Using the FRAIL scale to compare pre-existing demographic lifestyle and medical risk factors between non-frail, pre-frail and frail older adults accessing primary health care: a cross-sectional study.
Few studies in the scientific literature have analyzed frailty status as an ordinal variable (non-frail, pre-frail and frail) rather than as a binary variable (frail vs non-frail). These studies have found that pre-frailty behaves differently from frailty (no ordinality in the variable). However, although the comparison between pre-frail and frail individuals is clinically relevant to understanding how to treat pre-frailty, this comparison was not performed in previous studies. A cross-sectional observational study was designed with 621 older individuals aged ≥60 years in Spain in 2017-2018, determining factors associated with a higher frailty stage (non-frail, pre-frail and frail) and undertaking this comparison, in addition to measuring non-frailty. The factors assessed through a multinominal regression model were: age, sex, living alone, recent loss of the partner, income and total comorbidities. Of the total participants, 285 were non-frail (45.9%), 210 were pre-frail (33.8%) and 126 were frail (20.3%). Compared to non-frail individuals, pre-frail individuals were older, with more comorbidities and a lower income. Compared to non-frail individuals, frail individuals were more likely to be female, older, with more comorbidities and a lower income. Compared to pre-frail individuals, frail individuals were more likely to be female, older and with more comorbidities. Comparison between the pre-frail and frail groups showed that frail persons were more likely to have a lower income, be female, older and have a higher number of comorbidities.


Production of biosurfactant by Pseudomonas aeruginosa grown on cashew apple juice.
In this work, the ability of biosurfactant production by Pseudomonas aeruginosa in batch cultivation using cashew apple juice (CAJ) and mineral media was evaluated. P. aeruginosa was cultivated in CAJ, which was supplemented with peptone (5.0 g/L) and nutritive broth. All fermentation assays were performed in Erlenmeyer flasks containing 300 mL, incubated at 30 degrees C and 150 rpm. Cell growth (biomass and cell density), pH, and superficial tension were monitored vs time. Surface tension was reduced by 10.58 and 41% when P. aeruginosa was cultivated in nutrient broth and CAJ supplemented with peptone, respectively. These results indicated that CAJ is an adequate medium for growth and biosurfactant production. Best results of biosurfactant production were obtained when CAJ was supplemented with peptone.


Orchestrating brain-cell renewal: the role of immune cells in adult neurogenesis in health and disease.
Immune cells and immune molecules have recently been shown to support neurogenesis from neural stem and progenitor cells in the adult brain. This non-classical immune activity takes place constantly under normal physiological conditions and is extended under acute pathological conditions to include the attraction of progenitor cells and induction of neurogenesis in regions of the adult central nervous system (CNS) in which formation of new neurons does not normally occur. We suggest that the immune system should be viewed as a novel player in the adult neural stem cell niche and a coordinator of cell renewal processes after injury. We discuss these notions in light of the well-known facts that both immune-cell activity and cell renewal are inherently limited in the adult CNS and that immune and stem cells provide the body's mechanisms of repair.


Macrophages in tissues and in vitro.
Macrophages have specialized functions in different tissue microenvironments such as lymphohaemopoietic organs and the nervous system. Recently, progress has been made in defining cellular and molecular properties of isolated and tissue macrophages in the developing and adult animal.


A simple and sensitive enzyme immunoassay for determination of soluble type-specific polysaccharide from group B streptococci.
A method was developed for the determination of soluble group B streptococcal type-specific polysaccharide in diluted culture supernatant. The type-specific antigen was immobilized to the solid phase of an enzyme immunoassay using wheat germ agglutinin as a link between the plastic surface and the polysaccharide. The binding of monovalent rabbit antiserum to the type-specific polysaccharide was quantitated by an anti-rabbit IgG-enzyme conjugate. Antisera against each of the polysaccharide types Ia, Ib. II and III gave strong and specific reactions against the respective antigen. The ultimate sensitivity of the assay was 70 pg/ml, as determined for type III polysaccharide. Using this technique, it was found that the concentration of soluble type-specific antigen in a GBS, type III culture supernatant reached a steady-state approximately 3 h after the beginning of the stationary growth phase of the bacteria. Ten type III strains were investigated for synthesis of type-specific polysaccharide, and a positive correlation between the production of capsular and soluble type III antigen was found. There was also an inverse correlation between soluble antigen production and the buoyant densities of these strains. The method described may be used for the serotyping of encapsulated GBS and/or determination of soluble type-specific antigen synthesis.


Salvage CT-guided transgluteal cryoablation for locally recurrent prostate cancer: initial experiences.
Technical feasibility of a computed tomography (CT)-guided transgluteal approach for salvage cryoablation of inoperable locally recurrent prostate cancer was evaluated retrospectively. Five procedures were performed under general anesthesia in five patients previously treated with radiation therapy. Median age was 64 years, and average pretreatment prostate-specific antigen (PSA) level was 2.77 ng/dL (range, 0.56-4.23 ng/dL). Each cryoablation procedure was completed in one session. No complications were reported. Mean 3-month and 6-month PSA levels were 0.35 ng/dL (range, 0.16-0.54 ng/dL) and 0.51 ng/dL (range, 0.09-0.94 ng/dL), respectively, representing mean decreases of 84% (range, 71%-92%) and 81% (range, 78%-84%), respectively. Salvage CT-guided transgluteal cryoablation of the prostate therefore appears technically feasible.


Hepcidin - Potential biomarker of contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions.
Contrast-induced acute kidney injury (CI-AKI) is a common and potentially serious complication of percutaneous coronary interventions (PCI). In this study, we tested the hypothesis whether serum and urinary hepcidin could represent early biomarkers of CI-AKI in patients with normal serum creatinine undergoing PCI. In addition, we assessed serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, eGFR and serum creatinine in these patients. Serum and urinary hepcidin and NGAL, serum cystatin C, were evaluated before, and after 2, 4, 8, 24 and 48 h after PCI using commercially available kits. Serum creatinine was assessed before, 24 and 48 h after PCI. We found a significant rise in serum hepcidin as early as after 4 and 8 h when compared to the baseline values. Serum NGAL increased after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. We found a significant fall in urinary hepcidin after 8 and 24 h after PCI. Serum cystatin C increased significantly 8 h after PCI, reaching peak 24 h after PCI and then decreased after 48 h. The prevalence of CI-AKI was 8%. Urine hepcidin was significantly lower 8 and 24 h after PCI in patients with CI-AKI, while serum and urine NGAL were significantly higher in patients with CI-AKI. Our findings suggest that serum hepcidin might be an early predictive biomarker of ruling out CI-AKI after PCI, thereby contributing to early patient risk stratification. However, our data needs to be validated in large cohorts with various stages of CKD.


Anatomic Position and Durability of Polytetrafluoroethylene Conduit ≥18 mm: Single-Center Experience.
Conduit longevity after right ventricular outflow tract (RVOT) reconstruction is determined by the interaction of different factors. We evaluated the relationship between conduit anatomic position and long-term durability among ≥18 mm polytetrafluoroethylene (PTFE) conduits. A single-institution RVOT reconstructions using a PTFE conduit ≥18 mm were identified. Catheter-based interventions or the need for conduit replacement were comparatively assessed between orthotopic vs heterotopic conduit position. Time to the first reintervention, censored by death, was compared between the groups. A total of 102 conduits were implanted in 99 patients, with a median age of 13.2 years (interquartile range [IQR] 8.9-17.8 years), median weight of 47 kg (IQR, 29-67 kg), and body surface area of 1.4 m2 (IQR, 1-1.7 m2). Overall, 50.9% (n = 52) of conduits were placed in an orthotopic position after the Ross procedure in congenital aortic valve abnormalities (80% [n = 36]). Tetrology of Fallot in 39% (n = 18), followed by truncus arteriosus with 33% (n = 15), were the most common in the heterotopic position. Trileaflet configuration was similar (67% vs 69%; P = .32) between the groups. Survival free from reintervention was 91% (95% CI, 79-97) and 88% (95% CI, 71-95) in the orthotopic and the heterotopic group, respectively, at 5 years, without differences in the Kaplan Meier curves (log-rank >.05). RVOT reconstruction with PTFE conduits ≥ 8 mm showed >90% conduit survival free from replacement in our cohort at 5 years. The anatomic position of the PTFE conduit does not seem to impact intermediate durability.


Unilateral absence of the hand in second cousins.
This paper reports two second cousins with absence of the left hand.


Bidirectional association between executive and physical functions among older adults: A systematic review.
We aimed to examine the bidirectional associations between specific executive function (EF) and physical function (PF) subdomains among older adults. A systematic literature search (MEDLINE, EMBASE, PsycINFO, EBSCOHOST, Scopus and EmCare) was undertaken from February 2018 to May 2020. Observational studies measuring associations between EF and PF subdomains among older adults were included. Twenty-nine studies met the inclusion criteria. Twenty-seven studies reported associations between EF and PF. There were bidirectional associations between slower processing speed and slower gait speed; slower processing speed and lower muscle strength; and lower verbal fluency and slower gait speed. Lower muscle strength was unilaterally associated with lower working memory. We found consistent bidirectional associations between processing speed with gait speed and muscle strength, and verbal fluency and gait speed. There was a unidirectional association between muscle strength and working memory. Common causal mechanisms for EF and PF require further studies.


Evaluating the interview performance of internal medicine interns.
Limited primary data are available to indicate in which areas physicians' interview performances are deficient. Videotaped recordings of 48 house officers performing a complete medical history were evaluated using a checklist to assess content, questioning technique, and interview style. Frequent deficiencies included inadequate social, psychiatric, and drug reaction histories. Several house officers demonstrated a marked tendency toward an overly directed interview style. The use of a detailed checklist during the observation of a complete medical history facilitates both accurate evaluation and specific detailed feedback to house officers.


Myosin and SERCA isoform expression in denervated slow-twitch muscle of euthyroid and hyperthyroid rabbits.
Changes in the isoform patterns of myosin heavy chains (MHC) and Ca2+-ATPase (SERCA) were studied in long-term (72 days) denervated slow-twitch soleus muscles of euthyroid and hyperthyroid rabbits. MHC isoforms were separated electrophoretically. SERCA isoforms were assessed by electrophoretic separation of the trypsin-digested and phosphorylated fragments. Denervation led to pronounced slow-to-fast transitions with increases in the fast MHC and fast SERCA1a isoforms. Hyperthyroidism had no significant effect on the denervation-induced changes in SERCA isoforms, but led to slight increases in the relative concentrations of the fast MHC isoforms. A high correlation existed between the relative concentrations of slow myosin and SERCA2a in both innervated euthyroid and hyperthyroid soleus muscles. This correlation, however, seems to be less tight in denervated soleus muscles.


