Cardiopulmonary bypass duration is an independent predictor of morbidity and mortality after cardiac surgery.
The aim of this study was to determine if there is a direct relationship between the duration of cardiopulmonary bypass (CPB time [CPBT]) and postoperative morbidity and mortality in patients undergoing cardiac surgery. Retrospective study. Cardiac surgery unit, university hospital. Five thousand six patients, New York Heart Association classes 1 through 4, who underwent cardiac surgery between January 2002 and March 2008. All patients were subjected to CPB. The mean CPBT was 115 minutes (median 106). One hundred thirty-one patients (2.6%) died during the same hospitalization. The postoperative median blood loss was 600 mL. Reoperations for bleeding occurred in 193 patients (3.9%), and 1,001 patients received 3 or more units of red blood cells. There were 108 patients (2.2%) with neurologic sequelae, 391 patients (7.8%) with renal complications, 37 patients (0.7%) with abdominal complications, and 184 patients (3.7%) with respiratory complications. Seventy-two patients (1.4%) had an infective complication, and 80 patients (1.6%) had a postoperative multiorgan failure. The multivariate analysis confirmed the role of CPBT, considered in 30-minute increments, as an independent risk factor for postoperative death (odds ratio [OR] = 1.57, p < 0.0001), pulmonary (OR = 1.17, p < 0.0001), renal (OR 1.31, p < 0.0001), and neurologic complications (OR = 1.28, p < 0.0001), multiorgan failure (OR = 1.21, p < 0.0001), reoperation for bleeding (OR = 1.1, p = 0.0165), and multiple blood transfusions (OR = 1.58, p < 0.0001). Prolonged CPB duration independently predicts postoperative morbidity and mortality after cardiac surgery.


Elevated concentration and high Diversity of organophosphate esters (OPEs) were Discovered in Sediment from Industrial, and E-Waste Recycling Areas.
Aquatic environments in industrial, and e-waste recycling areas might undergo severe contamination; however, there are few studies comprehensively assessing the pollution status of organophosphate esters (OPEs) in these two areas. Here, we applied both atmospheric pressure chemical ionization (APCI) and electron spray ionization (ESI) sources in our target, suspect, and functional group-dependent screening strategy, which enhanced the confidence for confirmation on precursor ions of OPEs. Then, n=53 sediment samples (30 from the industrial area, and 23 from the e-waste recycling area) were analyzed. Twenty-three out of 30 target OPEs were quantifiable in these analyzed samples. Total OPE concentrations (Σ30OPEs) in samples from e-waste recycling area range from 12.8 to 9250 ng/g dry weight (dw), that are statistically significantly greater (t-test, p < 0.001) than those from industrial area (25.1-5520 ng/g dw). Σ30OPEs in the sediments from industrial, or e-waste recycling area are statistically significantly greater (one-way ANOVA, p < 0.001) as compared to those (32.0-369 ng/g dw) from Taihu Lake in our previous study. In sediment from three areas, suspect and non-target analysis fully or tentatively identified other 20 OPEs. Four of them have not been recorded or registered in any of online chemical databases, and they are tentatively named as ((methoxy(phenoxy)phosphoryl)oxy)phenyl diphenyl phosphate (mPPODP), (tert-butyl)phenyl (ethyne-oxidane) bis(2,4-di-tert-butylphenyl) phosphate (TPBDTP), bis(dichlorophenyl) propane-1,3-diyl bis(hexylated phosphate) (BDCBHP), and bis(2-hexadecoxyethyl) ethyl phosphate (BHEPP). Overall, this study provided new insights regarding both analytical methodology and pollution status of OPEs, and highlights that elevated concentrations and high diversity of OPEs exist in sediments from industrial, and e-waste recycling areas.


Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis.
Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics. We demonstrate that increased ICP can contribute to meningeal lymphatic dysfunction. Moreover, we show that pre-existing lymphatic dysfunction before TBI leads to increased neuroinflammation and negative cognitive outcomes. Finally, we report that rejuvenation of meningeal lymphatic drainage function in aged mice can ameliorate TBI-induced gliosis. These findings provide insights into both the causes and consequences of meningeal lymphatic dysfunction in TBI and suggest that therapeutics targeting the meningeal lymphatic system may offer strategies to treat TBI.


Partial trisomy 4q in two unrelated cases.
Two unrelated cases of 4q trisomy are described with trisomic segment 4q25 leads to 4qter. The most conspicuous symptoms are psychomotor retardation, microcephaly, malformed ears, retrognathia, finger and toe malformations and cryptorchism in a male. Both cases are compared with 19 previously reported ones.


Twenty-four months of bacterial colonialization and infection rates in patients with transcutaneous osseointegrated prosthetic systems after lower limb amputation-A prospective analysis.
Transcutaneous osseointegrated prosthesis systems (TOPS) are alternative rehabilitation methods to socket prosthetics, after limb amputation. TOPS compromise a two-step surgery: starting with the implantation of the stem which is then followed by the creation of the transcutaneous stoma through which the exoprosthesis can be connected. Immediately after surgery, this opening is permanently exposed to pathogens. This study aimed to investigate the dynamics of bacterial colonization of the stoma to analyze whether obligate bacterial colonization leads to a risk of periprosthetic infections after TOPS treatment. This prospective study analyzed data from 66 patients (aged 26-75 years) after TOPS treatment between 2017 and 2019. Microbiological swabs from the stoma were analyzed on the first postoperative day and 3, 6, 12, and 24 months after stoma creation. Infection rates, laboratory values (CRP, leukocyte count, hemoglobin), and body temperature were recorded at these points in time. Statistical analysis was performed using SPSS 28. The results show the formation of a stable environment dominated by Gram-positive bacteria in the stoma of TOPS patients over 24 months. Staphylococcus aureus, Staphylococcus spp., and Streptococcus spp. were the most common species found. With regard to the cohort up to the 3 months follow-up, 7.9% (five patients) developed infections surrounding the TOPS procedure. In relation to the whole cohort with loss to follow-up of 80.3% at the 24 months follow-up the infection rates increased up to 38.3%. The soft tissue inside and around the transcutaneous stoma is colonialized by multiple taxa and changes over time. A stable Gram-positive dominated bacterial taxa could be a protective factor for ascending periprosthetic infections and could possibly explain the relatively low infection rate in this study as well as in literature.


