MICRO syndrome: an entity distinct from COFS syndrome.
Children born with the findings of microcephaly, cataracts and microcornea can result not only from a prenatal viral infection, but also from an autosomal recessive Mendelian disorders. We present three pairs of affected siblings with MICRO syndrome, who were born with congenital microcephaly, microcornea, and cataracts. MICRO syndrome is an autosomal recessive syndrome consisting of congenital microcephaly, cortical dysplasia, microcornea, cataracts, optic atrophy, severe mental retardation, hypotonic diplegia, and hypogenitalism. At birth, MICRO syndrome resembles Cerebro-Oculo-Facio-Skeletal (COFS) syndrome, but it differs in the lack of the rapidly progressive neurologic features leading to severe brain atrophy with calcifications. Patients with MICRO syndrome manifest frontal cortical dysplasia, hypoplasia of the corpus callosum, cortical blindness with optic atrophy, profound mental retardation, and progressive joint contractures with growth failure. COFS syndrome shares also many clinical and cellular similarities with Cockayne syndrome (CS), and cultured cells in both conditions demonstrate hypersensitivity to ultraviolet (UV) radiation due to impaired nucleotide excision repair (NER). NER studies in cultured fibroblasts from MICRO patients give normal results, so MICRO syndrome should be considered in children with features resembling COFS syndrome and CS, but who have normal NER. MICRO should be distinguished from other similar clinical disorders with normal NER by the presence of significant visual impairment and cortical blindness despite early surgery for congenital cataracts, frontal polymicrogyria, thin corpus callosum, and cortical atrophy by MRI.


[Current smoking status and awareness of tobacco hazard in adults in Beijing, 2014].
Objective: To understand the status of current smoking and awareness of hazard in adults in Beijing, 2014. Methods: A total of 19 815 subjects were randomly selected with stratified multi-stage cluster sampling from 180 communities of 36 townships of 16 districts in Beijing. Each subject received a standardized questionnaire interview. Results: The current smoking rate of the adults was 26.6% (5 253/19 738), which was higher in men (52.2%) than in women (3.6%) and higher in suburb area (28.9%) than in urban area (25.0%). The adults aged 50-59 had higher rate of current smoking. The daily smoking rate was 23.7% (4 677/19 738). The average age when smoking started was 19.2 years. On average, one smoker consumed 15.2 cigarettes per day. The average score for smoking hazard awareness was 5.8, which was higher in smokers than in non-smokers (5.5 vs. 6.0) (t=-9.854, P=0.000). In the smokers, 5.7% (298/5 213) intended to give up smoking within one month. Doctors gave advice to stop smoking for 66.0% of current smokers. The current smoking rate of patients with chronic disease was 31.8% (3 703/11 628), and 5.5% (202/3 686) of them intended to stop smoking within one month. Conclusions: The smoking rate was still high in men in Beijing. The age of starting smoking every day decreased among younger people. The levels of awareness of tobacco hazard and passive smoking were still low. The willingness of smoking cessation was low. The rate of doctor giving smoking cessation advice was low.


Preparation and In Vivo Evaluation of Rosmarinic Acid-Loaded Transethosomes After Percutaneous Application on a Psoriasis Animal Model.
The topical use of rosmarinic acid (RA) in skin inflammatory pathologies is restricted due to its poor water solubility, poor permeability, and chemical instability. In this study, RA-loaded transethosomes-in-Carbopol® formulations have been developed to evaluate its anti-inflammatory activity on imiquimod-induced psoriasis-like skin inflammation in mice. In vitro release profiles demonstrated sustained behavior due to the retentive action of gel and the entrapment of RA into the vesicles. However, the low viscosity of the combined formulation increased the drug release rate. Animal evaluation of anti-inflammatory activity demonstrated that transethosomes-in-gel containing dexamethasone (Dex-TE-Gel), as positive control, showed effect in all the pro-inflammatory parameters evaluated, evidencing that these drug-loaded nanocarriers have been effectively reached the site of action. In addition, transethosomes-in-gel containing RA (RA-TE-Gel) formulations produced a great reduction in the punch edema (P < 0.001) and in TNF-α and IL-6 (P < 0.05). However, non-significant differences were obtained for IL-1β, IL17, and MPO. Despite the protecting effect of Carbopol® and transethosomes on oxidation index and antioxidant activity of RA over the 7 days of treatment, however, a degradation process of this antioxidant to caffeic acid may be the cause of these in vivo results. We have also checked that the pH existing into the intercellular space of damaged cells (pH 6.8) may be affecting. Therefore, our results suggest that RA-TE-Gel could act as an effective RA formulation for skin delivery; further studies will help to understand the loss of activity at the cellular level.


Involvement of local orphanin FQ in the tolerance induced by repeated microinjections of morphine into ventrolateral periaqueductal gray in rats.
The present study evaluated the role of ventrolateral periaqueductal gray (vlPAG)-located orphanin-FQ (OFQ) in the opioid tolerance induced by repeated microinjections of morphine (MOR) into vlPAG. Microinjection of MOR (5 microg/0.5 microl) into vlPAG caused antinociception as quantified with the tail flick and the hot plate tests. When MOR microinjection was repeated twice daily, the antinociceptive effect disappeared within 2 days (tolerance). However, if MOR microinjection was preceded by the OFQ receptor antagonist nocistatin (NST; 1 ng/0.5 microl), the microinjections of MOR did not induce tolerance. If NST microinjections were suspended, subsequent MOR microinjections induced tolerance. In MOR-tolerant rats, a single NST microinjection into vlPAG was enough to restore the antinociceptive effect of MOR. Furthermore, if OFQ (1 ng/0.5 microl) was microinjected into vlPAG, then a MOR microinjection administered 15 min later into vlPAG did not elicit antinociception. Finally, opioid tolerance induced by repeated systemic MOR injections (5 mg/kg, i.p.) was reversed by a single microinjection of NST into vlPAG. This emphasizes the central importance of vlPAG-located OFQ in the MOR tolerance.


Antioxidant polyphenols from tart cherries (Prunus cerasus).
Montmorency and Balaton tart cherries were lyophilized and sequentially extracted with hexane, ethyl acetate, and methanol. Methanolic extracts of dried Balaton and Montmorency tart cherries (Prunus cerasus) inhibited lipid peroxidation induced by Fe(2+) at 25 ppm concentrations. Further partitioning of this methanol extract with EtOAc yielded a fraction that inhibited lipid peroxidation by 76% at 25 ppm. Purification of this EtOAc fraction afforded eight polyphenolic compounds, 5,7,4'-trihydroxyflavanone (1), 5,7, 4'-trihydroxyisoflavone (2), chlorogenic acid (3), 5,7,3', 4'-tetrahydroxyflavonol-3-rhamnoside (4), 5,7,4'-trihydroxyflavonol 3-rutinoside (5), 5,7,4'-trihydroxy-3'methoxyflavonol-3-rutinoside (6), 5,7,4'-trihydroxyisoflavone-7-glucoside (7), and 6, 7-dimethoxy-5,8,4'-trihydroxyflavone (8), as characterized by (1)H and (13)C NMR experiments. The antioxidant assays revealed that 7-dimethoxy-5,8,4'-trihydroxyflavone (8) is the most active, followed by quercetin 3-rhamnoside, genistein, chlorogenic acid, naringenin, and genistin, at 10 microM concentrations.


Influence of nicotine and cotinine impregnation on the first step of periodontal regeneration: clot stabilization.
This study analyzes the clot stabilization on root surfaces of teeth impregnated with cotinine and nicotine and the influence of the scaling in the adhesion of blood components, observing the influence of new exposition to nicotine and/or cotinine after scaling. Fifteen human teeth extracted due to periodontal disease of non-smokers patients were selected and manually scaled. Four dentin blocks were obtained from each tooth (n = 60). Samples received blood application or reimpregnation with nicotine and/or cotinine, depending on the groups. Group 1: PBS immersion + root scaling + blood; group 2: nicotine + root scaling + blood; group 3: nicotine + root scaling + nicotine reapplication + blood; group 4: cotinine + root scaling + blood; group 5: cotinine + root scaling + cotinine reapplication+ blood; group 6: nicotine and cotinine + root scaling + nicotine and cotinine + blood. Samples were kept in 2 ml of each substance for 24 hours. Each group received a blood drop and was analyzed by SEM. The higher amount of blood components was present in teeth exposed to cotinine and the groups submitted to scaling and blood application in comparison with groups that received reapplication of toxic substances after scaling. The greater toxic effect on root dentin surface was after the exposure to nicotine and cotinine. Results suggest that periodontal healing may be delayed in smokers due to the direct inhibition of clot stabilization on the root surface when nicotine and cotinine are present concomitantly.


Estradiol promotes M1-like macrophage activation through cadherin-11 to aggravate temporomandibular joint inflammation in rats.
Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17β-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α-induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs.


Clinical trials of cancer therapies targeting prostate-specific membrane antigen.
Prostate cancer is the most common non-cutaneous cancer of men in the United States and represents their second-leading cause of cancer-related death. Metastatic disease is largely resistant to conventional chemotherapies, and targeted therapies are urgently needed. Prostate-specific membrane antigen (PSMA) is a prototypical cell-surface marker of prostate cancer. PSMA is an integral, non-shed, type 2 membrane protein with abundant and nearly universal expression in prostate carcinoma, but has limited extra-prostatic expression. In addition, PSMA is expressed in the neovasculature of other solid tumors. These findings have spurred development of PSMA-targeted therapies for cancer, and first-generation products have entered clinical testing. Vaccine approaches have included recombinant protein, nucleic acid and cell-based strategies, and anti-PSMA immune responses have been demonstrated in the absence of significant toxicity. Therapy with drug-conjugated and radiolabeled antibodies has yielded objective clinical responses as measured by reductions in serum prostate-specific antigen and/or imageable tumor volume. However, responses were observed in a minor fraction of patients and at doses near the maximum tolerated dose. Overall, these initial studies have provided measured proof of concept for PSMA-based therapies, and second-generation antibody and vaccine products may hold the key to exploit PSMA for molecularly targeted therapy of prostate and other cancers.