Photoaffinity labeling of three renal cyclic 3',5'-adenosine monophosphate-binding proteins.
Evidence is presented for the presence of multiple cyclic AMP binding components in the plasma membrane and cytosol fractions of porcine renal cortex and medulla. N6-(Ethyl-2-diazomalonyl)-3',5'-adenosine monophosphate, a photoaffinity label for cyclic AMP binding sites, exhibits non-covalent binding characteristics similar to cyclic AMP in membrane and soluble fractions. Binding data for either compound to the plasma membrane fraction yields biphasic Scatchard plots while triphasic plots are obtained with the dialyzed cytosol. When covalently labeled fractions are separated on SDS-polyacrylamide gel electrophoresis, the cyclic AMP photoaffinity label is found on 49 000 and 130 000 dalton components in each kidney fraction. DEAE-cellulose and gel filtration chromatography of the labeled cortical cytosol fraction establishes that the three components suggested by the binding data correspond to two 49 000 dalton species and a 130 000 component. The 49 000 species have higher affinities for cyclic AMP than the 130 000 component (Ka(1) = 2.0 . 10(9), Ka(2) = 1.7 . 10(8), Ka(3) = 1.0 . 10(7)). The 49 000 components are associated with protein kinase activity while the 130 000 component does not exhibit protein kinase, adenosine deaminase, or cyclic nucleotide phosphodiesterase activity. Immunologic results and effects of phosphorylation and cyclic GMP on cyclic AMP binding further suggest that the 49 000 components are regulatory subunits of cyclic AMP-dependent protein kinases. Cyclic AMP binding to the 130 000 component is markedly inhibited by adenosine and adenine nucleotides, but not cyclic GMP. Thus, this component may reflect an aspect of adenosine control or metabolism which may or may not be a cyclic AMP-related cellular function.


A randomized controlled pilot trial of video-modelling versus telementoring for improved hemorrhage control wound packing.
Exsanguination is the most preventable cause of death. Paradigms such as STOP THE BLEED recognize increased responsibility among the less experienced with Wound Packing (WP) being a critical skill. As even trained providers may perform poorly, we compared Video-modelling (VM), a form of behavioural modelling involving video demonstration prior to intervention against remote telementoring (RTM) involving remote real-time expert-guidance. Search and Rescue (SAR-Techs), trained in WP were asked to pack a wound on a standardized simulator randomized to RMT, VM, or control. 24 SAR-Techs (median age 37, median 16.5 years experience) participated. Controls were consistently faster than RTM (p = 0.005) and VM (p = 0.000), with no difference between RTM and VM. However, 50% (n = 4) Controls failed to pack properly, compared to 100% success in both VM and RTM, despite all SAR-Techs feeling the task was "easy". Performance of a life-saving technique was improved through either VM or RTM, suggesting that both techniques are beneficial and complementary to each other. Further work should be extended to law enforcement/lay public to examine logistical challenges.


Characteristics of omega-conotoxin GVI A and MVIIC binding to Cav 2.1 and Cav 2.2 channels captured by anti-Ca2+ channel peptide antibodies.
A New Binding Method (NBM) was used to investigate the characteristics of the specific binding of 125I-omega-conotoxin (omega-CTX) GVIA and 125I-omega-CTX MVIIC to Cav2.1 and Cav2.2 channels captured from chick brain membranes by antibodies against B1Nt (a peptide sequence in Car2.1 and Cav2.2 channels). The results for the NBM were as follows. (1) The ED50 values for specific binding of 125I-omega-CTX GVIA and 125I-omega-CTX MVIIC to Cav2.1 and Cav2.2 channels were about 68 and 60 pM, respectively, and very similar to those (87 and 35 pM, respectively) to crude membranes from chick brain. (2) The specific 125I-omega-CTX GVIA (100 pM) binding was inhibited by omega-CTX GVIA (0.5 nM), dynorphine A (Dyn), gentamicin (Gen), neomycin (Neo) and tobramicin (Tob) (100 microM each), but not by omega-agaconotoxin (Aga) IVA, calciseptine, omega-CTX SVIB, omega-CTX MVIIC (0.5 nM each), PN200-110 (PN), diltiazem (Dil) or verapamil (Ver) (100 microM each). Calmodulin (CaM) inhibited the specific binding in a dose-dependent manner (IC50 value of about 100 microg protein/ml). (3) The specific 125I-omega-CTX MVIIC (60 pM) binding was inhibited by omega-CTX MVIIC, omega-CTX GVIA, omega-CTX SVIB (0.5 nM each), Dyn, Neo and Tob (100 microM, each), but not by omega-Aga IVA, calciseptine (0.5 nM each), PN, Dil, Ver (100 microM each) or 100 microg protein/ml CaM. These results suggested that the characteristics of the specific binding of 125I-omega-CTX GVIA and 125I-omega-CTX MVIIC to Cav2.1 and Cav2.2 channels in the NBM were very similar to those to crude membranes from chick brain, although the IC50 values for CaM and free Ca2+ of CaM were about 33- and 5000-fold higher, respectively, than those for the specific binding of 125I-omega-CTX GVIA and 125I-omega-CTX MVIIC to crude membranes.


Fellow Eye Anti-VEGF 'Crunch' Effect in Retinopathy of Prematurity.
Anti-vascular endothelial growth factor (VEGF) therapy is increasing in popularity for treatment of retinopathy of prematurity (ROP). Despite many technical benefits, issues remain prompting further investigation. Retrospective case report and literature review. A 42-week-old postmenstrual age female with gestational age of 28 weeks and birth weight of 990 g presented with prominent progression of peripapillary purely tractional atypical stage 4A ROP in both eyes following intravitreal bevacizumab therapy in the right eye only. The authors present the first reported case, to their knowledge, of a "crunch" phenomenon tractional retinal detachment from fellow eye administration of bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e102-e104.].


Boys with overweight status lagged behind girls with overweight status in reading: evidence from mendelian randomization.
We investigated the relationship between childhood weight status and academic achievement across sexes and different school subjects in Norway. We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), which includes genetic data (N = 13,648, 8-year-old children). We employed within-family mendelian randomization, using a body mass index (BMI) polygenic risk score as an instrument to address unobserved heterogeneity. Contrary to most previous findings, we observed that overweight status (including obesity) has more detrimental effects on reading achievement in boys than in girls; the test scores of boys with overweight were about a standard deviation lower than those of normal weight boys, and the negative effects on reading achievement became stronger in the later grade. Previous obesity prevention studies have mainly targeted girls, based on the assumption that the obesity penalty is greater for girls. Our findings highlight that particular attention to boys with overweight may help reduce the existing gender gap in academic achievement.


Enhanced degradation of emerging contaminants by permanganate/quinone process: Case study with bisphenol A.
Permanganate (Mn(VII)) is widely used as a mild oxidant in water treatment. However, the reaction rates of some emerging contaminants with Mn(VII) are extremely low. In this study, benzoquinone (BQ), a redox mediator with the important component in dissolved organic matter (DOM), enhanced the oxidation of bisphenol A (BPA) by Mn(VII) in a wide pH range of 4.0-10.0. The redox cycle of BQ would produce semiquinone radicals, which could act as ligands to stabilize the formed Mn(III) in the system to promote the oxidation of BPA. Notably, the presence of BQ might promote the formation of MnO2. A novel mechanism was proposed that singlet oxygen (1O2), Mn(III)-ligands (Mn(III)-L) and in-situ formed MnO2 were the main contributors to accelerate BPA degradation in the Mn(VII)/BQ system. Under acidic conditions, the in-situ formed MnO2 involved in the redox reaction and part of the Mn(IV) was reduced to Mn(III), indicating that the electron transfer of BQ promoted the formation of active Mn species and enhanced the Mn(VII) oxidation performance. Semiquinone radicals generated by BQ transformation would couple with the hydrogen substitution products of BPA to inhibit BPA self-coupling and promote the ring-opening reactions of BPA. Mn(VII)/BQ had better effect in raw water than in pure water, indicating that the Mn(VII)/BQ system has high potential for practical application. This study provided insights into the role of DOM in enhancing the Mn(VII) oxidation in water treatment.


The immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 combination vaccine: results from four phase III multicenter trials across three continents.
This paper presents the results of four separate phase III trials, which assessed the immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 in comparison with licensed Tritanrix-Hep B (GlaxoSmithKline Biologicals) and Hiberix (10 microg PRP), given as separate or mixed injections (3 trials) or with or without hepatitis B vaccine at birth (1 trial). The immunogenicity of DTPw-HBV/Hib 2.5 was non-inferior to the reference vaccine regimen in terms of seropositivity rates. The overall reactogenicity profile of DTPw-HBV/Hib 2.5 was also similar to that of the reference vaccine regimen. These results confirm the previously established immunogenicity and safety of reduced dose PRP conjugated vaccine regimens.


Costing analysis of field implementation of hepatitis C case detection in rural Maung Russey operational district, Cambodia.
When a new health programme is introduced, it is crucial to estimate the costs for rational health policy decision-making. The aim of this study was to determine the costs of implementing two strategies for hepatitis C virus (HCV) screening in rural Cambodia. We retrospectively analysed clinical and cost data that were collected routinely for a demonstration project for scaling up HCV screening and testing in Cambodia. The programme data were collected between March and December 2018 in Maung Russey operational district in Battambang Province, Cambodia. During the study period, 24 230 people were screened; 1194 (5%) were HCV seropositive, of whom 793 (66%) were confirmed to be viraemic. During the study period, 18% of the estimated population of the operational district were screened, of whom 45% were estimated to be seropositive and 41% to be viraemic. With passive screening alone, 8% of the estimated population were screened, of whom 29% were estimated to be seropositive and 28% viraemic. The cost per detected viraemic case was US$ 194 for passive screening alone and US$ 283 for passive and active screening combined. Labour costs (31%) and tests and materials (29%) comprised the largest proportions of the cost. Combined active and passive screening per viraemic case detected was US$ 89 more expensive than passive screening alone but provided a higher yield (41% versus 28%) of viraemic cases. Therefore, adding active screening to passive screening is beneficial. Selective active screening strategies, such as targeting people over 45 years and other higher-risk groups, added value for HCV diagnosis.