Human DNA replication: fiber autoradiographic analysis of diploid cells from normal adults and from Fanconi's anemia and ataxia telangiectasia.
Fiber autoradiograms prepared from radioactive DNA of diploid skin fibroblasts and lymphocytes from normal adult humans show patterns of replication of chromosomal DNA that are closely similar to those from other mammalian cells. The rate of replication fork movement is 0.64 micrometer/min and 0.42 micrometer/min for fibroblasts and lymphocytes respectively. In both types of cells, replication units show a median length of about 70 micrometer. Replication proceeds bidirectionally from a central origin in most units and adjacents units initiate synthesis synchronously. In skin fibroblasts from individuals with Fanconi's anemia or ataxia telangiectasia, the autoradiographic patterns of DNA replication are the same as in controls. This suggests that S phase DNA synthesis is normal in these disorders.


Waist-to-height ratio, an optimal anthropometric indicator for metabolic dysfunction associated fatty liver disease in the Western Chinese male population.
Non-alcoholic fatty liver disease (NAFLD) has been entitled as metabolic-dysfunction associated fatty liver disease (MAFLD). Therefore anthropometric indicators of adiposity may provide a non-invasive predictive and diagnostic tool for this disease. This study intended to validate and compare the MAFLD predictive and diagnostic capability of eight anthropometric indicators. The study involved a population-based retrospective cross-sectional design. The Fangchenggang area male health and examination survey (FAMHES) was used to collect data of eight anthropometric indicators, involving body mass index (BMI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), body adiposity index (BAI), cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and abdominal volume index (AVI). Receiver operating characteristics (ROC) curves and the respective areas under the curves (AUCs) were utilized to compare the diagnostic capacity of each indicator for MAFLD and to determine the optimal cutoff points. Binary logistic regression analysis was applied to identify the odds ratios (OR) with 95% confidence intervals (95% CI) for all anthropometric indicators and MAFLD. The Spearman rank correlation coefficients of anthropometric indicators, sex hormones, and MAFLD were also calculated. All selected anthropometric indicators were significantly associated with MAFLD (P < 0.001), with an AUC above 0.79. LAP had the highest AUC [0.868 (95% CI, 0.853-0.883)], followed by WHtR [0.863 (95% CI, 0.848-0.879)] and AVI [0.859 (95% CI, 0.843-0.874)]. The cutoff values for WHtR, LAP and AVI were 0.49, 24.29, and 13.61, respectively. WHtR [OR 22.181 (95% CI, 16.216-30.340)] had the strongest association with MAFLD, regardless of potential confounders. Among all the anthropometric indicators, the strongest association was seen between LAP and sex hormones. All anthropometric indicators were associated with MAFLD. WHtR was identified as the strongest predictor of MAFLD in young Chinese males, followed by LAP and AVI. The strongest association was found between LAP and sex hormones.


Scent of Jasmine Attracts Alien Invaders and Records on Citizen Science Platforms: Multiple Introductions of the Invasive Lacebug Corythauma ayyari (Drake, 1933) (Heteroptera: Tingidae) in Italy and the Mediterranean Basin.
The jasmine lacebug Corythauma ayyari is a pest of cultivated and ornamental plants mainly associated to Jasminum spp. This invasive insect is native to Asia, and it has been recently introduced in several countries, mainly within the Mediterranean basin. Here, we updated the known distribution of this species, including five new Italian regions (Liguria, Tuscany, Latium, Apulia, and Calabria); Salamis Island in Greece, and the Occitanie region in France. Citizen-science data have significantly contributed to the knowledge on species distribution, and the online platform for sharing biodiversity information can represent an effective tool for the early detection. Molecular analyses revealed that the specimens collected in Peninsular Italy and Sicily belong to a unique clade, suggesting the possibility of a single introduction, whereas those from Menton (France) and Calabria (Southern Italy) are separated from the others and probably originate from separated introductions.


The binding of aromatic derivatives of beta-D-galactopyranosides to the FAB' of immunoglobulin J539. Observations on the nature of ligand-antibody interactions.
A number of D-galactopyranosides bearing aromatic substituents have been prepared, and their binding to immunoglobulin J539 (Fab') has been studied. It appears that the main contribution of the 6-O-aromatic moiety to binding arises from the fact that it imparts an increased hydrophobicity to the ligand, causing a decrease in its hydration (solubility) that results in a greater free-energy of binding. In the D-galactosides having an aromatic aglycon, the phenyl group appears to partake in actual interactions with the protein.


The effects of intranasal oxytocin on contagious yawning.
Contagious yawning is thought to represent a basic form of empathy involved in state matching. Despite recent evidence in support of this connection, the neurochemical basis of contagious yawning remains largely unknown. Here, we investigate whether intranasal oxytocin, a hormone and neuropeptide involved in empathic processing, bonding and social affiliation, influences contagious yawning among human participants in a laboratory setting. Using a double blind procedure, 60 male college students received 30 IU of intranasal oxytocin or placebo and were then recorded during exposure to a contagious yawning video stimulus. Contrary to the empathic modeling hypothesis, oxytocin did not increase contagious yawning but rather appeared to modulate its expression in ways indicative of an enhanced awareness of the social stigma associated with this behavior. In particular, individuals in the oxytocin condition were more likely to conceal their yawns and less likely to display overt cues associated with the behavior. Follow-up research could explore how social context and affiliation with the target stimulus alter this response.


High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006.
The treatment of metastatic renal cell carcinoma (RCC) with high-dose interleukin-2 (HD IL-2) has resulted in durable tumor regression in a minority of patients. The current study presents the authors' 20-year experience administering this immunotherapeutic agent. Patients with metastatic RCC (n = 259) were treated with HD IL-2 alone from January 13, 1986 through December 31, 2006 at the Surgery Branch of the National Cancer Institute. Potential predictive factors for response and survival, both pretreatment and treatment-related, were first subjected to univariate analysis and then to multivariate logistic regression or a Cox proportional hazards model. Finally, the authors investigated Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic factors for survival to assess their predictive value in the patient population in the current study. A total of 23 patients experienced a complete response and 30 patients achieved a partial response, for an overall objective response rate of 20%. All partial responders had developed disease recurrence at the time of last follow-up, but only 4 complete responders had experienced disease recurrence by that time. Despite toxicities, only 2 patients developed treatment-related mortalities over this same time period. A higher baseline weight (P = .05) and MSKCC prognostic factors (P = .02) were found to be the variables most associated with response. For survival >4 years and overall survival, several pretreatment and treatment-related factors maintained significance, but none more so than response (P < .0001). HD IL-2 can induce complete tumor regression in a small number of patients, and many patients have experienced extended disease-free intervals. Given its relative safety, HD IL-2 should still be considered a first-line therapy in patients with metastatic RCC who have an overall good performance status.


