Quality of life in bladder cancer patients receiving medical oncological treatment; a systematic review of the literature.
Previous quality of life (QoL) literature in bladder cancer (BC) patients has focused on finding the preferred urinary diversion while little is known about the QoL of patients in medical oncological treatment (MOT). We performed a systematic review to assess the existing literature on QoL in patients with muscle-invasive BC (MIBC) undergoing MOT. A systematic search of Pubmed and Embase was performed. Inclusion criteria were studies containing QoL data for patients undergoing chemo- and/or radiotherapy. We extracted all QoL scorings at different time intervals and on the six most prevalent domains: overall QoL, urinary, bowel sexual symptoms, pain and fatigue. The study was carried out according to PRISMA guidelines for systematic reviews and GRADE was used to rate the quality of evidence from the included studies. Of 208 papers reviewed, 21 papers were included. Twenty-one different QoL instruments were applied. The only data on QoL during chemotherapy was from patients in clinical trials investigating new treatments. No studies were found for patients in neoadjuvant treatment. The level of evidence at each time point was graded as very low to moderate. From the studies included the overall QoL seemed inversely related to the organ-specific impairment from sexual and urinary symptoms and increased with decreasing organ-specific symptoms for long term survivors > 6 months after treatment. Collection of data on QoL from patients with MIBC disease undergoing MOT has been sparse and diverse. The present data can act as a summary but prompts for more prospective collection of QoL data from BC patients.


Binary fission of Pneumocystis carinii trophozoites grown in vitro.
Trophozoites grown in vitro were shown to undergo binary fission by transmission electron microscopy (TEM). Standard fixation with subsequent embedding in Spurr was employed using 3% glutaraldehyde and 1% osmium tetroxide with 5% sucrose added to both fixatives and 0.1 M cacodylate buffer washes. Trophozoites were grown on WI-38 cells in vitro. Trophozoites were found in various stages of fission. The dividing trophozoite has daughter cells that are rounder than the pleomorphic, non-dividing trophozoites. Tubular forms external to the dividing trophozoites were decreased in number; tubular forms when present were concentrated around the forming septa. Nuclear material was sometimes, but not always, well defined in both daughter cells. There was no concentration of nuclear material at the poles. Vacuoles without membrane were present in the dividing forms. Separate nuclear regions were sometimes found in the dividing trophozoites. These observations suggest that binary fission does occur in culture; however, the significance of binary fission to the life cycle of Pneumocystis carinii (Pc) is not yet clear.


[COMPLETE RESECTION OF URACHAL CARCINOMA WITH SIGMOID COLON INVASION AFTER FOLFOX CHEMOTHERAPY: A CASE REPORT].
A 45-years-old man presented discharge of abscess from the umbilicus with lower abdominal pain. CT scan showed huge tumor from the bladder to the umbilical part with sigmoid colon invasion. He was diagnosed as urachal carcinoma, which was confirmed by pathological examination. We started FOLFOX chemotherapy according to advanced colon cancer. Approximately 80% of reduction was accomplished after 11 courses of FOLFOX. We performed radical cystectomy with sigmoid colon resection. Pathological examination revealed complete resection with negative surgical margin. No recurrence and metastasis were observed after 30 months of surgery. Urachal carcinoma is often advanced cancer when diagnosed. Effective chemotherapy is not established well. FOLFOX chemotherapy demonstrated the well antitumor effect in this case.


Quantitative psychometric testing and subclinical hepatic encephalopathy--comparative study between encephalopathic and non-encephalopathic patients with liver cirrhosis.
Six quantitative psychometric tests were performed on 51 healthy subjects, 19 cirrhotic patients with subclinical hepatic encephalopathy (SHE), 32 cirrhotic patients without SHE, and 26 patients with other diseases. Strong correlations between age and the results of all the psychometric tests were observed in the healthy subjects (p less than 0.005). Sex and etiology of liver cirrhosis did not affect the test results. SHE patients, compared with non-SHE and health subjects, presented impairment in the ability to perform the tests, even in the absence of obvious clinical and electroencephalogram findings. In SHE patients, trailmaking test A (TMT A) yielded the highest frequency of abnormal values, 63%. TMT A results were abnormal in 80% of SHE patients with abnormal scores in other tests, and thus it seemed to be the most sensitive test. Liver function tests did not correlate with psychometric testing in any of the groups. Blood ammonia levels in SHE patients with abnormal TMT A scores correlated with TMT A scores (r = 0.752, p less than 0.01); this was not the case in SHE nor non-SHE patients with normal TMT A results. These data demonstrate the usefulness of psychometric tests in detecting SHE.


PHASES score and treatment scoring with cigarette smoking in the long-term prediction of rupturing of unruptured intracranial aneurysms.
Treatment indications in unruptured intracranial aneurysms (UIAs) are challenging because of the lack of prospective natural history studies without treatment selection and the decreasing incidence of aneurysm rupture. The purpose of this study was to test whether the population, hypertension, age, size of aneurysm, earlier aneurysm rupture, site of aneurysm (PHASES) score obtained from an individual-based meta-analysis could predict the long-term rupture risk of UIAs. The series included 142 patients of working age with UIAs diagnosed before 1979, when these were not treated but were followed up until the first rupture, death, or the last contact. PHASES scores were recorded for all patients by using the baseline variables and compared with the new treatment score obtained from a recent cohort, consisting of age, smoking status, and aneurysm size and location. Of the 142 patients, 34 had an aneurysm rupture during a total follow-up of 3064 person-years. The median time between diagnosis and an aneurysm rupture was 10.6 years. The PHASES score at baseline was higher in those with an aneurysm rupture than in the others (5.3 ± 2.3 vs 4.2 ± 2.2, p = 0.012), and the difference relative to the new treatment score was 5.3 ± 2.4 versus 3.0 ± 2.2 (p < 0.001). The receiver operating characteristic curve of the PHASES score for predicting rupture showed a fair area under the curve (0.674, 95% CI 0.558-0.790) where the optimal cutoff point was obtained at ≥ 6 versus < 6 points for sensitivity (0.500) and specificity (0.811). The area under the curve of the new score was 0.755 (95% CI 0.657-0.853), with the optimal cutoff point at ≥ 5 versus < 5 points for sensitivity (0.607) and specificity (0.789). The PHASES and the new scores predicted the long-term aneurysm rupture risk moderately well, with the latter, which also included smoking, being slightly better and easier in clinical practice. The findings suggest that treatment decisions about UIAs in patients of working age can be done with an improved cost-effectiveness.


13C relaxation studies of the DNA target sequence for hhai methyltransferase reveal unique motional properties.
The goal of this work was to examine if sequence-dependent conformational flexibility in DNA plays a role in base extrusion, a common conformational change induced by many DNA-modifying enzymes. We studied the dynamics of the double-stranded DNA target of the HhaI methyltransferase by recording an extensive set of (13)C NMR relaxation parameters. We observe that the cytidine furanose rings experience fast (picosecond to nanosecond) motions that are not present in other nucleotides; the methylation site experiences particularly high mobility. We also observe that the bases of guanosine and cytidine residues within the HhaI recognition sequence GCGC experience motions on a much slower (1-100 micros) time scale. We compare these observations with previous solution and solid-state NMR studies of the EcoRI nuclease target sequence, and solid-state NMR studies of a similar HhaI target construct. While an increased mobility of cytidine furanose rings compared to those of other nucleotides is observed for both sequences, the slower motions are only observed in the HhaI target DNA. We propose that this inherent flexibility lowers the energetic barriers that must occur when the DNA binds to the HhaI methyltransferase and for extrusion of the cytidine prior to its methylation.


Misfit dislocation free InAs/GaSb core-shell nanowires grown by molecular beam epitaxy.
In this report, we present the growth and structural analyses of broken gap InAs/GaSb core-shell nanowires by molecular beam epitaxy using an Au-free approach. Depending on the shell growth temperature, two distinct growth regimes for the GaSb shells are identified resulting in conformal or tapered shells. Morphological analyses reveal a dodecagonal nanowire cross-section after GaSb shell growth. Detailed transmission electron microscope investigations from different zone axes confirm that the small lattice mismatch of 0.6% allows the deposition of 40 nm thick GaSb shells free of misfit dislocations. Additionally, an abrupt interface from InAs to GaSb is found. These nanowires are suitable for future devices such as TFETs.


Profile of HIV/AIDS Neurocognitive Impairment among HIV Positive Patients in North Central Nigeria.
Human Immunodeficiency Virus (HIV) dementia is an important complication in persons with HIV/AIDS, manifesting as neurocognitive and functional impairments which are detectable on neuropsychological testing. To determine the profile of HIV/AIDS neurocognitive impairment and associated risk factors among adults with HIV infection in our center and determine its associative factors. A total of 87 HIV-seropositive patients, aged between 18- 59 years were studied. Eighty seven (87) age, sex and education-matched HIV-seronegative individuals were recruited as controls. Clinical assessments were done using standardized questionnaires developed by the AIDS Clinical Trial Group (ACTG A5199). The study participants were screened for HIV associated dementia using the International HIV dementia scale (IHDS) and a 5-test neuropsychological battery. The scores of the neuropsychological parameters of the control subjects provided the normative data. The scores of the HIV-positive participants were compared against normative data. Multivariate logistic regression was carried out to determine significant predictors to HIV-associated neurocognitive impairment. The frequency of neurocognitive impairment from this study was 37.9%. Nineteen (2I.8%) patients had asymptomatic neurocognitive impairment (ANI), ten (11.5%) had mild neurocognitive disorder (MND) and four (4.6%) had HIV- associated dementia (HAD). There was a statistically significant difference in the test scores of all the cognitive domains between the persons living with HIV/AIDS and those without HIV infection, being higher in the HIV-subjects. Increased viral load and HIV positive patients not being on HAART were significantly associated with HIV-associated neurocognitive impairment (P<0.05). The frequency of neurocognitive impairment in HIV patients was quite high. Increased viral load and lack of treatment were associated factors, suggesting a need for early initiation of HAART. Neuropsychological testing will help identify the patients who need additional support in activities of daily living.