Epidemiology of pediatric primary tumors of the nervous system: a retrospective study of 633 cases from a single Moroccan institution.
There are several reports regarding the epidemiology of pediatric brain tumors. However, little is known about the profile of pediatric brain tumors in Africa especially in Morocco in particular. The authors report the results of epidemiological analysis of a retrospective review of childhood primary brain tumors in a single institution. A retrospective review of all cases of primary brain from 1 month to 15 years diagnosed at the Department of Pathology of the Hospital of Specialities of Rabat between January 1991 and December 2009 was performed. Six hundred and thirty-three primary tumors of the central nervous system were reviewed with a mean of 33.31 cases per year. According to the gender, 55% of the tumors occurred in males and 45% in females. The mean age was 8.36 years. Of all the tumors, 47% were situated in the supratentorial compartment, 48% in the infratentorial compartment, and 5% in spinal cord. In the infratentorial compartment, 82% of tumors are located in the cerebellum, 15% in the fourth ventricle, 2% in the brain stem and 1% in the cerebellar pontine angle. In the supratentorial compartment, two third of the tumors were located in the cerebral hemispheres and the sellar region. Thus 39% of tumors are located in the cerebral hemispheres followed by the sellar/suprasellar region (30%), lateral and third ventricles (11%), pineal region (8%), meninges (5%), choroid plexus (4%), and optic chiasma/tracts (3%). The most common types of tumors diagnosed were pilocytic astrocytoma and medulloblastoma together accounting for nearly half of the cases (46%) (23.1% and 22.9% respectively), followed by craniopharyngiomas (9%), ependymomas grade II (6.5%), glioblastomas (6%), astrocytomas grade II (4.4%), ependymomas grade III (3.9%). The other tumors represent 22.6%. We think that our results reflect fairly well the incidence of tumors of the nervous system in children due to the fact that this study was performed through many years in a single institution with a homogeneous neuropathological approach.


Electrophysiological changes induced by paradoxical sleep deprivation and lithium chloride poisoning in rats.
In an attempt to analyze the disruption of conditioned taste aversion (CTA) caused by pre-acquisition paradoxical sleep deprivation (PSD), the effect of poisoning (0.15 M LiCl, 4% body weight) on the sleep--wakefulness pattern was studied in 12 rats with chronically implanted electrodes. The polygraphic recording showed that poisoning reduced the total sleep time in the subsequent 3 h from 57 to 42% and REM sleep from 6 to 2%. The lithium chloride effect was still more pronounced after 24-h REM sleep deprivation: the total sleep time decreased from 67 to 46% and REM sleep from 13 to 2%. The change of sleep--wakefulness pattern, most pronounced during the first hour of poisoning, gradually returned to normal but REM sleep was significantly reduced even 3 h after poisoning. It is concluded that 24-h PSD does not alleviate the subsequent poisoning. On the other hand, the lithium chloride induced reduction of post-acquisition REM sleep many enhance the learning impairment caused by pre-acquisition PSD.


Semantic processing of neglected numbers.
While neglected stimuli can still be processed, few studies have directly addressed the issue of the unconscious access to semantics. In order to clarify this issue, we engaged four patients with unilateral left spatial neglect in a number comparison task. Each target number was preceded by a lateralized number prime, either in the intact or neglected hemifield (HF). Both group analyses and the intensive study of a single patient show that left (neglected) as well as right (consciously perceived) number primes affect performance: primes representing quantities that fall on the same side of the reference as the target lead to faster categorization. This congruency effect is highly suggestive of numerical semantic processing of neglected stimuli. Absence of conscious perception of neglected primes was evaluated using a combination of subjective and objective measures of performance in forced-choice tasks.


The Portuguese Version of the Schedule of Racist Events.
There is a lack of research tools in Portuguese to evaluate racial discrimination. The purpose of this study was to psychometrically assess the Portuguese version of the Schedule of Racist Events (SRE) in a sample of individuals enrolled in a research trial with antiretroviral medications in southern Brazil. Sample of 147 individuals living with HIV and/or AIDS. Research participants completed the Schedule of Racist Events and the WHOQOL-HIV BREF questionnaires. The SRE scores of non-white participants were significantly higher than the scores of white-participants. The Crombach's alpha coefficients, for the three subscales of the Portuguese version of the SRE, were high and significant. There were significant correlations between all subscales of the SRE and relevant domains of the WHOQOL-HIV BREF. The original English version of the SRE was successfully adapted to Portuguese. The Portuguese version of SRE constitutes a valid research instrument for evaluating racial discrimination.


[Thyreotoxic crisis triggered by stimulation of the adrenal gland medulla].
Thyroid storm was observed in a patient with Grave's disease after stimulation of release of epinephrine and norepinephrine with 2-DG. Measurements of catecholamine secretion before and during onset of thyrotoxic crisis suggested the important bearing of increased activity of the sympathetic nervous system on pathogenesis of thyroid storm.


A role for KIR gene variants other than KIR2DS1 in conferring susceptibility to psoriasis.
Recently we described an association between psoriasis and KIR2DS1, a gene for a stimulatory natural killer cell receptor, in a Polish population. The association was independently reported among Japanese and confirmed in a U.S. population. Prompted by these findings, we reanalyzed data by a multivariate approach in search of possible effects of KIR genes other than KIR2DS1 (non-KIR2DS1). The methodology was based on a stratified analysis and multiple logistic regression. We found that the non-KIR2DS1 genes had joint effects comparable to or stronger than the effects of KIR2DS1 in both the fraction of explained variance (0.174 vs 0.204, respectively, for KIR2DS1 and non-KIR2DS1) and the statistical significance (p = 0.000008 vs p = 0.000001, respectively). When individual genes were considered, a decrease in KIR2DS5 among patients vs controls (OR = 0.2, pcor = 0.0005) and a decrease in KIR2DS3 restricted to KIR2DS1-positive individuals (OR = 0.2, pcor = 0.005) were evident. We also performed a multivariate analysis of the HLA-Cw genotypes but failed to demonstrate any effects in addition to the known association with HLA-Cw*06. We conclude that the effect of the KIR genes on psoriasis susceptibility is complex, extending beyond the association with KIR2DS1 and involving protective effects and interactions.


Stereociliary bundle morphology in organotypic cultures of the mouse cochlea.
Organotypic cultures of the neonatal mouse cochlea have a band of hair cells consisting of 3-5 rows of outer hair cells and a single row of inner hair cells. The outer hair cell stereociliary bundles show progressive differentiation from the apical to the basal ends of the band. Undifferentiated apical bundles have a disk-like array of short stereocilia resembling microvilli. Partially differentiated bundles are hemispherical with poorly organized rows of thickly clustered stereocilia, which gradually increase in height in the direction of the kinocilium. More differentiated bundles remain hemispherical with many microvilli-like stereocilia, but have highly organized rows of sterocilia along the side nearest to the kinocilium, and well-defined height increments between the rows. Highly-differentiated, basal bundles usually have a 'V' or 'W' shape, although some can be almost polygonal. The basal bundles have 4-5 regular rows of stereocilia with a well-defined gradient in height across the rows, and very few microvilli-like stereocilia. Cross-links are only consistently observed in more differentiated bundles, where the rows of stereocilia are regular and have significant height increments across them. The links show a wide variety of forms and orientations not previously observed in other preparations. Spoke-like arrays of links project from the upper regions of many stereocilia and other stereocilia appear to bear distinct tip-to-side links, although with a variety of orientations. A similar variety of cross-links is observed in early postnatal cochleae in vivo, but not in the cochleae of adult mice, indicating that this variety may be a transient feature of sterociliary bundle development. In vitro, inner hair cell stereociliary bundles are often covered by overlying material from the developing tectorial membrane. The variations in morphology of inner hair cell bundles and their cross-links are similar to those of the outer hair cell bundles.


Angioedema associated with lisinopril.
Angioedema has been reported to occur in association with all angiotensin-converting enzyme inhibitors used in the United States. We reviewed nine cases of angioedema associated with lisinopril use seen in the emergency department at our hospital among 1,970 patients that had been prescribed lisinopril from March 1989 to May 1990. Cases were considered as probably (six cases) or possibly (three cases) drug related, depending on the temporal relationship of the initiation of therapy and the onset of angioedema. All of the cases had edema of the lips, buccal mucosa, and or face. None presented with laryngeal edema or stridor. The angioedema resolved within 1 to 2 days with diphenhydramine treatment and discontinuation of lisinopril. Our data suggest that the incidence of angioedema associated with lisinopril is greater than that associated with captopril or enalapril.


Ochratoxin A: a naturally occurring mycotoxin found in human milk samples from Norway.
The presence of ochratoxin A (OA) in human milk samples from different regions in Norway was investigated to determine the level of infant exposure to OA from human milk. OA was found in 38 (33%) of 115 human milk samples (range 10-130 ng l(-1)). It was found that 2-26% of the samples contained more than 40 ng l(-1) OA, which will cause a daily intake of OA from human milk exceeding the suggested tolerable dose of 5 ng kg(-1) body weight. Significant regional differences were found.


Manipulating selectivity of covalently-bonded hyperbranched anion exchangers toward organic acids. Part IV: General algorithm based on the variation of external part of the functional layer.
Novel anion exchangers with mono- and dialkanolamines in the external part of covalently-bonded hyperbranched functional layer were synthesized. Comparison of the chromatographic properties of the prepared stationary phases in suppressed ion chromatography (IC) mode using hydroxide eluent allowed us to evaluate the effect of the number of substituents at nitrogen atom in alkanolamine on selectivity of anion exchangers toward organic acids. Obtained anion exchangers were also examined together with previously described hyperbranched stationary phases with different mono- and diamines in the external part of the layer for evaluating the influence of various parameters on their selectivity. Effects of hydrophilicity, functionality of amine, and the number of substituents at nitrogen atom of amine used in the last modification cycle were established independently from each other, which provided the possibility to tailor selectivity toward organic acids when preparing anion exchanger for solving particular analytical task. Predominance of hydrophilicity as a key factor affecting the separation of weakly retained organic acids over other studied parameters was demonstrated.