Thin graphene oxide nanoflakes modulate glutamatergic synapses in the amygdala cultured circuits: Exploiting synaptic approaches to anxiety disorders.
Anxiety disorders (ADs) are nervous system maladies involving changes in the amygdala synaptic circuitry, such as an upregulation of excitatory neurotransmission at glutamatergic synapses. In the field of nanotechnology, thin graphene oxide flakes with nanoscale lateral size (s-GO) have shown outstanding promise for the manipulation of excitatory neuronal transmission with high temporal and spatial precision, thus they were considered as ideal candidates for modulating amygdalar glutamatergic transmission. Here, we validated an in vitro model of amygdala circuitry as a screening tool to target synapses, towards development of future ADs treatments. After one week in vitro, dissociated amygdalar neurons reconnected forming functional networks, whose development recapitulated that of the tissue of origin. When acutely applied to these cultures, s-GO flakes induced a selective modification of excitatory activity. This type of interaction between s-GO and amygdalar neurons may form the basis for the exploitation of alternative approaches in the treatment of ADs.


Complementary and alternative therapies for treatment of insomnia in women in postmenopause.
Menopause is an important episode in the life of women and, for the great majority of women, occurs in their fifties. The climacteric period, which is often associated with insomnia, represents one of the most important changes in the female reproductive cycle because it marks the end of reproductive capacity. Hormonal therapy has been considered the most useful and standardized method for treating menopause and climacteric-associated symptoms despite its side-effects. The present study is a review of the scientific literature about the efficacy, toxicity and safety of complementary and alternative therapies used as alternatives to hormone therapy to treat insomnia in menopausal women. Mind-body therapies and the use of isoflavonoids have exhibited promise as interventions for treating insomnia in the climacteric at our Walk-In Clinic of Sleep Disturbance at the Universidade Federal de São Paulo. This review will describe the use of complementary and alternative therapies and their effectiveness in treating insomnia in this period of a woman's life.


Antigen spacing on protein nanoparticles influences antibody responses to vaccination.
Immunogen design approaches aim to control the specificity and quality of antibody responses to enable the creation of next-generation vaccines with improved potency and breadth. However, our understanding of the relationship between immunogen structure and immunogenicity is limited. Here we use computational protein design to generate a self-assembling nanoparticle vaccine platform based on the head domain of influenza hemagglutinin (HA) that enables precise control of antigen conformation, flexibility, and spacing on the nanoparticle exterior. Domain-based HA head antigens were presented either as monomers or in a native-like closed trimeric conformation that prevents exposure of trimer interface epitopes. These antigens were connected to the underlying nanoparticle by a rigid linker that was modularly extended to precisely control antigen spacing. We found that nanoparticle immunogens with decreased spacing between closed trimeric head antigens elicited antibodies with improved hemagglutination inhibition (HAI) and neutralization potency as well as binding breadth across diverse HAs within a subtype. Our "trihead" nanoparticle immunogen platform thus enables new insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used to generate next-generation vaccines against influenza and other viruses.


Energy metabolism of human LoVo colon carcinoma cells: correlation to drug resistance and influence of lonidamine.
The relationship between modification of energy metabolism and extent of drug resistance was investigated in two sublines (LoVoDX and LoVoDX10) from human LoVo colon carcinoma cells that exhibit different degrees of resistance to doxorubicin. Results indicated that the extent of alteration in energy metabolism strictly correlated with degree of resistance. In LoVoDX cells, only 14CO2 production was enhanced, whereas in the more resistant LoVoDX10 cells, both 14CO2 and aerobic lactate production were stimulated. The basal and glucose-supported efflux rate and the amount of drug extruded by LoVoDX10 cells were significantly higher than in the resistant LoVoDX cells. Because the expression of surface P-170 glycoprotein was similar in both cell lines, this phenomenon was attributed to increased efflux pump activity resulting from greater ATP availability. Inhibition of 14CO2 production, aerobic glycolysis, and clonogenic activity by lonidamine (LND) increased with enhancement of the energy metabolism. Moreover, LND, by affecting energy-yielding processes, reduced intracellular ATP content, lowered the energy supply to the ATP-driven efflux pump, and inhibited, almost completely, doxorubicin extrusion by resistant LoVo cells. These findings strongly suggest that LND, currently used in tumor therapy, reduces drug resistance by restoring the capacity to accumulate and retain drug of cells with the MDR phenotype that overexpress P-170.


Chirp-induced dynamics of femtosecond filaments in air.
We investigate the influence of a chirped phase on femtosecond pulses propagating in air. Pulses with an initially negative chirp are temporally compressed by compensation with group-velocity dispersion. We demonstrate that this property, combined with plasma defocusing, can be used to trigger filamentation at different foci, increase self-guiding ranges, or even shorten pulse duration.


Ocular hypertension following Nd:YAG laser capsulotomy: a potentially blinding complication.
A dense secondary membrane was treated with a Nd:YAG laser capsulotomy with marked improvement in visual acuity, from count fingers to 6/9 (20/40). Four hours following therapy, visual acuity in the treated eye was no light perception, due to extreme ocular hypertension (over 80 mm Hg). The extreme elevation in intraocular pressure appears to have been caused by cellular debris obstructing the trabecular meshwork in an angle already compromised by angle recession. An emergency paracentesis was successful in restoring the visual acuity.


Identifying the factors that facilitate or hinder advance planning by persons with dementia.
We performed semistructured interviews with 30 family members of patients with advanced dementia to identify the factors that facilitate or hinder advance planning by persons with dementia. All interviews were analyzed using qualitative data analysis techniques. The majority (77%) of family members reported that their relative had some form of written advance directive, and at least half reported previous discussions about health care preferences (57%), living situation or placement issues (50%), and finances or estate planning (60%) with the patient. Family members reported some themes that prompted planning and others that were barriers to planning. Events that most often triggered planning were medical, living situation, or financial issues associated with a friend or family member of the patient (57%). Barriers to planning included both passive and active avoidance. The most common form of passive avoidance was not realizing the importance of planning until it was too late to have the discussion (63%). The most common form of active avoidance was avoiding the discussion (53%). These data suggest potentially remediable strategies to address barriers to advance planning discussions.


The impact of lipopolysaccharide on cerebrovascular function and cognition resulting from obesity-induced gut dysbiosis.
Obesity is a worldwide epidemic coinciding with a concomitant increase in the incidence of neurodegenerative diseases, particularly dementia. Obesity is characterised by increased adiposity, chronic low-grade systemic inflammation, and oxidative stress, which promote endothelial dysfunction. Endothelial dysfunction reduces cerebrovascular function leading to reduced cerebral blood flow and, eventually, cognitive decline, thus predisposing to a neurodegenerative disease. Obesity is also characterised by gut dysbiosis and a subsequent increase in the lipopolysaccharide which increasingly activates toll-like receptor 4 (TLR4) and further promotes chronic low-grade systemic inflammation. This also disrupts the crosstalk within the gut-brain axis, thus influencing the functions of the central nervous system, including cognition. However, the mechanisms by which obesity-related increases in oxidative stress, inflammation and endothelial dysfunction are driven by, or associated with, increased systemic lipopolysaccharide leading to reduced cerebrovascular function and cognition, beyond normal ageing, have not been elucidated. Hence, this review examines how increased concentrations of lipopolysaccharide and the subsequent increased TLR4 activation observed in obesity exacerbate the development of obesity-induced reductions in cerebrovascular function and cognition.


Domain specific relationships of 2D:4D digit ratio in risk perception and risk behavior.
The 2D:4D digit ratio (henceforth, 2D:4D) is accepted as a marker of prenatal testosterone, demonstrating gender differences. The present study reveals that 2D:4D shows not only gender differences but also individual differences in personality and risk-taking behavior. We measured individual participants' 2D:4D, structural personality, and risk-taking attitude scores. The result of the current study replicates the gender difference in 2D:4D in previous researches. However, we found different aspects of the correlations among 2D:4D, personality, and risk-taking attitude. Path analyses indicated that 2D:4D passes through personality factors before reaching the risk-taking attitude, particularly in the financial domain activities of investing and gambling. Also we observed a specific relationship between right-hand 2D:4D and emotionality and between left-hand 2D:4D and agreeableness. Finally, we suggest multiple path models of 2D:4D and personality in risk taking depending on the domain.


The role of colour Doppler ultrasonography in the diagnosis of fascial space infections - a cross sectional study.
(1) To evaluate the role of ultrasonography with colour Doppler in the diagnosis of fascial space infections, (2) To determine the nature, size and extent of the odontogenic infections which involve the primary and secondary fascial spaces of the maxilla and the mandible (3) To evaluate the sensitivity of ultrasonography in determining whether the inflammatory process is in a stage of cellulitis or abscess and to thus determine the appropriate time for a surgical intervention during the course of the infection and to correlate the clinical and radiographic findings with the ultrasonographic findings and (4) to determine the treatment plan. Thirty four patients with odontogenic infections which involved the superficial and the deep fascial spaces of the head and neck were subjected to ultrasonographic examinations over the suspected area in the transverse and axial directions to determine the stage of the infection, its anatomic location and the treatment plan. Ultrasonography showed 95.7% sensitivity and 100% specificity as compared to the clinical and radiographic diagnoses and it proved to be an effective investigation modality in the diagnosis of fascial space infections.