The cell surface glycosphingolipids SSEA-3 and SSEA-4 are not essential for human ESC pluripotency.
Pluripotent cells can be isolated from the human blastocyst and maintained in culture as self-renewing, undifferentiated, human ESCs (hESCs). These cells are a valuable model of human development in vitro and are the focus of substantial research aimed at generating differentiated populations for cellular therapies. The extracellular markers that have been used to characterize hESCs are primarily carbohydrate epitopes on proteoglycans or sphingolipids, such as stage-specific embryonic antigen (SSEA)-3 and -4. The expression of SSEA-3 and -4 is tightly regulated during preimplantation development and on hESCs. Although this might imply a molecular function in undifferentiated cells, it has not yet been tested experimentally. We used inhibitors of sphingolipid and glycosphingolipid (GSL) biosynthesis to block the generation of SSEA-3 and -4 in hESCs. Depletion of these antigens and their precursors was confirmed using immunostaining, flow cytometry, and tandem mass spectroscopy. Transcriptional analysis, immunostaining, and differentiation in vitro and in teratomas indicated that other properties of pluripotency were not noticeably affected by GSL depletion. These experiments demonstrated that the GSLs recognized as SSEA-3 and -4 do not play critical functional roles in maintaining the pluripotency of hESCs, but instead suggested roles for this class of molecules during cellular differentiation.


An approximate model for the adhesive contact of rough viscoelastic surfaces.
Surface roughness is known to easily suppress the adhesion of elastic surfaces. Here, a simple model for the contact of viscoelastic rough surfaces with significant levels of adhesion is presented. This approach is derived from our previous model (Barthel, E.; Haiat, G. Langmuir 2002, 18, 9362) for the adhesive contact of viscoelastic spheres. For simplicity, a simple loading/unloading history (infinitely fast loading and constant pull-out velocity) is assumed. The model provides approximate analytical expressions for the asperity response and exhibits the full viscoelastic adhesive contact phenomenology such as stress relaxation inside the contact zone and creep at the contact edges. Combining this model with a Greenwood-Williamson statistical modeling of rough surfaces, we propose a quantitative assessment of the adhesion to rough viscoelastic surfaces. We show that moderate viscoelasticity efficiently restores adhesion on rough surfaces over a wide dynamic range.


Use of infrared thermography in medical diagnostics: a scoping review protocol.
Thermography offers a non-invasive radiation-free methodology for diagnostic imaging and temperature measurement, but the extent of the current application is unclear, as is the level of evidence for each use case. Moreover, population-based thermographic reference values for diagnostic purposes are nearly unknown. The aim of this scoping review is to identify patient populations and diseases in which thermography is applied, cataloguing of technical and environmental modalities, investigation of the existence of specific reference data and finally exploration of gaps and future tasks. PubMed, Cochrane Database of Systematic Reviews and CENTRAL, Embase, Web of Science and OpenGrey are to be searched using pretested suitable search strategies, with no language restriction, but abstracts should be available in English or German and articles should not have been published before 2000. This limited time frame is due to the rapid technological progress, which makes it necessary to exclude reports based on outdated technology. The literature found will be selected on the basis of previously defined inclusion and exclusion criteria. Subsequently, relevant data will be extracted from the included references into a predesigned table. The selection and extraction process will be conducted by two researchers independently. The report of the results will be according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The entire review process will follow the Joanna Briggs Institute approach. The scoping review protocol is registered at the Open Science Framework. Ethical approval is not required for this work, but ethical medicine also obliges us to carefully consider diagnostic alternatives and compare them with current standards. The dissemination of the results will take place in a variety of ways. First and foremost through publication in an open access journal, but also through conference proceedings. In addition, this scoping review will serve to open up new research foci with regard to thermography.


Supported Ionic Liquids and their Applications in Organic Transformations.
Ionic liquids are one of the greener solvents which have emerged as a replacement for toxic and harmful volatile organic solvents. In the past decade, the concept of supported ionic liquids (SILs) has attracted the attention of the scientific community due to their unique chemical and physical properties. SILs can be synthesized by coating a thin layer of IL film onto/into the surface of solid support. They can be classified as supported IL phase catalyst, solid catalyst with IL and supported IL catalysis. SILs demonstrated the combined properties of both heterogeneous and homogeneous catalysts. These ILs offer several advantages such as enhanced stability, reusability, recoverability, easy product isolation, absence of IL leaching, as compared to conventional solvents. In this review, various aspects of SILs, classification, method of preparation and their applications in various organic transformations such as cross-coupling reactions, oxidation, reduction, synthesis of different heterocyclic compounds, biocatalytic reactions etc., have been discussed.


[The effect on left ventricular mass of treatment with amlodipine and diet therapy in obese patients with arterial hypertension].
Increased parietal stress, in hypertensive obese patients, produces a left ventricular hypertrophy. In this study we demonstrated that the association of amlodipine with hypocaloric diet can decrease the parietal stress. MATERIALS AND METHODS. From February to July 1993 32 hypertensive obese patients (17 males, 15 females) were treated with amlodipine 10 mg/day for six months. Sixteen patients were treated with amlodipine 10 mg/day (Group A) and 16 patients were treated with amlodipine 10 mg/day and hypocaloric diet (Group B). All patients included had a Body Mass Index > 30 and diastolic blood pressure > 100 mmHg. The patients were studied with 2D guided M-mode echocardiogram before treatment and after 6 months. RESULTS. In Group A the septal thickness, the posterior wall thickness and the left ventricular mass decreased significatively (p < 0.05). In the Group B also the left ventricular diastolic diameter and the left atrial diameter decreased. CONCLUSION. The association of a hypocaloric diet with amlodipine therapy, in hypertensive obese patients, improves the effect of the drug on ventricular hypertrophy.


[Effects of ulinastatin on erythrocyte lipid peroxidation in patients undergoing open heart surgery].
To investigate the effects of ulinastatin on erythrocyte lipid peroxidation in patients undergoing open heart surgery. Twenty adult patients with rheumatic heart disease undergoing elective value replacement were divided randomly into 2 groups of 10 patients each: a control group (group C) and an ulinastatin group (group W). The patients were premedicated with intramuscular morphine 0.08 mg/kg and scopolamine 0.06 mg/kg. Anesthesia was induced with midazolam 0.1 mg/kg, fentanyl 5 microg/kg and vecuronium 0.1 mg/kg. After the tracheal intubation, the patients were mechanically ventilated. Anesthesia was maintained with midazolam, fentanyl and isoflurane. Blood samples were taken from radial artery before the operation (T1), 30 min after the initiation of CPB (T2), at the end of the CPB (T3), 30 min after the aorta declamping (T4) and 24 h after the operation (T5) for the determination of plasma and erythrocyte MDA (P-MDA and E-MDA) and erythrocyte SOD (E-SOD). The levels of P-MDA and E-MDA increased significantly after the initiation of CPB and the level of E-SOD was higher than the baseline level at T2, and then decreased from T3 to T5 in group C (P <0.001). The levels of P-MDA and E-MDA didn't increased until T4 (P <0.001) and returned to the baseline level at T5 in group W. The levels of P-MDA and E-MDA were significantly higher in group C than those in group W and the level of E-SOD was markedly lower than that in group W (P <0.05). Ulinastatin can alleviate erythrocyte lipid peroxidation in patients undergoing open heart surgery.


Microwave-accelerated cross-dehydrogenative-coupling (CDC) of N-(quinolin-8-yl)amides with acetone/acetonitrile under metal-free conditions.
A highly selective remote C(sp3)-H acetonation of N-(quinolin-8-yl)amide scaffolds at the C5-position under microwave irradiation has been developed. In the absence of a transition-metal-catalyst, benzoyl peroxide (BPO)-promoted cross-dehydrogenation coupling (CDC) of N-(quinolin-8-yl)amides with acetone/acetonitrile occurred smoothly to generate the corresponding 5-acetonated/acetonitriled N-(quinolin-8-yl)amides in good yields. The transformation is operationally simple, rapid, easily scaled-up to the gram scale, and shows a broad substrate scope.


Effects of 8-bromo-cGMP on Ca2+ levels in vascular smooth muscle cells: possible regulation of Ca2+-ATPase by cGMP-dependent protein kinase.
The effects of 8-bromo-cGMP on intracellular calcium concentrations in cultured rat aortic smooth muscle cells were studied. Both angiotensin II and depolarizing concentrations of K+ stimulated Ca2+ accumulation in the cytoplasm. The increase in Ca2+ due to angiotensin II was associated with an increase in inositol phosphates, while that due to K+ was not. Preincubation of cells with 8-bromo-cGMP (100 microM) caused an inhibition of peak Ca2+ accumulation to either angiotensin II or K+. To probe the mechanism of action of cGMP in vascular smooth muscle, the effects of cGMP-dependent protein kinase on Ca2+-ATPase from the cultured cell particulate material were investigated. Ca2+-activated ATPase was stimulated approximately equal to 2-fold by exogenous calmodulin and up to 4-fold by low concentrations of purified cGMP-dependent protein kinase. The inclusion of both calmodulin and cGMP-dependent protein kinase resulted in an additive stimulation of Ca2+-ATPase. Stimulation of Ca2+-ATPase activity was observed at all Ca2+ concentrations tested (0.01-1.0 microM). cAMP-dependent protein kinase catalytic subunit and protein kinase C were either ineffective or less effective than cGMP-dependent protein kinase in stimulating the Ca2+-ATPase from rat aortic smooth muscle cells. These results suggest a possible mechanism of action for cGMP in mediating decreases in cytosolic Ca2+ through activation of a Ca2+-ATPase and the subsequent removal of Ca2+ from the cell.


Effect of maternal hypoxemia on behavior in unanesthetized normoxic or mildly hyperoxic fetal lambs.
To determine whether hypoxemia inhibits fetal activity by substances from the mother or placenta, six fetal lambs were chronically instrumented at 128-132 days gestation for extra-corporeal membrane oxygenation (ECMO). Severe maternal hypoxemia (arterial PO2 decreased to 6.00 +/- 0.60 kPa) was produced while fetal arterial PO2 was maintained normoxic or mildly hyperoxic using ECMO. The incidences of fetal breathing movements were 34.8 +/- 3.1% (SE) during baseline before ECMO, 36.8 +/- 3.4% during baseline with ECMO, and 21.4 +/- 3.5% (P < 0.05 compared with baseline with ECMO) during maternal hypoxemia. The durations of periods of breathing were 9.8 +/- 1.2 min before ECMO, 9.3 +/- 1.1 min with ECMO, and 10.5 +/- 1.7 min (P = NS) during maternal hypoxemia. In 7 of 14 maternal hypoxemia experiments, breathing activity stopped too late (7-23 min) to be attributed to maternal hypoxemia. Fetal electrocorticographic activity (P = NS), nuchal electromyographic activity (P = NS), and eye movements were normal before ECMO, with ECMO, and during maternal hypoxemia. Fetal blood pressure and heart rate did not change. We conclude that the inhibition of fetal activity during maternal hypoxemia does not seem to be mediated by release of factors from the maternal side of the placenta or the ewe.