Diagnostic accuracy of lumbopelvic motor control tests using pressure biofeedback unit in professional swimmers: A cross-sectional study.
To determine the effect of receiving the visual feedback of the sphygmomanometer on lumbopelvic motor control (LPMC) tests in professional swimmers. 31 professional swimmers to participate in the study. The outcome was maximum absolute mmHg variation in the pressure biofeedback unit's manometer with and without visual feedback on four LPMC tests. Test scores were significantly affected by visual feedback F = 10.07, p = 0.002, η2 p = 0.117 and the type of test F = 32.53, p < 0.001, η2 p = 0.300. Visual feedback has a positive effect on the Active Straight Leg Raise Test (ASLR), the Knee Lift Abdominal Test (KLAT) scores completed by professional swimmers.


Evaluation of an alpha-cypermethrin + PBO mixture long-lasting insecticidal net VEERALIN® LN against pyrethroid resistant Anopheles gambiae s.s.: an experimental hut trial in M'bé, central Côte d'Ivoire.
Long-lasting insecticidal nets (LLINs) are the primary method of malaria prevention. However, the widespread resistance to pyrethroids among major malaria vector species represents a significant threat to the continued efficacy of pyrethroid LLIN. Piperonyl butoxide (PBO) is a synergist that inhibits the activity of metabolic enzymes of the cytochrome P450 family known to detoxify insecticides including pyrethroids. Synergist LLIN incorporating PBO and a pyrethroid may provide improved control compared to pyrethroid-only LLIN. The efficacy of VEERALIN® LN (VKA polymers Pvt Ltd, India), an alpha-cypermethrin PBO synergist net was evaluated in experimental huts in M'bé, central Côte d'Ivoire against wild pyrethroid resistant Anopheles gambiae s.s. Comparison was made with a standard alpha-cypermethrin-treated net (MAGNet® LN, VKA polymers Pvt Ltd, India). Nets were tested unwashed and after 20 standardized washes. VEERALIN® LN demonstrated improved efficacy compared to MAGNet® LN against wild free-flying pyrethroid-resistant An. gambiae s.s. Before washing, VEERALIN® LN produced mortality of An. gambiae s.s. (51%) significantly higher than the standard pyrethroid-only net (29%) (P < 0.0001). Although there was a significant reduction in mortality with both LLINs after 20 washes, VEERALIN® LN remained superior in efficacy to MAGNet® LN (38 vs 17%) (P < 0.0001). Blood-feeding was significantly inhibited with both types of insecticide-treated nets relative to the untreated control net (P < 0.0001). Unwashed VEERALIN® LN induced significantly higher blood-feeding inhibition of An. gambiae s.s. (62.6%) compared to MAGNet® LN (35.4%) (P < 0.001). The difference persisted after washing, as there was no indication that either LLIN lost protection against biting or blood-feeding. The level of personal protection derived from the use of VEERALIN® LN was high (87%) compared to MAGNet® LN (66-69%) whether unwashed or washed. The AI content of VEERALIN® LN after 20 washes decreased from 6.75 to 6.03 g/kg for alpha-cypermethrin and from 2.95 to 2.64 g/kg for PBO, corresponding to an overall retention of 89% for each compound. The addition of the synergist PBO to pyrethroid net greatly improved protection and control of pyrethroid-resistant An. gambiae s.s. The pyrethroid-PBO VEERALIN® LN has the potential to reduce transmission in areas compromised by pyrethroid resistance.


The role of excitatory amino acids and substance P in the mediation of the cough reflex within the nucleus tractus solitarii of the rabbit.
We hypothesized that cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit is primarily mediated by glutamatergic neurotransmission at the level of the caudal portions of the medial subnucleus of the nucleus tractus solitarii (NTS) and the lateral commissural NTS where cough-related afferents terminate, and that this reflex is potentiated by local release of substance P. To test our hypothesis, we performed bilateral microinjections (30-50 nl) of ionotropic glutamate receptor antagonists or substance P into these locations in pentobarbitone anaesthetized, spontaneously breathing rabbits. Blockade of NMDA and non-NMDA receptors by 50mM kynurenic acid abolished the cough reflex without affecting the Breuer-Hering inflation reflex or the pulmonary chemoreflex. Blockade of non-NMDA receptors using 10mM CNQX or 5mM NBQX caused identical effects. Blockade of NMDA receptors by 10mM D-AP5 strongly reduced, but did not abolish cough responses. Microinjections of 1mM substance P increased peak and rate of rise of abdominal muscle activity as well as cough number. These results are the first to provide evidence that ionotropic glutamate receptors, especially non-NMDA receptors, located within specific regions of NTS are primarily involved in the mediation of cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit. Present findings on substance P cough-enhancing effects extend previous observations and are relevant to the tachykinin-mediated central sensitization of the cough reflex. They also may provide hints for further studies on centrally acting antitussive drugs.


The modified proteins in erythrocytes at hemodialysis patients.
The main goal of our research was to study the modified proteins and activity of integral band 3 protein in erythrocytes of patients with end-stage renal failure during hemodialysis. Depending on the starting nosological variant 2 groups were formed. The first group included 27 patients with end-stage renal failurein the outcome of chronic pyelonephritis, the second - 20 patients with end-stage renal failure, developed on a background of chronic glomerulonephritis. The control group consisted of 15 healthy subjects. The patients of 1-th and 2-nd groups were treated with hemodialysis. The concentration of reactive protein carbonyl derivates, membrane-binding hemoglobin were detected in erythrocytes. Activity of band 3 protein was detected following the protocol of I. Mindukshev et al. (2010). Comparison the results obtained was performed using non-parametric Mann-Whitney U-test (for independent variables). Before hemodialysis the significant increasing of concentration of reactive protein carbonyl derivates and membrane-binding hemoglobin in erythrocytes of both group patients in comparison with healthy ones was observed. During hemodialysis the further augmentation of modified proteins in erythrocytes took place. Different changes in the activity of the protein band 3 in erythrocytes of patients during hemodialysis were found. The similar type of protein band 3 activity changing was determined in erythrocytes of 1-th group patients. There was positive pair correlation between concentration of the reactive protein carbonyl derivates and protein band 3 activity (r= 0,31, p<0,05). Two different types of protein band 3 activity changing were determined in erythrocytes of 2-th group patients. Thus, the differences in modified proteins concentration and protein band 3 activity that occurred in the erythrocytes of patients during hemodialysis were established.


Localization of corticotropin- and endorphin-related peptides in the intermediate lobe of the rat pituitary.
The question is examined whether alpha-melanocyte stimulating hormone (alpha-MSH), adrenocorticotropic hormone (ACTH), met-enkephalin and beta-endorphin are detectable by enzyme immunocytochemistry in the cells of the intermediate lobe (PI) of the rat pituitary. By applying antibodies against alpha-MSH, ACTH and beta-endorphin on light microscopic sections, intense immunostaining was found in all PI-cells. At the ultrastructural level, after treatment of consecutive serial sections with these three antibodies the immunoreactivity was localized in the same secretory granules. No specific metenkephalin immunoreactivity could be detected in the cells of the intermediate lobe.


Cortical alpha-adrenoceptor downregulation by tricyclic antidepressants in the rat brain.
The aim of the present study was to examine the effect of chronic tricyclic antidepressants (TCAs) treatment on the density of alpha-adrenoceptors in the rat brain. Density of alpha1- and alpha2-adrenoceptors was measured in cortex and hippocampus of rats treated with imipramine (IMI, 5mg/kg body weight), desipramine (DMI, 10mg/kg body weight), clomipramine (CMI, 10mg/kg body weight) and amitriptyline (AMI, 10mg/kg body weight), for 40 days, using [3H]prazosin and [3H]clonidine, respectively. The density of cortical alpha1-adrenoceptors was significantly decreased with IMI (46%), DMI (21%), CMI (50%) and AMI (67%) treatment, without altering the affinity of the receptor. The density of cortical alpha2-adrenoceptors was also significantly decreased with DMI (69%), CMI (81%) and AMI (80%) treatment, without affecting the affinity for [3H]clonidine. The density of hippocampal alpha1-adrenoceptors was significantly decreased only with AMI treatment (47%), without affecting the affinity for [3H]prazosin. However, no change in hippocampal alpha2-adrenoceptor density was observed with any of these TCAs. The results suggest that chronic antidepressant (AD) treatment downregulates the cortical, but not hippocampal, alpha1- and alpha2-adrenoceptors in rat brain. The region-specific downregulation of alpha1- and alpha2-adrenoceptors density, which occur after prolonged AD treatment, may underline the therapeutic mechanism of action.


On the mechanism of cross-tolerance between morphine- and nicotine-induced antinociception: involvement of calcium channels.
The present study focused on the evaluation of a mechanism of nicotine-induced antinociception and cross-tolerance to antinociceptive effects between nicotine and morphine in mice. The results indicate that, at a dose of 3 mg/kg, nicotine produced a significant antinociception in the hot-plate test. Additionally, the L-type voltage-dependent calcium channel antagonists, nimodipine, verapamil and diltiazem (5, 10 and 20 mg/kg), as well as an opioid receptor antagonist naloxone (0.5 and 1 mg/kg), dose-dependently attenuated this nicotine-induced antinociception. In a second series of experiments, mice were treated with morphine (25 and 50 mg/kg) once daily, for 3 days. On the 4th day, the antinociceptive response of morphine (10 mg/kg) and nicotine (3 mg/kg) was measured. Tolerance to the effects of both drugs was observed only in mice pretreated with the highest dose of morphine. Furthermore, the administration of nimodipine, diltiazem, flunarizine (10 and 20 mg/kg), but not of verapamil (10 and 20 mg/kg) nor mecamylamine (1 and 2 mg/kg) prior to morphine injections, prevented this cross-tolerance to the antinociceptive effects of morphine and nicotine. These findings support the hypothesis that similar opioid- and calcium-dependent mechanisms are involved in morphine- and nicotine-induced antinociception and in the development of cross-tolerance between these drugs.