Development of the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement therapy (ERT) in CLN2 Disease" Based on 6 Years Treatment Experience in 48 Patients.
Intracerebroventricular enzyme replacement therapy (ICV-ERT) for CLN2 disease represents the first approved treatment for neuronal ceroid lipofuscinosis (NCL) diseases. It is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral ventricles to reach the central nervous system, the organ affected in CLN2 disease. If untreated, CLN2 children show first symptoms such as epilepsy and language developmental delay at 2-4 years followed by rapid loss of motor and language function, vision loss, and early death. Treatment with cerliponase alfa has shown to slow the rapid neurologic decline. However, the mode of administration by 4 hour-long intracerebroventricular infusions every 14 days represents a potentially greater risk of infection compared to intravenous enzyme replacement therapies. The Hamburg NCL Specialty Clinic was the first site worldwide to perform intracerebroventricular enzyme replacement therapy in children with CLN2 disease. In order to ensure maximum patient safety, we analysed data from our center from more than 3000 intracerebroventricular enzyme replacement therapies in 48 patients over 6 years with regard to the occurrence of device-related adverse events and device infections. Since starting intracerebroventricular enzyme replacement therapy, we have also developed and continuously improved the "Hamburg Best Practice Guidelines for ICV-Enzyme Replacement Therapy (ERT) in CLN2 Disease." Results from this study showed low rates for device-related adverse events and infections with 0.27% and 0.33%, respectively. Therefore, following our internal procedural guidelines has shown to improve standardization and patient safety of intracerebroventricular enzyme replacement therapy for CLN2 disease.


Inhibition of Pro-apoptotic BAX by a noncanonical interaction mechanism.
BCL-2 is a negative regulator of apoptosis implicated in homeostatic and pathologic cell survival. The canonical anti-apoptotic mechanism involves entrapment of activated BAX by a groove on BCL-2, preventing BAX homo-oligomerization and mitochondrial membrane poration. The BCL-2 BH4 domain also confers anti-apoptotic functionality, but the mechanism is unknown. We find that a synthetic α-helical BH4 domain binds to BAX with nanomolar affinity and independently inhibits the conformational activation of BAX. Hydrogen-deuterium exchange mass spectrometry demonstrated that the N-terminal conformational changes in BAX induced by a triggering BIM BH3 helix were suppressed by the BCL-2 BH4 helix. Structural analyses localized the BH4 interaction site to a groove formed by residues of α1, α1-α2 loop, and α2-α3 and α5-α6 hairpins on the BAX surface. These data reveal a previously unappreciated binding site for targeted inhibition of BAX and suggest that the BCL-2 BH4 domain may participate in apoptosis blockade by a noncanonical interaction mechanism.


Circulating carcinoembryonic antigen (CEA): relationship to clinical status of patients with inflammatory bowel disease.
Plasma levels of circulating carcinoembryonic antigen (CEA) were measured by zirconyl phosphate gel radioimmunoassay in 112 patients with chronic inflammatory bowel disease. The levels were then related to category, extent, duration, and severity of disease, as well as to the ages and surgical status of the patients. The distribution of CEA levels and their mean values were significantly raised over the levels in 33 normal control subjects, and were similar among patients with ulcerative colitis compared with those with granulomatous bowel disease. Positive values were defined as those in excess of 2.5 ng/ml. Positive assays occurred in 42% of ulcerative colitis patients, in 38% of Crohn's disease patients, and in 40% of the total group with inflammatory bowel disease. Among normal control subjects, only 3% were positive. Among inflammatory bowel disease patients, positive CEA assays occurred more frequently with more severe disease, more extensive anatomical involvement, younger ages, and shorter duration of disease. Those patients who had undergone total colectomy showed levels of circulating CEA and frequency of CEA positivity similar to those of an age-matched normal control group. Levels of CEA did not correspond with known cancer risk factors in patients with inflammatory bowel disease. Although rising or persisting plasma CEA values unrelated to severity and extent of disease may indicate an unfavourable prognosis in cancer, this study shows that a single CEA value in patients with chronic inflammatory bowel disease is not a reliable indicator of cancer risk.


Trisiloxane Surfactants Negatively Affect Reproductive Behaviors and Enhance Viral Replication in Honey Bees.
Trisiloxane surfactants are often applied in formulated adjuvant products to blooming crops, including almonds, exposing the managed honey bees (Apis mellifera) used for pollination of these crops and persisting in colony matrices, such as bee bread. Despite this, little is known regarding the effects of trisiloxane surfactants on important aspects of colony health, such as reproduction. In the present study, we use laboratory assays to examine how exposure to field-relevant concentrations of three trisiloxane surfactants found in commonly used adjuvant formulations affect queen oviposition rates, worker interactions with the queen, and worker susceptibility to endogenous viral pathogens. Trisiloxane surfactants were administered at 5 mg/kg in pollen supplement diet for 14 days. No effects on worker behavior or physiology could be detected, but our results demonstrate that hydroxy-capped trisiloxane surfactants can negatively affect queen oviposition and methyl-capped trisiloxane surfactants cause increased replication of Deformed Wing Virus in workers, suggesting that trisiloxane surfactant use while honey bees are foraging may negatively impact colony longevity and growth. Environ Toxicol Chem 2023;00:1-12. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.


Anticipatory postural muscle activity associated with bilateral arm flexion while standing in individuals with spastic diplegic cerebral palsy: A pilot study.
Compared to automatic postural responses to external perturbation, little is known about anticipatory postural adjustments in individuals with spastic diplegic cerebral palsy. In this study, we examined whether anticipatory activation of postural muscles would be observed before voluntary arm movement while standing in individuals with spastic diplegia. Seven individuals with spastic diplegia (SDCP(group), 12-22 years) and 7 age- and gender-matched individuals without disability (Control(group)) participated in this study. Participants performed bilateral arm flexion at maximum speed at their own timing while standing, during which electromyographic (EMG) activities of focal and postural muscles were recorded. In both groups, the erector spinae (ES) and medial hamstring (MH) muscles were activated in advance of the anterior deltoid muscle (AD), which is a focal muscle of arm flexion. Although start times of ES and MH with respect to AD were similar in the 2 groups, increases in EMG amplitudes of ES and MH in the anticipatory range from -150ms to +50ms, with respect to burst onset of AD, were significantly smaller in the SDCP(group) than in the Control(group). These findings suggest that individuals with spastic diplegia have the ability to anticipate the effects of disturbance of posture and equilibrium caused by arm movement and to activate postural muscles in advance of focal muscles. However, it is likely that the anticipatory increase in postural muscle activity is insufficient in individuals with spastic diplegia.


Hypercalcaemia in "non-secretory" myeloma.
A patient is described with hypercalcaemia due to myelomatosis without paraproteinaemia or Bence-Jones proteinuria. Immunological investigations yielded some evidence of intra-cellular immunoglobulin production. Histological features suggested the secretion of osteoclast activating factor. Relevant experimental work in support of this interpretation is reviewed.


Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function.
Adaptor protein, phosphotyrosine interaction, pleckstrin homology domain and leucine zipper containing 1 (APPL1) is an adapter protein that positively mediates adiponectin signalling. Deficiency of APPL1 in the target tissues of insulin induces insulin resistance. We therefore aimed, in the present study, to determine its role in regulating pancreatic beta cell function. A hyperglycaemic clamp test was performed to determine insulin secretion in APPL1 knockout (KO) mice. Glucose- and adiponectin-induced insulin release was measured in islets from APPL1 KO mice or INS-1(832/13) cells with either APPL1 knockdown or overproduction. RT-PCR and western blotting were conducted to analyse gene expression and protein abundance. Oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential were assayed to evaluate mitochondrial function. APPL1 is highly expressed in pancreatic islets, but its levels are decreased in mice fed a high-fat diet and db/db mice compared with controls. Deletion of the Appl1 gene leads to impairment of both the first and second phases of insulin secretion during hyperglycaemic clamp tests. In addition, glucose-stimulated insulin secretion (GSIS) is significantly decreased in islets from APPL1 KO mice. Conversely, overproduction of APPL1 leads to an increase in GSIS in beta cells. In addition, expression levels of several genes involved in insulin production, mitochondrial biogenesis and mitochondrial OCR, ATP production and mitochondrial membrane potential are reduced significantly in APPL1-knockdown beta cells. Moreover, suppression or overexproduction of APPL1 inhibits or stimulates adiponectin-potentiated GSIS in beta cells, respectively. Our study demonstrates the roles of APPL1 in regulating GSIS and mitochondrial function in pancreatic beta cells, which implicates APPL1 as a therapeutic target in the treatment of type 2 diabetes.


[External auditory canal cholesteatoma with chronic renal failure or hemodialysis].
External auditory canal cholesteatoma (EACC) is a rare otologic disease, characterized by focal osteonecrosis, sequestration and overlying epithelial loss of the bony external auditory canal (EAC). The etiology and pathogenesis of EACC remain controversial. There are only 2 reports on the association between EACC and chronic renal failure (CRF)/hemodialysis (HD). METHOD & RESULT: (1) This study reviewed seven EACC cases with CRF. The mean age was 68.4 years (range: 56 -81 years), and the male-female ratio was 5:2. There were 12 ears with EACC (5 cases were bilateral and 2 cases were unilateral). The EACCs were found in the inferior or posterior inferior part of the EAC in 11 ears. The number of the ears in stage III or IV was 6. Five cases were on HD. (2) Seventy-six cases with CRF on HD were examined for EACC, and 2 out of those 70 cases were diagnosed as having EACC. (3) A comparative study of the 7 EACC cases on HD and 68 non-EACC cases on HD revealed no significant differences in the sex, age, period on CRF/HD, complications (diabetes mellitus or skin disease), smoking, ear cleaning and the use of an earphone or a hearing aid. Six out of all 9 EACC cases with CRF developed bilaterally, and in the inferior or posterior inferior part of the EAC, which implies a common pathological condition that contributes to the development of EACC. The mean age of 9 patients with EACC was relatively older (66.7 years), therefore age-related changes in the EAC are suspected in the cases with CRF on HD. The patients with CRF on HD have a high incidence of EACC. This strongly suggests the association between EACC and CRF/HD, but the mechanism of this pathogenesis has not been revealed.