Stable and Dynamic Coding for Working Memory in Primate Prefrontal Cortex.
Working memory (WM) provides the stability necessary for high-level cognition. Influential theories typically assume that WM depends on the persistence of stable neural representations, yet increasing evidence suggests that neural states are highly dynamic. Here we apply multivariate pattern analysis to explore the population dynamics in primate lateral prefrontal cortex (PFC) during three variants of the classic memory-guided saccade task (recorded in four animals). We observed the hallmark of dynamic population coding across key phases of a working memory task: sensory processing, memory encoding, and response execution. Throughout both these dynamic epochs and the memory delay period, however, the neural representational geometry remained stable. We identified two characteristics that jointly explain these dynamics: (1) time-varying changes in the subpopulation of neurons coding for task variables (i.e., dynamic subpopulations); and (2) time-varying selectivity within neurons (i.e., dynamic selectivity). These results indicate that even in a very simple memory-guided saccade task, PFC neurons display complex dynamics to support stable representations for WM.SIGNIFICANCE STATEMENT Flexible, intelligent behavior requires the maintenance and manipulation of incoming information over various time spans. For short time spans, this faculty is labeled "working memory" (WM). Dominant models propose that WM is maintained by stable, persistent patterns of neural activity in prefrontal cortex (PFC). However, recent evidence suggests that neural activity in PFC is dynamic, even while the contents of WM remain stably represented. Here, we explored the neural dynamics in PFC during a memory-guided saccade task. We found evidence for dynamic population coding in various task epochs, despite striking stability in the neural representational geometry of WM. Furthermore, we identified two distinct cellular mechanisms that contribute to dynamic population coding.


Autistic traits and positive psychotic experiences modulate the association of psychopathic tendencies with theory of mind in opposite directions.
Various clinical disorders, including psychopathy, and autism and schizophrenia spectrum disorders, have been linked with impairments in Theory of Mind (ToM). However, although these conditions can co-occur in the same individual, the effect of their inter-play on ToM abilities has not been investigated. Here we assessed ToM abilities in 55 healthy adults while performing a naturalistic ToM task, requiring participants to watch a short film and judge the actors' mental states. The results reveal for the first time that autistic traits and positive psychotic experiences interact with psychopathic tendencies in opposite directions to predict ToM performance-the interaction of psychopathic tendencies with autism traits was associated with a decrement in performance, whereas the interaction of psychopathic tendencies and positive psychotic experiences was associated with improved performance. These effects were specific to cognitive rather than affective ToM. These results underscore the importance of the simultaneous assessment of these dimensions within clinical settings. Future research in these clinical populations may benefit by taking into account such individual differences.


Bioconversion Using Lactic Acid Bacteria: Ginsenosides, GABA, and Phenolic Compounds.
Lactic acid bacteria (LAB) are used as fermentation starters in vegetable and dairy products and influence the pH and flavors of foods. For many centuries, LAB have been used to manufacture fermented foods; therefore, they are generally regarded as safe. LAB produce various substances, such as lactic acid, β-glucosidase, and β-galactosidase, making them useful as fermentation starters. Existing functional substances have been assessed as fermentation substrates for better component bioavailability or other functions. Representative materials that were bioconverted using LAB have been reported and include minor ginsenosides, γ-aminobutyric acid, equol, aglycones, bioactive isoflavones, genistein, and daidzein, among others. Fermentation mainly involves polyphenol and polysaccharide substrates and is conducted using bacterial strains such as Streptococcus thermophilus, Lactobacillus plantarum, and Bifidobacterium sp. In this review, we summarize recent studies of bioconversion using LAB and discuss future directions for this field.


Genetic and environmental influences on socio-emotional behavior in toddlers: an initial twin study of the infant-toddler social and emotional assessment.
Relatively little is known about the genetic architecture of childhood behavioral disorders in very young children. In this study, parents completed the Infant-Toddler Social and Emotional Assessment, a questionnaire that assesses symptoms of childhood disorders, as well as socio-emotional competencies, for 822 twin pairs (49.3% female; age 17-48 months) participating in the Wisconsin Twin Project. Psychometric, rater bias, and sex-limitation models explored the role of genetic and environmental influences on (1) externalizing and internalizing behavior; (2) less commonly assessed behaviors pertaining to physical and emotional dysregulation, general competencies, social relatedness; and (3) infrequent behaviors such as those associated with pervasive developmental delays. Heritable influences accounted for the majority (56% or more) of variation in behavior that was commonly observed by both parents. The remaining variance was associated with non-shared environmental factors, with the exception of competency and atypical behavior, which were also influenced by shared environmental factors. In contrast, for most behaviors, the variation unique to mother and father ratings was split between variation due to shared environment or rater biases and to measurement error. Little evidence emerged for sex differences in the underlying causes of variation.


Impaired orientation in acute stroke: frequency, determinants, and time-course of recovery. The Copenhagen Stroke Study.
Orientation is an indicator of general intellectual function and is defined as the ability to report time, place, and personal data. Our knowledge of orientation in acute stroke is sparse. We examined the frequency of impaired orientation in acute stroke, its determinants, and recovery in 653 consecutive patients with acute stroke who were not unconscious and who were without severe aphasia. Prospective assessments of orientation and stroke severity were done by the Scandinavian Neurologic Stroke Scale at the time of acute admission and hereafter weekly until the end of rehabilitation. Impaired orientation was found in 23% of the patients on acute admission and in 12% of the survivors after completed rehabilitation. A stationary level of orientation was achieved by 80% of the patients within 2 weeks and by 95% within 6 weeks. A multiple linear regression analysis found neurological score (B = 0.027, SE(B) = 0.003), age (B = -0.013, SE(B) = 0.003), and comorbidity (B = -0.023, SE(B) = 0.078), but not sex, prior stroke, handedness, or side of stroke lesion to be significant independent determinants of orientation score on acute admission. Lesions involving the anterior and medial thalamus and/or any of the cerebral lobes were associated with impaired orientation. In conclusion, impaired orientation is frequent in acute stroke and the time-course of recovery is similar to what has been found in other neuropsychological impairments with the major part of recovery early after stroke onset.


Overexpression of HO-1 Contributes to Sepsis-Induced Immunosuppression by Modulating the Th1/Th2 Balance and Regulatory T-Cell Function.
Countervailing anti-inflammatory response and immunosuppression can cause death in late sepsis. Depletion and dysfunction of T cells are critical for developing sepsis-induced immunosuppression. Heme oxygenase-1 (HO-1) has a regulatory effect on differentiation and function of T cells and anti-inflammatory properties. We therefore investigated the immunosuppressive role of HO-1 in sepsis with a focus on its effects on helper T-cell (Th) differentiation and regulatory T cells (Treg). Sepsis was induced by cecal ligation and puncture (CLP). Mice were intraperitoneally injected with zinc protoporphyrin (ZnPP; 25 mg/kg), an HO-1 inhibitor, or hemin (20 mg/kg), an HO-1 inducer, at 24 and 36 hours post-CLP. Splenocytes were isolated 48 hours post-CLP. Mice were intranasally infected with Pseudomonas aeruginosa 4 days post-CLP as a secondary pneumonia infection model. ZnPP improved survival and bacterial clearance, whereas hemin had the opposite effect in septic mice. CLP induced lymphocyte apoptosis and a proinflammatory Th1 to anti-inflammatory Th2 shift, which was attenuated by ZnPP. ZnPP attenuated the CLP-induced Treg population and protein expression of inhibitory costimulatory molecules. Furthermore, ZnPP improved survival in the secondary pneumonia infection model. Our findings suggest that HO-1 overexpression contributes to sepsis-induced immunosuppression during late phase sepsis by promoting Th2 polarization and Treg function.


Seeking quantitative morphological characters for species identification in soldiers of Puerto Rican Heterotermes (Dictyoptera, Blattaria, Termitoidae, Rhinotermitidae).
Subterranean termites in the genus Heterotermes Froggatt (Rhinotermitidae: Heterotermitinae) are pantropical wood feeders capable of causing significant structural damage. The aim of this study was to investigate soldier morphological attributes in three Puerto Rican species of Heterotermes previously identified by sequencing of two mitochondrial genes and attributed to Heterotermes tenuis (Hagen), H. convexinotatus (Snyder) and H. cardini (Snyder). Soldiers (n = 156) were imaged and measured using the Auto-Montage image-stacking program. We demonstrated that Puerto Rican Heterotermes soldiers could not be identified to species level based upon seven morphometric indices or any combination thereof. Nor could differences in soldier head pilosity be used to discriminate species, in contrast to previous findings. However, previously described characters of the soldier tergal setae were reported to be useful in discriminating H. tenuis from both of its Puerto Rican congeners.


Effect of Milk Powder Supplementation with Different Calcium Contents on Bone Mineral Density of Postmenopausal Women in Northern China: A Randomized Controlled Double-Blind Trial.
The objective of this study is to examine the effect of milk powder supplementation with different calcium contents on bone mineral density (BMD) in postmenopausal Chinese women, and to determine a more appropriate dose of calcium supplementation. A 2-year, randomized controlled double-blind trial. Postmenopausal women (n = 210) aged 50-65 years were recruited and assigned randomly into three calcium supplementation groups. All participants received milk powder supplementation with different calcium contents (300, 600, and 900 mg per day for groups A, B, and C, respectively) and all groups received 800 IU of vitamin D per day. During the follow-up period, BMD of the left hip and lumbar spine (as the main indicator) was measured using dual-energy X-ray absorptiometry at the baseline, 1 and 2 years. Both three BMD measures and the changes of BMD over 2 years were used to analyze. Before adjusting for covariates, BMD in group A of the lumbar spine and groups A and B of greater trochanter decreased significantly from the baseline over time but increased significantly in the rest groups of the lumbar spine and greater trochanter and in three groups of Ward's triangle. There were significant differences across the three groups for changes of BMD in the greater trochanter and Ward's triangle. When adjusting for covariates, there were significant decreases with time in group A of the spine (P = 0.001), groups A and B of greater trochanter (P = 0.0002 and P = 0.04, respectively) and increases in groups B and C of Ward's triangle (P = 0.03 and P = 0.004, respectively). BMD change in the greater trochanter was significantly different among three groups. For healthy postmenopausal women, high calcium milk powder supplementation was better in retarding bone loss than medium and low calcium in the greater trochanter. Considering the dietary calcium intake of postmenopausal women in north of China, a dose of 900 mg/day is considered as the most appropriate calcium supplementation for greater trochanter but not for other sites.