Degradation of Direct Red 81 mediated by Fenton reactions: multivariate optimization, effect of chloride and sulfate, and acute ecotoxicity assessment.
The role of different operational parameters related to Fenton reactions (pH, concentration of Fe2+ and H2O2, and reaction time) and of Cl- and SO 4- was investigated in the degradation of the azo dye Direct Red 81, expressed in terms of its decolorization. The factorial design and Pareto's charts showed that only Fe2+ concentration and pH influence the decolorization under the conditions evaluated. So, only these parameters were optimized using the response surface model. Under the best experimental conditions (initial pH 2.5, 11 mg L-1 Fe2+, 78 mg L-1 H2O2, and 20 min of reaction), 94 % of decolorization was achieved. However, even under the these conditions, but in the presence of Cl- and SO 4- , a striking loss of efficiency was observed as the concentration of these ions was increased, due the formation of chloride- and sulfate-iron complexes and less reactive inorganic radicals (Cl2•- and SO4•-). The results show that the presence of Cl- is more deleterious, since sulfate-iron complexes are more reactive towards H2O2, and the SO4•- turns out to favor the degradation. On the other hand, the negative effect of Cl- can be compensated by increasing the chloride concentration up to 300 mmol L-1. In addition, although a high degradation level has been obtained by monitoring the dye absorbance and by HPLC-UV, a low mineralization occurred, being generated degradation products of higher ecotoxicity to Vibrio fischeri, showing the need of subsequent studies to identify these compounds as well as the application of additional treatments aiming the complete mineralization of the dye.


Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy.
The importance of human papilloma virus (HPV) infection in the outcome of cervical cancer after radiotherapy remains unknown. Our study explored whether the HPV status of tumors is associated with the outcome of radiotherapy in patients with cervical cancer. A total of 84 patients with cervical cancer (6 Stage I, 10 Stage II, 49 Stage III, and 19 Stage IV) who underwent definitive radiotherapy between January 1995 and June 2000 were included in this study. Tumor samples were obtained from all patients by punch biopsy before radiotherapy. The presence of HPV and its type were analyzed by polymerase chain reaction (PCR) based assay using the consensus primers for E6 and L1 regions. Actuarial methods were used to calculate overall survival and disease-free survival. A total of 42 patients (50%) had cancer recurrence after radiotherapy. HPV-positive tumors were found in 76.2% (64 cases) of patients. HPV-negative patients survived for significantly shorter time periods compared to the HPV-positive patients in the overall survival (p = 0.007) and the disease-free survival (p = 0.005). According to multivariate analysis, HPV status is a significant predictor of both overall (p = 0.02) and disease-free survival time (p = 0.005). The results of this study suggest that HPV-negative patients with cervical carcinoma have a significantly poorer prognosis after radiotherapy, and HPV status may be used as a marker to optimize the treatment of patients with this type of cancer.


Electroactive films of heme protein-coated multiwalled carbon nanotubes.
A novel method for fabricating protein-MWNT films on pyrolytic graphite (PG) electrodes was described. Positively charged hemoglobin (Hb) or myoglobin (Mb) in buffers at pH 5.5 or 5.0 was first adsorbed on the surface of acid-pretreated, negatively charged multiwalled carbon nanotubes (MWNTs) mainly by electrostatic interaction, forming a core-shell structure. The aqueous dispersion of protein-coated MWNTs was then cast on PG electrodes, forming protein-MWNT films after evaporation of solvent. The protein-MWNT films exhibited a pair of well-defined, quasi-reversible cyclic voltammetric peaks, characteristic of heme Fe(III)/Fe(II) redox couples. The protein films were characterized by voltammetry, UV-vis spectroscopy, and scanning electron microscopy (SEM). This approach for assembly of protein-MWNT films showed higher surface concentration of electroactive proteins than the simple cast method, and the amount of proteins in the films could be controlled more precisely compared with the dipping method. Furthermore, the film assembly using this method was more stable than that using simple cast method. The proteins in MWNT films retained their near-native structure, and electrochemically catalyzed reduction of oxygen and hydrogen peroxide, suggesting the potential applicability of the films as the new type of biosensors or bioreactors based on direct electrochemistry of enzymes.


Endosulfan causes oxidative stress in the liver and brain that involves inhibition of NADH dehydrogenase and altered antioxidant enzyme status in rat.
Endosulfan, a neurotoxic, highly persistent organochlorine insecticide, is known for its acute and chronic toxicity. We have shown that a single sublethal dose of endosulfan caused high induction of oxidative stress in the liver and brain by altering the antioxidant status, as shown by reduction in the antioxidant enzymes SOD, GPx, GST, GR along with increased ROS and lipid peroxidation. The cerebral region in the brain showed a higher level of oxidative stress than the cerebellum, revealing differential sensitivity of the brain regions to endosulfan. Depletion of natural antioxidants causes the imbalance of redox status in cells, and the role of mitochondrial distress causally related to the cellular oxidative stress in vivo is not well understood. We have shown that reduction in the mitochondrial NADH dehydrogenase activity in the brain is associated with the induction of ROS in endosulfan-treated rats. Although oxidative stress is induced in both the liver and brain, the oxidative damage to the brain has implications for the toxic outcome in view of the brain's lower antioxidant defenses and high oxygen consumption.


Subjective well-being and its domains across different age groups: an Israeli sample.
Subjective well-being (SWB) across the life span was studied in a representative Israeli sample by a national survey of 1183 subjects, ranging from 18 to 80 years of age. Subjects were given "life scales", on which they rated their SWB in their present life, as well as their satisfaction regarding health, relations with friends, family, work, economic status, sense of personal achievement, and sense of control. The results indicate that: (a) SWB is negatively correlated with chronological age; (b) the relative strength of most of SWB domains changes in the different age groups; (c) SWB is best explained by different sets of domains in different age groups; and (d) economic status is the strongest domain, accounting for SWB in 6 out of 8 age groups. Explanations for these results confronted the developmental view of changing tasks across the life span vs cohort-based differences between the age groups. The decreasing number of domains that account for SWB variance with progressing age, as well as some unexpected findings with regard to the oldest age group (71-80) are also discussed.


Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-a pilot study.
We evaluated the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure frequency in adult patients with medically intractable extratemporal lobe epilepsy (ETLE). Seven patients with medically intractable ETLE received low-frequency rTMS at 0.9 Hz, basically two sets of 15 min stimulation per day for five days in a week, with the stimulus intensity of 90% of resting motor threshold (RMT). The number of seizures during two weeks before and after the stimulation of one week was compared. Furthermore, RMT and active motor threshold (AMT) were measured before and after rTMS for each daily session. After low-frequency rTMS of one week, the frequency of all seizure types, complex partial seizures (CPSs) and simple partial seizures was reduced by 19.1, 35.9 and 7.4%, respectively. The patients with smaller difference between RMT and AMT before rTMS had higher reduction rate of CPSs. A favorable tendency of seizure reduction, though not statistically significant, during two weeks after low-frequency rTMS was demonstrated in medically intractable ETLE patients. As far as CPSs are concerned, smaller decrease of motor threshold by voluntary muscle contraction was associated with better response to rTMS.


SENSDeep: An Ensemble Deep Learning Method for Protein-Protein Interaction Sites Prediction.
The determination of which amino acid in a protein interacts with other proteins is important in understanding the functional mechanism of that protein. Although there are experimental methods to detect protein-protein interaction sites (PPISs), these are costly, time-consuming, and require expertise. Therefore, many computational methods have been proposed to accelerate this type of research, but they are generally insufficient to predict PPISs accurately. There is a need for development in this field. In this study, we introduce a new PPISs prediction method. This method is a sequence-based Stacking ENSemble Deep (SENSDeep) learning method that has an ensemble learning model including the models of RNN, CNN, GRU sequence to sequence (GRUs2s), GRU sequence to sequence with an attention layer (GRUs2satt) and a multilayer perceptron. Two embedded features, secondary structure, and protein sequence information are added to the training data set in addition to twelve existing features to improve the prediction performance of the method. SENSDeep trained on the training data set without two extra features obtains a better performance on some of the independent testing data sets than that of the other methods in the literature, especially on scoring metrics of sensitivity, F1, MCC, and AUPRC, having increments up to 63.5%, 19.3%, 18.5%, 11.4%, respectively. It is shown that the added extra features improve the performance of the method by having almost the same performance with less data as the method trained on the data set without these added features. On the other hand, different sizes of the sliding window are tried on the data sets and an optimal sliding window size for SENSDeep is found. Moreover, SENSDeep has also been compared to structure-based methods. Some of these methods have been found to perform better. Using SENSDeep obtained by training with both training data sets, PPISs prediction examples of various proteins that are not in these training data sets are also presented. Furthermore, execution times for SENSDeep and its submodels are shown. https://github.com/enginaybey/SENSDeep.


Surface proteins and antigens of adult Schistosoma mansoni tegumental membranes detached onto poly-lysine coated beads.
Poly-lysine coated beads attached readily onto Schistosoma mansoni. On detachment, the beads removed membranes from the surface of the tegument. Analysis of the proteins of the detached membranes showed that three major proteins of 94, 73 and 62 kDa were present in contrast to a more complex range of proteins present in the phosphate-buffered saline released membranes. The membranes attached to beads were radio-iodinated and the antigens examined in immunoprecipitates by sodium dodecyl sulphate-polyacrylamide gel electrophoresis using various antisera. In addition to the well-established 32 and 20 kDa antigens of the tegument, other major antigens of 200, 25 and 11-12 kDa were iodinated in the membranes attached to the beads. The results suggest that the major antigens studied in the tegument may not correspond to the major proteins identified. The present approach shows promise for deducing the topography of the surface antigens and proteins of schistosomes.


Characterisation of ribosomes from drug resistant strains of Schizosaccharomyces pombe in a poly U directed cell free protein synthesising system.
Mutants of Schizosaccharomyces pombe were isolated as resistant either to trichodermin or to anisomycin. Growth tests showed that the majority of mutants isolated were cross resistant to both drugs and also to cycloheximide. A limited genetic analysis showed that mutants at least four loci, tri3, tri4, ani1 and ani2, had this phenotype as was also the case for mutants at three cycloheximide resistant loci, cyh2, cyh3 and cyh4 reported previously (Ibrahim and Coddington, 1976). Allelism tests showed that the tri3, ani2 and cyh4 strains were allelic. A mutant at another trichodermin resistant locus, tri5, was cross resistant to anisomycin but sensitive to cycloheximide. Ribosomes from wild type and selected strains were analysed in a poly U directed cell free protein synthesising system. Three strains, cyh1-C7, ani1-F1 and tri-N15 (probably a tri5 allele) possessed ribosomes which were more resistant than the wild type to the drugs used in their isolation. In each case the site of the resistance was in the 60S subunit. Ribosomes from the cyh2, cyh3 and cyh4 strains were as sensitive to cycloheximide as those from wild type.


