Negative regulation of the androgen receptor gene promoter by NFI and an adjacently located multiprotein-binding site.
The upstream promoter of the rat androgen receptor (AR) gene contains a strong negative regulatory region located at the -388 to -340 nucleotide position. The distal part (-388/-373) of this regulatory region binds NFI, a ubiquitous transcription factor, while the proximal portion (-372/-340) contains an overlapping binding site for two nuclear proteins. This composite regulatory region (-388/-340) was initially defined by deoxyribonuclease I footprinting as the continuous stretch of a nuclease-protected site. NFI specificity of the distal portion (-388/-373) of the footprint was established through cross-competition in electrophoretic mobility shift assay (EMSA) using the well characterized NFI element of the adenovirus major late promoter and by immunoreactivity to the NFI antibody. EMSA with oligonucleotide duplexes corresponding to the proximal domain (-372/-340) indicated multiple retarded bands with at least two major DNA-protein complexes. Further analysis with truncated oligonucleotide duplexes showed that these two major proteins bind to this domain in an overlapping manner. Within this overlapping area, the position spanning -359 to -347 is essential for the formation of either of these two complexes. Substitution of four G with T residues in the overlapping area totally abolished all protein binding at the downstream -372/-340 site. Point mutations that abolish specific binding at either the NFI or immediately downstream multiprotein-binding site caused about a 10-fold increase in AR promoter activity in transfected HepG2 cells. Double mutation involving both the NFI and proximal overlapping protein-binding sites failed to cause any additional increase in promoter function. From these results we conclude that the AR promoter contains a composite negative regulatory region at -388/-340, and the repressor function may involve a coordinate interaction between NFI and at least two other nuclear factors.


Effects of photoperiod during the dry period on cellular immune function of dairy cows.
Recent studies suggest that exposure of cattle to photoperiod can influence immune function. The objective of this study was to determine whether treatment of cows with short day photoperiod (SDPP; 8 h light: 16 h darkness) during the dry period alters immune function, relative to cows subjected to a long day photoperiod (LDPP; 16 h light: 8 h darkness). Multiparous Holstein cows (n = 39) were dried 62 d before calving and exposed to photoperiod treatment until parturition; thereafter, cows were exposed to natural photoperiod. General health was monitored weekly during the dry period and cellular immune function was examined monthly during the dry period and at calving. Concentrations of prolactin and cortisol were measured from 10 d before calving to 2 d after calving. The periparturient prolactin surge in plasma was greater in LDPP cows (54.6 ng/ mL) than SDPP (22.4 ng/mL). Relative to LDPP cows, neutrophil chemotaxis and lymphocyte proliferation were enhanced in SDPP cows during the dry period. Neutrophil chemotaxis averaged 142.5 and 178.8 cells/ well during the dry period for LDPP and SDPP, respectively. Lymphocyte proliferation during the dry period averaged 197.6 and 326.5% for LDPP and SDPP cows, respectively. Physiological characteristics of the cows were not affected by treatment during the dry period. However, differences between treatments were observed within 2 d of parturition. Potential implications of photoperiod management for cow health and well-being merit further investigation.


Skeletal Muscle Mass Index Is Positively Associated With Bone Mineral Density in Hemodialysis Patients.
Background: Patients with chronic kidney disease (CKD) are at risk for bone loss and sarcopenia because of associated mineral and bone disorders (MBD), malnutrition, and chronic inflammation. Both osteoporosis and sarcopenia are associated with a poor prognosis; however, few studies have evaluated the relationship between muscle mass and bone mineral density (BMD) in hemodialysis (HD) patients. The present study examined the association between skeletal muscle mass index (SMI) and BMD in the lumbar spine and femoral neck in HD patients. Methods: Fifty HD patients (mean age, 69 ± 10 years; mean HD duration, 9.0 ± 8.8 years) in Minami-Uonuma City Hospital were evaluated. BMD was measured by dual-energy X-ray absorptiometry, and SMI was measured by bioelectrical impedance analysis (InBodyTM) after HD. The factors affecting lumbar spine and femoral neck BMD were investigated, and multivariate analysis was performed. Results: In simple linear regression analysis, the factors that significantly affected the lumbar spine BMD were sex, presence of hypertension, presence of diabetes mellitus, body mass index, triglyceride level, grip strength, and SMI; the factors that significantly affected the femoral neck BMD were sex, HD duration, serum creatinine level, tartrate-resistant acid phosphatase 5b level, undercarboxylated osteocalcin (ucOC) level, N-terminal propeptide of type I procollagen level, grip strength, and SMI. In multivariate analysis, SMI (standardized coefficient: 0.578) was the only independent factor that affected the lumbar spine BMD; the independent factors that affected the femoral neck BMD were SMI (standardized coefficient: 0.468), ucOC (standardized coefficient: -0.366) and sex (standardized coefficient: 0.231). Conclusion: SMI was independently associated with the BMD in the lumbar spine and femoral neck in HD patients. The preservation of skeletal muscle mass could be important to prevent BMD decrease in HD patients, in addition to the management of CKD-MBD.


Macro creatine kinases: results of isoenzyme electrophoresis and differentiation of the immunoglobulin-bound type by radioassay.
In 2.9% of sera from 1253 unselected patients we detected two different types of macromolecular creatine kinases (CK; EC 188.8.131.52). One macro type was represented by immunoglobulin-linked CK: in sera containing macro CK-BB isoenzyme, 125I-labeled CK-BB was bound with high affinity to the immunoglobulin fraction. Furthermore, during electrophoresis, macro CK-BB mostly migrated between CK-MB and CK-MM, and was fixed to Protein A from Staphylococcus aureus. We therefore propose radioelectrophoresis as a specific, highly sensitive, and simple method for detecting this type of macro CK. This form occurs predominantly in elderly women, is not correlated to any specific disease, and persists in blood over a long period of time. In contrast, a second type (macro-CK type 2) never bound radiolabeled CK isoenzymes, and was not adsorbed to Protein A. Electrophoretic migration of this macro-CK type 2 was generally cathodic to CK-MM. We observed this type in severely ill patients, frequently those suffering from malignant tumors. Clinical observations and biochemical data suggest that macro-CK type 2 is of mitochondrial origin.


Computer-generated patient education materials: do they affect professional practice? A systematic review.
A systematic search of seven electronic databases was done to identify randomized controlled trials that assessed the effect of computer-generated patient education material (PEM) on professional practice. Three studies met the authors' criteria. All three studies involved preventive care. All used a complex intervention of which computer-generated PEM was a major component. Improvements in practice were seen in all studies, although these gains were generally modest. One study showed improvement in patient outcomes. Mann-Whitney statistics calculated for the studies' outcome measures ranged from 0.48 to 0.66, equivalent to risk differences of -4 to 32 percent. Computer-generated PEM seems to have a small, positive effect on professional practice. The small number of included studies and the complex nature of the interventions makes it difficult to draw conclusions about the ability of computer-generated PEM to change professional practice. Future work should involve well-defined interventions that can be clearly evaluated in terms of effect and cost.


[Donor supply of scalp and specificities of hair transplantation in Asians].
In 2005--2007 in a hair transplantation clinic 'Talizi' the flow of international patients increased dramatically, including those from Central and Eastern Asia. During this period 211 ethnic Asian patients underwent operations, including 146 patients from South Korea, 2--from China, 62-- from Kazakhstan and 1--from Philippines. Black and straight hair give impact of low density due to considerable contrast with characteristic for Asians light color scalp; therefore, from the very beginning we tried to transplant as many grafts (follicular units - FU) as possible. For the operation we chose strip version (FUSS) that enables to receive large number of grafts. The scale of transplantation varied in a range of 1200-3800 FU, on average--2500-3000 FU. Though, even from the very first cases we faced specificities of ethnic Asian scalp that significantly complicated our work: low density and low hair/graft ratio in donor zone in contrast to information from special literature, and low laxity (flexibility) of the scalp. We set an objective to specify indicators of donor density (number of FU on a sq.cm and hair/FU ratio), to study bio-mechanical specificities of ethnic Asian scalp and develop optimal surgical tactics for these patients after the evaluation of transplantation results. Observation group was composed of 211 patients from abovementioned countries and a sub-group--50 Korean patients for medium-scale hair transplantation (2000-3000 FU) by strip version. Study of donor characteristics of these patients revealed low density--74 FU/cm2; on 1 cm2 grow only 121 hairs, whereas hair/FU ration was 1,63. Strength required to close would edges (scalp tension power) varied from 1,4 kg-f to 2,6 kg-f depending on scalp flexibility and number of transplanted grafts (strip width), and amounted on average to 2,16 +/- 0,02 kg-f, p < 0,001%. This indicator is about 1,5 times exceeding the one of ethnic Caucasian patient group (1,47 +/- 0,02 kg-f, p < 0,001%). Low donor density of our Korean patients compelled us to increase width of the obtained skin strip (sometimes to 2,5 cm) in order to get required number of grafts (FU). In case of low flexibility of the scalps this resulted in high percentage (10-15%) of wide (4-10 mm) scar formation in donor area. In order to find the way out from this situation (restrict the width of the strip to 1,5 cm without affecting FU to be transplanted in one operation), we proposed the combination of the strip version (FUSS) with FU extraction (FUE). While this solution increased the duration and price of the operation, we believe that it is the most optimal version in case of large-scale hair transplantation for the ethnic Asian patients.


Community-Based Care in the ANRS-IPERGAY Trial: The Challenges of Combination Prevention.
ANRS-IPERGAY was a community-based randomized trial investigating the efficacy of sexual activity-based HIV pre-exposure prophylaxis (PrEP) in a population of males and transgender females who had sex with men and were at high risk of HIV infection. We qualitatively analyzed the support provided to participants by community-based health workers (CBHW) throughout the trial's double-blind and open-label extension phases. In particular, we showed that the relationship between participants and CBHW strongly influenced self-managed pill intake. The delicate construction of this relationship, balanced between trust and dependence, played an important role in PrEP adherence. CBHW had to deal with various issues surrounding participants' feelings of empowerment regarding their role in the trial, as well as related tensions between various logics and rationalities. They were essential to participants' continued involvement.