Comparison of impurity effect between two Tc domes in LaFeAsO(1-x)H(x).
Hydrogen-doped LaFeAsO(1-x)H(x) system has a unique 2-dome structure. The effects of Zn impurities on the first and second superconducting domes in LaFe(1-y)Zn(y)AsO(1-x)H(x) (x = 0.10 for the first superconducting phase (SC1) and 0.35 for the second superconducting phase (SC2)) are examined by electrical resistivity, Hall effect and magnetization measurements. Substitution with Zn strongly suppresses the critical temperature (Tc) and behaves as a nonmagnetic impurity. The suppression rates are: 17(4) K/% (SC1) and 6.9(5) K/% (SC2). It was considered that Zn impurities induced Anderson localization, which triggered the disappearance of the superconductivity, but no decisive conclusions on the dominant pairing symmetry for each dome were obtained.


TYRO3 Knockdown Suppresses the Growth of Myeloid Leukaemia Cells.
TYRO3 is a member of the TAM family (TYRO3, AXL, and MERTK) of receptor tyrosine kinases. While the roles of activated AXL and MERTK in the growth of leukaemia cells have been reported, the effect of TYRO3 has not been determined. Therefore, we examined the effects of TYRO3 knockdown on the growth of leukaemia cell lines. Three human leukaemia cell lines (AA derived from pure erythroid leukaemia, OCI/AML2, and K562), which express TYRO3 protein were used in this study. To induce TYRO3 knockdown, small interfering RNA (siRNA) against TYRO3 was transfected using an electroporation system. Cell growth was assessed by a colorimetric assay. The expression levels and activation of various signalling proteins were examined by immunoblotting. Changes in comprehensive gene expression after TYRO3 knockdown were examined by microarray analysis. TYRO3 knockdown suppressed cell growth in the leukaemia cell lines tested. Additionally, the knockdown suppressed phosphorylation of signal transducer and activator of transcription-3 in AA cells, and extracellular signal-regulated kinase (ERK) 1/2 in AA and OCI/AML2 cells; both are downstream molecules of TYRO3 signalling. TYRO3 knockdown also suppressed the expression of survivin in all the cell lines. TYRO3 knockdown potently suppressed TYRO3 mRNA expression but not that of AXL and MERTK. Furthermore, TYRO3 knockdown suppressed cyclin D1 mRNA expression, which is a downstream molecule of ERK. TYRO3 plays a role in leukaemia cell growth and is a potential therapeutic target for leukaemia.


Identification of small GTP-binding rab proteins in human platelets: thrombin-induced phosphorylation of rab3B, rab6, and rab8 proteins.
The activation of platelets by specific agonists is a tightly regulated mechanism that leads to the secretion of the dense- and alpha-granule contents. Platelets have been shown to possess small GTP-binding proteins thought to be involved in central biological processes; however, no rab proteins, which may regulate the exocytic process at different stages, have been reported. This study has shown that rab1, rab3B, rab4, rab6, and rab8 proteins, but not rab3A protein, were present in platelets and in endothelial cells. To probe their functional significance in platelets, rab3B, rab6, and rab8 proteins were further characterized with regard to their intracellular localization and their phosphorylation properties. Whereas rab3B protein was found to be mainly cytosolic, rab6 and rab8 proteins were preferentially targeted to the plasma membrane and to the alpha granules. The activation of platelets by thrombin, a potent inducer of secretion, resulted in the phosphorylation of rab3B, rab6, and rab8 proteins, whereas no phosphorylation was observed in the presence of prostaglandin E1, which stimulates cAMP-dependent protein kinase and inhibits the secretion process. These findings provide evidence that members of the subfamily of rab proteins, rab6 and rab8, are localized in platelets to one type of specific secretory vesicle, the alpha granule, and would suggest their possible implication in the secretion process through phosphorylation mechanisms.


Music to reduce pain and anxiety in cystoscopy: a systematic review and meta-analysis.
Background To assess the effectiveness and harms of music to reduce anxiety and pain in cystoscopy. Methods We searched MEDLINE (OVID), EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. We included clinical trials, involving the assessment of the effect of music in cystoscopy. The primary outcomes were pain and anxiety measured by any scale and the secondary outcomes were length of stay, physiological parameters (blood pressure or heart rate) and adverse effects. Cochrane Collaboration tool was used to assess the risk of bias. We performed the statistical analysis in R and reported information about mean difference (MD) with 95% CI. Heterogeneity was evaluated using the I2 test. Results We included six studies in our qualitative and quantitative analysis. Five studies used a flexible cystoscope and the other one performed the procedure with a rigid cystoscope. Music was played during the procedure in five studies, while the other was before it. All studies compared music vs. no intervention. Almost all items were assessed as low risk of bias; however, the allocation concealment was unclear in all the studies. We found a MD of -1.33 (95% CI -2.45 to -0.21) (I2=97.2%) favoring music for pain and a MD of -8.42 (95% CI -15.02, -1.82) (I2=99.6%) was found, favoring music for anxiety. Conclusions Playing music might be an effective intervention that lowers pain and anxiety in patients who undergo cystoscopy.


Healthcare in the Himalayan Kingdom of Bhutan: Lessons for the United States and other western healthcare systems.
Bhutan has demonstrated a trajectory of advances in healthcare, while still remaining true to its culture and traditional forms of medicine. Most recently, Bhutan gained international attention when it implemented a strategic Covid-19 vaccination programme that protected a greater percentage of its population than observed in Western industrialised nations. This accomplishment supports the idea that there are lessons from Bhutan to be shared with the rest of the world. In this work, we delineate our observations of the Bhutanese healthcare system, based on field observations in several Bhutanese cities, and results from surveys of Bhutanese physicians. We identify a number of unique practices that influence patient compliance, health education, and access to care in the Bhutanese system, that may be of particular interest and applicability to other healthcare systems. These include housing multiple health services at one location, fully funded medical visits, using non-physician teachers for health education and use of Gross National Happiness (GNH) measures in care.


CIRH1A augments the proliferation of RKO colorectal cancer cells.
Accumulating evidence suggests that ribosomal proteins may have extraribosomal functions in various physiological and pathological processes, including cancer. We analyzed the expression of the CIRH1A ribosomal protein in colorectal carcinoma and para-carcinoma samples by bioinformatics analyses of data extracted from The Cancer Genome Atlas and in colorectal cancer cell lines in vitro by qPCR. CIRH1A was highly expressed in carcinoma samples and colorectal cancer cells. We also transduced the RKO colorectal cancer (CRC) cell line with lentivirus-mediated small interfering RNAs (siRNAs) and studied the impact that this knockdown of CIRH1A expression had on cell growth. RNA interference (RNAi)-mediated inhibition of CIRH1A expression significantly suppressed proliferation and increased apoptosis of transduced cells, and tended to arrest them in G1 phase. Our data suggest that CIRH1A plays a critical role in the proliferation, cell cycle distribution, and apoptosis of human malignant colorectal cells, and might therefore be a potential target for therapeutic strategies.


The impact of cognitive load on processing efficiency and performance effectiveness in anxiety: evidence from event-related potentials and pupillary responses.
Anxiety has been associated with poor attentional control, as reflected in lowered performance on experimental measures of executive attention and inhibitory control. Recent conceptualisations of anxiety propose that individuals who report elevated anxiety symptoms worry about performance and will exert greater cognitive effort to complete tasks well, particularly when cognitive demands are high. Across two experiments, we examined the effect of anxiety on task performance and across two load conditions using (1) measures of inhibitory control (behavioural reaction times and eye-movement responses) and (2) task effort with pupillary and electrocortical markers of effort (CNV) and inhibitory control (N2). Experiment 1 used an oculomotor-delayed-response task that manipulated load by increasing delay duration to create a high load, relative to a low load, condition. Experiment 2 used a Go/No-Go task and load was manipulated by decreasing the No-Go probabilities (i.e., 20% No-Go in the high load condition and 50% No-Go in the low load condition). Experiment 1 showed individuals with high (vs. low) anxiety made more antisaccade errors across load conditions, and made more effort during the high load condition, as evidenced by greater frontal CNV and increased pupillary responses. In Experiment 2, individuals with high anxiety showed increased effort (irrespective of cognitive load), as characterised by larger pupillary responses. In addition, N2 amplitudes were sensitive to load only in individuals with low anxiety. Evidence of reduced performance effectiveness and efficiency across electrophysiological, pupillary, and oculomotor systems in anxiety provides some support for neurocognitive models of frontocortical attentional dysfunction in anxiety.


An automated immunoradiometric assay for human thyrotropin.
In this two-site immunoradiometric assay for thyrotropin, developed for use in the "Kemtek 3000" automated radioimmunoassay system, commercially available monoclonal antibody to thyrotropin is labeled with 125I, and the solid-phase antibody is an IgG fraction of sheep antiserum to thyrotropin, covalently coupled to reprecipitated aminocellulose. There are two incubations, totalling 3 h, the sensitivity is 0.03 milli-int. unit/L. The mean thyrotropin value for 82 healthy euthyroid subjects was 1.7 milli-int. units/L (range 0.4-3.6). For 19 overtly clinically and biochemically hyperthyroid subjects the values ranged from undetectable to 0.2 milli-int. unit/L. In this assay, euthyroid and hyperthyroid subjects can be distinguished with assay of a single basal sample. The assay appears suitable for routine use as a first-line test of thyroid function.