[Organization and preservation of the collection of pathogenic and fungal symbionts of insects and other arthropods from CEPAVE (CONICET-UNLP), La Plata, Argentina].
The collection of fungal pathogens and symbionts of insects and other arthropods of the Centro de Estudios Parasitológicos y de Vectores, La Plata, Argentina, is unique because it preserves in vivo and in vitro cultures of fungal pathogens. This culture collection is open for research, teaching, consulting services, and strain deposit. It contains 421 strains belonging to 23 genera (16 Ascomycota, 4 Entomophthoromycotina, 2 Glomeromycota and 1 Oomycota), and the cultures are preserved by different methods such as cryopreservation in freezer at -20°C and -70°C, paper, distilled water and lyophilization. Fungi were isolated from insects, other arthropods, and soil (by using insect baits and selective media). Species were identified by morphological features and in a few strains by molecular taxonomy (PCR of rDNA). This collection is a reference center for species identification/certifications, research and teaching purposes, strain deposit, transference and consultancy services, and its overall goal is to preserve the fungal germplasm and ex situ diversity. Most of the strains are native of Argentina. The collection was originated in 1988 and is registered in the Latin American Federation for Culture Collections and in the World Federation of Culture Collections.


A novel way of treating mallet finger injuries.
Standard treatment protocols following a mallet finger injury involve lengthy periods of immobilization in an effort to ensure the terminal extensor tendon is able to maintain the distal interphalangeal joint in extension. This author describes a technique that utilizes a combination of an orthosis and kinesiotape, thereby creating a treatment protocol that shortens the immobilization phase for these patients. - Victoria Priganc, PhD, OTR, CHT, CLT, Practice Forum Editor.


Comparative analysis of two species of Asari Radix et Rhizoma by electronic nose, headspace GC-MS and chemometrics.
Traditional Chinese medicines (TCM) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. In this paper, electronic nose, headspace gas chromatography-mass spectrometry (GC-MS) and chemometrics methods were applied to differentiate two species of Asari Radix et Rhizoma by their odors. The samples used were the dried roots and rhizomes of Asarum heterotropoides var. mandshuricum (AH) and Asarum sieboldii (AS). The electronic nose was used to determine the odors of the samples and enabled rapid differentiation of AH and AS when coupled with principal component analysis. Headspace GC-MS was utilized to reveal the differences between the volatile constituents of AH and AS. In all, 54 volatile constituents were identified, and 9 major constituents (eucalyptol, eucarvone, 3,5-dimethoxytoluene, 3,4,5-trimethoxytoluene, methyleugenol, 2,3,5-trimethoxytoluene, croweacin, pentadecane and asaricin) could be used as chemical markers to distinguish these two species. AH contained higher relative contents of eucarvone (1.79-16.76%), 3,5-dimethoxytoluene (6.64-26.52%), 3,4,5-trimethoxytoluene/methyleugenol (6.43-31.67%) and 2,3,5-trimethoxytoluene (1.64-6.66%), whereas AS had higher relative contents of eucalyptol (14.06-24.95%), croweacin (5.64-13.55%), pentadecane (8.44-20.82%) and asaricin (7.03-13.45%). Moreover, AH and AS could be distinguished according to the contents of either all 54 identified volatile constituents or only the 9 major constituents by employing cluster analysis. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two species of Asari Radix et Rhizoma by their odors.


Cleavage of pm7G from mRNA 5' terminal cap structures by pyrophosphatase activity in embryonic chick lens cells.
The presence of pyrophosphatase activity in embryonic lens cells which cleaves pm7G and ppGm from m7G(5')pppGm was demonstrated. It was also found that m7G(5')pppG, but not G(5')pppG, was hydrolyzed, and conversion of m7GpppG to m7G*pppG, in which the 5-membered ring of the m7G moiety is open, abolished its hydrolysis. For the caps hydrolyzed, pm7G was released only in the presence of lens cellular fraction; pm7G inhibited cap hydrolysis.


Lhermitte's Sign following VMAT-Based Head and Neck Radiation-Insights into Mechanism.
We observed a number of patients who developed Lhermitte's sign (LS) following radiation to the head and neck (H/N), since instituting volumetric modulated arc therapy (VMAT). We aimed to investigate the incidence of LS following VMAT-based RT without chemotherapy, and determine the dosimetric parameters that predict its development. We explored whether the role of inhomogeneous dose distribution across the spinal cord, causing a "bath-and-shower" effect, explains this finding. From 1/20/2010-12/9/2013, we identified 33 consecutive patients receiving adjuvant RT using VMAT to the H/N without chemotherapy at our institution. Patients' treatment plans were analyzed for dosimetric parameters, including dose gradients along the anterior, posterior, right, and left quadrants at each cervical spine level. Institutional Review Board approval was obtained. 5 out of 33 (15.2%) patients developed LS in our patient group, all of whom had RT to the ipsilateral neck only. LS patients had a steeper dose gradient between left and right quadrants across all cervical spine levels (repeated-measures ANOVA, p = 0.030). Within the unilateral treatment group, LS patients received a higher mean dose across all seven cervical spinal levels (repeated-measures ANOVA, p = 0.046). Dose gradients in the anterior-posterior direction and mean doses to the cord were not significant between LS and non-LS patients. Dose gradients along the axial plane of the spinal cord may contribute to LS development; however, a threshold dose within the high dose region of the cord may still be required. This is the first clinical study to suggest that inhomogeneous dose distributions in the cord may be relevant in humans. Further investigation is warranted to determine treatment-planning parameters associated with development of LS.


When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.
Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or <72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a Pao2/FiO2 ratio<150 mm Hg, a norepinephrine dose >1 μg/kg per minute and a serum lactate level >9 mmol/L. Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.


Assessment of risk factors for postoperative nausea and vomiting.
To determine the risk factors for postoperative nausea and vomiting. Quasi-experimental study with prospective data collection. The study was conducted at Dow Medical College University and Civil Hospital, Karachi from January to December 2004. Data on patients' characteristic, anesthesia, surgery and postoperative nausea and vomiting was collected in operating theatre, postanesthesia care unit and wards. During postoperative 24 hours period, 60 out of a total of 200 patients experienced nausea and vomiting. The factors associated with an increased risk of Postoperative Nausea and Vomiting (PONV) were gender (female odds ratio 3), patients with previous history of nausea and vomiting or motion sickness (odds ratio 4), laparoscopic cholecystectomy (odds ratio 3.5) and eye surgery (odds ratio 3.9), all of these were statistically significant (p<0.05). No statistically significant difference was found between the other parameters. The incidence of PONV was found significantly higher in female gender, patients with previous history of nausea and vomiting or motion sickness, patient undergoing laparoscopic cholecystectomy and eye surgery.


Membrane binding of oligomeric alpha-synuclein depends on bilayer charge and packing.
Membrane disruption by oligomeric alpha-synuclein (alphaS) is considered a likely mechanism of cytotoxicity in Parkinson's disease (PD). However, the mechanism of oligomer binding and the relation between binding and membrane disruption is not known. We have visualized alphaS oligomer-lipid binding by fluorescence microscopy and have measured membrane disruption using a dye release assay. The data reveal that oligomeric alphaS selectively binds to membranes containing anionic lipids and preferentially accumulates into liquid disordered (Ld) domains. Furthermore, we show that binding of oligomers to the membrane and disruption of the membrane require different lipid properties. Thus membrane-bound oligomeric alphaS does not always cause bilayer disruption.


Diabetes mellitus and venous thromboembolism: A systematic review and meta-analysis.
Diabetes mellitus (DM) may be a risk factor for venous thromboembolism (VTE) but results are inconsistent. We conducted a systematic review and meta-analysis of epidemiologic studies to quantify the association between DM and VTE. We included studies identified in PubMed, Web of Science, and CINAHL through 07/31/2014. We identified 19 studies that met our selection criteria. We pooled RRs using a random-effects model: the pooled RR for the association of DM with VTE was 1.10 (95% CI: 0.94-1.29). Between-study heterogeneity was explored with a forest plot, funnel plot, meta-regression, and a stratified analysis. Between-study heterogeneity was observed and not explained by study design, method of DM assessment, or degree of adjustment for confounding. Sensitivity analyses omitted one study at a time to assess the influence of any single study on the pooled estimate. These analyses indicated that one large study was highly influential; when this study was excluded, the pooled estimate increased and just reached statistical significance: 1.16 (95% CI: 1.01-1.34). This meta-analysis suggests either no association or a modest positive one between DM and VTE in the general population. DM is unlikely to play a major role in VTE development.


Hepatocellular HO-1 mediated iNOS-induced hepatoprotection against liver ischemia reperfusion injury.
Hepatocyte-derived inducible nitric oxide synthase (iNOS) was proved to impart protection against liver ischemia reperfusion (I/R) injury in our prior analysis. However, the mechanism for this hepatoprotection remains incompletely understood. Bone marrow chimeric mice were generated using expression of iNOS in a hepatocyte-selective manner against an iNOS-knockout background. The function of heme oxygenase 1 (HO-1) in iNOS-stimulated hepatoprotection and the molecular mechanisms were explored in vitro and in vivo, respectively. Hepatocyte-derived iNOS conferred protection from I/R injury and anoxia/reoxygenation stimulation. Mechanistically, iNOS activated nuclear factor erythroid 2-related factor 2 (Nrf-2) and subsequently, stimulated the transcription of HO-1. Results from our study led to the conclusion that HO-1 is another potent mediator of iNOS-mediated protection after liver I/R.


Tracking of serum lipids in healthy children on a year-to-year basis.
To assess the stability of lipid profiles throughout childhood and evaluate their onset and dynamic. Lipid markers were longitudinally measured in more than 1300 healthy children from the LIFE Child study (Germany) and categorized into normal, at-risk, or adverse. Year-to-year intra-person persistence of the categories during follow-ups was examined and Pearson's correlation coefficient was calculated. We found strong positive correlations for TC, LDL-C and ApoB (r > 0.75, p < 0.001) from the age of four years. Correlations were lowest during the first two years of life. Most children with normal levels also had normal levels the following year. Children with at-risk levels showed a tendency towards normal levels at the follow-up visit. Adverse levels of TC, LDL-C, ApoB (all ages), and HDL-C (from age 15) persisted in more than half of the affected children. Age-dependent patterns of stability were most pronounced and similar for TC, LDL-C, and ApoB. Normal levels of serum lipids show high stability and adverse levels stabilized in early childhood for TC, LDL, and ApoB. At-risk and adverse levels of TC, LDL-C or ApoB may warrant further or repeated diagnostic measurements with regards to preventing CVD in the long run.