Isolation of an N-acetyl-DL-phenylalanine beta-naphthyl esterase from rabbit peritoneal polymorphonuclear leukocytes.
An N-acetyl-DL-phenylalanine beta-naphthyl esterase has been purified 26-fold from rabbit peritoneal polymorphonuclear leukocytes. The purified enzyme was inhibited by 10(-7) M p-nitrophenylethyl-5-chloropentylphosphonate. The apparent Km for hydrolysis of N-acetyl-DL-phenylalanine beta-naphthyl ester is 71 muM. Optimal reaction rates were observed at pH 6-8. No divalent cation requirement for the activation of the enzyme activity was observed. The esterase activity was neither inhibited nor stimulated by bacterial factor, complement component C5a, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) which are attractants or repellents for polymorphonuclear leukocytes. High chemotactic activity was observed in the partially purified fraction of the enzyme. The chemotactic activity, like the enzyme activity, was completely inhibited by 10(-7) M phosphonate.


5-A Fourier map of gramicidin A phased by deuterium-hydrogen solvent difference neutron diffraction.
Crystals of ion-free gramicidin A (P212121: a = 24.61, b = 32.28, c = 32.52) have been investigated using neutron diffraction. A difference analysis of crystals soaked in ethanol/H2O as opposed to ethanol-d6/D2O has led to single isomorphous replacement Fourier projections of the structure at 5-A resolution. The gramicidin dimer appears to be a 32-A-long cylinder oriented parallel to the c-axis in these crystals.


Camptothecin encapsulated into functionalized MCM-41: In vitro release study, cytotoxicity and kinetics.
The application of MCM-41 functionalized by 12-tungstophosphoric acid (TPA) as drug carrier for cancer treatment was studied by loading of camptothecin (CPT). In-vitro controlled release study of CPT in Simulated Body Fluid (pH 7.4, 37 °C) was carried out under stirring as well as static conditions. The systems were also evaluated on cancer cells (HepG2) and the carriers are found to be non-toxic to the cancer cells. In order to see the influence of inorganic moiety on release rate of drug, study was also carried out with CPT loaded unfunctionalized MCM-41. A detailed study on release kinetics and release mechanism using First Order Release Kinetic Model, Higuchi Model, Koresmeyer-Pepps Model and Extended kinetic model was also carried out.


Description of Spiniola hanaro Park, gen. and sp. nov., and three new species of Torodora Meyrick, 1894 (Lepidoptera, Lecithoceridae, Torodorinae) from the Afrotropical Region.
A new genus, Spiniola Park, gen. nov., is described from Malawi, based on the type species, S. hanaro Park, sp. nov., and three new species of Torodora Meyrick, 1894 are described: T. batillana Park Koo, sp. nov. from Kenya, and T. chrysotes Park Koo, sp. nov. and T. manalis Park Koo, sp. nov. from Uganda. Images of adults and genitalia of the new species are provided.


The effects of cholecystokinin and cholecystokinin-octapeptide on intestinal lymph flow in the rat.
Intravenous cholecystokinin and its synthetic C-terminal octapeptide were found to cause a transient augmentation of intestinal lymph flow in the rat. Concomitant increase in lymph protein transport suggests that this reflects the increase in intestinal blood flow which is known to occur in response to these agents.


Characterization and adsorption properties of tetrabutylammonium montmorillonite (TBAM) clay: thermodynamic and kinetic calculations.
The montmorillonite has been subjected to modification through ion-exchange reaction by tetrabutylammonium bromide (TBAB). The modified sample was studied by X-ray diffraction (XRD) technique, Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) methods. The basal spacing of modified montmorillonite was determined as 14.40 A. The IR spectra of modified montmorillonite showed CH vibrations. The characterization of tetrabutylammonium montmorillonite (TBAM) and the adsorption of p-chlorophenol (p-CP) on organomontmorillonite was studied as a function of the solution concentration and temperature. The observed adsorption rates were found to fit to the pseudo-second-order kinetics. The rate constants were calculated for temperatures ranging between 25.0-35.0 degrees C at constant concentration. The adsorption energy, E, and adsorption capacity, (q(m)), for phenolic compounds adsorbing on organomontmorillonite were estimated using the Dubinin-Radushkevich (D-R) equation. Thermodynamic parameters (delta g(a) = -11.063 and -11.802 kJ/mol, delta h(a) = -30.032 and -30.789 kJ/mol, delta s(a) = -0.0636 and -0.0637 kJ/mol K for 298 and 308 K, respectively) were calculated by a new approximation from the adsorption isotherms of p-CP on organomontmorillonite. These isotherms were modeled according to Freundlich and Dubinin-Radushkevich adsorption isotherms, through which the first-order and second-order coefficients (K(1ads) = 0.0152 and 0.0127 micromol/g min, K(2ads) = 0.0130 and 0.0108 L/min micromol, respectively) were obtained at 298 and 308 K.


Lower number of K-complexes and K-alphas in sleep bruxism: a controlled quantitative study.
Although patients with sleep bruxism (SB) show a higher incidence of rhythmic masticatory muscle activity (RMMA) during sleep than matched normal controls, they are good sleepers. Sleep macrostructure (e.g. total sleep time, sleep latency, number of awakenings or sleep stage shifts and sleep stage duration) is similar between groups. Differences in sleep microstructure between SB patients and normals have been investigated only in few studies. The aim of the present study was to quantify number of microarousals, K-complexes, K-alphas, EEG spindles, and the density of slow wave activity, in both groups, in order to better understand the pathophysiology of SB. Ten normal sleepers were matched for age and gender with 10 patients who exhibited frequent tooth-grinding during sleep. Using quantitative polysomnographic measures, we compared the above-mentioned sleep variables in both groups. Data are presented as indices for total sleep and for consecutive non-rapid eye movement (non-REM) episodes over non-REM to rapid eye movement (REM) cycles and per hour of sleep. SB patients showed 6 times more RMMA episodes per hour of sleep than normals (P<0.001), with a higher frequency in the second and third non-REM to REM cycles. SB patients presented 42.7% fewer K-complexes per hour of stage 2 sleep, but only normals showed a decline from the first to fourth non-REM episode. Only 24% of SB-RMMA episodes were associated with K-complexes in 60 s. The number of K-alphas was 61% lower in SB patients, no change across non-REM episodes was noted. While no difference in electroencephalographic (EEG) spindles or slow wave activity (SWA) was observed between groups, EEG spindles increased and SWA decreased linearly over consecutive non-REM to REM cycles. According to our observations, good sleep in SB patients is characterized by a low incidence of K-complexes or K-alphas and by the absence of any difference in other sleep microstructure variables or SWA.