The Effect of Expert Feedback on Antibiotic Prescribing in Pediatrics: Experimental Evidence.
Background. Inappropriate prescribing of antibiotics, which is common in pediatric care, is a key driver of antimicrobial resistance. To mitigate the development of resistance, antibiotic stewardship programs often suggest the inclusion of feedback targeted at individual providers. Empirically, however, it is not well understood how feedback affects individual physicians' antibiotic prescribing decisions. Also, the question of how physicians' characteristics, such as clinical experience, relate to antibiotic prescribing decisions and to responses to feedback is largely unexplored. Objective. To analyze the causal effect of descriptive expert feedback (and individual characteristics) on physicians' antibiotic prescribing decisions in pediatrics. Design. We employed a randomized, controlled framed field experiment, in which German pediatricians (n=73) decided on the length of first-line antibiotic treatment for routine pediatric cases. In the intervention group (n=39), pediatricians received descriptive feedback in form of an expert benchmark, which allowed them to compare their own prescribing decisions with expert recommendations. The recommendations were elicited in a survey of pediatric department directors (n=20), who stated the length of antibiotic therapies they would choose for the routine cases. Pediatricians' characteristics were elicited in a comprehensive questionnaire. Results. Providing pediatricians with expert feedback significantly reduced the length of antibiotic therapies by 10% on average. Also, the deviation of pediatricians' decisions from experts' recommendations significantly decreased. Antibiotic therapy decisions were significantly related to pediatricians' clinical experience, risk attitudes, and personality traits. The effect of feedback was significantly associated with physicians' experience. Conclusion. Our results indicate that descriptive expert feedback can be an effective means to guide pediatricians, especially those who are inexperienced, toward more appropriate antibiotic prescribing. Therefore, it seems to be suitable for inclusion in antibiotic stewardship programs.


Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes.
CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined. Expression of CDC25A, CDC25B, CDC25C and phosphorylated (phospho)-CDC25C (Ser216) were examined in 300 vulvar carcinomas using immunohistochemistry. Western blot analysis was utilized to demonstrate CDC25s expression in vulvar cancer cell lines. Kinase and phosphatase assays were performed to exclude cross reactivity among CDC25s isoform antibodies. High nuclear CDC25A and CDC25B expression were observed in 51% and 16% of the vulvar carcinomas, respectively, whereas high cytoplasmic CDC25C expression was seen in 63% of the cases. In cytoplasm, nucleus and cytoplasm/nucleus high phospho-CDC25C (Ser216) expression was identified in 50%, 70% and 77% of the carcinomas, respectively. High expression of CDC25s correlated significantly with malignant features, including poor differentiation and infiltration of vessel for CDC25B, high FIGO stage, presence of lymph node metastases, large tumor diameter, poor differentiation for CDC25C and high FIGO stage, large tumor diameter, deep invasion and poor differentiation for phospho-CDC25C (Ser216). In univariate analysis, high expression of phospho-CDC25C (Ser216) was correlated with poor disease-specific survival (p = 0.04). However, such an association was annulled in multivariate analysis. Our results suggest that CDC25C and phospho-CDC25C (Ser216) play a crucial role and CDC25B a minor role in the pathogenesis and/or progression of vulvar carcinomas. CDC25B, CDC25C and phospho-CDC25C (Ser216) were associated with malignant features and aggressive cancer phenotypes. However, the CDC25s isoforms were not independently correlated to prognosis.


Maternal high salt diet altered Adenosine-mediated vasodilatation via PKA/BK channel pathway in offspring rats.
High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via protein kinase A (PKA) pathway in coronary arteries. Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K+ channels and Adenosine signal pathways. Adenosine-mediated vasodilatation was reduced in coronary arteries in HS. There was no difference in gene expression of A2A receptors between the two groups. After pretreatment with PKA inhibitor, vasodilatation to Adenosine was decreased to a smaller extent in HS than that in control. Forskolin (activator of adenylate cyclase)-mediated vasodilatation was decreased in HS. Iberiotoxin (large-conductance Ca2+ -activated K+ channel [BK channel] inhibitor) attenuated Forskolin-induced vasodilatation in control, not in HS group. Currents of BK channels decreased in coronary artery smooth muscle cells, and PKA-modulated BK channel functions were declined. Protein levels of BK β1 and PKA C-subunits in coronary arteries of HS offspring were reduced. Prenatal HS diets altered Adenosine-mediated coronary artery vasodilatation in the offspring, which was linked to downregulation of cAMP/PKA/BK channel pathway.


Pregnancy of Unknown Location: The Value of Frozen Section Analysis and Its Relation to Beta-hCG Levels and Endometrial Thickness.
Frozen section examination is a rapid method for identifying products of conception in endometrial curetting, yet its accuracy is inconclusive. The purposes of this study is to determine the accuracy of frozen section analysis of endometrial curetting in pregnancies of unknown location, and to verify the relation of β-human chorionic gonadotrophin (hCG) level and endometrial thickness to the assessed accuracy. We reviewed data from January 2009 to December 2014 of diagnostic curettages from women with suspected ectopic pregnancies sent for frozen section examination at a medical center. A frozen section diagnosis was considered accurate if it concurred with the final pathologic diagnosis. Of 106 frozen section studies, the diagnosis was accurate in 94 (88.7%). Of 79 specimens interpreted as negative on frozen sections (no products of conception noted), 9 (11.4%) were positive on final pathologic review. Three of the 27 (11.1%) specimens interpreted as positive by a frozen section failed to demonstrate products of conception on a final pathologic section. The sensitivity of frozen sections in the diagnosis of ectopic pregnancy was 72.7%, specificity 95.9%, positive predictive value 88.9%, negative predictive value 88.6%, and accuracy 88.6%. A statically significant correlation was found between β-hCG level and high accuracy of the frozen section technique (p < 0.001). No correlation was found between endometrial thickness and the accuracy of the frozen section technique. The accuracy of frozen section examination was high and was found to correlate with β-hCG level, but not with endometrial thickness.


Montreal Cognitive Assessment Performance among Community-Dwelling African Americans.
To report descriptive and normative data for the Montreal Cognitive Assessment (MoCA) in a population-based African American sample. The MoCA was administered to 1,419 African American participants (mean age 49.89 years, range 18-75, 64% female). After excluding those with subjective cognitive complaints (n = 301), normative data were generated by education and overlapping age ranges (n = 1,118). Pearson correlations and analysis of variance were used to examine the relationship to demographic variables, and frequency of missed items was reviewed. Total MoCA scores (mean 22.3, SD 3.9) were lower than previously published normative data derived from an elderly Caucasian Canadian population with 80% falling below the suggested cutoff (<26) for impairment. Several MoCA items were missed by a large portion of the sample, including cube drawing (72%), delayed free recall (66% <4/5 words), sentence repetition (63%), and abstraction items (45%). This is the first study to examine normative performance on the MoCA specific to community-dwelling African Americans. Findings suggest that certain aspects of this measure and previously established cutoff scores may not be well-suited for some populations.


Bilingual children's language abilities and early reading outcomes in Head Start and kindergarten.
The purpose of this study was to investigate the relationship between Head Start children's receptive language development and their kindergarten reading outcomes. Eighty-eight bilingual children who were eligible to attend Head Start for 2 years participated in the study. Growth curve models were used to examine the relationship between children's language abilities during 2 years in Head Start and end-of-kindergarten reading outcomes. The results revealed that children's English and Spanish receptive language abilities increased during Head Start, and children's early reading abilities in English were within the typical range of monolingual norms at the end of kindergarten. Children's early reading abilities in Spanish were nearly 1 SD below the test mean or lower. The results also showed that children's growth in their English and Spanish language abilities during Head Start predicted their early reading abilities in English and Spanish. The findings imply that preschool programs are needed that target children's growth in language and not their performance measured at a particular point in time. Also, the results demonstrate the importance of early and regular evaluation of bilingual children's development in both languages in order to monitor children's growth in their two languages.


Impact of diabetes on employment and income in Manitoba, Canada.
To compare employment and income of working-age (18-64 years) people with and without diabetes. We conducted a prospective population-based cohort study based in Manitoba, Canada, consisting of 25,554 individuals without diabetes and 608 with diabetes, of whom 242 had a complication of the disease. Adjusted odds ratios (ORs) of employment and income variables were determined. Diabetic individuals with complications were twice as likely not to be in the labor force (OR 2.07 [95% CI 1.49-2.87]) than nondiabetic individuals. This difference was not evident for diabetic individuals without complications (OR 1.20 [0.93-1.56]). Diabetic individuals without complications had incomes similar to those of nondiabetic individuals. The total income of diabetic individuals with complications was 72% of the income of nondiabetic individuals. When the analysis was limited to only those in the labor force, diabetic workers with complications still had only 85% the employment income of nondiabetic people. Diabetic individuals with complications received 58% more social support income. In a separate analysis of aboriginal individuals, complicated diabetes was not associated with an increased likelihood of not working or a decrease in employment income. In general, complications of diabetes and the absence of the disease affect the ability to earn income in Manitoba, Canada. This effect was not identified in the aboriginal population of the province.