[Phosphohydrolases of the phytopathogenic fungus Phytophthora infestans (Mont) de Bary].
ATPase, pyrophosphatase and tripolyhosphatase activities were found in a cell-free Phytophtora infestans micelium extract. No polyphosphatase activity, hydrolyzing high molecular weigh polyphosphates to orthophosphate, was observed in the fungi. It was demonstrated that, unlike ATPase, the activity of pyrophosphatase was inhibited by Ca2+ at concentrations from 0.1 to 20 mM, and it was considerably decreased in the presence of a Ca2+ transport inhibitor, ruthenium red (0.01--0.1 mM). Possible relation of Ph. infestans pyrophosphatase activity with the process of active calcium transport is suggested.


Are NCI Cancer Centers Providing Adolescents and Young Adults With Cancer Focused Clinical Services? A National Survey.
This study sought to evaluate the current services and delivery models of adolescent and young adult oncology (AYAO)-specific programs at NCI-designated Cancer Centers (NCI-CCs). NCI, academic, and community cancer centers were electronically sent surveys from October to December 2020 and administered via REDCap. Survey responses were received from 50 of 64 (78%) NCI-CCs, primarily completed by pediatric oncologists (53%), adult oncologists (11%), and social workers (11%). Half (51%) reported an existing AYAO program, with most (66%) started within the past 5 years. Although most programs combined medical and pediatric oncology (59%), 24% were embedded within pediatrics alone. Most programs saw patients aged 15 (55%) to 39 years (66%) mainly via outpatient clinic consultation (93%). Most centers reported access to a range of medical oncology and supportive services, but dedicated services specifically for adolescent and young adults (AYAs) were available at a much lower extent, such as social work (98% vs 58%) and psychology (95% vs 54%). Although fertility preservation was offered by all programs (100%), only two-thirds of NCI centers (64%) reported providing sexual health services to AYAs. Most NCI-CCs (98%) were affiliated with a research consortium, and a lesser extent (73%) reported collaboration between adult and pediatric researchers. Nearly two-thirds (60%) reported that AYA oncology care was important/very important to their respective institution and reported providing good/excellent care to AYAs with cancer (59%), but to a lesser extent reported good/excellent research (36%), sexual health (23%), and education of staff (21%). Results of this first-ever national survey to assess AYAO programs showed that only half of NCI-CCs report having a dedicated AYAO program, and that areas of improvement include staff education, research, and sexual health services for patients.


Association between early care and education centres policies and practices and children's healthy behaviours.
To examine the impact of nutritional and physical activity (PA) policies and practices at early care and education centres on behavioural changes among children ages 2-5. The study population included 586 children from 25 education centres throughout the state of Georgia. Policies and practices were measured using the Georgia Nutrition and PA Assessment at the start of school year in Fall 2017. Survey data were collected at the beginning of school year September/October 2017 and at the end of school year April/May 2018 to measure changes in children's nutritional and PA behaviour over the school year. We used generalised estimating equations to estimate odds ratios and 95% confidence intervals. Children at centres with a high nutrition assessment score had higher odds of increasing vegetable consumption (OR = 2.1; 95% CI: 1.1, 4.0) while the odds of increasing fruit (OR = 1.4; 95% CI: 0.8, 2.4) and water (OR = 1.2; 95% CI: 0.5, 2.7) consumption increased non-significantly. The odds of improving PA were similar between children at centres with a high versus a low PA assessment score. The results, though insignificant, indicate that policies and practices could influence children's health behaviours. Further research is warranted to examine whether improvements in policies and practices could explain changes in children's health behaviours, the impact of educator's knowledge on children's health behaviours and the implementation of and adherence to policy and practice improvement plans.


Renewable energy and foreign direct investment: does the governance matter for CO2 emissions? Application of CS-ARDL.
Climate change is a global problem, and the policy-makers are trying their best to mitigate the impacts of drastic climate variability. Considering the mandate of Kyoto Protocol, this work investigates the individual and interactive impacts of renewable energy, economic growth, government effectiveness, and foreign investment towards carbon emissions in selected South Asian countries of India, Pakistan, Sri Lanka, and Bangladesh. The annual data of 1996-2019 has been analyzed by adopting advance methods. After confirming the cross-sectional dependence in the panel data, Westerlund cointegration test confirms the strong association of 1% level among the variables. Cross-sectional autoregressive distributed lag approach is employed to present long- and short-run coefficient values, which shows all data is having cross-sectional dependence at 1% level. Renewable energy and its interactive terms with government effectiveness and FDI are environmental friendly. A 1% increase in renewable energy is lowering CO2 emissions by 13.95%. Moreover, 1% increase in governance is reducing carbon emissions by 7.68%. This shows that these governments should integrate the FDI with renewable energy in the context of strict environmental policies. The attention should be on to generate more renewable energy. This can be done by importing latest technologies and to develop the domestic research and development expenditures.


Elevated levels of ZAC1 disrupt neurogenesis and promote rapid in vivo reprogramming.
The zinc finger transcription factor Zac1 is expressed in dividing progenitors of the nervous system with expression levels negatively controlled by genomic imprinting. To explore the consequences of elevated ZAC1 levels during neurogenesis we overexpressed it in the developing CNS. Increased levels of ZAC1 rapidly promoted upregulation of CDK inhibitors P57 and P27 followed by cell cycle exit. Surprisingly this was accompanied by stalled neuronal differentiation. Genome wide expression analysis of cortical cells overexpressing Zac1 revealed a decrease in neuronal gene expression and an increased expression of imprinted genes, factors regulating mesoderm formation as well as features of differentiated muscle. In addition, we observed a rapid induction of several genes regulating pluripotency. Taken together, our data suggests that expression levels of Zac1 need to be kept under strict control to avoid premature cell cycle exit, disrupted neurogenesis and aberrant expression of non-neuronal genes including pluripotency associated factors.


Femtosecond laser cataract surgery.
Femtosecond laser (FSL) cataract surgery is in its infancy but is rapidly gaining popularity due to the improved consistency and predictability for corneal incisions and anterior capsulorhexis. It enables subsequently less phacoemulsification energy and time to be employed, which has gains in terms of reduced corneal oedema. In addition, the FSL allows better circularity of the anterior capsulotomy, capsule overlap, intraocular lens (IOL) placement and centration of the IOL. These advantages have resulted in improved visual and refractive outcomes in the short term. Complication rates are low which reduce with surgeon experience. This review article focuses on the Alcon LenSx system.


Successful robotic proximal gastrectomy with side overlap esophagogastrostomy following preoperative chemotherapy: A case report.
Adenocarcinoma of the esophagogastric junction (AEJ) has been on the rise in recent years, but the technical aspects of reconstruction and reflux prevention are unsolved problems. This case report aimed to illustrate the usefulness of preoperative chemotherapy for tumor shrinkage and the advantage of robotic surgery for stable reconstruction with reflux prevention. A 69-year-old male patient was diagnosed with AEJ cT3N0M0 cStage IIB. Three courses of doublet chemotherapy with 80 mg/m2/day of S-1 on days 1-14 and 100 mg/m2 of oxaliplatin on day 1 were administered every 3 weeks before surgery. After chemotherapy, the tumor shrunk, and the proximal margin changed from 1.5 cm above the esophagogastric junction (EGJ) to be the gastric side of the EGJ. A radical robotic proximal gastrectomy with D2 lymphadenectomy was performed. Since sufficient length of the esophagus was secured in the hiatus due to tumor shrinkage, reconstruction was performed by the side-overlap esophagogastrostomy (mSOFY) method. The postoperative course was uneventful with no reflux symptoms two months after surgery, even without medication. Preoperative chemotherapy is expected to improve the rates of complete resection and survival. In the present case, preoperative treatment with SOX resulted in tumor shrinkage, which enabled reconstruction using the mSOFY method. Robotic surgery may be useful for such complex reconstruction procedures. To our knowledge, this is the first report of robotic reconstruction using the mSOFY method after proximal gastrectomy for AEG tumors. This work was reported in line with the SCARE 2020 criteria.


Comparison of two nonlinear registration techniques to investigate brain atrophy patterns in normal aging.
Automated anatomical labeling (AAL) provides an automatic brain region segmentation method to allow objective measurement of regional brain volume. Nonlinear registration plays a critical role in such automated region-based volumetry. The aim of this study was to compare age-related brain regional volume changes using two nonlinear registration methods in statistical parametric mapping (SPM). The study included 176 right-handed healthy participants (age range: 18-94years). A total of 90 brain regions for each subject were automatically extracted, based on the AAL atlas, and two nonlinear registration methods (Normalization and DARTEL Toolbox in SPM5) were applied. Three-way ANOVA was performed to estimate the effects of brain region, each registration method and each hemisphere on regional volumes. Age-related brain-volume changes were also investigated by linear regression analysis for each nonlinear registration method. Significant differences were found in volume among different brain regions (P<0.001) with the two nonlinear registration methods (P=0.011). Volumes of the corresponding brain region were significantly different (P=0.037) between two hemispheres, and age-related volume reductions were unevenly distributed across regions. The most dramatic decreases in volume were found in the bilateral insula, middle frontal regions and cingulum. Rankings of the decreased brain regional volumes differed between the two registration techniques and adjustment methods. The inferred age-related volume atrophy patterns based on the AAL atlas were largely dependent on the choice of registration methodology.


Common targets for a deadly duo of diabetes mellitus and colon cancer: Catching two fish with one worm.
Colon cancer is a major health issue and number of cases are increasing every year. Diabetes mellitus is also a significant health issue that is growing day by day worldwide having negative influences on the survival of individuals. Research has shown a strong relationship between the two malignant diseases. The risk of colon cancer with patients who have type 2 diabetes mellitus has spiked by 30%. The scientific research suggests insulin has a major role in the spread of cancer and the condition unifying between the two diseases is hyperinsulinemia. Several anti-diabetic agents are used for the treatment of type 2 diabetesmellitus. However, their mechanism of action against cancer activity is a question and only a few agents have shown positive signs of action in colon cancer associated with type 2 diabetesmellitus. Hence, the identification of targets, which is common for both colon cancer, associated with type 2 diabetesmellitus has become an urgent requirement. Novel targets such as Liver X receptors, Histone deacetylase inhibitors (HDACi), Glucose Transporters (GLUTs), Peroxisome proliferator activator receptors (PPARs), Dipeptidyl peptidase-IV inhibitors (DPP4i), Cyclin-dependent kinase 4 inhibitors (CDK4i), Estrogen receptors,Mechanistic target of rapamycin (mTOR), Insulin-like growth factor receptors (IGF) are some of the targets which are common for both, type 2 diabetesmellitus and colon cancer. This current review gives an overview of the targets (using one worm) which are common for both viz. diabetes mellitus and colon cancer (two fish).