Antiarrhythmic drug treatment: need for continuous vigilance.
Any physician treating cardiac arrhythmias should be aware of a possible worsening of the arrhythmia (so-called arrhythmogenesis) after the start of antiarrhythmic drug treatment. To facilitate the recognition of that complication the type and possible mechanisms of arrhythmogenesis are reviewed. Recognition also requires an understanding of (a) the time of appearance of arrhythmogenic effects after different drugs, (b) the value of non-invasive and invasive tests, and (c) the profile of the patient most likely to develop this problem. Guidelines are given to reduce the incidence of the arrhythmogenic effects of antiarrhythmic drugs and a plea is made that the physician should be always on the alert for this complication.


The impact of sexual self-concept ambiguity on alcohol approach bias and consumption.
The current work sought to examine both intra-individual and situational features that can predict heightened alcohol misuse among individuals who report sexual-orientation self-concept ambiguity (SSA). It was hypothesized that situations that evoke the salience of individuals' sexuality will contribute to alcohol misuse among individuals who report heightened SSA. In the first experiment, fifty-nine students were recruited from psychology subject pools at two large state universities. Following a writing manipulation, used to evoke a state of heightened self-focus on an individual's sexuality, participants completed the Alcohol Approach-Avoidance Task, which served as a marker of implicit bias toward alcohol-related cues. In the second experiment, ninety-four women between the ages of 21 and 35 were recruited into a lab-based study. Utilizing procedures similar to the first experiment, we attempted to test our research questions in an ad lib drinking study. Among young adults with greater SSA, situations that induced heightened self-focus were predictive of increased approach bias toward alcohol-related cues and increased consumption of an ostensibly alcoholic beverage. Evidence supported a causal link between the situational salience of sexuality and acute risk of alcohol-approach bias and consumption behavior among those with heightened SSA. Preventive interventions may highlight variation in risk of alcohol misuse based on identity-related risk factors, such as sexual self-concept ambiguity, and drinking motivations.


A Holistic Assessment of Polyethylene Fiber Ingestion in Larval and Juvenile Japanese Medaka Fish.
Microplastic pollution is of public concern for global environmental health, aquaculture, and fisheries. Toxicity studies have shown that microplastic ingestion may cause intestinal damage, microbiota dysbiosis, and disturb the lipid and energy metabolism in fish. To determine the impact of environmentally relevant, chronic, low dose microplastic fibers on fish health, medaka larvae, and juveniles were exposed to five concentrations of polyethylene (PE) fibers for 21 days through the feed. Fish growth and condition were assessed to determine the overall impact on fish health. To identify impaired energy intake, the gastrointestinal tract (GIT) integrity was evaluated at the molecular and cellular levels. Microbiota analysis was performed by comparing the top seven most abundant phyla present in both larval and juvenile fish exposed to 0, 1.5, and 3 PE fibers/fish/day. A shift in the phyla Proteobacteria and Bacteroidetes were observed. Larval samples demonstrated decreased proteobacteria abundance, while juvenile samples displayed an increase in abundance. Relative gene expression of key digestive genes from GIT tissue was quantified using real time-quantitative polymerase chain reaction. An effect on digestive gene expression potentially affecting nutrient absorption and antioxidant production was indicated via a significant decrease of solute carrier family 6 member 6 expression in larvae exposed to 6 fibers/fish/day. No significant molecular changes were observed in juvenile GIT tissue, although a non-monotonous dose-response was observed. GIT morphology was analyzed using histomorphological observations of the GIT mucus and cell types. No significant impairment of the GIT epithelial layers was observed in larvae or juveniles. To assess growth and condition, Fulton's condition factor was measured. No differences were observed in larval or juvenile growth. Comparisons of different developmental stages allowed for identifying vulnerable developmental stages for microplastic exposure; larvae were more susceptible to molecular changes, while shifts in juvenile microbial communities were similar to changes reported post-polystyrene microplastic sphere exposure. This study is one of the first to provide toxicological data on the risk of PE fiber ingestion during fish development stages. Results indicate no imminent threat to fish condition at current measured environmental levels of microplastics; however, close monitoring of vital spawning grounds for commercially important fishes is recommended.


Historical account on gaining insights on the mechanism of crown gall tumorigenesis induced by Agrobacterium tumefaciens.
The plant tumor disease known as crown gall was not called by that name until more recent times. Galls on plants were described by Malpighi (1679) who believed that these extraordinary growth are spontaneously produced. Agrobacterium was first isolated from tumors in 1897 by Fridiano Cavara in Napoli, Italy. After this bacterium was recognized to be the cause of crown gall disease, questions were raised on the mechanism by which it caused tumors on a variety of plants. Numerous very detailed studies led to the identification of Agrobacterium tumefaciens as the causal bacterium that cleverly transferred a genetic principle to plant host cells and integrated it into their chromosomes. Such studies have led to a variety of sophisticated mechanisms used by this organism to aid in its survival against competing microorganisms. Knowledge gained from these fundamental discoveries has opened many avenues for researchers to examine their primary organisms of study for similar mechanisms of pathogenesis in both plants and animals. These discoveries also advanced the genetic engineering of domesticated plants for improved food and fiber.


Functional MRI of the spinal cord: will it solve the puzzle of pain?
Whether stimulation of the median nerve could evoke an fMR imaging response at 1.5 T in the cervical spinal cord was investigated and the response pattern was compared with that obtained by fist clenching. Eleven subjects performed the fist-clenching task and in seven of them electrical stimulation was also applied. fMRI was performed using a T2* sensitive echo-planar imaging sequence gated by the heartbeat signal. A dynamic cardiac-gated T2*-weighted imaging sequence was used to quantify cervical spinal cord activation. Cord activation was measured in the sagittal and transverse imaging planes. With the fist-clenching task, activation of the spinal cord in the cervical intumescence could be seen in seven of eleven subjects in the sagittal plane and in six of nine subjects in whom axial images were acquired. When median nerve stimulation was applied, cord activation was seen in the sagittal images in five out of seven, and in the axial plane in two out of six subjects. A consistent cross-sectional localization of the activity measured in the spinal cord was not detected, either in terms of the right and left sides or in terms of the posterior and anterior directions. In the sagittal plane, median nerve stimulation at the elbow can evoke an fMR imaging response in the lower cervical spinal cord. The activation pattern was comparable with that obtained by fist clenching.


Baseline Wandering Removal in Optical Mapping Measurements With PID Control in Phase Space.
Optical imaging methods on ex-vivo hearts have had large impact in furthering our understanding of cardiac electrophysiology. One common problem in this method is a baseline wandering of the fluorescence signals over time, caused by dye photo-bleaching, small variation of the excitation light source, or other similar artifacts. Due to its relative magnitude, the removal of baseline wandering can be a nontrivial task and has major implications for analyzing important physiological dynamics such as traveling waves and alternans. Here we present a computational technique for the removal of such baseline wandering based on Proportional-Integral-Derivative (PID) closed loop feedback. The PID method applied a continuous control stimulus to the input Vm based on an error value which is defined by Euclidean distance from a pre-computed setpoint in phase space. We quantify and validate the PID control method by adding a linear combination of arbitrary sinusoidal drift, of frequency less than the signal pacing frequency, to the system signal Vm. The PID control loop effectively removed the baseline wandering with minimal degradation to the input Vm, and thus provides a viable tool for baseline wandering removal when implemented in an appropriate phase space. The computational simplicity of the method also lends itself to implementation in embedded systems, such as Arduinos and Raspberry-Pis.


The online world as a means of connection and disconnection during the COVID-19 pandemic: A test of the interpersonal-connections-behaviour framework.
The interpersonal-connections-behaviour framework proposes that social media is helpful/unhelpful to the individual to the extent that it facilitates/hinders satisfaction of core needs for acceptance and belonging (connecting and disconnecting pathways). However, little research has, to date, explicitly tested this framework. Both pathways were explored in a cross-sectional sample of UK adults at the start of the pandemic (N = 632) and in longitudinal (cross-lagged) analyses (N = 227-240). Participants completed measures of online and offline socialising with friends and family (connecting pathway), and online and offline social comparisons (disconnecting pathway), anxiety, depression and loneliness. In cross-sectional analyses higher levels of online comparisons were associated with poorer mental health, an effect that survived after controlling for offline comparisons, and was partially mediated by loneliness. Counter to our predictions, online socialising was also associated with poorer mental health. Longitudinal analyses did not support predicted directions of causality. Limitations include a lack of testing of individual-level moderators, the use of single item questions to probe some constructs, and an inability to test for effects potentially operating at different time-scales. The findings reported partially support the interpersonal-connections-behaviour framework in highlighting a disconnecting (but not connecting) pathway between online engagement and mental health. From a clinical perspective they highlight the importance of including people's online lives when considering mental health risk and resilience, particularly (one might argue) during periods of social isolation.


Large improvement of photo-response of CuPc sensitized Bi(2)WO(6) with enhanced photocatalytic activity.
In order to harvest the solar energy more efficiently, a novel photocatalyst was designed by introducing an organic dye sensitizer, copper phthalocyanine (CuPc), into an inorganic semiconductor Bi(2)WO(6). This composite photocatalyst exhibited an improved photo-response in the whole visible spectrum and even the near infrared region. Under a red LED (λ = 620 nm) irradiation, the CuPc/Bi(2)WO(6)/FTO electrode showed photocurrent response. The photo-degradation of RhB and phenol under simulated solar light demonstrated that the CuPc-Bi(2)WO(6) composite exhibited much higher photocatalytic activity than bare Bi(2)WO(6). Moreover, the composite photocatalyst also showed photo-activity under a red LED (λ = 620 nm) irradiation, further testifying the sensitization effect of CuPc. This study provides a new strategy to increase the utilization rate of solar energy substantially.