Effects of enhanced UV-B radiation on the interaction between rice and Magnaporthe oryzae in Yuanyang terrace.
Enhanced ultraviolet-B (UV-B) radiation affected the growth of rice and Magnaporthe oryzae, and changed the interactions between them. Increased UV-B radiation (5.0 kJ m-2 d-1) on rice leaves in a Yuanyang terrace was conducted before, during, and after infection of the leaves with Magnaporthe oryzae. The relationship between rice blast and UV-B radiation on the disease resistance of rice and the pathogenicity of M. oryzae was studied, and the effects of enhanced UV-B radiation on the interactions between rice and M. oryzae were analysed. The results indicated the following: (1) enhanced UV-B radiation significantly reduced the rice blast disease index, but as infection progressed, the inhibitory effect of UV-B radiation on the disease was weakened. (2) UV-B radiation treatment before infection with M. oryzae (UV-B + M.) significantly increased the activity of the enzymes related to disease resistance (phenylalanine ammonia lyase, lipoxygenase, chitinase, and β-1,3-glucanase), and the plants exhibited light-induced resistance. (3) Exposure to UV-B radiation after M. oryzae infection (M. + UV-B) did not induce disease course-related protein (PR) activity, but the content of soluble sugar increased. The osmotic stress caused by pathogenic fungi infection was alleviated by active accumulation of soluble sugar; due to this lack of nutrients, it was difficult for the rice blast fungus to grow. (4) Enhanced UV-B radiation significantly inhibited the production of conidia by M. oryzae, and the expression of the pathogenic genes Chitinase, MGP1, MAGB, and CPKA was significantly downregulated. The pathogenicity of M. oryzae was reduced by UV-B radiation. The resistance of rice leaves was weakened by simultaneous exposure to UV-B radiation and M. oryzae (UV-B/M.). Hence, UV-B radiation can weaken the infectivity of M. oryzae, improve the resistance of traditional rice, and contain the disease.


Determinants of obstetric outcomes: a study of primiparae in central Saudi Arabia.
In a prospective study, 200 consecutive Saudi patients having their first labour and delivery were compared with 80 non-Saudi primiparae. The duration of labour and mode of delivery were similar in both groups, but the Saudis were younger, required less sedation, and had lighter babies. The perinatal mortality rate was 10 per 10,000 in the Saudis and 25 per 1,000 in the non-Saudis. Anxiety played a more significant role in the labour and delivery of the foreigners. Lifestyles rather than racial or ethnic differences may explain differences in obstetric outcomes between different populations.


Developing AIDS vaccine trials educational programs in Uganda.
In preparation for HIV vaccine trials, data on a cohort's knowledge about vaccines and vaccine studies are required so as to tailor educational materials to adequately meet local needs. Interviews (n = 1,182) conducted as part of a 3-year prospective study of Ugandan military men aged 18 to 30 years determined what information, in addition to standard trials information, would be required to ensure comprehension of trial procedures. The interviews highlighted four points: (1) the cohort has a lot of knowledge about vaccines but conflates whether vaccines cure or prevent disease; (2) there is a general lack of knowledge about clinical trials procedures; (3) the desire to be protected from HIV/AIDS is a common reason for being willing to participate in a hypothetical vaccine trial; and (4) concern about side effects is a common reason for being unwilling to participate in a trial. These four points guided the focus of the vaccine trials education, which used locally appropriate analogies to introduce complex unfamiliar concepts such as placebos and blinding. This case study highlights the value of incorporating baseline interviews to assess the educational needs of study populations.


An experimental evaluation of cyclic voltammetry of multicharged species at macrodisk electrodes in the absence of added supporting electrolyte.
The reversible reduction of [S2Mo18O62]4- to [S2Mo18O62]5- and [S2Mo18O62]6- at a glassy carbon macrodisk electrode has been studied by cyclic voltammetry in acetonitrile as a function of the concentration of [(C6H13)4N]4[S2Mo18O62] in the absence and presence of [(C6H13)4N]ClO4 as the added supporting electrolyte. Consideration is given to the influence of scan rate, reference-working electrode distance, [(C6H13)4N]4[S2Mo18O62], and electrolyte concentrations. Experimental data confirm theoretical predictions that cyclic voltammetry at a macrodisk electrode is a viable technique for studies of multiply charged electroactive species without added electrolyte, provided the influence of enhanced complexities associated with effects of increased solution resistance, the mass transport contribution from migration, and convection arising from enhanced density gradients are considered. Enhanced density gradients present in the absence of added supporting electrolyte give rise to a more marked dependence of voltammograms on the angle of the electrode and hence lead to significant distortion of wave shapes at low scan rates. The summation of all these obstacles implies that quantitative evaluation of cyclic voltammograms of multiply charged species requires significantly greater care in the absence than in the presence of added supporting electrolyte.


Rapid genetic and morphologic divergence between captive and wild populations of the endangered Leon Springs pupfish, Cyprinodon bovinus.
The Leon Springs pupfish (Cyprinodon bovinus) is an endangered species currently restricted to a single desert spring and a separate captive habitat in southwestern North America. Following establishment of the captive population from wild stock in 1976, the wild population has undergone natural population size fluctuations, intentional culling to purge genetic contamination from an invasive congener (Cyprinodon variegatus) and augmentation/replacement of wild fish from the captive stock. A severe population decline following the most recent introduction of captive fish prompted us to examine whether the captive and wild populations have differentiated during the short time they have been isolated from one another. If so, the development of divergent genetic and/or morphologic traits between populations could contribute to a diminished ability of fish from one location to thrive in the other. Examination of genomewide single nucleotide polymorphisms and morphologic variation revealed no evidence of residual C. variegatus characteristics in contemporary C. bovinus samples. However, significant genetic and morphologic differentiation was detected between the wild and captive populations, some of which might reflect local adaptation. Our results indicate that genetic and physical characteristics can diverge rapidly between isolated subdivisions of managed populations, potentially compromising the value of captive stock for future supplementation efforts. In the case of C. bovinus, our findings underscore the need to periodically inoculate the captive population with wild genetic material to help mitigate genetic, and potentially morphologic, divergence between them and also highlight the utility of parallel morphologic and genomic evaluation to inform conservation management planning.


[Evaluation of preoperative non-invasive ventilation in thoracic surgery for lung cancer: the preOVNI study GFPC 12-01].
Surgical resection is the best treatment for stage I and II non-small cell lung cancer. Despite an improvement in the perioperative management of cancer patients and specialization of surgical teams, morbidity and mortality remains significant. Non-invasive ventilation (NIV) is an effective therapeutic option in hypercapnic respiratory failure. It also improves functional and gasometric parameters when undertaken before surgery. The objective of the preOVNI study is to demonstrate that preoperative non-invasive ventilation for 7 days, at home, reduces the postoperative respiratory and cardiovascular complications of lung resection surgery, in a high-risk population. A prospective, randomized, controlled open-labelled multicentric French study, under the supervision of the Groupe Français de Pneumocancérologie (GFPC), comparing 7 days of preoperative non-invasive ventilation with standard treatment. Inclusion criteria are: patients suitable for lobectomy or segmentectomy for primary bronchial carcinoma and presenting with obstructive or restrictive lung disease, obesity or chronic cardiac insufficiency. The primary criterion is a composite one, including all respiratory and cardiac complications. The number of patients is 150 in each treatment arm, 300 in total. We think that preoperative NIV will be able to reduce the rate of postoperative complications. If this objective is achieved, the management of these patients could be changed.


The prediction of obstructive sleep apnea severity based on anthropometric and Mallampati indices.
Obstructive sleep apnea (OSA) is a common health issue with serious complications. Regarding the high cost of the polysomnography (PSG), sensitive and inexpensive screening tools are necessary. The objective of this study was to evaluate the predictive value of anthropometric and Mallampati indices for OSA severity in both genders. In a cross-sectional study, we evaluated anthropometric data and the Mallampati classification for the patients (n = 205) with age >18 and confirmed OSA in PSG (Apnea-Hypopnea Index [AHI] >5). For predicting the severity of OSA, we applied a decision tree (C5.0) algorithm, with input and target variables considering two models (Model 1: AHI ≥15 with Mallampati >2, age >51 years, and neck circumference [NC] >36 cm and Model 2: AHI ≥30 with condition: gender = female, body mass index (BMI) >35.8, and age >44 years or gender = male, Mallampati ≥2, and abdominal circumference (AC) >112 then AHI ≥30). About 54.1% of the patients were male. Mallampati, age, and NCs are important factors in predicting moderate OSA. The likelihood of moderate OSA severity based on Model 1 was 94.16%. In severe OSA, Mallampati, BMI, age, AC, and gender are more predictive. In Model 2, gender had a significant role. The likelihood of severe OSA based on Model 2 in female patients was 89.98% and in male patients was 90.32%. Comparison of the sensitivity and specificity of both models showed a higher sensitivity of Model 1 (93.5%) and a higher specificity of Model 2 (89.66%). For the prediction of moderate and severe OSA, anthropometric and Mallampati indices are important factors.


Immunological properties of gold nanoparticles.
In the past decade, gold nanoparticles have attracted strong interest from the nanobiotechnological community owing to the significant progress made in robust and easy-to-make synthesis technologies, in surface functionalization, and in promising biomedical applications. These include bioimaging, gene diagnostics, analytical sensing, photothermal treatment of tumors, and targeted delivery of various biomolecular and chemical cargos. For the last-named application, gold nanoparticles should be properly fabricated to deliver the cargo into the targeted cells through effective endocytosis. In this review, we discuss recent progress in understanding the selective penetration of gold nanoparticles into immune cells. The interaction of gold nanoparticles with immune cell receptors is discussed. As distinct from other published reviews, we present a summary of the immunological properties of gold nanoparticles. This review also summarizes what is known about the application of gold nanoparticles as an antigen carrier and adjuvant in immunization for the preparation of antibodies in vivo. For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Thus, this review presents a detailed analysis of data on interaction of gold nanoparticles with immune cells. Emphasis is placed on the systematization of data over production of antibodies by using gold nanoparticles and adjuvant properties of gold nanoparticles. Specifically, we start our discussion with current data on interaction of various gold nanoparticles with immune cells. The next section describes existing technologies to improve production of antibodies in vivo by using gold nanoparticles conjugated with specific ligands. Finally, we describe what is known about adjuvant properties of bare gold or functionalized nanoparticles. In the Conclusion section, we present a short summary of reported data and some challenges and perspectives.