Radiologic findings in nasopharyngeal angiofibromas.
Juvenile nasopharyngeal angiofibromas produce radiographic changes which are sufficiently characteristic to render a diagnosis without resorting to biopsy. Computed tomography is also of value, particularly in following the response of these tumors to therapeutic irreadiation.


Cerebral perfusion in type 2 diabetes mellitus: A preliminary study with MR perfusion.
Type 2 diabetes mellitus (T2DM) is associated with altered cerebral vasoreactivity, cognitive impairment, and functional decline. Magnetic Resonance (MR) perfusion can be used to assess cerebral blood flow (CBF). The aim of this study is to analyze the association between diabetes mellitus and cerebral perfusion. The study included 52 patients diagnosed with T2DM and 39 healthy individuals. The diabetic patients were classified into three groups (PRP: proliferative retinopathy, NPRP: non-proliferative retinopathy, Non-RP: non-retinopathy DM). The rCBF measurements of cortical gray matter and thalami were carried out using the region of interest. Reference quantitative measurements were performed from ipsilateral white matter. The comparison between the T2DM group and the control group revealed that rCBF values of bilateral frontal lobes, cingulate gyrus, medial temporal lobe, thalami and right occipital lobe were measured to be significantly lower in the T2DM group (p < 0.05). No significant difference was detected between the two groups in terms of rCBF values of the left occipital lobe and anterior aspect of the left temporal lobe (p > 0.05). The rCBF values were lower in the anterior aspect of the right temporal lobe and the difference showed borderline statistical significance (p = 0.058). No significant difference was detected regarding mean rCBF values measured in the regions of cerebral hemispheres among the three patient groups with T2DM (p˃0.05). Regional hypoperfusion was encountered in most of the lobes in the T2DM group when compared with the healthy group. However, in terms of rCBF values, there was no significant difference among the three groups with T2DM.


Early childhood adversity and body mass index in childhood and adolescence: linking registry data on adversities with school health records of 53,401 children from Copenhagen.
We examined whether childhood adversity experienced in early childhood (0-5 years) is related to body mass index (BMI) in childhood (6-7 years) and adolescence (12-15 years). This study combined data from the nationwide register-based DANLIFE study on childhood adversities with data on height and weight of school children in Copenhagen. Data were available for 53,401 children born in Denmark between 1980 and 1996. Children were divided into groups of early childhood adversity by applying group-based multi-trajectory modelling using their yearly count of childhood adversity in three dimensions (i.e., material deprivation, loss or threat of loss, and family dynamics) from 0-5 years. Direct and total associations between the early childhood adversity groups and BMI z-scores in childhood and adolescence were estimated using sex-stratified structural equation models. Five exclusive and exhaustive groups of early childhood adversity were identified, which were characterized by low adversity (51%), moderate material deprivation (30%), high material deprivation (14%), loss or threat of loss (3%) and high adversity (2%). Boys and girls exposed to moderate or high material deprivation and loss or threat of loss had a slightly higher BMI z-score, especially in adolescence, compared with those in the low adversity group, with the strongest association found for girls in the loss or threat of loss group (b (95% CI) = 0.18 (0.10, 0.26)). Additionally, boys in the high adversity group had a slightly lower BMI z-score in childhood than boys in the low adversity group (b (95% CI) = -0.12 (-0.22, -0.02)). Whereas associations with BMI were found for children and adolescents exposed to material deprivation, loss or threat of loss, and high adversity, the effect sizes were generally small. Contrary to prevailing hypotheses, weight changes in childhood is probably not a major explanatory mechanism linking early childhood adversity with later-life morbidity.


Editorial Commentary: Iatrogenic Instability of the Hip: A Perfect Storm.
Iatrogenic instability of the hip is likely a perfect storm with enough factors coming together just wrong to create the problem. Capsular neglect is but one potential component. Instability is also just one of a myriad of problems that can be encountered following hip arthroscopy that ranges on a spectrum from too loose to too stiff with numerous reasons in between for incomplete pain relief and residual dysfunction. Proper capsular management does not always mean capsular repair.


Use of Standardized Outcome Measures for People With Lower Limb Amputation: A Survey of Prosthetic Practitioners in the United States.
To assess the clinical resources available for the assessment of health outcomes in people with lower limb amputation and to understand barriers and facilitators associated with use of standardized outcome measures in clinical practice. Cross-sectional survey. General community (online). A volunteer sample of prosthetic practitioners was recruited through national professional organizations. Eligible participants were practitioners certified by a professional prosthetics organization and currently practicing as a prosthetist, prosthetist-orthotist, or prosthetic assistant. Not applicable. A custom-designed online survey on clinical use of patient-reported and performance-based standardized outcome measures to assess patients with lower limb amputation. A total of 375 participants completed the survey. Most participants (79%) reported that they are encouraged or required to administer standardized outcome measures in their clinic or facility. Most participants reported that use of patient-reported and performance-based outcome measures are within their scope of practice (88%) and that they have the knowledge required for outcomes measurement (84%). Few participants agreed that outcomes measurement is standardized across the profession (30%). Most participants had access to small spaces and equipment for outcomes measurement, such as short hallways (65%-94%), stairs (69%), and tablets with wireless internet connection (83%). Most participants reported that they would be willing to spend between 5 (36% of participants) and 10 (43% of participants) minutes on self-reported surveys, and between 10 (41% of participants) and 20 (28% of participants) minutes on performance-based tests. Outcomes measurement is encouraged or expected in contemporary prosthetic practice. Strategies to improve standardization and efficiency of administration are needed to facilitate routine use of outcome measures in clinical care.