Music therapy for individuals with dementia: areas of interventions and research perspectives.
This contribution focuses on the definition of music therapy as a specific applicative context to be seen as distinct from the generic use of music in a variety of pathologies. Music therapy is presented as a discipline grounded both upon relationship and upon the theoretical-methodological principles peculiar to each applicative model. The therapeutic nature proper to music therapy is highlighted with specific reference to the domain of the dementias. Music therapy facilitates expression, communication and relationship in the non-verbal context. Such an opportunity allows persons with dementia to establish contact, to express, and even contrive an organisation/regulation of their emotions, through the sonorous-musical relationship with the music therapist. On the basis of a brief analysis of the relevant literature, attention is drawn to the importance of both evidence-based clinical practice and music therapy evaluations, aimed at proving the effectiveness of music therapy, while promoting its correct application.


Telomerase activity in thyroid fine needle aspirates.
To study the utility of telomerase activity (TA) detection in thyroid fine needle aspirates (FNAs). One hundred two thyroid nodules were studied: 70 in FNA samples and 32 in frozen tumors. From among FNA samples, there were 57 nodules of the goiter, 1 adenoma, 7 papillary carcinomas, 1 medullary carcinoma and 1 lymphoma. Three cases of thyroiditis were excluded. The 32 frozen tissue tumors consisted of 5 follicular adenomas, 4 follicular carcinomas and 23 papillary carcinomas. TA was analyzed by Telomerase PCR ELISA (Roche Diagnostics, Indianapolis, Indiana, U.S.A.). TA was negative in the 57 nonneoplastic nodules and 6 follicular adenomas and positive in 3 of 4 follicular carcinomas and 10 of 30 papillary carcinomas. TA sensitivity was 41.4% and specificity 100%. Sensitivity for malignancy was higher (85.7%) in FNAs than in TA. TA seems highly specific for neoplasms of the thyroid. Further studies are needed to confirm whether TA detection could contribute to identifying neoplasms when FNAs are inconclusive for malignancy and in cases of scanty material.


Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: lessons from ghrelin knockout mice.
Neurogenesis occurs in the adult hippocampus and is enhanced by dietary restriction (DR), and neurogenesis enhancement is paralleled by circulating ghrelin level enhancement. We have previously reported that ghrelin modulates adult neurogenesis in the hippocampus. In order to investigate the possible role of ghrelin in DR-induced hippocampal neurogenesis in adult mice, ghrelin knockout (GKO) mice and wild-type (WT) mice were maintained for 3 months on DR or ad libitum (AL) diets. Protein levels of ghrelin in the stomach and the hippocampus were increased by DR in WT mice. One day after BrdU administration, the number of BrdU-labeled cells in the hippocampal dentate gyrus was decreased in GKO mice maintained on the AL diet. DR failed to alter the proliferation of progenitor cells in both WT and GKO mice. Four weeks after BrdU injection, the number of surviving cells in the dentate gyrus was decreased in AL-fed GKO mice. DR increased survival of newborn cells in WT mice, but not in GKO mice. Levels of brain-derived neurotrophic factor protein in the hippocampus were similar between WT and GKO mice, and were increased by DR both in WT and GKO mice. These results suggest that elevated levels of ghrelin during DR may have an important role in the enhancement of neurogenesis induced by DR.


Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes.
Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes during the Omicron surge is limited. We sought to determine the effectiveness of nirmatrelvir-ritonavir and molnupiravir for the outpatient treatment of COVID-19. We conducted three retrospective target trial emulation studies comparing matched patient cohorts who received nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir in the Veterans Health Administration (VHA). Participants were Veterans in VHA care at risk for severe COVID-19 who tested positive for SARS-CoV-2 in the outpatient setting during January and February 2022. Primary outcomes included all-cause 30-day hospitalization or death and 31-180-day incidence of acute or long-term care admission, death, or post-COVID-19 conditions. For 30-day outcomes, we calculated unadjusted risk rates, risk differences, and risk ratios. For 31-180-day outcomes, we used unadjusted time-to-event analyses. Participants were 90% male with median age 67 years and 26% unvaccinated. Compared to matched untreated controls, nirmatrelvir-ritonavir-treated participants (N=1,587) had a lower 30-day risk of hospitalization (27.10/1000 versus 41.06/1000, risk difference [RD] - 13.97, 95% CI -23.85 to -4.09) and death (3.15/1000 versus 14.86/1000, RD -11.71, 95% CI - 16.07 to -7.35). Among persons who were alive at day 31, further significant reductions in 31-180-day incidence of hospitalization (sub-hazard ratio 1.07, 95% CI 0.83 to 1.37) or death (hazard ratio 0.61, 95% CI 0.35 to 1.08) were not observed. Molnupiravir-treated participants aged ≥65 years (n=543) had a lower combined 30-day risk of hospitalization or death (55.25/1000 versus 82.35/1000, RD -27.10, 95% CI -50.63 to -3.58). A statistically significant difference in 30-day or 31-180-day risk of hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants. Incidence of most post-COVID conditions was similar across comparison groups. Nirmatrelvir-ritonavir was highly effective in preventing 30-day hospitalization and death. Short-term benefit from molnupiravir was observed in older groups. Significant reductions in adverse outcomes from 31-180 days were not observed with either antiviral.


Further verification of an in vitro tier system for the identification of cosmetic ingredients that are not ocular irritants.
A tier evaluation system for the identification of cosmetic ingredients that are not ocular irritants was applied to 59 cosmetic ingredients, for which in vivo data were available. The tier system employs monolayer cultures of SIRC cells, an established cell line originally derived from rabbit cornea, and a threedimensional living dermal model (LDM; MATREX(TM)), which consists of human dermal fibroblasts in a contracted collagen lattice. The effects of ingredients on monolayer cultures of SIRC cells were determined by Crystal Violet staining (in the SIRC-CVS assay), and the effects on the LDM were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (in the LDM-MTT assay). The classifications of eye irritancy predicted by the in vitro system were compared with previously reported data obtained with the in vivo Draize rabbit eye test. The in vivo classification was based on appearance of corneal damage, or a maximal average score (MAS) of 15 as the cut-off point. The SIRC-CVS assay was effective in the prediction of compounds that would be non-irritants at a concentration of 10%, while the subsequent LDM-MTT assay could predict non-irritancy at various lower and higher concentrations, including 10%. The tier system gave very few false-negative predictions, though false positives were unavoidable. Performing the LDM-MTT assay with an additional 73 ingredients gave similar results in the prediction of non-irritancy at various concentrations. Our findings indicate that the tier system may be suitable for the safety assessment of eye irritancy of ingredients intended to be used in cosmetics and medicated cosmetics in Japan.


Physical Function, Cognitive Function, and Daily Activities in Patients Hospitalized Due to COVID-19: A Descriptive Cross-Sectional Study in Sweden.
An estimated 14-20% of people infected with COVID-19 require medical care. The aim of the present study was to evaluate physical function, cognitive function, and daily activities in patients hospitalized due to COVID-19, and to investigate differences depending on age and admission to the intensive care unit (ICU). This prospective descriptive cross-sectional study included a consecutive sample of 211 patients (mean age 65.1 years, 67.3% men) hospitalized due to COVID-19 in Sweden. Data regarding physical function and daily activities were collected in hospital from July 2020 to February 2021. The average length of hospital stay was 33.8 days, and 48.8% of the patients were admitted to the ICU. Physical function (grip- and lower body strength) was reduced in both groups, and significantly more in the older group, ≥65 years old, compared to the younger. Furthermore, the older group also had significantly less ability to perform activities in daily life, and had significantly reduced cognitive function as compared to the younger age group. In patients treated in the ICU, physical impairments as well as the activity level were significantly more pronounced compared to patients not treated in the ICU. Patients hospitalized due to COVID-19 are physically impaired, have mild cognitive impairments, and have difficulties performing daily activities. The findings in this study indicate the need for out-patient follow-up and rehabilitation for patients hospitalized due to COVID-19, especially in older patients and patients treated in the ICU.


Crinkling and crumpling: an auditory fMRI study of material properties.
Knowledge of an object's material composition (i.e., what it is made of) alters how we interact with that object. Seeing the bright glint or hearing the metallic crinkle of a foil plate for example, confers information about that object before we have even touched it. Recent research indicates that the medial aspect of the ventral visual pathway is sensitive to the surface properties of objects. In the present functional magnetic resonance imaging (fMRI) study, we investigated whether the ventral pathway is also sensitive to material properties derived from sound alone. Relative to scrambled material sounds and non-verbal human vocalizations, audio recordings of materials being manipulated (i.e., crumpled) in someone's hands elicited greater BOLD activity in the right parahippocampal cortex of neurologically intact listeners, as well as a cortically blind participant. Additional left inferior parietal lobe activity was also observed in the neurologically intact group. Taken together, these results support a ventro-medial pathway that is specialized for processing the material properties of objects, and suggest that there are sub-regions within this pathway that subserve the processing of acoustically-derived information about material composition.