Intraspecific and Interspecific Variations in the Mitochondrial Genomes of Nilaparvata (Hemiptera: Delphacidae).
Planthoppers in the genus Nilaparvata Distant are serious pests of rice and many other crops in tropical and temperate Asia, and northern Australia. In this study, the mitochondrial genomes of four Nilaparvata planthoppers were sequenced, three in Nilaparvata lugens Stål and one in Nilaparvata muiri China. Mitochondrial genome of Nilaparvata contain the standard set of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a control region. The nucleotide composition of Nilaparvata mitochondrial sequence is biased toward adenine and thymine, and the amino acid composition is affected to a similar degree by the bias to AT. We compare the four mitochondrial genomes and find intra- and interspecific variation in gene length, base composition, nucleotide and amino acid substitutions, intergenic spacer length, and gene overlap. The intra- and interspecific variations reveal that nucleotide and amino acid substitutions in mitochondrial protein-coding genes make a contribution to the formation of various insect biotypes in one species. Furthermore, the accumulation of nonsynonymous substitutions in the mitochondrial protein-coding genes, as well as differences in start codons, the length of intergenic spacers, and gene overlap regions contribute to differences between the two species investigated here. In addition, cox is the most conserved gene family and nad4-nad4l cluster is variable in Nilaparvata mitochondrial genes for the intra- and interspecific variation.


Why is Life Expectancy in Busan Shorter than in Seoul? Age and Cause-Specific Contributions to the Difference in Life Expectancy between Two Cities.
Seoul and Busan are the two largest cities in Korea. However, life expectancy (LE) in Busan is shorter than in Seoul and among the total Korean population. This study was conducted to decompose age- and cause-specific contributions to the LE difference between Seoul and Busan. We obtained population and mortality data for Seoul and Busan between 2015 and 2017 from Statistics Korea. We applied Arriaga's decomposition method to life table data to estimate age- and cause-specific contributions to the LE difference between Seoul and Busan. During 2015-2017, LE in Busan was shorter than in Seoul by 2.22 years. Roughly two-thirds of the LE gap between Seoul and Busan was due to excess mortality among elderly people in Busan. The ≥85 age group alone contributed to approximately 20% of the LE gap, while no meaningful contribution was made by the 1-24 age groups. Cardiovascular disease accounted for over 40% of the total LE gap between Seoul and Busan, and this factor was more prominent in women. The top 15 leading specific causes of deaths explained nearly the entire LE difference between Seoul and Busan. The difference in LE between Seoul and Busan was due to higher mortality rate in Busan than in Seoul, especially in the elderly population and from cardiovascular diseases. Information on age- and cause-specific contributions to the LE difference between Seoul and Busan may guide health policy-makers to plan strategies for reducing the gap in LE.


An ELISA Lab-on-a-Chip (ELISA-LOC).
Laminated object manufacturing (LOM) technology using polymer sheets is an easy and affordable method for rapid prototyping of Lab-on-a-Chip (LOC) systems. It has recently been used to fabricate a miniature 96 sample ELISA lab-on-a-chip (ELISA-LOC) by integrating the washing step directly into an ELISA plate. LOM has been shown to be capable of creating complex 3D microfluidics through the assembly of a stack of polymer sheets with features generated by laser micromachining and by bonding the sheets together with adhesive. A six layer ELISA-LOC was fabricated with an acrylic (poly(methyl methacrylate) (PMMA)) core and five polycarbonate layers micromachined by a CO(2) laser with simple microfluidic features including a miniature 96-well sample plate. Immunological assays can be carried out in several configurations (1 × 96 wells, 2 × 48 wells, or 4 × 24 wells). The system includes three main functional elements: (1) a reagent loading fluidics module, (2) an assay and detection wells plate, and (3) a reagent removal fluidics module. The ELISA-LOC system combines several biosensing elements: (1) carbon nanotube (CNT) technology to enhance primary antibody immobilization, (2) sensitive ECL (electrochemiluminescence) detection, and (3) a charge-coupled device (CCD) detector for measuring the light signal generated by ECL. Using a sandwich ELISA assay, the system detected Staphylococcal enterotoxin B (SEB) at concentrations as low as 0.1 ng/ml, a detection level similar to that reported for conventional ELISA. ELISA-LOC can be operated by a syringe and does not require power for operation. This simple point-of-care (POC) system is useful for carrying out various immunological assays and other complex medical assays without the laboratory required for conventional ELISA, and therefore may be more useful for global healthcare delivery.


The Facial Characteristics of Individuals with Posterior Crossbite: A Cross-Sectional Study.
Facial morphology is known to be influenced by genetic and environmental factors. Scientific evidence regarding facial parameters in patients with posterior crossbite is lacking. This study aimed to investigate the association between posterior crossbite and facial parameters. This cross-sectional study included 34 adolescents with and 34 adolescents without posterior crossbite in the age range from 13 to 15 years. Facial surface scans were acquired with a 3dMD imaging system, and landmark-based analysis was performed. Data were analyzed using the Mann-Whitney U test and Spearman's correlations. Individuals in the control group had lower face heights (females: p = 0.003, r = 0.45; males: p = 0.005, r = 0.57). The control group females presented with smaller intercanthal width (p = 0.04; r = 0.31) and anatomical nose width (p = 0.004; r = 0.43) compared with the crossbite group females. The males in the control group had wider nostrils. In the control group, significant correlations among different facial parameters were more common, including the correlations between eye width and other transversal face measurements. On the contrary, the facial width was correlated with nasal protrusion (r = 0.657; p < 0.01) and the morphological width of the nose (r = 0.505; p < 0.05) in the crossbite group alone. In both groups, the philtrum width was linked with the anatomical and morphological widths of the nose. Conclusions: Patients with posterior crossbites have increased face height and different patterns of facial proportions compared with individuals without crossbites.


Mechanism of growth retardation following chronic administration of beta-adrenoceptor antagonists to developing rats.
A total of 112 3-week old Wistar rats were separated into eight groups: control groups I-IV (n = 62) and propranolol-treated groups V-VIII (n = 50). Propranolol hydrochloride (100 mg/kg) was present in the rats' drinking water until 26 weeks of age and growth rates of all groups were monitored daily until 53 days of age and thereafter every third day throughout the study. Chronic oral propranolol administration produced growth retardation (P less than 0.05) in both sexes that was reversible when treatment was discontinued. Organ weights were generally smaller in propranolol-treated rats; on the other hand, the ratio of most organ weights per 100 g of body weight was greater in propranolol-treated rats (especially females). The radio-immunological determination of plasma growth hormone showed increased concentrations of growth hormone in propranolol-treated rats (P less than 0.05), whereas hypothalamic somatostatin content was not significantly changed. The results showed that the retarded growth rate following chronic oral propranolol administration to growing rats was independent of changes in plasma growth hormone and hypothalamic somatostatin concentrations, and that retardation was entirely reversible when the beta-adrenoceptor antagonist was discontinued.


LAPAROSCOPIC RADICAL PROSTATECTOMY: SINGLE CENTER CASE SERIES.
Laparoscopic radical prostatectomy (LRP) is traditionally characterized as a technically difficult procedure with a long learning curve but it is successfully performed worldwide. The aim of this paper was to assess the initial learning curve and clinical outcomes for LRP in our center. We performed a retrospective study including 63 LRP cases, in the course of 22 months, performed by 2 urologists, with no previous LRP experience. All patients were previously assessed by a multidisciplinary team and were selected on the basis of low and intermediate risk disease attributes according to the classification of prostate cancer risk groups of the European Association of Urology. The main outcomes of follow-up are procedure duration, estimated blood loss, complications, positive surgical margins, biochemical relapse and urinary continence. The median follow-up was 19.6 months. The median procedure duration was 196.8 minutes and median blood loss 257.1 mL. Significant decrease in both outcomes was observed when comparing first and last cases in the series. There were 5 (7.9%) Clavien Dindo grade II complications. Undetectable prostate specific antigen (PSA) was observed in 59 (93.6%) patients, and fifty-five patients (87.3%) were continent. Following a methodical learning approach, LRP can be safely mastered with favorable outcomes.


Ischaemic necrosis of the lesser curvature of the stomach as a complication of proximal selective vagotomy.
After a survey a the European literature of lesser curvature ischaemic necrosis, a special complication of proximal selective vagotomy, the pathogenesis, and the clinical and pathological forms of the complication as well as the possibilities of its treatment and prevention are analysed. The case of two patients with lesser curvature necrosis is presented.


Corneal confocal sub-basal nerve plexus evaluation: a review.
The aim of this study was to review the most recent data about corneal sub-basal nerve plexus (SNP) evaluated with the use of corneal confocal microscopy (CCM). For this purpose, an electronic search was conducted based on PubMed and Google Scholar and Web of Science databases from 2008 up to the end of 2016. Ninety-eight articles in English were cited, as well as abstracts in other languages, concerning the morphology and function of corneal SNP in various diseases. Changes in corneal SNP as a result of local treatment were also introduced. Figures with scans from confocal microscopy from our Department were included. The main conclusion of this review was that both corneal SNP diminishment and high tortuosity as well as low sensitivity are in principle related to the presence or level of pathology. In addition, increased nerve tortuosity may represent a morphological determinant of nerve regeneration. However, the presented literature shows that SNP changes are not characteristic for one unified corneal pathology; rather, they reflect the non-specific pathological process present in many diseases. Future studies should use automatized biometric software and also examine the effects of new treatments on SNP.