Measurement of histamine release from human lung tissue ex vivo by microdialysis technique.
Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. Microdialysis fibers of 216 microm were inserted into lung tissue and perfused with Krebs Ringer buffer at a rate of 3 microl/min. After a 15 min period of steady-state perfusion, anti-IgE and vehicle were injected into the lung tissue above individual fibers. Samples from each fibre were collected for 20 min at 2 min intervals. Histamine was assayed fluorometrically. Anti-IgE concentrations of 40-40,000 U/ml dose-dependently released histamine, significant histamine release being demonstrated with anti-IgE concentrations of 400 U/ml and greater. The kinetics of histamine release showed peak values 2-8 min after the injection. Great individual responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue. The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment.


Craniofacial arteriovenous metameric syndrome (CAMS) 3--a transitional pattern between CAM 1 and 2 and spinal arteriovenous metameric syndromes.
We report a rare case of craniofacial arteriovenous metameric syndrome (CAMS) 3 arteriovenous malformations of the mandible, left VIII nerve and petrous bone. The patient, a 19-year-old girl, presented with profuse gingival bleeding during a dental procedure and we diagnosed CAMS 3 during a pre-embolisation angiogram. The distribution of the vascular lesions suggests that CAMS 3 is intermediate CAMS 1 and 2 and spinal arteriovenous metameric syndrome (SAMS).


Reproduction in chinchilla (Chinchilla lanigera): current status of environmental control of gonadal activity and advances in reproductive techniques.
A review of the biology of reproduction of chinchilla, focusing on environmental control of the gonadal activity, is presented. Chinchilla is a South American hystricomorph rodent genus currently considered almost extinct in the wild. However, a domestic form is still widespread in breeding farms around the world. Information regarding their reproductive biology has been obtained from studies on captive animals. In the case of Chinchilla lanigera, a seasonal reproductive pattern has been frequently reported in breeding facilities, but factors that might trigger gonadal activity have not been identified. The available information on reproductive productivity in farms worldwide shows a range of 1.2 to 2.4 deliveries per female per yr (with up to 2.1 weaned young per female per yr). Indeed, as found in all rodents, chinchillas can multiply at high fecundity and fertility rates (4 to 6 follicles mature during estrous cycles). Some new research avenues are postulated to improve the control of gonadal activity by means of environmental and/or pharmacologic factors. Furthermore, reproductive techniques that have been validated in chinchilla are reviewed (noninvasive hormone monitoring, semen collection, sperm cryopreservation, estrus induction), and several technical steps are proposed to be able to achieve AI. Because domesticated chinchilla still share some genomic characteristics with their counterparts in the wild, validated reproductive techniques in chinchilla males and females might contribute to the success of breeding programs.


Evaluation of a Primary Care Weight Management Program in Children Aged 2⁻5 years: Changes in Feeding Practices, Health Behaviors, and Body Mass Index.
Primary care offers a promising setting for promoting parenting practices that shape healthy eating and physical activity behaviors of young children. This study assessed the impact of a parent-based, primary care intervention on the feeding habits, health behaviors, and body mass index (BMI) of 2⁻5 year olds with elevated or rapidly-increasing BMI. Four private pediatric offices in West Michigan were assigned as control (n = 2) or intervention (n = 2) sites based on patient load and demographics. Treatment families were recruited at well-child visits to receive physician health-behavior counseling and four visits with a registered dietitian nutritionist (RDN) over a 6-month period. Intervention outcomes were age- and sex-specific BMI metrics, including BMI z-scores and percent of the 95th percentile (%BMIp95), the Family Nutrition and Physical Activity survey (FNPA), and the Feeding Practices and Structure Questionnaire (FPSQ). Of 165 enrolled families, 127 completed follow-up measures (77% retention). Mean (±SD) FNPA scores improved in treatment vs. control (4.6 ± 4.6 vs. 0.1 ± 4.2; p < 0.001), and screen time (h/day) decreased (-0.9 ± 1.8 vs. 0.3 ± 1.1; p < 0.001). Non-responsive feeding practices (i.e., reward for behavior (p = 0.006) and distrust in appetite (p < 0.015)) and structure-related feeding practices (structured meal timing (p < 0.001)) improved in treatment parents vs. controls. Reductions in child BMI measures did not differ between groups. Families with preschool children participating in a low-intensity, primary care intervention improved obesogenic health behaviors, parent feeding habits, and child screen time, but not child adiposity. Future research should assess the sustainability of these family lifestyle improvements, and evaluate their future impact on the health and development of the children.


Down-regulation of WWP2 aggravates Type 2 diabetes mellitus-induced vascular endothelial injury through modulating ubiquitination and degradation of DDX3X.
Endothelial injury caused by Type 2 diabetes mellitus (T2DM) is considered as a mainstay in the pathophysiology of diabetic vascular complications (DVCs). However, the molecular mechanism of T2DM-induced endothelial injury remains largely unknown. Here, we found that endothelial WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) act as a novel regulator for T2DM-induced vascular endothelial injury through modulating ubiquitination and degradation of DEAD-box helicase 3 X-linked (DDX3X). Single-cell transcriptome analysis was used to evaluate WWP2 expression in vascular endothelial cells of T2DM patients and healthy controls. Endothelial-specific Wwp2 knockout mice were used to investigate the effect of WWP2 on T2DM-induced vascular endothelial injury. In vitro loss- and gain-of-function studies were performed to assess the function of WWP2 on cell proliferation and apoptosis of human umbilical vein endothelial cells. The substrate protein of WWP2 was verified using mass spectrometry, coimmunoprecipitation assays and immunofluorescence assays. The mechanism of WWP2 regulation on substrate protein was investigated by pulse-chase assay and ubiquitination assay. The expression of WWP2 was significantly down-regulated in vascular endothelial cells during T2DM. Endothelial-specific Wwp2 knockout in mice significantly aggravated T2DM-induced vascular endothelial injury and vascular remodeling after endothelial injury. Our in vitro experiments showed that WWP2 protected against endothelial injury by promoting cell proliferation and inhibiting apoptosis in ECs. Mechanically, we found that WWP2 is down-regulated in high glucose and palmitic acid (HG/PA)-induced ECs due to c-Jun N-terminal kinase (JNK) activation, and uncovered that WWP2 suppresses HG/PA-induced endothelial injury by catalyzing K63-linked polyubiquitination of DDX3X and targeting it for proteasomal degradation. Our studies revealed the key role of endothelial WWP2 and the fundamental importance of the JNK-WWP2-DDX3X regulatory axis in T2DM-induced vascular endothelial injury, suggesting that WWP2 may serve as a new therapeutic target for DVCs.


STING deletion alleviates podocyte injury through suppressing inflammation by targeting NLRP3 in diabetic kidney disease.
An increasing number of studies have shown that immune inflammatory response plays a vital role in diabetic kidney disease (DKD). Nod-like receptor protein 3 (NLRP3) inflammasome-dependent inflammatory response is a key mechanism in the initiation and development of DKD. The stimulator of interferon genes (STING) is an adaptor protein that can drive noninfectious inflammation and pyroptosis. However, the mechanism of STING regulating immune inflammation and the interaction with NLRP3-dependent pyroptosis in high glucose state still remains unclear. This study evaluated the potential role of STING in high glucose (HG)-induced podocyte inflammation response. STING expression was significantly increased in db/db mice, STZ-treated diabetic mice, and HG-treated podocytes. Podocyte-specific deletion of STING alleviated podocyte injury, renal dysfunction, and inflammation in STZ-induced diabetic mice. STING inhibitor (H151) administration ameliorated inflammation and improved renal function in db/db mice. STING deletion in podocytes attenuated the activation of the NLRP3 inflammasome and podocyte pyroptosis in STZ-induced diabetic mice. In vitro, modulated STING expression by STING siRNA alleviated pyroptosis and NLRP3 inflammasome activation in HG-treated podocytes. NLRP3 over-expression offset the beneficial effects of STING deletion. These results indicate that STING deletion suppresses podocyte inflammation response through suppressing NLRP3 inflammasome activation and provide evidence that STING may be a potential target for podocyte injury in DKD.


The ovarian phenotype of the aromatase knockout (ArKO) mouse.
Targeted disruption of exon 9 of the cyp19 gene gives rise to a non-functional aromatase enzyme incapable of converting androgens to oestrogens. The aromatase knockout (ArKO) mouse is, thus, characterised by a dysfunctional pituitary-gonadal axis, which manifests in non-detectable levels of oestrogen in serum. These mice also exhibit elevated levels of circulating gonadotrophins (luteinising hormone (LH) and follicle stimulating hormone (FSH)) and testosterone. The ArKO mouse is infertile due to folliculogenic disruption and a failure to ovulate. The age-dependent ovarian phenotype revealed a block in follicular development at the antral stage and a complete absence of corpora lutea. By 21-23 weeks of age haemorrhagic cystic follicles were present and by 1 year there were abnormal follicles, an absence of secondary and antral follicles and atretic primary follicles. Interstitial tissue remodelling was extensive and exemplified by an increase in collagen deposition and an influx of macrophages, coincident with the loss of follicles. In mice, maintained on a soy-free and, thus, phytoestrogen-free diet, the ovarian phenotype was accelerated and exacerbated. In conclusion, the ovarian phenotype of the ArKO mouse can be attributed to the altered hormonal environment brought about by the absence of aromatase and the failure of androgens to be converted to oestrogens in the presence of elevated gonadotropins.


The experience of couples being given an oxygen concentrator to use at home: A longitudinal interpretative phenomenological analysis.
This longitudinal study explores the lived experience of four couples where one person from each couple is prescribed an oxygen concentrator to use at home. Transcripts were analysed using interpretative phenomenological analysis. The findings reported here focus on two super-ordinate themes: 'the journey of acceptance' and 'negotiating changing relationships'. Participants described a gradual process of accepting the device into their lives, the impact on couple's relationships and the role that expectations have in mediating that process. These themes suggest that patient education that considers the psychological and social issues may prove useful in facilitating the acceptance process.