In vitro and in vivo evaluation of tannic acid as an antibacterial agent in broilers infected with Salmonella Typhimurium.
This study was conducted to evaluate tannic acid (TA) as an antibacterial agent against Salmonella Typhimurium in in vitro and in vivo chicken models. The TA formed an inhibitory zone against Salmonella enterica serotypes including S. Typhimurium, S. Enteritidis, and S. Infantis. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of TA against Salmonella Typhimurium nalidixic acid resistant strain (STNR) were determined as 40 and 700 μg/mL, respectively. Sublethal doses of TA (5, 10, and 20 μg/mL) restricted swimming and swarming motility and biofilm formation of STNR compared to the control group (0 μg/mL) (P < 0.05). The TA-bovine serum albumin (BSA) complex formed at simulated gastric pH (pH 3.75) was hydrolyzed at pH 6.75 and 7.25 (P < 0.05), and the hydrolysis of the TA-BSA complex was stronger at pH 7.25 compared to the pH 6.75 (P < 0.05). The inhibitory zone of the TA-BSA complex against STNR at pH 6.75 was lower than TA without BSA at 30 and 60 min (P < 0.05), but not at 120 min (P > 0.1). The inhibitory zone of the TA-BSA complex against STNR at pH 7.25 was not decreased at 0, 30, and 60 min compared to TA without BSA (P > 0.1). The recovery rate of TA was 83, 54.8, 10.5, and 19.6% in the gizzard, jejunum, ileum, and ceca, respectively, in broiler chickens. The STNR-infected broilers fed 0.25 g/kg of TA had significantly lower unweighted beta diversity distance compared to the sham-challenged control (SCC) and challenged controlled (CC) group on D 21. TA supplementation linearly (P < 0.05) and quadratically (tendency; P = 0.071) reduced relative abundance of the family Peptostreptococcaceae in broilers infected with STNR on D 7. TA supplementation linearly (P < 0.05) and quadratically (tendency; P = 0.06) increased the relative abundance of the family Erysipelotrichaceae in broilers infected with STNR on D 21. Therefore, TA has potential to be used as an antibacterial agent against the S. Typhimurium infection in broilers.


IgA deposition in alcoholic liver disease.
Immunoglobulin deposition in alcoholic and non-alcoholic liver disease was studied using an indirect immunoperoxidase technique. A continuous pattern of IgA deposition, with IgA outlining the sinusoids, was shown to be a specific and sensitive marker for liver disease caused by alcohol in both cirrhotic and non-cirrhotic livers. The sensitivity was lowest in cases of alcoholic disease showing fatty change alone. In one case it was possible to show the absence of IgA in liver disease caused by a drug, which was histologically indistinguishable from alcoholic hepatitis.


Solution-Synthesized Extended Graphene Nanoribbons Deposited by High-Vacuum Electrospray Deposition.
Solution-synthesized graphene nanoribbons (GNRs) facilitate various interesting structures and functionalities, like nonplanarity and thermolabile functional groups, that are not or not easily accessible by on-surface synthesis. Here, we show the successful high-vacuum electrospray deposition (HVESD) of well-elongated solution-synthesized GNRs on surfaces maintained in ultrahigh vacuum. We compare three distinct GNRs, a twisted nonplanar fjord-edged GNR, a methoxy-functionalized "cove"-type (or also called gulf) GNR, and a longer "cove"-type GNR both equipped with alkyl chains on Au(111). Nc-AFM measurements at room temperature with submolecular imaging combined with Raman spectroscopy allow us to characterize individual GNRs and confirm their chemical integrity. The fjord-GNR and methoxy-GNR are additionally deposited on nonmetallic HOPG and SiO2, and fjord-GNR is deposited on a KBr(001) surface, facilitating the study of GNRs on substrates, as of now not accessible by on-surface synthesis.


Patient-reported outcome measures in reconstructive breast surgery: is there a role for generic measures?
Patient-reported outcomes provide an invaluable tool in the assessment of outcomes in plastic surgery. Traditionally, patient-reported outcomes have consisted of either generic or ad hoc measures; however, more recently, there has been interest in formally constructed and validated questionnaires that are specifically designed for a particular patient population. The purpose of this systematic review was to determine whether generic measures still have a role in the evaluation of breast reconstruction outcomes, given the recent popularity and push for use of specific measures. A systematic review was performed to identify all articles using patient-reported outcomes in the assessment of postmastectomy breast reconstruction. Frequency of use was tabulated and the most frequently used tools were assessed for success of use, using criteria described previously by the Medical Outcomes Trust. To date, the most frequently used measures are still generic measures. The 36-Item Short-Form Health Survey was the most frequently used and most successfully applied showing evidence of responsiveness in multiple settings. Other measures such as the Hospital Anxiety and Depression Scale, the Hopwood Body Image Scale, and the Rosenberg Self-Esteem Scale were able to show responsiveness in certain settings but lacked evidence as universal tools for the assessment of outcomes in reconstructive breast surgery. Despite the recent advent of measures designed specifically to assess patient-reported outcomes in the breast reconstruction population, there still appears to be a role for the use of generic instruments. Many of these tools would benefit from undergoing formal validation in the breast reconstruction population.


A new continuous fluorometric assay for acetylcholinesterase activity and inhibitor screening with emissive core-shell silica particles containing tetraphenylethylene fluorophore.
Emissive core-shell silica particles with tetraphenylethylene moieties were prepared and characterized. Fluorescence quenching was observed for the silica particles upon addition of compound 2 (Dabcyl-ACh). This was attributed to the electrostatic interaction between the silica particles and 2 and the resulting photoinduced energy transfer between them. After incubation with AChE, the fluorescence intensity started to increase. The fluorescence enhancement became more significant when the concentration of AChE was higher. The reaction kinetic parameters for AChE were successfully estimated with the silica particles and 2. These results reveal that the ensemble of the silica particles and 2 can be utilized for AChE assay. Moreover, the fluorescence spectra of the ensemble of the silica particles and 2 containing AChE were also measured after further addition of either neostigmine or tacrine which are typical inhibitors of AChE. The results manifest that the ensemble of the emissive silica particles and 2 is also useful for screening the inhibitors of AChE.


Differential upregulation of CD38 on different T-cell subsets may influence the ability to reconstitute CD4+ T cells under successful highly active antiretroviral therapy.
Immune activation is an independent surrogate marker of CD4 T-cell depletion in HIV-infected patients. Highly active antiretroviral therapy (HAART) reduces disease progression as a direct consequence of suppressing HIV replication. Immune function does not normalize completely in most subjects on HAART, however, perhaps reflecting residual HIV replication. So far, it is unclear to what extent immune activation may influence the evolution of CD4 T-cell counts in patients on HAART. The expression of CD38 on naive and memory subsets of CD4+ and CD8+ T cells was measured quantitatively by flow cytometry in 62 drug-naive HIV-positive and 30 HIV-uninfected controls. In addition, the evolution of this marker as well as that of some virologic parameters (plasma viremia and proviral load) and CD4 counts were assessed in 25 HIV-infected individuals who initiated HAART and were followed for 12 months. The mean level of CD38 on memory CD4+ and CD8+ T cells as well as in naive CD8+ cells was significantly higher in drug-naive HIV-positive subjects than in HIV-negative controls. Moreover, it was highly correlated with viral load titers. In patients on successful HAART, immune activation declined in all T-cell subsets, particularly among memory CD8+ cells. It remained elevated with respect to HIV-negative controls, however, even after 12 months of HAART. There was a significant correlation between the CD8+ T-cell activation decay and the increase of CD4+ T cells on HAART. Patients with the highest decline in CD8 activation were those showing the highest CD4 T-cell gains after 12 months of therapy. The level of CD38 expression on different T-cell subsets is differentially upregulated in drug-naive HIV-infected patients. After successful HAART, immune activation decreases in all T-cell subsets, although it still remains elevated in most cases after 12 months of HAART. The extent of immune deactivation under successful HAART correlates with the ability to reconstitute CD4 counts.


HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.
The rigorous evaluation of the impact of combination HIV prevention packages at the population level will be critical for the future of HIV prevention. In this review, we discuss important considerations for the design and interpretation of cluster randomized controlled trials (C-RCTs) of combination prevention interventions. We focus on three large C-RCTs that will start soon and are designed to test the hypothesis that combination prevention packages, including expanded access to antiretroviral therapy, can substantially reduce HIV incidence. Using a general framework to integrate mathematical modelling analysis into the design, conduct, and analysis of C-RCTs will complement traditional statistical analyses and strengthen the evaluation of the interventions. Importantly, even with combination interventions, it may be challenging to substantially reduce HIV incidence over the 2- to 3-y duration of a C-RCT, unless interventions are scaled up rapidly and key populations are reached. Thus, we propose the innovative use of mathematical modelling to conduct interim analyses, when interim HIV incidence data are not available, to allow the ongoing trials to be modified or adapted to reduce the likelihood of inconclusive outcomes. The preplanned, interactive use of mathematical models during C-RCTs will also provide a valuable opportunity to validate and refine model projections.


[Analysis of mortality by civil status. Tumors of the digestive system].
Mortality data for the years 1981-1984 have been analyzed by marital status, sex and residence area. Results show high levels of mortality in widowers and widows, especially in areas with high mortality risks. In stomach cancer the widowers/widows mortality excess, compared to married and unmarried, is constant all over the country and does not change in the areas with high levels of mortality. Also for liver cancer mortality the widows show, everywhere, a constant excess compared to unmarried women. Widowers and unmarried men, if resident in north-west, show similar rates; while mortality levels for unmarried men approach those of married ones as the latitude of residence areas decreases and in the south they are equal. Mortality by ages confirms differences by marital status and shows, for many sites, larger variation in the age classes younger than 65-69 years.


[FICTION as a new tool to early lung cancer diagnosis].
Lung cancer is one of the most frequent causes of cancer death in Western countries. Overall 5-year survival rate is lower than 15% mainly due to the late diagnosis of the disease. Primary prevention (reduction of tobacco consumption) and more effective methods for early detection are needed. Some studies have recently shown that low-dose spiral computed tomography (CT) is a useful technique to the detection of pulmonary malignant nodules in early stages. Studies are developing to evaluate its efficacy in series of high-risk patients. A new cytogenetic technique has been developed: the FICTION technique (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms). This technique allows the simultaneous study of immunophenotypic markers and genetic abnormalities present in tumour cells. The goal of our project is optimise this technique in sputum and bronchoalveolar lavage specimens from lung cancer patients. The overall goal of this project is evaluate the usefulness of this technique, together with the new radiological techniques, in early detection programs of lung cancer in high-risk patients. In the present study we review the cytogenetic studies on lung cancer carried out in the recent years. We also introduce the basic methodological aspects that will be developed in our project.