Interventions for palliative symptom control in COVID-19 patients.
Individuals dying of coronavirus disease 2019 (COVID-19) may experience distressing symptoms such as breathlessness or delirium. Palliative symptom management can alleviate symptoms and improve the quality of life of patients. Various treatment options such as opioids or breathing techniques have been discussed for use in COVID-19 patients. However, guidance on symptom management of COVID-19 patients in palliative care has often been derived from clinical experiences and guidelines for the treatment of patients with other illnesses. An understanding of the effectiveness of pharmacological and non-pharmacological palliative interventions to manage specific symptoms of COVID-19 patients is required. To assess the efficacy and safety of pharmacological and non-pharmacological interventions for palliative symptom control in individuals with COVID-19. We searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), Embase, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), medRxiv); Web of Science Core Collection (Science Citation Index Expanded, Emerging Sources); CINAHL; WHO COVID-19 Global literature on coronavirus disease; and COAP Living Evidence on COVID-19 to identify completed and ongoing studies without language restrictions until 23 March 2021. We screened the reference lists of relevant review articles and current treatment guidelines for further literature. We followed standard Cochrane methodology as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We included studies evaluating palliative symptom management for individuals with a confirmed diagnosis of COVID-19 receiving interventions for palliative symptom control, with no restrictions regarding comorbidities, age, gender, or ethnicity. Interventions comprised pharmacological as well as non-pharmacological treatment (e.g. acupressure, physical therapy, relaxation, or breathing techniques). We searched for the following types of studies: randomized controlled trials (RCT), quasi-RCTs, controlled clinical trials, controlled before-after studies, interrupted time series (with comparison group), prospective cohort studies, retrospective cohort studies, (nested) case-control studies, and cross-sectional studies. We searched for studies comparing pharmacological and non-pharmacological interventions for palliative symptom control with standard care. We excluded studies evaluating palliative interventions for symptoms caused by other terminal illnesses. If studies enrolled populations with or exposed to multiple diseases, we would only include these if the authors provided subgroup data for individuals with COVID-19. We excluded studies investigating interventions for symptom control in a curative setting, for example patients receiving life-prolonging therapies such as invasive ventilation. DATA COLLECTION AND ANALYSIS: We used a modified version of the Newcastle Ottawa Scale for non-randomized studies of interventions (NRSIs) to assess bias in the included studies. We included the following outcomes: symptom relief (primary outcome); quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; serious adverse events; and grade 3 to 4 adverse events. We rated the certainty of evidence using the GRADE approach. As meta-analysis was not possible, we used tabulation to synthesize the studies and histograms to display the outcomes. MAIN RESULTS: Overall, we identified four uncontrolled retrospective cohort studies investigating pharmacological interventions for palliative symptom control in hospitalized patients and patients in nursing homes. None of the studies included a comparator. We rated the risk of bias high across all studies. We rated the certainty of the evidence as very low for the primary outcome symptom relief, downgrading mainly for high risk of bias due to confounding and unblinded outcome assessors. Pharmacological interventions for palliative symptom control We identified four uncontrolled retrospective cohort studies (five references) investigating pharmacological interventions for palliative symptom control. Two references used the same register to form their cohorts, and study investigators confirmed a partial overlap of participants. We therefore do not know the exact number of participants, but individual reports included 61 to 2105 participants. Participants received multimodal pharmacological interventions: opioids, neuroleptics, anticholinergics, and benzodiazepines for relieving dyspnea (breathlessness), delirium, anxiety, pain, audible upper airway secretions, respiratory secretions, nausea, cough, and unspecified symptoms. Primary outcome: symptom relief All identified studies reported this outcome. For all symptoms (dyspnea, delirium, anxiety, pain, audible upper airway secretions, respiratory secretions, nausea, cough, and unspecified symptoms), a majority of interventions were rated as completely or partially effective by outcome assessors (treating clinicians or nursing staff). Interventions used in the studies were opioids, neuroleptics, anticholinergics, and benzodiazepines. We are very uncertain about the effect of pharmacological interventions on symptom relief (very low-certainty evidence). The initial rating of the certainty of evidence was low since we only identified uncontrolled NRSIs. Our main reason for downgrading the certainty of evidence was high risk of bias due to confounding and unblinded outcome assessors. We therefore did not find evidence to confidently support or refute whether pharmacological interventions may be effective for palliative symptom relief in COVID-19 patients. Secondary outcomes We planned to include the following outcomes: quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; serious adverse events; and grade 3 to 4 adverse events. We did not find any data for these outcomes, or any other information on the efficacy and safety of used interventions. Non-pharmacological interventions for palliative symptom control None of the identified studies used non-pharmacological interventions for palliative symptom control. We found very low certainty evidence for the efficacy of pharmacological interventions for palliative symptom relief in COVID-19 patients. We found no evidence on the safety of pharmacological interventions or efficacy and safety of non-pharmacological interventions for palliative symptom control in COVID-19 patients. The evidence presented here has no specific implications for palliative symptom control in COVID-19 patients because we cannot draw any conclusions about the effectiveness or safety based on the identified evidence. More evidence is needed to guide clinicians, nursing staff, and caregivers when treating symptoms of COVID-19 patients at the end of life. Specifically, future studies ought to investigate palliative symptom control in prospectively registered studies, using an active-controlled setting, assess patient-reported outcomes, and clearly define interventions. The publication of the results of ongoing studies will necessitate an update of this review. The conclusions of an updated review could differ from those of the present review and may allow for a better judgement regarding pharmacological and non-pharmacological interventions for palliative symptom control in COVID-19 patients.


Effect of antidiuretic hormone on human small intestinal water and solute transport.
The effect of i.v. Pitressin (ADH) in a dose of 1 U/hr on permeability characteristics and on absorptive capacity of the normal human small intestine was investigated. The method of continuous intestinal perfusion was employed with polyethylene glycol 4000 as a nonabsorbable marker. Unidirectional flux rates of Na and H(2)O were calculated from the disappearance of (22)Na and of (3)HOH from isotonic saline solution within the intestinal lumen. Each study consisted of two successive perfusion periods: one while the subject was hydrated, the other during ADH infusion or while the subject was dehydrated. Water and sodium absorption from isotonic NaCl occurred in the hydrated state and was abolished by ADH as well as by dehydration in the jejunum. In some instances, net gain of water and sodium in the lumen occurred. In the ileum, ADH and dehydration caused a decrease in water and sodium absorption rate. By contrast, unidirectional flux into the intestinal lumen of water and sodium, as well as dextrose and D-xylose diffusion, remained unchanged by ADH. During perfusions with hypertonic urea solutions the rates of sodium and water entry into the intestine were greatly increased during i.v. ADH infusion, whereas urea loss from the study segment remained constant. ADH in the dosage used did not affect human intestinal motility. The results suggest that circulating ADH in physiologic concentrations affects the small intestine in one of two ways: increased secretion of water and salt into the lumen or direct interference with the active sodium transport mechanism.


Lymphogranuloma venereum. Outbreak in a university community.
One aspect of the current epidemic of venereal diseases is the spread of lymphogranuloma venereum (LGV). Formerly confined to the lower echelons of society, it now affects more affluent classes as well. A cluster of four cases was seen in a small college town. Serial LGV complement fixation tests, the most valuable diagnostic tool, may reveal many more cases than reported previously. Early treatment is important. We recommend therapy for all persons sexually exposed to LGV who have any LGV complement fixation test anomaly, whether or not clinical signs develop.


Barriers to Increasing Use of Peritoneal Dialysis in Bangladesh: A Survey of Patients and Providers.
Despite a lower requirement for technology and equipment than hemodialysis (HD), peritoneal dialysis (PD) is an underutilized modality in low- and middle-income countries (LMICs). Bangladesh has the lowest use of PD in the world (fewer than 2% of prevalent patients). We evaluated nephrologists' attitudes toward PD and examined differences between patients on HD and PD in Dhaka. We asked nephrologists to fill out an English-language questionnaire. Using convenience sampling but targeting both public and private hospitals in Dhaka, we asked trained nurses to administer a Bangla-language questionnaire to patients on HD (n = 116) and PD (n = 41). We validated the questionnaires on a sub-sample (n = 10 for each group). Of the 43 nephrologists surveyed, 27 (63%) had patients on PD. When compared with nephrologists without patients on PD, those with patients on PD were less likely to believe that survival and quality of life on PD was worse than on HD (odds ratio [OR] = 0.21, 95% confidence interval [CI] 0.05 - 0.83 and OR = 0.11, 95% CI 0.02 - 0.67 respectively) but were not more likely to have received training for PD. Nephrologists named cost of PD as the predominant barrier to increasing use of PD, followed by concerns about patient hygiene and lack of trained nurses. Fifty-two HD patients (45%) did not know about a home-based modality. When compared with patients on HD, patients on PD were more likely to have been educated by non-nephrologists about dialysis, to be "forewarned" about the need for dialysis, to be paying fully, and to be living in a permanent home with a non-communal water source. Some barriers to increasing access to PD-i.e., patient living conditions and cost-are unique to LMICs. Our study also highlights that issues encountered in high-income countries-i.e., nephrologists' subjective preference and lack of patient knowledge about an alternate modality to HD-may play a role as well.


Circulating motilin, ghrelin, and GLP-1 and their correlations with gastric slow waves in patients with chronic kidney disease.
Patients with chronic kidney disease (CKD) commonly complain upper gastrointestinal (GI) symptoms, especially anorexia. Hemodialysis (HD) has been noted to improve GI symptoms; however, the underlying mechanisms are unclear. This study was designed 1) to study effects of HD on GI symptoms and gastric slow waves; and 2) to investigate possible roles of ghrelin and glucagon-like peptide-1 (GLP-1): the study recruited 13 healthy controls, 20 CKD patients without HD (CKD group), and 18 CKD patients with HD (HD group). Dyspeptic symptoms, autonomic functions, gastric slow waves, and plasma level of ghrelin and GLP-1 were analyzed. First, the CKD patients with HD showed markedly lower scores of anorexia (0.6 ± 0.2 vs. 3.2 ± 0.4, P < 0.001) compared with patients without HD. Second, the CKD group but not HD group showed a significant reduction (25.6%) in the percentage of normal gastric slow waves, compared with controls. Third, the CKD group exhibited a significantly lower ghrelin level compared with the HD group (26.8 ± 0.9 vs. 34.1 ± 2.3 ng/l, P < 0.02) and a higher GLP-1 level (29.4 ± 2.8 vs. 20.0 ± 2.1 pmol/l, P < 0.05) compared with controls. Moreover, the percentage of normal slow waves was positively correlated with ghrelin (r = 0.385, P = 0.019) but negatively correlated with GLP-1 (r = -0.558, P < 0.001) in all CKD patients. Hemodialysis improves upper GI symptoms and gastric slow waves in CKD patients. An increase in ghrelin and a decrease in GLP-1 might be involved in the HD-induced improvement in gastric slow waves.


Cartilage in the walls of odontogenic keratocysts.
Only one histologically documented case of cartilage in the wall of an odontogenic keratocyst has been reported in the English language literature. Four new cases are presented with the clinical, radiographic and histopathologic features described. To our knowledge this finding has not been reported in association with any other type of odontogenic cyst.