Identifying and articulating the student experience in the Intercalated Enrichment Year.
Benefits of intercalation during an undergraduate medical degree are well-recognized. The University of Hong Kong implemented a compulsory Enrichment Year (EY) in its Bachelor of Medicine and Bachelor of Surgery degree programme (MBBS) in 2016. In their third year of study, students could work on an area of interest in any of three programme categories (i) intercalation/ university exchange (IC); (ii) research (RA); (iii) service/ humanitarian work (SH). This study aimed to explore the barriers, enablers, and overall student learning experiences from the first cohort of EY students in order to inform future development of the EY. An exploratory sequential mixed-method study in 2019-20. Twenty students were purposively selected to attend three semi-structured focus group interviews. Conventional thematic analysis was employed and results assisted the design of a cross-sectional questionnaire. Sixty-three students completed the questionnaire. ANOVA or chi-square test was used to compare the difference in student's characteristics, barriers, enablers and perspectives on EY between programme categories. Adjusting student's characteristics, logistic regressions were conducted to identify the effect of programme categories on the EY experience. Most students (95% in the questionnaire) agreed that EY was worthwhile and more rewarding than expected. EY was positively regarded for enhancing personal growth and interpersonal relationships. The main barriers were financial difficulties, scholarship issues and insufficient information beforehand. A few students had practical (i.e. accommodation, cultural adaptation) problems. Potential enablers included better financial support, more efficient information exchange and fewer assignments and preparation tasks. Similar barriers were encountered by students across all three categories of EY activities. Personal growth was the most important benefit of the EY. Barriers were consistent with those identified in the literature except for cultural adaptation, which could be related to Hong Kong's unique historical context. Financial limitation was the most concerning barrier, as it could result in unequal access to educational opportunities. Better and timely access to scholarships and other funding sources need to be considered. Ethics approval was obtained from the local Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 19-585 ).


Perception of overseas experiences among medical students in Japan: a national online survey.
Data on the perceptions of medical students on international experience in non-English-speaking high-income countries (HICs) are very limited. This study aimed to assess the perceptions of medical students in Japan toward overseas experience while in school and post-graduation, as well as to characterize the support they require to pursue their profession in international settings. A cross-sectional national survey was administered online between September 16, 2020, and October 8, 2020. Participants were recruited from 69 medical schools using snowball sampling through acquaintances and social media platforms. The survey results were analyzed by two researchers. A total of 548 students from 59 medical schools responded to the survey. Among them, 381 respondents (69%) expressed interest in working abroad, while only 40% seriously considered it. The majority of students responded that they would like to pursue clinical training abroad for a short term or while they were medical students (54%) or during a residency/fellowship (53%). The most popular regions among the respondents for future international experiences were North America and Europe. Finally, the most reported reasons for hesitation to work abroad were language barriers (70%), followed by lack of clarity regarding career options after working abroad (67%), difficulties obtaining medical licensure abroad (62%), and the lack of role models (42%). Although nearly 70% of participants reported a high interest in working overseas, various barriers to working abroad were identified. Our findings identified key problem areas that could be targeted when promoting international experiences for medical students in Japan.


Advantages and disadvantages of one-stage and two-stage surgery for arrhythmias and Ebstein's anomaly.
To evaluate efficacy of one-step and two-step surgery approach in patients with arrhythmias combined with Ebstein's anomaly. Fifty-three patients with Ebstein's anomaly combined with tachyarrhythmias (58.5% men, 41.5% women, mean age 21.6+/-10.7 years) were operated on. In group A (32 patients), one-step surgical correction (simultaneous intraoperative elimination of arrhythmias and congenital heart defect repair) was performed, whereas in group B (21 patients), two-step surgery was performed with initial elimination of arrhythmogenic substrate by transcatheter radiofrequency ablation (first step) and following surgical repair of congenital heart defect (second step). In group A, total hospital mortality was 3.1% (1 patient) due to initial severe condition of this patient. One-step surgery was effective in 93.5% of cases. Mortality was not observed in group B. Efficacy of transcatheter radiofrequency ablation was 76.2%. One-stage and two-stage surgery of arrhythmias and Ebstein's anomaly are highly effective. First step of surgery of combined pathology reduces cardiopulmonary bypass time, complications and mortality while performing the second step of congenital heart defect surgery. However, simultaneous approach (one-step surgery) is better in terms of arrhythmia elimination.


Phenotypic and molecular identification of Coccidioides posadasii in a patient evaluated for bilateral lung transplantation.
Coccidioidomycosis is an endemic fungal infection caused by Coccidioides immitis and Coccidioides posadasii. It can be particularly severe in transplant recipients that have a current or a previous coccidioidal infection. Fatal case of coccidioidomycosis has been described in this group of patients. We report a severe case of pneumonia caused by C. posadassi in a 29 year-old white woman that had been admitted to hospital as part of the evaluation for bilateral lung transplantation. The patient was a native and resident of Catamarca, Argentina. Molecular methodologies contributed to the species identification. Clinical, laboratory records and microbiological tests were carried out to diagnose the infection and to identify C. posadasii. A fungus was isolated from BAL culture. Phenotypic characterization, specific PCR and experimental animal inoculation demonstrated the presence of C. posadasii. The patient responded well to amphotericin B deoxycholate. Lung transplantation was postponed. Specific PCR can be an important alternative for the correct identification of C. immitis or C. posadasii in laboratories with implemented molecular biology tools. This case emphasizes the need for a systematic assessment in organ transplant units of patients inhabiting endemic areas of coccidioidomycosis.


The effect of curcumin-piperine on cardiometabolic, inflammatory and oxidative stress factors and macular vascular density in optical coherence tomography angiography (OCTA) in patients with non-proliferative diabetic retinopathy: Study protocol for a randomized, double-blind controlled trial.
Curcumin is a safe phytochemical with antioxidant, anti-inflammatory, antidiabetic, and lipid-lowering effects. This study aims to investigate the efficacy of curcumin-piperine in non-proliferative diabetic retinopathy. In this double-blind randomized trial, 60 diabetic retinopathy patients after meeting the inclusion criteria will be randomly assigned to two groups of curcumin-piperine supplementation (1000 mg per day for 12 weeks) or receiving placebo. The density of small blood vessels in the retina by optical coherence tomography angiography (OCTA), fasting blood glucose, triglyceride, renal indices (blood urea nitrogen and creatinine), high-sensitivity C-reactive protein, total antioxidant capacity, total oxidant status, body mass index, waist circumference, and weight will be measured. If the beneficial effects of curcumin on diabetic retinopathy are observed, this safe, this natural and inexpensive herbal supplement can be considered a therapeutic solution in these patients.