Transmural gradients in myocardial gas tensions in regionally ischemic canine left ventricle.
Previous studies from this laboratory have demonstrated the usefulness of myocardial gas tensions as measured by mass spectrometry for the quantitative assessment of regional myocardial ischemia (Khuri et al., 1975a). Progressive increases in myocardial carbon dioxide tensions were noted when progressive reduction in coronary blood flow was created by means of a variable constrictor. The present study was designed to determine if changes in myocardial oxygen and carbon dioxide tension were greater in deep, compared to more superficial, myocardial layers. In eight anesthetized dogs, progressive reduction in circumflex coronary flow was associated with a progressive reduction in myocardial oxygen tension and a progressive increase in myocardial carbon dioxide tension and intramyocardial ST-segment voltage. Evidence of a transmural gradient in the severity of ischemia was present at all degrees of flow reduction. These results confirm the findings of previous metabolic studies, which demonstrated gradients in lactate and high-energy phosphates. Myocardial carbon dioxide tension, which can be monitored continuously by mass spectrometry, would appear to provide a useful means of quantitatively assessing changes in regional myocardial metabolism.


Caffeine Intake throughout Pregnancy, and Factors Associated with Non-Compliance with Recommendations: A Cohort Study.
Maternal caffeine consumption is associated with adverse gestational outcomes. The aim of this study was to assess the intake of caffeine and factors associated with the non-adherence to caffeine intake recommendations in a cohort of 463 women before (T0) and in each trimester of gestation (T1, T2, and T3), by using validated questionnaires. Caffeine intake (median (mg/day), IQR) was 100.0 (181.1) at T0, 9.42 (66.2) at T1, 12.5 (65.6) at T2, and 14.0 (61.1) at T3 (p < 0.001). Non-compliance prevalence (intake > 200 mg/day) was 6.2% at T1, 4.2% at T2, and 2.7% at T3. Not being an active smoker at T1 (OR = 0.17; 95% CI 0.05−0.59) and T2 (OR = 0.22; 95% CI 0.09−0.52), adherence to the Mediterranean Diet at T1 (OR = 0.50; 95% CI 0.28−0.88) and T2 (OR = 0.39; 95% CI 0.15−1.02), and moderate physical activity at T1 (OR = 0.50; 95% CI 0.28−0.88) were inversely associated with caffeine consumption. Although caffeine intake may be considered low, intake prevalence increases throughout pregnancy. Although the main source of caffeine during pregnancy is coffee, attention must be also paid to the increasingly intake of chocolate, of which the effect during pregnancy is controversial. Smoking, non-adherence to a good quality diet, and light physical activity are associated with a higher caffeine intake and a lower compliance with caffeine intake recommendations. Perinatal dietary and lifestyle educational policies are needed.


Microbial community potentially responsible for acid and metal release from an Ostrobothnian acid sulfate soil.
Soils containing an approximately equal mixture of metastable iron sulfides and pyrite occur in the boreal Ostrobothnian coastal region of Finland, termed 'potential acid sulfate soil materials'. If the iron sulfides are exposed to air, oxidation reactions result in acid and metal release to the environment that can cause severe damage. Despite that acidophilic microorganisms catalyze acid and metal release from sulfide minerals, the microbiology of acid sulfate soil (ASS) materials has been neglected. The molecular phylogeny of a depth profile through the plough and oxidized ASS layers identified several known acidophilic microorganisms and environmental clones previously identified from acid- and metal-contaminated environments. In addition, several of the 16S rRNA gene sequences were more similar to sequences previously identified from cold environments. Leaching of the metastable iron sulfides and pyrite with an ASS microbial enrichment culture incubated at low pH accelerated metal release, suggesting microorganisms capable of catalyzing metal sulfide oxidation were present. The 16S rRNA gene analysis showed the presence of species similar to Acidocella sp. and other clones identified from acid mine environments. These data support that acid and metal release from ASSs was catalyzed by indigenous microorganisms adapted to low pH.


Left ventricular function before and after repair of an anomalous left coronary artery arising from the pulmonary trunk.
We report an infant with an abnormal left coronary artery arising from the pulmonary trunk in whom, subsequent to surgical repair, sequential improvements in regional left and right systolic and diastolic myocardial function were quantified by the new ultrasound-based method of regional strain and strain rate imaging. The regional radial and longitudinal myocardial function of the left ventricle was homogeneously reduced prior to repair, while the time course of their recovery differed subsequent to repair. We discuss the concepts and advantages behind this quantitative approach to monitoring regional myocardial function in children.


Steroidal regulation of uterine edema and tissue inhibitors of metalloproteinase (TIMP)-3 messenger RNA expression is altered in TIMP-1-deficient mice.
Tissue inhibitors of metalloproteinases (TIMPs) are expressed within the uteri of virtually all species where they are postulated to control extracellular matrix turnover, cellular apoptosis, and proliferation. The objective of the current study was to examine the steroidal regulation of uterine TIMP expression and to determine the potential role of the TIMP-1 gene product in this regulation. To accomplish these goals, ovariectomized female TIMP-1 wild-type and null mice were treated with estradiol, progesterone, or estradiol and progesterone and killed at various times after steroid administration. Estradiol induced a significant reduction in uterine TIMP-3 expression in wild-type mice at 8 and 24 h post-steroid administration, but the ability of this steroid to decrease TIMP-3 expression was impaired in the uteri of TIMP-1 null mice. Further, estrogen-induced uterine wet-weight gain/edema was enhanced in the TIMP-1 null mice, and the antiestrogen compound ICI 182780 or progesterone could only partially block this estrogenic effect. It is concluded from this study that steroidal modulation of uterine TIMP-3 expression and regulation of wet-weight gain/edema are altered in TIMP-1 null mice. These observations suggest that steroids induce uterine TIMP-1 expression and, in turn, that TIMP-1 influences TIMP-3 mRNA expression and uterine edema.


Response Diversity and Resilience in Social-Ecological Systems.
Recent work in ecology suggests that the diversity of responses to environmental change among species contributing to the same ecosystem function can strongly influence ecosystem resilience. To render this important realization more useful for understanding coupled human-natural systems, we broaden the concept of response diversity to include heterogeneity in human decisions and action. Simply put, not all actors respond the same way to challenges, opportunities, and risks. The range, prevalence, and spatial and temporal distributions of different responses may be crucial to the resilience or the transformation of a social-ecological system, and thus have a bearing on human vulnerability and well-being in the face of environmental, socioeconomic, and political change. Response diversity can be seen at multiple scales (e.g., household, village, region) and response diversity at one scale may act synergistically with or contrary to the effects of diversity at another scale. Although considerable research on the sources of response diversity has been done, our argument is that the consequences of response diversity warrant closer attention. We illustrate this argument with examples drawn from our studies of two East African pastoral populations and discuss the relationship of response diversity to characteristics of social-ecological systems that can promote or diminish resilience.


First records of Synthesiomyia nudiseta (Diptera: Muscidae) from forensic cases in Italy.
The knowledge of the fauna associated with carrions and cadavers for a specific region plays a fundamental role in the estimation of the time since death in forensic cases. In the last years global warming and globalization have affected the insect species distribution. This phenomenon is affecting also the species of forensic interest associated with the cadaver decomposition. The species distribution shift, in the forensic context, has been mainly observed in Diptera of different family: Calliphoridae, Stratiomyidae and Phoridae. In the last decade the presence of the carrion feeding species, Synthesiomyia nudiseta (Diptera: Muscidae), was reported from forensic cases in Spain and in the last year from Italy where the species was collected from 5 bodies in different decomposition stages in the Genoa district. All the records concern indoor cases with the presence of other species belonging to the first colonization waves (e.g. Calliphoridae, Sarcophagidae). Different hypothesis about the presence of the species in Italy can be suggested, but the molecular analysis and the importation records support the introduction trough commercial exchanges with Asian countries instead of a variation in the species distribution area from the Iberian Peninsula.


Chronic toxicity of fluorotelomer acids to Daphnia magna and Chironomus dilutus.
Saturated and unsaturated fluorotelomer carboxylic acids (fluorotelomer acids: FTAs) represent important intermediates in the degradation of fluorotelomer alcohols to perfluorinated carboxylic acids (PFCAs). Recent studies have detected FTAs at low concentrations (ng/L) in precipitation and surface waters; however, information regarding chronic toxicity is lacking. The present study assessed the chronic toxicity of the 8:2 saturated fluorotelomer carboxylic acid (8:2 FTCA) to Chironomus dilutus and the 10:2 saturated and unsaturated fluorotelomer carboxylic acids (10:2 FTCA and 10:2 fluorotelomer unsaturated carboxylic acid [FTuCA]) to Daphnia magna in separate life-cycle tests. In D. magna tests the FTCA was consistently more toxic than the FTuCA. Lethal concentrations (LC50s) were 150 and >60 microg/L for FTuCA and FTCA, respectively. Reproduction was significantly reduced relative to the controls, with respective median effective concentrations (EC50s) for time to first brood and mean number of offspring/female of 287 and 214 microg/L for FTuCA and 50 and 48 microg/L for FTCA. In tests with C. dilutus, EC50s for survival and growth at 20 d were 2,610 and 1,250 microg/L. Total emergence and time to first emergence, the most sensitive endpoints, yielded EC50s of 440 and 890 microg/L. Few adults emerged and no reproduction occurred at the two highest concentrations (600 and 1540 microg/L). Mean number of eggs/female was not affected. These results represent the first chronic toxicity data for FTCAs and additional evidence that FTCAs are more toxic than some PFCAs. While the results indicate that current environmental concentrations of FTAs likely pose negligible risk to aquatic biota, additional quantification of FTAs in surface waters and assessment of their toxicity is needed before meaningful assessments of potential risks to aquatic biota are possible.