Facial pain and headache associated with brachial plexus compression in the thoracic inlet.
Among the sources for confusion related to brachial plexus compression in the thoracic inlet are the name for this clinical entity (thoracic outlet syndrome) and the fact that some of its associated symptoms occur outside the upper extremity, such as face and neck pain (FP) and occipital headaches (OH). With the realization that scalenus anticus (SA) contraction is the primary source of brachial plexus compression, it is possible to understand the occurrence of both FP and OH in this syndrome. It was hypothesized that SA contraction compresses the cervical plexus as it exits deep to this muscle. Furthermore, it was hypothesized that tension on the origin of this muscle from the transverse cervical processes causes compression of the occipital nerves. To evaluate this, a consecutive series of 32 patients who had resection of the SA between January 2004 and December 2007 were evaluated to determine prevalence of FP and OH, and the extent to which these symptoms were relieved postoperatively after SA resection. It was found that 25% of the patients had FP and that 50% had OH. Postoperatively, for those patients with neck pain, with or without facial pain, 75% were completely relieved, 18% were partially relieved. OH was completely relieved in 81% and partially relieved in 13% of the patients. In conclusion, symptoms of FP and OH associated with brachial plexus compression is due to cervical plexus compression by SA muscle, and symptoms can be relieved by resection of the SA.


Rodent sperm analysis in field-based ecological risk assessment: pilot study at Ravenna army ammunition plant, Ravenna, Ohio.
Ecological risk assessment (ERA) guidance recommends that field-truthing efforts proceed when modeled hazard quotients (HQs) suggest that toxicological effects are occurring to site receptors. To date, no field methods have been proposed by the regulatory community that can lead to definitive determinations of acceptable or unacceptable risk for birds and mammals, the two terrestrial classes of receptors that are commonly assessed using the HQ method. This paper describes rodent sperm analysis (RSA) as a viable method to be applied in the field at sites with historical contamination. RSA is capable of detecting biological differences that bear on reproduction, a highly regarded toxicological endpoint of concern in USEPA Superfund-type ERAs. The results of RSA's first application at a study site are reported and discussed. The paper also provides the rationale for RSA's efficacy in the context of Superfund and other environmental cleanup programs, where limited time and money are available to determine and evaluate the field condition.


Childhood glaucoma surgery in the 21st century.
Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma.


Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: search for signals.
Idiosyncratic drug-induced liver injury (DILI) is traditionally thought not to be dose-related. However, it has been pointed out that most medicines that were withdrawn from marketing or received a black-box warning because of hepatotoxicity were prescribed at daily doses greater than 50 mg/day. To examine the relationship between daily dose of medications and idiosyncratic DILI, we conducted a study with two aims. First, using two pharmaceutical databases, we examined the relationship between daily dose of commonly prescribed medicines in the United States and reported frequency of their selected hepatic adverse events. Second, we examined serious DILI cases reported to the Swedish Adverse Drug Reactions Advisory Committee (1970-2004) for any signals supporting the relationship between daily dose and idiosyncratic DILI. Medications were categorized into < or =10 mg/day, 11-49 mg/day, and > or =50 mg/day groups. Among US prescription medicines, a statistically significant relationship was observed between daily dose of oral medicines and reports of liver failure (P = 0.009), liver transplantation (P < 0.001), and death caused by DILI (P = 0.004) but not alanine aminotransferase (ALT) > 3 x upper limit of normal (P = 0.10) or jaundice (P = 0.16). Of 598 eligible Swedish DILI cases, 9% belonged to the < or =10 mg/day group, 14.2% to the 11-49 mg/day group, and 77% of cases were caused by medications given at dose > or =50 mg/day. A statistically significant relationship was noted between daily dose and poor outcome (death or liver transplantation) of Swedish DILI cases (2%, 9.4%, and 13.2% in < or =10, 11-49, and > or =50 mg/day groups, respectively, P = 0.03). These data suggest a relationship between daily doses of oral prescription medications and idiosyncratic DILI. More studies are needed to validate these observations and to explore their implications.


Learning from peer assessment: the role of the external quality assurance multilaboratory thrombophilia test process.
The quality control process is a critical feature of pathology best practice. In addition to internal quality control processes applied on a test-to-test or day-to-day basis, the participation of laboratories in external quality assurance programs (QAPs) is critical to achieving ongoing test accuracy. There are several such programs operating in the international arena. With respect to thrombophilia, these include the Australia-based Royal College of Pathologists of Australia QAP, the United Kingdom-based National External Quality Assessment Service, and the International Thrombophilia External Quality Assessment Scheme, based in the Netherlands. Although there are some similarities between the programs, some diversity is also apparent. Each of the programs assess for the common markers of congenital thrombophilia, such as antithrombin, protein C, protein S, and activated protein C resistance. Testing of some acquired markers of thrombophilia, such as lupus anticoagulant, and genetic tests such as factor V Leiden and prothrombin G20210A mutation, are also available. This report focuses on some recent trends from these programs.


Morbidity & Mortality Survey of Spinal Deformity Surgery in 2012-Report by the Japanese Scoliosis Society.
The Japanese Scoliosis Society (JSS) planned to make a longitudinal survey of the mortality and morbidity (M&M) of spinal deformity surgery and established the M&M Committee in 2012. We reported the analysis of the surgical complication (M&M) survey in 2012. A request to participate in this survey was mailed to all JSS members. Questionnaires were sent by email to members who agreed to cooperate, and their answers were obtained. Diagnosis was grouped into idiopathic scoliosis, congenital scoliosis, neuromuscular scoliosis, spondylolisthesis, pediatric kyphosis, and adult spinal deformity. Complications were grouped into death, blindness, neurological deficit, infection, massive bleeding, hematoma, pneumonia, cardiac failure, DVT/PE, gastrointestinal perforation, and instrumentation failure. A total of 2,906 patients were reported from sixty-eight hospitals: idiopathic 488, congenital 91, neuromuscular 82, others 214, spondylolisthesis 1,241, pediatric kyphosis 41, and adult spinal deformity 749. Complications were death in 3, neurological deficit in 49, early infection in 37, late infection in 14, massive bleeding in 91, hematoma in 18, pneumonia in 6, cardiac failure in 1, DVT/PE in 9, gastrointestinal perforation in 2, and instrumentation failure in 73. The complication rate of having a neurological deficit, massive bleeding, and instrumentation failure was 4.88%, 7.32%, and 4.88% respectively in patients with pediatric kyphosis, and 3.07%, 8.01%, and 5.21% respectively in patients with an adult spinal deformity. The complication rate of early infection was 4.88% in the patients with pediatric kyphosis. The complication rates of pediatric kyphosis and adult spinal deformity were high.


Treatment of mammalian cells with the endoplasmic reticulum-proliferator compactin strongly induces recombinant and endogenous xenobiotic metabolizing enzymes and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro.
Some xenobiotics induce membrane-bound drug metabolizing enzymes (Xme) and a profound proliferation of the endoplasmic reticulum (ER) in vivo. However these effects are much weaker in vitro, possibly due to absence of certain transcription factors. We tested the possibility that ER proliferation can affect the level of ER-resident enzymes even in the absence of transcriptional activation. For this purpose we analysed the effects of compactin, which has been shown to induce ER proliferation in vitro, on recombinant Xme, which were expressed from a constitutive viral promoter. High levels of recombinant UDP-glucuronosyltransferase UGT1A6 were achieved by amplification of the UGT1A6 cDNA using the dihydrofolate reductase cDNA as selectable marker in DHFR- CHO cells. Treatment of the resulting cell lines with lipoprotein-deficient serum in the absence and presence of compactin for 5 days resulted in a 1.3- and 2.3-fold, respectively, increase of the UGT enzyme activity towards 4-methylumbelliferone, paralleled by an induction of immunoreactive UGT1A6 protein. Similarly, treatment with this 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor increased the endogenous P450 reductase activity 2.6-fold, concomitant with an increase of immunodetectable protein. As expected compactin induced the level of 3-hydroxy-3-methylglutaryl-CoA reductase. Increased levels of this protein have been associated with a proliferation of the ER. Compactin treatment of a separate cell line that expressed recombinant human P450 reductase increased this enzyme activity fivefold. Pulse-chase experiments revealed that the induction of the recombinant Xme by compactin was most likely due to decreased protein degradation. Our results show that enzyme systems unrelated to those involved in cholesterol biosynthesis are affected by compounds known to affect membrane biogenesis. Since this effect extends to heterologously expressed enzymes, it also provides an efficient means by which to increase the levels of recombinant ER proteins.


The effect of indomethacin on Achilles tendon healing in rabbits.
In a randomized, blind study, percutaneous tenotomy was performed on the right Achilles tendon complex of 32 male, New Zealand rabbits. The rabbits were placed in long-leg casts to approximate the tendon. Sixteen rabbits received oral therapeutic doses (1.5 mg/kg/day) of indomethacin elixir; the remaining 16 rabbits received no medication and comprised the control group. At two and six weeks following tenotomy, eight rabbits in each group were sacrificed and the Achilles tendon complexes were resected. Each tendon was evaluated for tensile force-to-failure by uniaxial tensile loading using an Instron Materials Testing Machine at a velocity of 0.85 cm/second. Histologic evaluation assigned the specimens to categories of either "relatively mature" or "relatively immature," based on the degree of cellularity, neovascularity, and collagen orientation that had occurred in the healing process. The mean force-to-failure two weeks post-tenotomy for the experimental group was 75.7 +/- 42.3 Newtons (N), and 96.6 +/- 35.2 N for the control group; at six weeks post-tenotomy, the mean force-to-failure for the experimental group was 165.5 +/- 34.3 N and 160.2 +/- 31.6 N for the control group. Statistical analysis revealed no significant differences in tensile force-to-failure or histologic appearance between the experimental and control groups at either time interval. These results suggest that indomethacin, and potentially other nonsteroidal antiinflammatory drugs, may be used in conjunction with a tendon injury without significantly affecting the early healing process.


