyloid precursor protein (APP), beta-secretase 1 (BACE1), and increased the expressions of insulin-degrading enzyme (IDE) and a disintegrin and metalloproteinase domain 10 (ADAM10) in rat hippocampus. Furthermore, icariin afforded beneficial actions in suppressing transforming growth factor-β1 (TGF-β1) signaling via inhibition of Smad2/3 phosphorylation. In summary, icariin is effective in improving cognitive deficits and hippocampus morphological alterations subjected to BCCAO. This protection appears to be due to the decreased expressions of both APP and BACE1, and the increased expressions of both IDE and ADAM10, resulting in a decrease in the level of insoluble Aβ fragments in rat hippocampus. Inhibitions of TGF-β1 signaling and Smad2/3 phosphorylation are involved in the course.