Development and validation of the Johns Hopkins Disruptive Clinician Behavior Survey.
Although the negative impact of disruptive clinician behavior on quality health care delivery has gained attention recently, little systematic effort to address this issue has been reported. To facilitate empirical research to reduce disruptive clinician behaviors, an assessment tool (Johns Hopkins Disruptive Clinician Behavior Survey [JH-DCBS]) with 5 discrete subscales was developed using a 2-step design. First a pool of items was generated from focus group studies and the literature, and then a psychometric evaluation of the survey was conducted with a sample of clinicians (N = 1198) practicing in a large urban academic medical center. The results indicated that the tool was reliable (Cronbach α = .79-.91), showed high content validity (Content Validity Index = .97), and had significantly high correlations with theoretically selected variables. The study team concluded that the JH-DCBS provides a valid empirical assessment of disruptive behavior. Assessment results may be used to design strategies to improve the health and safety of practice environments.


Guided principal component analysis (GPCA): a simple method for improving detection of a known analyte.
There is increasing interest in the application of Raman spectroscopy in a medical setting, ranging from supporting real-time clinical decisions e.g. surgical margins to assisting pathologists with disease classification. However, there remain a number of barriers for adoption in the medical setting due to the increased complexity of probing highly heterogeneous, dynamic biological materials. This inherent challenge can also limit the deployment of higher level analytical approaches such as Artificial Intelligence (AI) including convolutional neural networks (CNN), as there is a lack of a ground truth required for training purposes i.e. in complex clinical samples. Principal component analysis (PCA) is an unsupervised data reduction approach (orthogonal linear transformation) that has been used extensively in spectroscopy for 30+ years, due to its capability to simplify analysis of complex spectroscopic data. However, due to PCA being unsupervised features will inherently appear mixed and their rank may vary between experiments. Here we propose Guided PCA (GPCA), a simple approach that allows PCA to be guided with spectral data to ensure a consistent rank of a key target moiety by the inclusion of a reference (guiding) spectrum to the data set. This simplifies analysis, increases robustness of PCA analysis and improves quantification and the limits of detection and decreases RMSE.


Brachyspira hyodysenteriae and B. pilosicoli Proteins Recognized by Sera of Challenged Pigs.
The spirochetes Brachyspira hyodysenteriae and B. pilosicoli are pig intestinal pathogens that are the causative agents of swine dysentery (SD) and porcine intestinal spirochaetosis (PIS), respectively. Although some inactivated bacterin and recombinant vaccines have been explored as prophylactic treatments against these species, no effective vaccine is yet available. Immunoproteomics approaches hold the potential for the identification of new, suitable candidates for subunit vaccines against SD and PIS. These strategies take into account the gene products actually expressed and present in the cells, and thus susceptible of being targets of immune recognition. In this context, we have analyzed the immunogenic pattern of two B. pilosicoli porcine isolates (the Spanish farm isolate OLA9 and the commercial P43/6/78 strain) and one B. hyodysenteriae isolate (the Spanish farm V1). The proteins from the Brachyspira lysates were fractionated by preparative isoelectric focusing, and the fractions were analyzed by Western blot with hyperimmune sera from challenged pigs. Of the 28 challenge-specific immunoreactive bands detected, 21 were identified as single proteins by MS, while the other 7 were shown to contain several major proteins. None of these proteins were detected in the control immunoreactive bands. The proteins identified included 11 from B. hyodysenteriae and 28 from the two B. pilosicoli strains. Eight proteins were common to the B. pilosicoli strains (i.e., elongation factor G, aspartyl-tRNA synthase, biotin lipoyl, TmpB outer membrane protein, flagellar protein FlaA, enolase, PEPCK, and VspD), and enolase and PEPCK were common to both species. Many of the identified proteins were flagellar proteins or predicted to be located on the cell surface and some of them had been previously described as antigenic or as bacterial virulence factors. Here we report on the identification and semiquantitative data of these immunoreactive proteins which constitute a unique antigen collection from these bacteria.


Just the Tip: Resection of a Narcotic Catheter-Tip Granuloma: 2-Dimensional Operative Video.
The catheter tip "granuloma" is a rare inflammatory mass that forms in about 3% of patients with an intradural catheter, most commonly from a morphine pump. It has also been seen with other narcotic pumps, narcotic-non-narcotic combinations, and baclofen pumps. Mass formation is associated with increased opioid dose and concentration. It typically presents with increasing pain requiring increasing doses of medication, with minimal improvement, although it may present with neurologic deficits or be asymptomatic. On MRI, it appears as a round, rim-enhancing lesion that is low intensity with a hypointense rim on both T1 and T2. In the absence of neurologic deficits, there are many treatment options, ranging from a temporary stopping of the pump to catheter replacement. When the lesion presents with neurologic deficits, surgical intervention, beyond catheter replacement or repositioning, is indicated. A laminectomy is performed, with intradural exploration and careful resection of the mass, which is likely adherent to the spinal cord. Postoperative worsening of symptoms is common due to the mass being densely adherent to the spinal cord, requiring spinal cord manipulation. This worsening is usually temporary, and many patients make excellent recoveries. We present a case of a hydromorphone pump inflammatory mass, which initially presented with increasing pain, then progressive neurologic deficits, requiring referral and mass resection. We achieved only a partial resection due to the lesion's adherent nature. This surgical video demonstrates our intradural technique for resection of this rare and technically difficult mass, with 6-mo patient follow-up. The patient has consented to this case report.


Macrophage inflammatory protein-1 alpha production in lipopolysaccharide-stimulated human adherent blood mononuclear cells is inhibited by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine.
The release of chemokines such as macrophage-inflammatory protein-1 alpha (MIP-1 alpha) from activated macrophages is a crucial step in cell recruitment necessary for establishing local inflammatory responses. To ascertain the importance of the L-arginine/nitric oxide (NO) pathway in LPS-induced MIP-1 alpha release, we stimulated human adherent PBMC with LPS in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). L-NMMA decreased LPS-induced MIP-1 alpha protein release (45.5% inhibition) and steady state levels of mRNA (48% inhibition) in adherent PBMC. The concentration of L-NMMA for inhibition of MIP-1 alpha release was dependent on the concentration of L-arginine in the cell culture medium, emphasizing the L-arginine-related action of the drug. Most of the MIP-1 alpha release was attributed to the activity of IL-1 and TNF, since coincubation of LPS-stimulated PBMC with IL-1R antagonist and TNF-binding protein abrogated LPS-induced MIP-1 alpha release (by 76.8%). Analysis of cytokine secretion revealed that, in addition to MIP-1 alpha, L-NMMA inhibited the release of mature IL-1 beta (by 70%) and TNF-alpha (by 53%). In contrast, release of macrophage chemoattractant protein-1 was unaffected; IL-10 was augmented (123.4%) by L-NMMA. In the presence of exogenous NO provided by NO donors, LPS-induced MIP-1 alpha release was enhanced. We concluded that endogenous NO acts as a mediator of inflammation. Since IL-10 is a potent anti-inflammatory cytokine, these data also suggest that L-NMMA acts as an anti-inflammatory agent by specifically altering the balance of pro- and anti-inflammatory cytokines released from LPS-stimulated human PBMC.


Persistent neonatal thyrotoxicosis in a neonate secondary to a rare thyroid-stimulating hormone receptor activating mutation: case report and literature review.
To report the case of a neonate presenting with nonautoimmune thyrotoxicosis and failure to thrive in whom an activating TSHR mutation was suspected. We describe the clinical and laboratory findings in a neonate who presented with nonautoimmune thyrotoxicosis and failure to thrive, including results of DNA analysis of TSHR, which encodes the thyroid-stimulating hormone receptor (TSHR). Relevant literature is also reviewed. The proband was born spontaneously at 35 weeks' gestation, and his early neonatal period was remarkable for meconium aspiration, pneumothorax, hepatomegaly with associated elevated transaminases, and direct hyperbilirubinemia. On days 9 and 11 of life, thyroid function studies revealed hyperthyroidism, which remained persistent on day 26 of life. On day 44 of life, the infant was admitted to the hospital. The mother reported he had an increased activity level, disturbed sleep, jitteriness, and exaggerated startle response. Weight was at the third percentile. After additional workup, Lugol's iodine solution, propanolol, and propylthiouracil were prescribed, which led to improvement in thyroid function. No TSHR antibodies were detected in the mother's or patient's sera. Analysis of the patient's DNA revealed a heterozygous T-to-C substitution at amino acid 568 in exon 10 (Ile568Thr), which predicts an isoleucine to threonine conversion in the second extracellular loop of TSHR. The mutation was not identified in the parents' DNA. A mutation causing constitutive activation of TSHR was confirmed in this patient, a finding that has implications for genetic counseling and consideration of total thyroidectomy or long-term thionamide therapy followed by radioiodide ablation as treatment options. Although rare, TSHR mutations should be considered in an infant presenting with thyrotoxicosis in absence of demonstrable TSHR antibodies in serum.


Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity.
Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia.


New holostean fishes (Actinopterygii: Neopterygii) from the Middle Triassic of the Monte San Giorgio (Canton Ticino, Switzerland).
The new neopterygian genus Ticinolepis, including two new species T. longaeva and T. crassidens is described from Middle Triassic carbonate platform deposits of the Monte San Giorgio. The anatomy of this fish shows a mosaic of halecomorph and ginglymodian characters and, thus, the new taxon probably represents a basal holostean. During the latest Anisian to earliest Ladinian the two new species coexisted in the intraplatform basin represented by the uppermost Besano Formation, but only T. longaeva sp. nov. inhabited the more restricted basin represented by the Ladinian Meride Limestone (except for the Kalkschieferzone). The more widely distributed type species shows interesting patterns of intraspecific variation including ontogenetic changes and morphological variation over time. The second species presents anatomical features that strongly indicate a strictly durophagous diet. The different distribution of the species is interpreted as a result of habitat partitioning and different adaptability to palaeoenvironmental changes.