B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction - Relevance to Age-Related Left Ventricular Modeling in Japanese.
Heart failure (HF) with preserved ejection fraction (HFpEF) is increasing with aging of the population. Plasma levels of B-type natriuretic peptide (BNP) increase in proportion to the severity of left ventricular (LV) dysfunction. The object of this study was to examine the plasma levels of BNP in HFpEF to better understand the pathogenesis of HFpEF as compared with HF with reduced EF (HFrEF).Methods and Results:The study subjects comprised 468 HFpEF patients (158 men, 310 women, mean age 81.3±9.6 years) and 126 HFrEF patients (77 men, 49 women, mean age 75.4±12.0 years) who underwent echocardiography and routine clinical examinations including plasma BNP. Age, female prevalence, systolic blood pressure and pulse pressure were higher in the HFpEF patients than in the HFrEF patients (P<0.0001, P<0.001, P<0.0001, and P<0.0001, respectively). Plasma BNP levels, LV diastolic dimensions, and LV mass index (LVMI) were lower (P<0.0001, P<0.0001, and P<0.0001, respectively), while relative wall thickness was higher (P<0.0001) in the HFpEF patients than in the HFrEF patients. Multiple regression analysis revealed that LVMI, EF, plasma levels of albumin, C-reactive protein, and uric acid were the predictors of BNP levels (P<0.001, P<0.001, P=0.009, P=0.012, and P=0.018, respectively). Plasma BNP levels were lower and related to aging-related LV concentric remodeling/hypertrophy in HFpEF patients as compared with HFrEF patients, who were associated predominantly with eccentric LV hypertrophy.


Comparison of body fat mass changes during the third trimester and at one month postpartum between lactating and nonlactating Japanese women.
The purpose of the present study was to compare which parts of the body fat mass tended to increase during the third trimester and at 1 month postpartum between lactating and nonlactating Japanese women. This prospective study examined 49 healthy pregnant women in the third trimester, and at 1 month postpartum. Demographic data, including lactation status, were obtained from a self-administered questionnaire. Newborn information was obtained from hospital charts. Anthropometric data, including body fat mass, were measured by the bioelectrical impedance analysis (BIA) method in the third trimester, and at 1 month postpartum. At 1 month postpartum, 16 mothers (32.7%) were lactating and 33 (67.3%) were mainly feeding formula. There were no significant differences between the lactating and nonlactating women regarding their demographic data, energy intakes and body fat mass changes during the third trimester of pregnancy. The trunk fat mass change showed a significant difference (p = 0.008) between the third trimester and 1 month postpartum, after adjustment by age and parity using repeated measurement ANCOVA, in the lactating and nonlactating women. In conclusion, the total body fat mass and body fat mass in the trunk at 1 month postpartum was significantly greater in lactating women than in nonlactating women.


Optical characterization of periodically-poled KTiOPO4.
We demonstrate how the Maker fringes that are observable in spontaneous parametric down-conversion (SPDC) give a direct visualization of the poling quality of a periodically-poled crystal. Identical Maker fringes are observed in the optical spectrum of collinear SPDC and the temperature dependence of second harmonic generation. We analyze these Maker fringes via a unified treatment of the tuning curve in crystals with small and slowly-varying deformations of the poling structure. Our theoretical model, based on a Fourier analysis of the poling deformations, distinguishes between duty-cycle variations and variations of the poling phase. The analysis indicates that the poling phase is approximately fixed, while the duty-cycle typically varies between 36% and 64%.


[NF-κb inhibitor PDTC enhances tumor necrosis factor α-induced apoptosis of gastric cancer cell SGC-7901].
To investigate the effect of PDTC (inhibitor of NF-κb) on apoptosis of human gastric cancer cell line SGC-7901 induced by tumor necrosis factor α (TNF-α) and explore the related mechanisms. After the treatment with different concentrations of PDTC, TNF-α or PDTC combined with TNF-α on gastric cancer cell line SGC-7901, the growth inhibition of SGC-7901 was measured by MTT assay. Hoechst was used to assess SGC-7901 cell apoptosis. The protein expressions of survivin and caspase-3 were detected by Western blot assay. The growth inhibition rate of SGC-7901 induced by PDTC (15, 30, 60, 100 μmol/L) was (12.14±0.91)%, (20.00±1.11)%, (37.63±1.01)% and (41.46±1.07)%. Different concentrations of PDTC all inhibited the growth of SGC-7901 significantly (all P<0.01), The growth inhibition rate of SGC-7901 induced by 25 mg/L TNF-α was (2.38±0.67)%, which could not significantly inhibit the growth of SGC-7901 [control (1.50±0.81)%], while TNF-α of 50, 100, 150 mg/L could inhibit the growth of SGC-7901 significantly [(4.53±0.85)%, (4.43±0.70)% and (4.74±1.07)%, all P<0.05]. PDTC (15 μmol/L) combined with TNF-α (25, 50, 100, 150 mg/L) significantly increased the cell growth inhibition rate compared with TNF-α alone or PDTC 15 μmol/L alone (all P<0.01). Hoechst assay showed that 100 mg/L TNF-α, 15 μmol/L PDTC and combination of above two all induced cell apoptosis (P<0.01), and the combination group had significantly higher percentage of cell apoptosis (P<0.01). Survivin protein was significantly down-regulated in combination group as compared with single TNF-α (100 mg/L) group, but was not significant down-regulated as compared with single PDTC (15 μmol/L) group. Caspase-3 protein expression was significantly increased in combination group as compared with other two groups. PDTC can enhance the cell apoptosis induced by TNF-α, which may be associated with the blocking of TNF-α-activated NF-κB signaling pathway by PDTC, the down-regulation of survivin expression, and up-regulation of caspase-3 expression.


Consumer beliefs about healthy foods and diets.
The U.S. Food and Drug Administration has begun a public process to redefine how companies are allowed to use the term "healthy" on food packages. Although the definition is formulated based on the latest consensus in nutrition and epidemiological research, it is also important to understand how consumers define and understand the term if it is to be behaviorally relevant. This research is an exploratory study designed to provide a descriptive account of consumers' perceptions of and beliefs about the meaning of "healthy" food. A nationwide U.S. sample of 1,290 food consumers was surveyed in December 2018. Respondents answered 15 questions designed to gauge perceptions of healthy food and to elicit preference for policies surrounding healthy food definitions. Responses are weighted to demographically match the population. Categorical variables have a sampling error of ±2.7%. Exploratory factor analysis is used to determine latent dimensions of health perceptions related to food type. Consumers were about evenly split on whether a food can be deemed healthy based solely on the foods' nutritional content (52.1% believing as such) or whether there were other factors that affect whether a food is healthy (47.9% believing as such). Consumers were also about evenly split on whether an individual food can be considered healthy (believed by 47.9%) or whether this healthiness is instead a characteristic of one's overall diet (believed by 52.1%). Ratings of individual food products revealed that "healthy" perceptions are comprised of at least three underlying latent dimensions related to animal origin, preservation, and freshness/processing. Focusing on individual macronutrients, perceived healthiness was generally decreasing in a food's fat, sodium, and carbohydrate content and increasing in protein content. About 40% of consumers thought a healthy label implied they should increase consumption of the type of food bearing the label and about 15% thought the label meant they could eat all they wanted. Results suggest consumer's perceptions of "healthy," which is primarily based on fat content, partially aligns with the FDA definition but also suggest consumers perceive the word as a broader and more nuanced concept that defies easy, uniform definition. Results highlight areas where nutrition education may be needed and suggest disclosures may need to accompany health claims so that consumers know what, precisely, is being communicated.


Determinants of sex hormone-binding globulin concentrations in a cross-sectional study of healthy men randomly selected.
Sex-hormone binding globulin (SHBG) is a glycoprotein synthesised in the liver and it is a transport protein which is primary modulator of the androgen signal. This cross-sectional study prompted us to investigate the relati-onship between SHBG and, age, anthropometric, body composition variables, the IGF-I system and leptin in a group of healthy adult men randomly selected. Included 134 men, aged 41.6 years, range 15-70 years. Body mass index (BMI) was calculated, and body composition was determined by a bioelectrical impedance analyser. Serum total IGF-I concentrations after acid-ethanol extraction, free IGF-I concentrations, IGFBP3, leptin, testosterone and SHBG were determined. Testosterone concentrations increased in the 2th decade and SHBG concentrations increased in the 4th decade. We observed an increase in leptin in the 4th decade with a decrease in IGF-I, free IGF-I and IGFBP3 throughout the decades. Total IGF-I correlated with waist/hip ratio; free IGF-I with BMI and waist/hip ratio and IGFBP3 did not correlated with any variable. As expected, there was a positive correlation between leptin and BMI, waist/hip ratio, fat free mass and fat mass. On the other hand, SHBG was negatively correlated with BMI, fat mass, total IGF-I, free IGF-I, IGFBP3 and leptin. Testosterone did not correlated with any anthropometric or body composition variable, IGF-I system components, leptin or SHBG. The multiple linear regression analysis produced a model that explained the 40.5% of SHBG variability; only fat mass and IGFBP3 brought an independent significant contribution to SHBG variability. In conclusion, in this population of healthy men randomly selected, we found that they had significant negative correlation between SHBG concentrations and anthropometric, body composition variables, the IGF-I system and leptin levels, and that fat mass and IGFBP3 may be the main determinants of SHBG changes.


Angiosarcoma of the breast.
The clinical histories, operative reports, and pathologic slides of 20 patients seen between 1907 and 1984 with diagnoses of angiosarcoma, hemangiosarcoma, and hemangioendothelioma were reviewed. The mean age of the 19 female patients and one male patient was 40.05 years (range, 16 to 67 years). Ten patients had the right breast involved, and five patients had contralateral breast involvement. Presenting symptoms included a mass in 20 patients, pain in ten patients, and breast discoloration in six patients. Before referral, ten patients had the misdiagnosis of a benign breast lesion. Because of the deceptively benign appearance of many angiosarcomas, these lethal tumors are often misdiagnosed as benign hemangiomas. Simple mastectomy is the treatment of choice, while adjuvant therapy remains to be evaluated.