Lewis acid promoted carbon-carbon bond cleavage of gamma-silyloxy-beta-hydroxy-alpha-diazoesters.
Cyclic gamma-silyloxy-beta-hydroxy-alpha-diazoesters undergo efficient rupture of the Cbeta-Cgamma bond when treated with tin tetrachloride to provide tethered aldehyde ynoate products in high yield.


Cancer in Yogyakarta, Indonesia: relative frequencies.
Some 1220 male and 2102 female cases of malignant neoplasms diagnosed histologically at the Department of Pathology of the Gadjah Mada University in Yogyakarta during the period 1970-73 were analysed. The most frequent tumour sites were among men: nasopharyngeal cancer, 21-8% and skin cancer, 17-6%. Among women the genital cancers were the most frequent with: cervix uteri, 25-7% chorionepithelioma, 3-7%, other uterus, 4-4% and ovary, 7-4%. Breast cancer comprised 17-0%, skin 9-6% and nasopharyngeal cancer 7-9%. Low frequencies were observed in both sexes for cancers of the gastro-intestinal tract and of the respiratory organs; previous reports of the rarity of gastric cancer were confirmed. The observed distribution is discussed in the light of possible biases, and compared with other material on the frequency of cancer from South East Asia.


Single shot of intravenous iron in cardiac surgery: The ICARUS study.
Iron deficiency (ID), with or without anemia, is commonly observed among patients scheduled for cardiac surgery. We investigated if screening ID in the immediate preoperative period and treating ID patients regardless of anemia could reduce perioperative transfusion requirements. This is an observational single-center propensity score-matched study including candidates to elective cardiac surgery prospectively and retrospectively enrolled. Prospectively enrolled patients were screened for ID at hospital admission: if ferritin was ≤100 μg/L or ≤ 300 μg/L with transferrin saturation index ≤20% they received intravenous ferric carboxymaltose, B12-vitamin, and folic acid. A retrospective series of patients not screened for ID and matched for gender, type of surgery, BMI, Goudie transfusion risk score, hemoglobin level, and red blood cell (RBC) indices, served as controls. The primary outcome was the proportion of patients requiring ≤1 packed RBC (pRBC) unit within day 7 or discharge The main secondary outcomes were intraoperative and postoperative pRBC transfusions, duration of hospitalization, and cost-effectiveness of ID screening and treatment. We included 479 prospective and 833 retrospective cases: 442 patients screened for ID and 442 matched controls with unknown iron status were analyzed. ID was observed in 196 patients (44.3%) and iron was administered 1 day (IQR 1-2) before surgery. Overall, 76.9% of patients in the prospective group and 69.7% of controls received ≤1 pRBC transfusion (p = 0.014). The risk for multiple transfusions was lower in patients screened for ID (OR 0.689, 95% CI 0.510-0.930). Despite similar Hb levels at day 7, patients in the prospective group received fewer postoperative pRBC transfusions (p < 0.001) and had a shorter hospital length of stay (p < 0.001). Globally, hospitalization costs were lower in patients screened and treated for ID. Short-term pre-operative iron therapy is associated with a reduction in postoperative transfusions in anemic and non-anemic ID cardiac surgery patients and has a favorable impact on hospitalization costs. NCT04744181.


History Page: Leaders in MSK Radiology.
This history page in the series "Leaders in MSK Radiology" is dedicated to the memory and achievements of the French physician Jacques Forestier, whose name is connected with the medical eponym Forestier's disease, later referred to as diffuse idiopathic skeletal hyperostosis.


Infrared LED irradiation applied during high-intensity treadmill training improves maximal exercise tolerance in postmenopausal women: a 6-month longitudinal study.
Reduced aerobic fitness is associated with an increased risk of cardiovascular diseases among the older population. The aim of this study was to investigate the effects of LED irradiation (850 nm) applied during treadmill training on the maximal exercise tolerance in postmenopausal women. At the beginning of the study, 45 postmenopausal women were assigned randomly to three groups, and 30 women completed the entire 6 months of the study. The groups were: (1) the LED group (treadmill training associated with phototherapy, n = 10), (2) the exercise group (treadmill training, n = 10), and (3) the sedentary group (neither physical training nor phototherapy, n = 10). The training was performed for 45 min twice a week for 6 months at intensities between 85% and 90% maximal heart rate (HRmax). The irradiation parameters were 39 mW/cm(2), 45 min and 108 J/cm(2). The cardiovascular parameters were measured at baseline and after 6 months. As expected, no significant differences were found in the sedentary group (p ≥ 0.05). The maximal time of tolerance (Tlim), metabolic equivalents (METs) and Bruce stage reached significantly higher values in the LED group and the exercise group (p < 0.01). Furthermore, the HR, double product and Borg score at isotime were significantly lower in the LED group and in the exercise group (p < 0.05). However, the time of recovery showed a significant decrease only in the LED group (p = 0.003). Moreover, the differences between before and after training (delta values) for the Tlim, METs and HR at isotime were greater in the LED group than in the exercise group with a significant intergroup difference (p < 0.05). Therefore, the infrared LED irradiation during treadmill training can improve maximal performance and post-exercise recovery in postmenopausal women.


The contribution of cell wall proteins to the organization of the yeast cell wall.
Our knowledge of the yeast cell wall has increased rapidly in the past few years, allowing for the first time a description of its structure in molecular terms. Two types of cell wall proteins (CWPs) have been identified that are covalently linked to beta-glucan, namely GPI-CWPs and Pir-CWPs. Both define a characteristic supramolecular complex or structural unit. The GPI building block has the core structure GPI-CWP-->beta1,6-glucan-->beta1,3-glucan, which may become extended with one or more chitin chains. The Pir building block is less well characterized, but preliminary evidence points to the structure, Pir-CWP-->beta1,3-glucan, which probably also may become extended with one or more chitin chains. The molecular architecture of the cell wall is not fixed. The cell can make considerable adjustments to the composition and structure of its wall, for example, during the cell cycle or in response to environmental conditions such as nutrient and oxygen availability, temperature, and pH. When the cell wall is defective, dramatic changes can occur in its molecular architecture, pointing to the existence of cell wall repair mechanisms that compensate for cell damage. Finally, evidence is emerging that at least to a considerable extent the cell wall of Saccharomyces cerevisiae is representative for the cell wall of the Ascomycetes.