Histological types of lung cancer among smelter workers exposed to arsenic.
The histological distribution of lung cancer was investigated in 93 men who had worked at a Swedish smelter with high levels of arsenic. A comparison was made with a group of 136 patients with lung cancer from the county where the smelter was located. Company records provided information on occupational exposure and data on smoking habits were obtained from a next of kin of each subject. No pronounced differences in the histological types of lung carcinomas between smelter workers and the reference group could be seen for smokers. Some analyses indicated an increased proportion of adenocarcinomas among the smelter workers, which confirmed earlier data, but these findings were difficult to interpret. Cases among smelter workers who had never smoked showed a histological distribution resembling that in smokers, indicating that the work environment at the smelter and smoking had a similar influence on the risk for different types of lung cancer.


Urea denaturation of staphylococcal nuclease monitored by Fourier transform infrared spectroscopy.
Fourier transform infrared (FTIR) amide I spectroscopy has not been widely used as a method to study protein folding. Some thorough studies of thermal unfolding have been carried out; however, protein unfolding in the presence of the widely used denaturants guanidine hydrochloride and urea has only recently been reported. Guanidine hydrochloride and urea both absorb strongly in the amide I region, as does H2O. Here, we have used deuterated 13C-urea as the chemical denaturant and monitored the unfolding transition with deuterium-exchanged staphylococcal nuclease (SNase) in D2O. These conditions circumvent all subtraction difficulties as the absorption bands of D2O and denaturant are shifted out of the amide I' region [Fabian, H., and Manstch, H. H. (1995) Biochemistry 34, 13651-13655]. A very reproducible unfolding transition is obtained for SNase. 13C-Urea-induced unfolding of SNase was found not only to be comparable to previous FTIR thermal unfolding data but also to have a denatured-state spectrum similar to those of other thermally denatured proteins. The unfolding is approximately two-state. The infrared spectra in the denatured state show evidence of some residual beta-sheet structure as well as other band components not attributable to random structure.


Suicide risk by military occupation in the DoD active component population.
Suicide risk based on occupational cohorts within the U.S. military was investigated. Rates of suicide based on military occupational categories were computed for the Department of Defense (DoD) active component population between 2001 and 2010. The combined infantry, gun crews, and seamanship specialist group was at increased risk of suicide compared to the overall military population even when adjusted for gender, age, and deployment history. The results provide useful information that can help inform the DoD's suicide prevention mission. Data limitations and recommended areas for future research are discussed.


Surface characteristics and in vitro biofilm formation on glass ionomer and composite resin.
In the initial stages of dental plaque formation, early colonizing bacteria bind to receptor structures in the pellicle, a proteinaceous film formed instantly after cleaning of the tooth surface. Dental restorative materials with surface characteristics different from the tooth might affect pellicle formation and the ability of bacteria to colonize the oral cavity. In this study (i) roughness and chemical composition of glass ionomer and composite resin surfaces before and after polishing, and (ii) the adsorption of salivary proteins and bacterial adherence to the pellicle-coated surfaces were examined. Compared with unpolished composite resin, unpolished glass ionomer had higher surface roughness, contained more inorganic, positively charged components, collected more proteins, and promoted better bacterial adherence. Polishing had the most pronounced effect on the composite resin, giving an enlarged and a rougher surface with a more inorganic character. Polishing the composite resin also led to increased biofilm formation.


Intramucosal bacterial microcolonies exist in chronic rhinosinusitis without inducing a local immune response.
Although chronic rhinosinusitis (CRS) causes very significant morbidity, much about its pathogenesis remains uncertain. Recent studies have identified polymicrobial biofilms on the surface of sinus mucosa and Staphylococcus aureus within the sinus mucosa of patients with CRS, both with and without nasal polyps. The pathogenic implications of intramucosal bacteria in CRS are unknown. This study was designed to determine the prevalence and species of bacterial colonies within the sinus mucosa of adult patients with and without CRS and to describe the relationship of these bacterial colonies to the host immune response. Sinus mucosa from patients with and without CRS was examined using Gram and Giemsa staining, immunohistochemistry, bacterial culture, and fluorescence in situ hybridization techniques. Bacterial microcolonies were observed within the mucosa in 14 of 18 patients with CRS. In 10 of these patients colonies were positively identified as S. aureus. Staphylococcal microcolonies were observed at a lower level (1 of 8 patients) in normal sinus mucosa. There was no correlation between detection of S. aureus on the mucosal surface and microcolonization of the mucosa. Surprisingly, there was no evidence of an immune reaction to microcolonies. Indeed, fewer T lymphocytes (p = 0.03) and eosinophils (p = 0.03) were counted immediately surrounding the microcolonies compared with uninfected areas of the same tissue. Bacterial microcolonies are prevalent within paranasal sinus mucosa and are commonly S. aureus. These microcolonies do not provoke immune detection and may represent a phenotype that actively evades host immunity. This may underpin the recalcitrance of CRS to antibiotic therapy. These findings challenge classic views of both infection and mucosal immunity in human chronic disease. The presence of intramucosal bacteria in samples of normal sinus mucosa also questions the sensitivity of detecting nasal carriage of pathogens by swabbing the surface of the anterior nares.


Habituation of laser-evoked potentials by migraine phase: a blinded longitudinal study.
Migraineurs seem to have cyclic variations in cortical excitability in several neurophysiological modalities. Laser-evoked potentials (LEP) are of particular interest in migraine because LEP specifically targets pain pathways, and studies have reported different LEP-changes both between and during headaches. Our primary aim was to explore potential cyclic variations in LEP amplitude and habituation in more detail with a blinded longitudinal study design. We compared N1 and N2P2 amplitudes and habituation between two blocks of laser stimulations to the dorsal hand, obtained from 49 migraineurs with four sessions each. We used migraine diaries to categorize sessions as interictal (> one day from previous and to next attack), preictal (< one day before the attack), ictal or postictal (< one day after the attack). Also, we compared 29 interictal recordings from the first session to 30 controls. N1 and N2P2 amplitudes and habituation did not differ between preictal, interictal and postictal phase sessions, except for a post hoc contrast that showed deficient ictal habituation of N1. Habituation is present and similar in migraineurs in the interictal phase and controls. Hand-evoked LEP amplitudes and habituation were mainly invariable between migraine phases, but this matter needs further study. Because hand-evoked LEP-habituation was similar in migraineurs and controls, the present findings contradict several previous LEP studies. Pain-evoked cerebral responses are normal and show normal habituation in migraine.


Manganese superoxide dismutase signals matrix metalloproteinase expression via H2O2-dependent ERK1/2 activation.
Manganese-superoxide dismutase (Sod2) removes mitochondrially derived superoxide (O(2)) at near-diffusion limiting rates and is the only antioxidant enzyme whose expression is regulated by numerous stimuli. Here it is shown that Sod2 also serves as a source of the intracellular signaling molecule H(2)O(2). Sod2-dependent increases in the steady-state levels of H(2)O(2) led to ERK1/2 activation and subsequent downstream transcriptional increases in matrix metalloproteinase-1 (MMP-1) expression, which were reversed by expression of the H(2)O(2)-detoxifying enzyme, catalase. In addition, a single nucleotide polymorphism has recently been identified (1G/2G) at base pair--1607 that creates an Ets site adjacent to an AP-1 site at base pair --1602 and has been shown to dramatically enhance transcription of the MMP-1 promoter. Luciferase promoter constructs containing either the 1G or 2G variation were 25- or 1000-fold more active when transiently transfected into Sod2-overexpressing cell lines, respectively. The levels of MMP-2, -3, and -7 were also increased in the Sod2-overexpressing cell lines, suggesting that Sod2 may function as a "global" redox regulator of MMP expression. In addition, Sod2(-/+) mouse embryonic fibroblasts failed to respond to the cytokine-mediated induction of the murine functional analog of MMP-1, MMP-13. This study provides evidence that the modulation of Sod2 activity by a wide array of pathogenic and inflammatory stimuli may be utilized by the cell as a primary signaling mechanism leading to matrix metalloproteinase expression.


[Acupuncture and moxibustion in Tunisia].
The development status of acupuncture and moxibustion in Tunisia is introduced in this article. Although acupuncture and moxibustion only has a history of more than 30 years in Tunisia, it is very popular among the local people. Until now, there is one acupuncture and moxibustion center aided and built with the help of the Chinese government. Acupuncture and moxibustion clinical department has been set in some of the hospitals, and acupuncture and moxibustion clinical practice is also carried out in some private clinics. Cost of acupuncture and moxibustion in public hospitals has already been covered by medical insurance. As for education of acupuncture and moxibustion, training courses were set up in medical colleges of Tunisia by Tunisian government which is lectured by Chinese acupuncture experts. Acupuncture and moxibustion has been used to treat many diseases in Tunisia and is warmly welcomed by Tunisian.


Addressing false discoveries in network inference.
Experimentally determined gene regulatory networks can be enriched by computational inference from high-throughput expression profiles. However, the prediction of regulatory interactions is severely impaired by indirect and spurious effects, particularly for eukaryotes. Recently, published methods report improved predictions by exploiting the a priori known targets of a regulator (its local topology) in addition to expression profiles. We find that methods exploiting known targets show an unexpectedly high rate of false discoveries. This leads to inflated performance estimates and the prediction of an excessive number of new interactions for regulators with many known targets. These issues are hidden from common evaluation and cross-validation setups, which is due to Simpson's paradox. We suggest a confidence score recalibration method (CoRe) that reduces the false discovery rate and enables a reliable performance estimation. CoRe considerably improves the results of network inference methods that exploit known targets. Predictions then display the biological process specificity of regulators more correctly and enable the inference of accurate genome-wide regulatory networks in eukaryotes. For yeast, we propose a network with more than 22 000 confident interactions. We point out that machine learning approaches outside of the area of network inference may be affected as well. Results, executable code and networks are available via our website http://www.bio.ifi.lmu.de/forschung/CoRe. email@example.com Supplementary data are available at Bioinformatics online.