Hypogravity modeling of upper extremities: an investigation of manual handling in the workplace.
Experiments on the lower limbs are the only approaches being used to study how hypogravity (HG) (0 < g < 1, e.g., Moon: 1/6 g, Mars: 3/8 g) affects human movement. The goal of this study was to expand this field experimentally by investigating the effect of HG on the upper extremities during one-handed manual handling tasks in a sitting posture: static weight holding with an outstretched arm, and slow repetitive weight lifting and lowering motions. The hypothesis was that while completing static and dynamic tasks with elements of repetition in HG, the upper body's tilt (angle regarding the vertical axis) would change differently from Earth's gravity. Specifically, upper arm and spine angles, joint torques, and forces were investigated. Twenty-four healthy participants aged 33.6 ± 8.2 years were involved in the trial. Joint angles were examined using vision-based 3D motion analysis. According to this investigation, there is a correlation between a body tilting backward and a gravity level reduction (p < 0.01). Thus, HG causes postural deviation, and this shows that workplace design must be adapted according to the level of gravity to promote comfortable and balanced body alignment, minimizing stress on muscles and joints. To lower the risk of musculoskeletal disorders (MSDs), enhance overall performance, and increase job satisfaction, proper support systems and restrictions for sitting positions should be taken into account, concerning different levels of gravity.


Changes in Microbiome Activity and Sporadic Viral Infection Help Explain Observed Variability in Microcosm Studies.
The environmental conditions experienced by microbial communities are rarely fully simulated in the laboratory. Researchers use experimental containers ("bottles"), where natural samples can be manipulated and evaluated. However, container-based methods are subject to "bottle effects": changes that occur when enclosing the plankton community that are often times unexplained by standard measures like pigment and nutrient concentrations. We noted variability in a short-term, nutrient amendment experiment during a 2019 Lake Erie, Microcystis spp. bloom. We observed changes in heterotrophic bacteria activity (transcription) on a time-frame consistent with a response to experimental changes in nutrient availability, demonstrating how the often overlooked microbiome of cyanobacterial blooms can be altered. Samples processed at the time of collection (T0) contained abundant transcripts from Bacteroidetes, which reduced in abundance during incubation in all bottles, including controls. Significant biological variability in the expression of Microcystis-infecting phage was observed between replicates, with phosphate-amended treatments showing a 10-fold variation. The expression patterns of Microcystis-infecting phage were significantly correlated with ∼35% of Microcystis-specific functional genes and ∼45% of the cellular-metabolites measured across the entire microbial community, suggesting phage activity not only influenced Microcystis dynamics, but the biochemistry of the microbiome. Our observations demonstrate how natural heterogeneity among replicates can be harnessed to provide further insight on virus and host ecology.


Membrane composition determines the fate of aggregated vesicles.
Vesicles incorporating a fluorescent metal-chelating lipid can be linked together by addition of copper(II) and poly-L-histidine, but the stability of adhering vesicles towards fusion depends upon membrane composition.


Biomedical applications of optical imaging.
Developments in imaging offer real-time visualisation of biological processes at the cellular and molecular level. This article considers how micro- and nanotechnology may enhance the application of optical imaging for in vivo and in vitro diagnostics.


Effect of weight reduction on leptin, total ghrelin and obestatin concentrations in prepubertal children.
The aim of the study was to evaluate fasting levels of glucose, insulin, leptin, total ghrelin, and obestatin in a group of prepubescent obese children before and after weight loss. We enrolled 64 prepubescent obese children, but only 35 completed the study (mean age 7.6 +- 0.9 years, 19 females) and 20 normal-weight prepubescent children as controls. Fasting plasma concentration of glucose, insulin, Homeostasis Model assessment for insulin resistance (HOMA-IR), and leptin, total ghrelin, and obestatin levels were measured at baseline and after a 6-month lifestyle intervention (i.e. improved nutrition and increased physical activity). At baseline, obese children showed significantly (p less than 0.001) higher leptin and obestatin levels, and lower total ghrelin concentrations than control subjects. Weight loss significantly (p less than 0.001) diminished plasma leptin and insulin levels and increased ghrelin and obestatin concentrations. Weight loss in prepubescent children is associated with a significant change in leptin, ghrelin and obestatin concentrations. These results confirm the hypothesis that levels of these hormones are closely associated with obesity in childhood and might take part, as consequence but not as a cause, in glucose, fat, and energy metabolism.


Site-directed mutagenesis reveals regions implicated in the stability and fiber formation of human λ3r light chains.
Light chain amyloidosis (AL) is a disease that affects vital organs by the fibrillar aggregation of monoclonal light chains. λ3r germ line is significantly implicated in this disease. In this work, we contrasted the thermodynamic stability and aggregation propensity of 3mJL2 (nonamyloidogenic) and 3rJL2 (amyloidogenic) λ3 germ lines. Because of an inherent limitation (extremely low expression), Cys at position 34 of the 3r germ line was replaced by Tyr reaching a good expression yield. A second substitution (W91A) was introduced in 3r to obtain a better template to incorporate additional mutations. Although the single mutant (C34Y) was not fibrillogenic, the second mutation located at CDR3 (W91A) induced fibrillogenesis. We propose, for the first time, that CDR3 (position 91) affects the stability and fiber formation of human λ3r light chains. Using the double mutant (3rJL2/YA) as template, other variants were constructed to evaluate the importance of those substitutions into the stability and aggregation propensity of λ3 light chains. A change in position 7 (P7D) boosted 3rJL2/YA fibrillogenic properties. Modification of position 48 (I48M) partially reverted 3rJL2/YA fibril aggregation. Finally, changes at positions 8 (P8S) or 40 (P40S) completely reverted fibril formation. These results confirm the influential roles of N-terminal region (positions 7 and 8) and the loop 40-60 (positions 40 and 48) on AL. X-ray crystallography revealed that the three-dimensional topology of the single and double λ3r mutants was not significantly altered. This mutagenic approach helped to identify key regions implicated in λ3 AL.


Age-related variability in elbow joint capsule thickness in asymptomatic children and adults.
The purpose of this study was to establish normal ultrasonographic measurements for elbow joint capsule thickness in children. Transverse posterior ultrasonographic images of 53 elbow joints in asymptomatic patients were digitized, and off-line measurements were performed and compared to the corresponding scale present on each image to yield a reliable measurement in millimeters. Joint capsule thickness measurements regressed with age. Significant differences existed between three age groups. Joint capsule thickness is under 1 mm in children 1 month to 2 years of age, increased significantly to just over 1 mm from 2 to 15 years of age, and approached 2 mm in thickness at and after 15 years of age.


Environmental health assessment of primary schools in southeastern Nigeria: implication for a healthy school environment in developing countries.
In this cross-sectional descriptive study, we used a validated school health program evaluation scale (SHPE) to assess the environmental health status of primary schools in Ebonyi State, southeastern Nigeria. Parameters assessed included water supply, sewage and refuse disposal, school building ventilation, lighting and seating, as well as the availability of toilet tissue, basins for washing hands, regular cleaning of toilets, and so forth. Of all the schools assessed, only two schools, both private, attained the minimum acceptable SHPE score of 57. The mean SHPE score of the private schools (50.40) was significantly higher than that of the public schools (28.69) (t-test, p=.00). Policy reforms are needed that would ensure a healthy primary school environment in Nigeria and in other developing countries with similar settings.


Pharmacologic regulation of AMPK in breast cancer affects cytoskeletal properties involved with microtentacle formation and re-attachment.
The presence of tumor cells in the circulation is associated with a higher risk of metastasis in patients with breast cancer. Circulating breast tumor cells use tubulin-based structures known as microtentacles (McTNs) to re-attach to endothelial cells and arrest in distant organs. McTN formation is dependent on the opposing cytoskeletal forces of stable microtubules and the actin network. AMP-activated protein kinase (AMPK) is a cellular metabolic regulator that can alter actin and microtubule organization in epithelial cells. We report that AMPK can regulate the cytoskeleton of breast cancer cells in both attached and suspended conditions. We tested the effects of AMPK on microtubule stability and the actin-severing protein, cofilin. AMPK inhibition with compound c increased both microtubule stability and cofilin activation, which also resulted in higher McTN formation and re-attachment. Conversely, AMPK activation with A-769662 decreased microtubule stability and cofilin activation with concurrent decreases in McTN formation and cell re-attachment. This data shows for the first time that AMPK shifts the balance of cytoskeletal forces in suspended breast cancer cells, which affect their ability to form McTNs and re-attach. These results support a model where AMPK activators may be used therapeutically to reduce the metastatic efficiency of breast tumor cells.


Clinical and Translational Science Personas: Expansion and use cases.
Twelve evidence-based profiles of roles across the Clinical and Translational Science (CTS) workforce and two patient profiles were developed by CTS Personas collaborators in 2019 as part of the CTSA Program National Center for Data to Health (CD2H). Based on feedback received from the community, CTS Personas team members collaborated to produce five additional Personas to broaden representation of the CTS workforce and enhance the existing portfolio. This paper presents the rationale and methodology used in the latest CTS Personas initiative. This work also includes an implementation scenario incorporating multiple Personas. Using the new National Institutes of Health's (NIH) Data Management and Sharing Policy as an example, we demonstrate how administrators, researchers, support staff, and all CTS collaborators can use the Personas to respond to this new policy while considering the needs of service providers and users, CTS employees with short- and long-term needs, and interdisciplinary perspectives.


PSD3 is an oncogene that promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in papillary thyroid cancer.
Background: The morbidity of thyroid cancer is gradually increasing, meanwhile, the average age of the morbidity population also becomes younger. Mechanisms genomic variations serve an important function for the pathogenesis of many cancer types. Pleckstrin and sec7 domain-containing 3 (PSD3), also known as EFA6R, was shown to be associated with some cancers such as acute myeloid leukemia, breast cancer metastasis, and astrocytoma. But it was unknown that whether PSD3 took effect and how did it work in thyroid cancer. Methods: We guessed that PSD3 might play an important role in thyroid cancer by consulting previous literature. Then, we analyzed the level of PSD3 expression in thyroid malignancy and the connection with clinical manifestation in The Cancer Genome Atlas (TCGA). And RNA extraction, reverse transcription, and real-time quantitative polymerase chain reaction (qRt-PCR) of 40 pairs of local samples were done to verify the result of TCGA. Then, PSD3 was knocked down by small interfering RNA (siRNA) for flowing functional experiments. Results: Bioinformatics and qRt-PCR analysis shown PSD3 was overexpressed in papillary thyroid cancer (PTC) and connected with the histological type (P=0.009) and risk of lymph node metastasis (P=0.016). In vitro assays, we confirmed that down-regulation PSD3 could not only suppress the cell proliferation, colony formation, cell migration, cell invasion, and G1/S cell cycle transition but also promote apoptosis in PTC cells. Conclusion: PSD3 promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in PTC and a possible biomarker in PTC.