Assessing Effectiveness of Colonic and Gynecological Risk Reducing Surgery in Lynch Syndrome Individuals.
Colorectal (CRC) and endometrial cancer (EC) are the most common types of cancer in Lynch syndrome (LS). Risk reducing surgeries (RRS) might impact cancer incidence and mortality. Our objectives were to evaluate cumulative incidences of CRC, gynecological cancer and all-cause mortality after RRS in LS individuals. Retrospective analysis of 976 LS carriers from a single-institution registry. Primary endpoints were cumulative incidence at 75 years of cancer (metachronous CRC in 425 individuals; EC and ovarian cancer (OC) in 531 individuals) and all-cause mortality cumulative incidence, comparing extended (ES) vs. segmental surgery (SS) in the CRC cohort and risk reducing gynecological surgery (RRGS) vs. surveillance in the gynecological cohort. Cumulative incidence at 75 years of metachronous CRC was 12.5% vs. 44.7% (p = 0.04) and all-cause mortality cumulative incidence was 38.6% vs. 55.3% (p = 0.31), for ES and SS, respectively. Cumulative, incidence at 75 years was 11.2% vs. 46.3% for EC (p = 0.001) and 0% vs. 12.7% for OC (p N/A) and all-cause mortality cumulative incidence was 0% vs. 52.7% (p N/A), for RRGS vs. surveillance, respectively. RRS in LS reduces the incidence of metachronous CRC and gynecological neoplasms, also indicating a reduction in all-cause mortality cumulative incidence in females undergoing RRGS.


An unexpected discovery toward argon-rich water amelioration of cadmium toxicity in Medicago sativa L.
Argon has organ-protective effects on animals. However, whether or how argon influences plant responses remains elusive. In this study, we discovered that the growth inhibition of hydroponically cultured alfalfa seedlings under 100 μM CdCl2 condition was significantly ameliorated by 100 % saturated argon-rich water (ARW). Less Cd uptake and accumulation were also observed in both root and shoot parts, which could be explained by the modified root cell walls, including the increased cell wall thickness, lignin content, and demethylation degree of covalently bound and ion-bound pectin, as well as the down-regulated expression of natural-resistance-associated-macrophage protein1 (Nramp1) encoding a heavy metal ion transporter in root tissue. The hindered Cd translocation from root to shoot achieved by ARW addition was validated by the decreased expression of heavy metal ATPase 2/4 (HMA2/4) in roots and decreased Cd content in xylem saps. The reestablished glutathione (GSH) homeostasis and redox balance, two important indicators of plant defense against Cd poisoning, were also observed. Further greenhouse experiments demonstrated that the phenotypic and physiological performances of alfalfa plants cultured in Cd-contaminated soil were significantly improved by irrigating with ARW. Above results implied that ARW confers plants tolerance against cadmium toxicity by impairing Cd uptake and accumulation and restoring GSH and redox homeostasis. These findings might open a new window for understanding argon biology in higher plants.


Reach and representativeness of ethnic minority women in the Health Is Power Study: a longitudinal analysis.
Reach is a key factor in translating research to practical application. This study examined reach and representativeness of a multi-city, randomized controlled community health trial in African American (AA) and Hispanic or Latina (HL) women. Participants completed measures of demographics, body mass index (BMI), percent body fat, resting heart rate, and blood pressure followed by a run-in procedure and a randomization meeting. AA were more likely to be screened out initially; HL were more likely to drop out. Participation did not differ by city or recruitment method. Women who completed the post-intervention assessment were more likely to be AA, older, and have higher socioeconomic status (p values < .05). This study showed moderate levels of reach but overrepresented higher educated, wealthier, and older women at the completion of the study. Representativeness can change over the course of the study and impact the practicality of translating research to practice.


Intriguing two-dimensional assembly of cobaloxime with a [Zn2(OOCR)4] center.
We report the synthesis and crystallographic studies of paddlewheel-based methyl cobaloxime assembly formed from methyl cobaloxime, isonicotinic acid, and Zn(NO(3))(2). The cobaloxime units are assembled over two-dimensional metal-organic polyhedra constructed from isonicotinate and Zn metal ions.


Altered protein S-glutathionylation depicts redox imbalance triggered by transition metal oxide nanoparticles in a breastfeeding system.
Nanosafety has become a public concern following nanotechnology development. By now, attention has seldom been paid to breastfeeding system, which is constructed by mammary physiological structure and derived substances (endogenous or exogenous), cells, tissues, organs, and individuals (mother and child), connecting environment and organism, and spans across mother-child dyad. Thus, breastfeeding system is a center of nutrients transport and a unique window of toxic susceptibility in the mother-child dyad. We applied metabolomics combined with redox proteomics to depict how nanoparticles cause metabolic burden via their spontaneous redox cycling in lactating mammary glands. Two widely used nanoparticles [titanium dioxide (nTiO2) and zinc oxide (nZnO)] were exposed to lactating mice via intranasal administration. Biodistribution and biopersistence of nTiO2 and nZnO in mammary glands destroyed its structure, reflective of significantly reduced claudin-3 protein level by 32.1% (P < 0.01) and 47.8% (P < 0.01), and significantly increased apoptosis index by 85.7 (P < 0.01) and 100.3 (P < 0.01) fold change, respectively. Airway exposure of nTiO2 trended to reduced milk production by 22.7% (P = 0.06), while nZnO significantly reduced milk production by 33.0% (P < 0.01). Metabolomics analysis revealed a metabolic shift by nTiO2 or nZnO, such as increased glycolysis (nTiO2: fold enrichment = 3.31, P < 0.05; nZnO: fold enrichment = 3.68, P < 0.05), glutathione metabolism (nTiO2: fold enrichment = 5.57, P < 0.01; nZnO: fold enrichment = 4.43, P < 0.05), and fatty acid biosynthesis (nTiO2: fold enrichment = 3.52, P < 0.05; nZnO: fold enrichment = 3.51, P < 0.05) for tissue repair at expense of lower milk fat synthesis (35.7% reduction by nTiO2; 51.8% reduction by nZnO), and finally led to oxidative stress of mammary glands. The increased GSSG/GSH ratio (57.5% increase by nTiO2; 105% increase by nZnO) with nanoparticle exposure confirmed an alteration in the redox state and a metabolic shift in mammary glands. Redox proteomics showed that nanoparticles induced S-glutathionylation (SSG) modification at Cys sites of proteins in a nanoparticle type-dependent manner. The nTiO2 induced more protein SSG modification sites (nTiO2: 21; nZnO:16), whereas nZnO induced fewer protein SSG modification sites but at deeper SSG levels (26.6% higher in average of nZnO than that of nTiO2). In detail, SSG modification by nTiO2 was characterized by Ltf at Cys423 (25.3% increase), and Trf at Cys386;395;583 (42.3%, 42.3%, 22.8% increase) compared with control group. While, SSG modification by nZnO was characterized by Trfc at Cys365 (71.3% increase) and Fasn at Cys1010 (41.0% increase). The discovery of SSG-modified proteins under airway nanoparticle exposure further supplemented the oxidative stress index and mammary injury index, and deciphered precise mechanisms of nanotoxicity into a molecular level. The unique quantitative site-specific redox proteomics and metabolomics can serve as a new technique to identify nanotoxicity and provide deep insights into nanoparticle-triggered oxidative stress, contributing to a healthy breastfeeding environment.