The clinical response on bone metastasis from breast and lung cancer during treatment with zoledronic acid is inversely correlated to skeletal related events (SRE).
Current management of bone metastases involves a multimodal approach. Aminobisphosphonates (BPs) are a valid weapon in the treatment of skeletal localization of tumour disease. Patients with bone metastases from breast and lung cancer were enrolled in order to evaluate the impact of the addition of bisphosphonates therapy to standard treatments in terms of (i) pain control, (ii) quality of life (QoL) and (iii) toxicity and to evaluate (iv) any relations between clinical activity and the occurrence of SREs. A total of 60 patients were included in the study. Median age was 76 years (range 40-83). The majority of patients were treated with chemotherapy or hormonal therapy. All patients received zoledronic acid (ZOL) (4 mg) every 3-4 weeks for at least 3 cycles. No significant improvement in Performance Status of patients after 12 cycles of ZOL (p = 0.1672) was recorded. A statistically significant early and long-lasting amelioration of both pain, narcotic scores and QoL was found. Twenty-one patients (48%) experienced at least one SRE during the study. The most common SRE was radiation to bone (30% of patients). An inverse correlation between bone tumour response and SREs was also found (p = 0.019). ZOL addition induces a clinical benefit and improves QoL of patients with bone metastases. Moreover, the occurrence of bone clinical response is related to a reduced risk of SREs.


Assessing the impact of prescribed medicines on health outcomes.
This paper reviews methods that can be used to assess the impact of medicine use on population health outcomes. In the absence of a gold standard, we argue that a convergence of evidence from different types of studies using multiple methods of independent imperfection provides the best bases for attributing improvements in health outcomes to the use of medicines. The major requirements are: good evidence that a safe and effective medicine is being appropriately prescribed; covariation between medicine use and improved health outcomes; and being able to discount alternative explanations of the covariation (via covariate adjustment, propensity analyses and sensitivity analyses), so that medicine use is the most plausible explanation of the improved health outcomes. The strongest possible evidence would be provided by the coherence of the following types of evidence: (1) individual linked data showing that patients are prescribed the medicine, there are reasonable levels of patient compliance, and there is a relationship between medicine use and health improvements that is not explained by other factors; (2) ecological evidence of improvements in these health outcomes in the population in which the medicine is used. Confidence in these inferences would be increased by: the replication of these results in comparable countries and consistent trends in population vital statistics in countries that have introduced the medicine; and epidemiological modelling indicating that changes observed in population health outcomes are plausible given the epidemiology of the condition being treated.


Propofol Reduces Epithelial to Mesenchymal Transition, Invasion and Migration of Gastric Cancer Cells through the MicroRNA-195-5p/Snail Axis.
BACKGROUND Gastric cancer (GC) is a life-threating malignancy worldwide. Accumulating studies suggest propofol has anti-tumor functions in addition to the anesthetic effect. This study aimed to figure out the effects of propofol treatment in GC development. MATERIAL AND METHODS Human GC SGC-7901 and NCI-N87 cells were treated with different doses of propofol. Then the invasion and migration of GC cells was measured. SGC-7901 cells following 10 μM propofol treatment were applied in the following experiments. MicroRNAs (miRNAs) with differential expression in cells with or without propofol treatment were analyzed. Expression of miR-195-5p, Snail, vimentin and E-cadherin in SGC-7901 cells was measured, and then loss-of-function of miR-195-5p and gain-of-function of Snail were performed. Target relation between miR-195-5p and Snail was confirmed using luciferase assay. Xenograft tumor was induced in nude mice to identify the effect of propofol on GC in vivo. RESULTS Propofol reduced epithelial to mesenchymal transition (EMT), invasion and migration of GC cells in a dose-dependent manner. Propofol elevated miR-195-5p expression but reduced Snail expression, and it reduced vimentin but increased E-cadherin expression in SGC-7901 cells. miR-195-5p directly bound to Snail. miR-195-5p inhibition or Snail promotion reversed propofol-inhibited malignant behaviors of SGC-7901 cells. In vitro results were reproduced in in vivo experiments. CONCLUSIONS Our study found that propofol could inhibit EMT, invasion, and migration of GC cells by promoting miR-195-5p expression and suppressing Snail expression. This study may provide novel insights in GC treatment.


Acute lung Injury in a healthy donor during mobilization of peripheral blood stem cells using granulocyte-colony stimulating factor alone.
Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor, is widely used to accelerate recovery from neutropenia after severe chemotherapy, both decreasing the risk of infection and mobilizing peripheral blood stem cells. Adverse effects occur with G-CSF use in approximately 30% of cases, comprised predominantly of bone pain, headache, and general fatigue. Pulmonary toxicity is very rare. Here, we describe a healthy donor for allogeneic hematopoietic stem cell transplantation who developed acute lung injury (ALI) after 4 days of G-CSF administration. Among the serum cytokines examined, only Interleukin (IL)-1beta level was elevated in this case. As a high level of IL-1beta was detected at the onset of ALI, on day 4 after G-CSF administration, and decreased to below the level of detection on day 11, it is possible in a certain part that IL-1beta was involved in the onset of G-CSF-related ALI in the present case. Granulocyte-colony stimulating factor (G-CSF) is commonly administered to healthy donors to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse events from G-CSF use in healthy donors have been described in approximately 30% of cases, and are comprised predominantly of bone pain, headache, and general fatigue. Pulmonary complications caused by G-CSF include cough, dyspnea, and interstitial or alveolar pulmonary edema with mild-to-severe deterioration of blood oxygen level. Few cases of acute respiratory distress syndrome (ARDS) following G-CSF administration have been reported. The present report describes a healthy donor for allo-HSCT with acute lung injury (ALI) after 4 days of G-CSF administration. The cytokine-related mechanisms of G-CSF administration that contribute to ALI are discussed.


Relation between calcium burden, echocardiographic stent frame eccentricity and paravalvular leakage after corevalve transcatheter aortic valve implantation.
Paravalvular aortic leakage (PVL) after transcatheter aortic valve implantation (TAVI) is a complication with potentially severe consequences. The relation between native aortic root calcium burden, stent frame eccentricity and PVL was not studied before. Two-hundred-and-twenty-three consecutive patients with severe aortic stenosis who underwent TAVI with a Medtronic CoreValve System© and who had available pre-discharge transthoracic echocardiography were studied. Echocardiographic stent inflow frame eccentricity was defined as major-minor diameter in a short-axis view >2 mm. PVL was scored according to the updated Valve Academic Research Consortium (VARC-2) recommendations. In a subgroup of 162 (73%) patients, the calcium Agatston score was available. Stent frame eccentricity was seen in 77 (35%) of patients. The correlation between the Agatston score and stent frame eccentricity was significant (ρ = 0.241, P = 0.003). Paravalvular leakage was absent in 91 cases (41%), mild in 67 (30%), moderate in 51 (23%), and severe in 14 (6%) cases. The correlation between stent frame eccentricity and PVL severity was significant (ρ = 0.525, P < 0.0001). There was a relation between particular eccentric stent frame shapes and the site of PVL. Calcification of the aortic annulus is associated with a subsequent eccentric shape of the CoreValve prosthesis. This eccentric shape results in more PVL, with the localization of PVL related to the shape of stent frame eccentricity.


Commonalities and differences in similarity comparisons.
Similarity is a central component of many cognitive processes. Current research suggests that similarity is well characterized as a comparison of structured representations. This process yields commonalities, differences related to the commonalities (alignable differences), and differences not related to the commonalities (nonalignable differences). In the first study, further evidence for this tripartite distinction is provided in a commonality and difference listing study involving pairs of pictures. This study indicates that alignable differences rather than nonalignable differences are central to the comparison process by virtue of their connection to the commonalities. The second study further demonstrates that alignable differences count more against the similarity of a pair than do nonalignable differences. We end by discussing implications of the distinction between alignable and nonalignable differences for other cognitive processes involving comparisons.


Thermality of eigenstates in conformal field theories.
The eigenstate thermalization hypothesis (ETH) provides a way to understand how an isolated quantum mechanical system can be approximated by a thermal density matrix. We find a class of operators in (1+1)-dimensional conformal field theories, consisting of quasiprimaries of the identity module, which satisfy the hypothesis only at the leading order in large central charge. In the context of subsystem ETH, this plays a role in the deviation of the reduced density matrices, corresponding to a finite energy density eigenstate from its hypothesized thermal approximation. The universal deviation in terms of the square of the trace-square distance goes as the eighth power of the subsystem fraction and is suppressed by powers of inverse central charge (c). Furthermore, the nonuniversal deviations from subsystem ETH are found to be proportional to the heavy-light-heavy structure constants which are typically exponentially suppressed in sqrt[h/c], where h is the conformal scaling dimension of the finite energy density state. We also examine the effects of the leading finite-size corrections.


Community awareness about risk factors, presentation and prevention and obstetric fistula in Nabitovu village, Iganga district, Uganda.
Obstetric fistula is a worldwide problem that is devastating for women in developing countries. The cardinal cause of obstetric fistula is prolonged obstructed labour and delay in seeking emergency obstetric care. Awareness about obstetric fistula is still low in developing countries. The objective was to assess the awareness about risk factors of obstetric fistulae in rural communities of Nabitovu village, Iganga district, Eastern Uganda. A qualitative study using focus group discussion for males and females aged 18-49 years, to explore and gain deeper understanding of their awareness of existence, causes, clinical presentation and preventive measures for obstetric fistula. Data was analyzed by thematic analysis. The majority of the women and a few men were aware about obstetric fistula, though many had misconceptions regarding its causes, clinical presentation and prevention. Some wrongly attributed fistula to misuse of family planning, having sex during the menstruation period, curses by relatives, sexually transmitted infections, rape and gender-based violence. However, others attributed the fistula to delays to access medical care, induced abortions, conception at an early age, utilization of traditional birth attendants at delivery, and some complications that could occur during surgical operations for difficult deliveries. Most of the community members interviewed were aware of the risk factors of obstetric fistula. Some respondents, predominantly men, had misconceptions/myths about risk factors of obstetric fistula as being caused by having sex during menstrual periods, poor usage of family planning, being a curse.