Xylem conductivity and vulnerability to cavitation of ponderosa pine growing in contrasting climates.
We examined the effects of increased transpiration demand on xylem hydraulic conductivity and vulnerability to cavitation of mature ponderosa pine (Pinus ponderosa Laws.) by comparing trees growing in contrasting climates. Previous studies determined that trees growing in warm and dry sites (desert) had half the leaf/sapwood area ratio (A(L)/A(S)) and more than twice the transpiration rate of trees growing in cool and moist sites (montane). We predicted that high transpiration rates would be associated with increased specific hydraulic conductivity (K(S)) and increased resistance to xylem cavitation. Desert trees had 19% higher K(S) than montane trees, primarily because of larger tracheid lumen diameters. Predawn water potential and water potential differences between the soil and the shoot were similar for desert and montane trees, suggesting that differences in tracheid anatomy, and therefore K(S), were caused primarily by temperature and evaporative demand, rather than soil drought. Vulnerability to xylem cavitation did not differ between desert and montane populations. A 50% loss in hydraulic conductivity occurred at water potentials between -2.61 and -2.65 MPa, and vulnerability to xylem cavitation did not vary with stem size. Minimum xylem tensions of desert and montane trees did not drop below -2.05 MPa. Foliage turgor loss point did not differ between climate groups and corresponded to mean minimum xylem tensions in the field. In addition to low A(L)/A(S), high K(S) in desert trees may provide a way to increase tree hydraulic conductivity in response to high evaporative demand and prevent xylem tensions from reaching values that cause catastrophic cavitation. In ponderosa pine, the flexible responses of A(L)/A(S) and K(S) to climate may preclude the existence of significant intraspecific variation in the vulnerability of xylem to cavitation.


Effect of histamine on lung contractile elements in growing cattle.
To determine the effect of histamine on the contractile elements of the respiratory tract in neonatal calves and young adult cattle. Samples of trachealis muscle, bronchi, and intrapulmonary arteries and veins dissected from the respiratory tracts of healthy bovids (2 to 8 days and 16 to 20 months old). Histamine cumulative concentration-effect curves (10(-6) to 10(-3) M) were constructed in duplicate smooth muscle samples mounted in organ baths. Contractile responses to histamine were compared with reference contractions elicited by methacholine (10(-5) M) for airways or KCl (127 mM) for vessels. In young adult cattle, trachealis muscle had a substantial contractile response to histamine (84% of methacholine-induced contraction), whereas bronchi reacted slightly (15 and 20% for large and small bronchi, respectively). Although contractile responses to KCl were comparable in arteries and veins, histamine-induced contractions were greater for intrapulmonary veins than for arteries (202 vs 48% of KCl-induced contraction). In neonatal calves, histamine-induced contraction of veins also exceeded that of arteries (230 vs 54% of KCl-induced contraction); however, unlike in young adult cattle, histamine produced notable contraction of large and small bronchi (48 and 60% of methacholine-induced contraction, respectively). Compared with intrapulmonary arteries, intrapulmonary veins have greater contractile responses to histamine in neonatal and young adult cattle. Data suggest loss of histamine responsiveness in bronchial smooth muscle as neonatal calves grow to young adults. Venodilation may be useful in treatment of lung edema in cattle.


Prospective randomized controlled trial comparing laser lithotripsy with pneumatic lithotripsy in miniperc for renal calculi.
The energy source used for stone fragmentation is important in miniperc. In this study, we compared the stone fragmentation characteristics and outcomes of laser lithotripsy and pneumatic lithotripsy in miniperc for renal calculi. After Institutional Review Board approval, 60 patients undergoing miniperc for renal calculi of 15 to 30 mm were equally randomized to laser and pneumatic lithotripsy groups. Miniperc was performed using 16.5F Karl Storz miniperc sheath and a 12F nephroscope. Laser lithotripsy was performed using a 550-μm laser fiber and 30 W laser with variable settings according to the need. Pneumatic lithotripsy was performed using the EMS Swiss lithoclast. Patient demographics, stone characteristics, intraoperative parameters, and postoperative outcomes were analyzed. The baseline patient demographics and stone characteristics were similar in both groups. The total operative time (P = 0.433) and fragmentation time (P=0.101) were similar between the groups. The surgeon assessed that the Likert score (1 to 5) for fragmentation was similar in both groups (2.1 ± 0.8 vs 1.9 ± 0.9, P=0.313). Stone migration was lower with the laser (1.3 ± 0.5 vs 1.7 ± 0.8, P=0.043), and fragment removal was easier with the laser (1.1 ± 0.3 vs 1.7 ± 1.1, P=0.011). The need for fragment retrieval using a basket was significantly more in the pneumatic lithotripsy group (10% vs 37%, P=0.002). The hemoglobin drop, complication rates, auxiliary procedures, postoperative pain, and stone clearance rates were similar between the groups (P>0.2). Both laser lithotripsy and pneumatic lithotripsy are equally safe and efficient stone fragmentation modalities in miniperc. Laser lithotripsy is associated with lower stone migration and easier retrieval of the smaller fragments it produces.


Comprehensive analysis of cellular senescence-related genes in the prognosis, tumor microenvironment, and immunotherapy/chemotherapy of clear cell renal cell carcinoma.
The transcriptome public database and advances in biological discoveries contributed to significant progresses in identifying the drivers of cancer progression. Cellular senescence (CS) is considered as a leading factor resulting in cancer development. The purpose of this study was to explore the significance of CS-related genes in the molecular classification and survival outcome of clear cell renal cell carcinoma (ccRCC). CS-related genes were obtained from the CellAge database, and patients from TCGA-KIRC dataset and ICGC dataset were clustered by ConsesusClusterPlus. The characteristics of overall survival (OS), genomic variation, and tumor microenvironment (TME) of each cluster were analyzed. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was conducted to develop a CS-related risk model to score ccRCC patients and assess the risk scores in predicting patients' response to immunotherapy and chemotherapy. A nomogram based on the risk model was established to improve the risk stratification of patients. CcRCC was divided into three molecular subtypes based on CS-related genes. The three molecular phenotypes showed different OS and clinical manifestations, mutation patterns, and TME states. Five genes were obtained from nine differentially expressed CS-related genes in the three molecular subtypes to develop a risk model. Patients with ccRCC were divided into high- and low-risk subgroups. The former showed an unfavorable OS, with a significantly higher genomic variation rate, TME score, and numerous immune checkpoint expressions when compared to the low-risk subgroup. Risk score reflected the response of patients to axitinib, bortezomib, sorafenib, sunitinib, and temsirolimus. In general, CS-related genes divided ccRCC into three molecular subtypes with distinct OS, mutation patterns, and TME states. The risk model based on the five CS-related genes can predict the prognosis and therapeutic outcome of ccRCC patients, providing a theoretical basis for further study on the molecular mechanism of CS-related ccRCC.


The COMPASS pilot study: a total worker Health™ intervention for home care workers.
To develop a team-based Total Worker Health™ (injury prevention + health promotion) intervention for home care workers and estimate intervention effects on workers' well-being and health and safety behaviors. Home care workers (n = 16) met monthly in teams for education and social support using a scripted, peer-led approach. Meeting process measures and pre-/postintervention outcome measures were collected. Knowledge gains averaged 18.7% (standard deviation = 0.04), and 62.0% (standard deviation = 0.13) of participants reported making safety or health changes between meetings. Workers' well-being improved significantly (life satisfaction, d = 0.65, P < 0.05; negative affect, d = 0.64, P < 0.05), and the majority of other safety and health outcomes changed in expected directions. COMPASS is a feasible intervention model for simultaneously preventing injuries and promoting health among home care workers.


[Adenocarcinoma arising on colo-rectal endometriosis: clinico-pathological considerations].
Colo-rectal endometriosis represents a rare pathological event. Exceptionally, a malignant colo-rectal endometrioid carcinoma arising from endometriosis has been reported. In the present case, we describe a 32 year-old woman with clinical and radiological signs of large bowel sub-occlusive syndrome. Histologically, a sigmoid endometrioid adenocarcinoma associated with submucosal foci of eutopic endometrium was observed. Moreover, endometriotic tissue was observed at the level of the colonic left flexura and appendix. Colo-rectal endometriosis must be considered among risk factors for the development of large bowel adenocarcinoma in young female patients.


Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain.
Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype.


Personality predicting military morale and the role of positive and negative affectivity.
Military morale is defined as the enthusiasm and persistence with which a member of the group engages in the prescribed activities of that group and is considered to be closely related to performance. The current study uses the conceptualization of military morale through the elements of work engagement and burnout. Nevertheless, our personality traits, and how we interpret or react to our environment, including group atmosphere, may also be related to perception of morale alongside positive and negative affectivity. The article investigates the relations between perceptions of morale, personality traits (the Big Five) and positive or negative affectivity in a military context. A sample of Estonian military conscripts (N = 354) from the soldiers' basic military training course responded to the questionnaire. Three measures were used for data collection: a short personality questionnaire (40 items) for Big Five personality traits; the Positive and Negative Affect Schedule (PANAS; 20 items) for state affectivity (both positive and negative); and a 16-item instrument for military morale (8 items for both work engagement and burnout). Structural equation modelling was used to evaluate relationships between study variables. The results indicated that openness to experience and agreeableness did not have a significant effect on military morale (as work engagement and burnout) either directly or indirectly (through affectivity). However, conscientiousness was found to have a significant effect on military morale and extraversion indirectly through positive affectivity. Positive and negative affectivity as the mediators strengthened the relations between personality traits and military morale. The results emphasize the reinforcing power of positive emotions to enhance high morale.