Supporting band 5 practitioners in professional and leadership roles.
Interest in professionalism and leadership has increased within the nursing and midwifery community. The NHS Lanarkshire Practice Development Centre established a study day on these concepts for band 5 practitioners. This formed part of NHS Lanarkshire's implementation of Scotland's nursing and midwifery leadership development strategy, Leading Better Care. The aims of the study day were to reinforce individual professional responsibility, promote the principles of professionalism and explore the concept of leadership in the band 5 role. This article reports on the development, implementation and evaluation of the study day.


Psychological distress and intensive care unit stay after cardiac surgery: The role of illness concern.
To examine the association between psychological factors and length of intensive care unit (ICU) stay in patients undergoing elective coronary artery bypass graft (CABG) surgery. We studied 212 adults undergoing CABG surgery preoperatively to assess depression symptoms, anxiety symptoms, and illness perceptions and then followed them up during the in-hospital stay to measure length of ICU stay. Greater preoperative concern about the illness (B = .200, 95% CI [.094, .305], p = < .001), but not depression or anxiety symptoms, was significantly related to longer ICU stays after controlling for demographic, clinical, and behavioral covariates. Illness concern may be particularly relevant for CABG recovery, though more work is needed to delineate the exact mechanisms of this effect.


An enhanced password authentication scheme for session initiation protocol with perfect forward secrecy.
The Session Initiation Protocol (SIP) is an extensive and esteemed communication protocol employed to regulate signaling as well as for controlling multimedia communication sessions. Recently, Kumari et al. proposed an improved smart card based authentication scheme for SIP based on Farash's scheme. Farash claimed that his protocol is resistant against various known attacks. But, we observe some accountable flaws in Farash's protocol. We point out that Farash's protocol is prone to key-compromise impersonation attack and is unable to provide pre-verification in the smart card, efficient password change and perfect forward secrecy. To overcome these limitations, in this paper we present an enhanced authentication mechanism based on Kumari et al.'s scheme. We prove that the proposed protocol not only overcomes the issues in Farash's scheme, but it can also resist against all known attacks. We also provide the security analysis of the proposed scheme with the help of widespread AVISPA (Automated Validation of Internet Security Protocols and Applications) software. At last, comparing with the earlier proposals in terms of security and efficiency, we conclude that the proposed protocol is efficient and more secure.


Differential impacts of juvenile hormone, soldier head extract and alternate caste phenotypes on host and symbiont transcriptome composition in the gut of the termite Reticulitermes flavipes.
Termites are highly eusocial insects and show a division of labor whereby morphologically distinct individuals specialize in distinct tasks. In the lower termite Reticulitermes flavipes (Rhinotermitidae), non-reproducing individuals form the worker and soldier castes, which specialize in helping (e.g., brood care, cleaning, foraging) and defense behaviors, respectively. Workers are totipotent juveniles that can either undergo status quo molts or develop into soldiers or neotenic reproductives. This caste differentiation can be regulated by juvenile hormone (JH) and primer pheromones contained in soldier head extracts (SHE). Here we offered worker termites a cellulose diet treated with JH or SHE for 24-hr, or held them with live soldiers (LS) or live neotenic reproductives (LR). We then determined gene expression profiles of the host termite gut and protozoan symbionts concurrently using custom cDNA oligo-microarrays containing 10,990 individual ESTs. JH was the most influential treatment (501 total ESTs affected), followed by LS (24 ESTs), LR (12 ESTs) and SHE treatments (6 ESTs). The majority of JH up- and downregulated ESTs were of host and symbiont origin, respectively; in contrast, SHE, LR and LS treatments had more uniform impacts on host and symbiont gene expression. Repeat "follow-up" bioassays investigating combined JH + SHE impacts in relation to individual JH and SHE treatments on a subset of array-positive genes revealed (i) JH and SHE treatments had opposite impacts on gene expression and (ii) JH + SHE impacts on gene expression were generally intermediate between JH and SHE. Our results show that JH impacts hundreds of termite and symbiont genes within 24-hr, strongly suggesting a role for the termite gut in JH-dependent caste determination. Additionally, differential impacts of SHE and LS treatments were observed that are in strong agreement with previous studies that specifically investigated soldier caste regulation. However, it is likely that gene expression outside the gut may be of equal or greater importance than gut gene expression.


Mitochondria and oxygen homeostasis.
Molecular oxygen possesses a dual nature due to its highly reactive free radical property: it is capable of oxidizing metabolic substrates to generate cellular energy, but can also serve as a substrate for genotoxic reactive oxygen species generation. As a labile substance upon which aerobic life depends, the mechanisms for handling cellular oxygen have been fine-tuned and orchestrated in evolution. Protection from atmospheric oxygen toxicity as originally posited by the Endosymbiotic Theory of the Mitochondrion is likely to be one basic principle underlying oxygen homeostasis. We briefly review the literature on oxygen homeostasis both in vitro and in vivo with a focus on the role of the mitochondrion where the majority of cellular oxygen is consumed. The insights gleaned from these basic mechanisms are likely to be important for understanding disease pathogenesis and developing strategies for maintaining health.


Treatment of steroid-refractory immune checkpoint Inhibitor-induced intestinal pseudo-obstruction with infliximab.
Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a relatively new therapeutic approach for patients with several cancer types including non-small cell lung cancer1. Targeted monoclonal antibodies based drugs can activate anti-tumor immunity by blocking immune checkpoint receptors (CTLA-4, PD-1 receptor and its ligand PD-L1), in order to restore T-cell effector function2,3. However, the use of immune checkpoint inhibitors can lead to a unique side effect profile termed as immune-related adverse events (irAEs). Loss of T-cell inhibition results in an enhanced immune response driven by T-cell activation and is capable of inducing an autoimmune-related inflammation in normal tissue as a consequence of impaired self tolerance4. These irAEs can potentially involve every organ system including gastrointestinal, dermatologic, hepatic, and endocrine toxicities. For example, Fernandez-Gordon Sanchez et al reported a patient with immune-mediated colitis and nonimmune-mediated cholestasic injury induced by pembrolizumab that was successfully treated with Ustekinumab5. We report a steroid-refractory case of lung adenocarcinoma patient with an unusual irAE (intestinal pseudo-obstruction) during the treatment with immune checkpoint inhibitors that could be successfully managed by the administration of infliximab.


Healing touch for older adults with persistent pain.
The purpose of this report was to provide an in-depth review of responses from older adults residing in long-term care facilities receiving Healing Touch (HT) for pain management. Persistent pain is common in this population and, while the mainstay for pain management is analgesics, HT may provide supportive therapy. Twenty older adults from 5 facilities in the southwestern United States participated in the study, with 12 receiving the active intervention of HT and 8 receiving the control of presence care. A convergent mixed-methods approach was used in this secondary report, using the providers' descriptions of 84 HT sessions and quantitative findings to provide an in-depth within-case analysis. Outcome measures included quantitative measures of pain, daily living, and quality of life, as well as qualitative descriptors of the HT sessions. The findings suggest that the experience is highly varied and on a continuum from no perceived or noticeable benefit to a decrease in pain and improvement in other physiological and psychosocial symptoms. Therefore, HT may be beneficial for some older adults within long-term care facilities as an adjunct for chronic pain.


Maternal high-fat diet decreases milk endocannabinoids with sex-specific changes in the cannabinoid and dopamine signaling and food preference in rat offspring.
Maternal high-fat (HF) diet during gestation and lactation programs obesity in rat offspring associated with sex-dependent and tissue-specific changes of the endocannabinoid system (ECS). The ECS activation induces food intake and preference for fat as well as lipogenesis. We hypothesized that maternal HF diet would increase the lipid endocannabinoid levels in breast milk programming cannabinoid and dopamine signaling and food preference in rat offspring. Female Wistar rats were assigned into two experimental groups: control group (C), which received a standard diet (10% fat), or HF group, which received a high-fat diet (29% fat) for 8 weeks before mating and during gestation and lactation. Milk samples were collected to measure endocannabinoids and fatty acids by mass spectrometry. Cannabinoid and dopamine signaling were evaluated in the nucleus accumbens (NAc) of male and female weanling offspring. C and HF offspring received C diet after weaning and food preference was assessed in adolescence. Maternal HF diet reduced the milk content of anandamide (AEA) (p<0.05) and 2-arachidonoylglycerol (2-AG) (p<0.05). In parallel, maternal HF diet increased adiposity in male (p<0.05) and female offspring (p<0.05) at weaning. Maternal HF diet increased cannabinoid and dopamine signaling in the NAc only in male offspring (p<0.05), which was associated with higher preference for fat in adolescence (p<0.05). Contrary to our hypothesis, maternal HF diet reduced AEA and 2-AG in breast milk. We speculate that decreased endocannabinoid exposure during lactation may induce sex-dependent adaptive changes of the cannabinoid-dopamine crosstalk signaling in the developing NAc, contributing to alterations in neurodevelopment and programming of preference for fat in adolescent male offspring.


Mixed-realism simulation of adverse event disclosure: an educational methodology and assessment instrument.
Physicians have an ethical duty to disclose adverse events to patients or families. Various strategies have been reported for teaching disclosure, but no instruments have been shown to be reliable for assessing them.The aims of this study were to report a structured method for teaching adverse event disclosure using mixed-realism simulation, develop and begin to validate an instrument for assessing performance, and describe the disclosure practice of anesthesiology trainees. Forty-two anesthesiology trainees participated in a 2-part exercise with mixed-realism simulation. The first part took place using a mannequin patient in a simulated operating room where trainees became enmeshed in a clinical episode that led to an adverse event and the second part in a simulated postoperative care unit where the learner is asked to disclose to a standardized patient who systematically moves through epochs of grief response. Two raters scored subjects using an assessment instrument we developed that combines a 4-element behaviorally anchored rating scale (BARS) and a 5-stage objective rating scale. The performance scores for elements within the BARS and the 5-stage instrument showed excellent interrater reliability (Cohen's κ = 0.7), appropriate range (mean range for BARS, 4.20-4.47; mean range for 5-stage instrument, 3.73-4.46), and high internal consistency (P < 0.05). We have demonstrated a comprehensive methodology using a mixed-realism simulation that engages learners in an adverse event and allows them to practice disclosure to a structured range of patient responses. We have developed a reliable 2-part instrument with strong psychometric properties for assessing disclosure performance.