Outsourcing drug discovery to India and China: from surviving to thriving.
Global pharmaceutical companies face an increasingly harsh environment for their primary business of selling medicines. They have to contend with a spiraling decline in the productivity of their R&D programs that is guaranteed to severely diminish their growth prospects. Outsourcing of drug discovery activities to low-cost locations is a growing response to this crisis. However, the upsides to outsourcing are capped by the failure of global pharmaceutical companies to take advantage of the full range of possibilities that this model provides. Companies that radically rethink and transform the way they conduct R&D, such as seeking the benefits of low-cost locations in India and China will be the ones that thrive in this environment. In this article we present our views on how the outsourcing model in drug discovery should go beyond increasing the efficiency of existing drug discovery processes to a fundamental rethink and re-engineering of these processes.


Voided volume may not impact stone outcomes: Review of a large institutional nephrolithiasis cohort.
Urologic guidelines universally recommend increasing fluid intake for kidney stone prevention. Increased voided volume is thought to help reduce stone recurrence and severity, but supporting evidence is limited. Nephrolithiasis outcomes and 24-h urine data for patients from the Registry for Stones of the Kidney and Ureter (ReSKU), a registry of nephrolithiasis patients collected between 2015 and 2020, were retrospectively analysed. Outcome was stone events, either an office visit where a patient reports symptomatic passage of stones or surgery for stone removal. We identified 450 stone patients with 24-h urine and kidney stone outcome data. There was no significant difference in 24-h voided volume between patients with one stone event and patients with two or more stone events. On multivariable logistic regression, after controlling for age, gender, BMI, and 24-h sodium and creatinine per kilogram, no significant associations were found between voided volume and stone events. There was a statistically significant negative correlation noted between voided volume and stone events in calcium oxalate dihydrate stone formers (Spearman R = -0.42, p = 0.04), but not others. Twenty-four-hour voided volume was not associated with stone events in a large institutional cohort, and subset analysis reveals that some stone formers may benefit more from increased voided volume than others; identifying such patients represents a novel precision medicine opportunity.


Opioid modulation of social play reward in juvenile rats.
Social play behaviour is a vigorous form of social interaction abundant during the juvenile and adolescent phases of life in many mammalian species, including rats and humans. Social play is thought to be important for social, emotional and cognitive development. Being a rewarding activity, the expression of social play depends on its pleasurable and motivational properties. Since opioids have been widely implicated in reward processes, in the present study we investigated the role of opioids in the pleasurable and motivational properties of social play behaviour in rats. To assess social play motivation, an operant conditioning setup was used in which rats responded for social play under a progressive ratio schedule of reinforcement. Treatment with the opioid receptor agonist morphine reduced responding for social play at the highest dose tested, likely due to its rate-limiting effects. Morphine treatment increased the expression of social play behaviour during reinforced periods. The acquisition of social play-induced conditioned place preference (CPP) in a subeffective conditioning protocol was enhanced by treatment with morphine. Morphine treatment alone also induced CPP. In contrast, antagonizing opioid receptors with naloxone reduced responding for social play, the expression of social play and blocked the development of social play-induced CPP. These data implicate opioid neurotransmission in both the pleasurable and the motivational aspects of social play behaviour in rats. This article is part of the Special Issue entitled 'The neuropharmacology of social behavior: from bench to bedside'.


GM1 ganglioside treatment promotes recovery of electrically-stimulated [3H]dopamine release in striatal slices from rats lesioned with kainic acid.
The electrically-evoked release of [3H]dopamine ([3H]DA) from rat striatal slices was studied after a monolateral intrastriatal injection of kainic acid (KA). The release in the KA-lesioned striatum measured 4 days after the lesion was largely reduced (by 80%) with respect to the contralateral striatum. Administration of GM1 ganglioside (GM1) beginning on the day of the lesion resulted in restoration of the catecholamine release. Significant recovery was observed when GM1 was administered i.p. daily at the dose of 3 mg/kg for 6 days. The ganglioside given for 6 days at 30 mg/kg restored to near normal the electrically-evoked [3H]DA release. Similar recovery from the KA-induced injury occurred spontaneously but required 50 days.


Endovascular Versus Surgical Arteriovenous Fistulas: A Systematic Review and Meta-analysis.
To facilitate the process of dialysis for patients with kidney failure, an arteriovenous fistula (AVF) is created using either a surgical or percutaneous approach. We sought to compare the efficacy and procedural outcomes in creating an AVF percutaneously using Ellipsys (Avenu Medical) or WavelinQ (Becton Dickinson Medical) with surgery in all patients with kidney failure requiring a permanent AVF for dialysis. Systematic review and meta-analysis. All patients requiring a permanent AVF for dialysis. We included studies that compared either the Ellipsys device or WavelinQ directly with surgery to create an AVF for long-term dialysis. Two reviewers independently reviewed the studies and extracted the data. Conflicts were resolved with a discussion and approval from the senior author. Fixed-effects or random-effects models were used to pool the fixed sizes and 95% CIs based on the level of heterogeneity. There was no statistically significant difference observed between surgical AVF and endovascular AVF when comparing the primary outcomes of procedural success (OR = 1.44; 95% CI, 0.35, 5.88; P = 0.61; I2 = 0%), complications (OR = 0.28; 95% CI, 0.06, 1.46; P = 0.13; I2 = 69%), and the secondary outcomes of interest that included follow-up time (mean difference [MD] = -17.71; 95% CI, -189.53, 154.12; P = 0.84; I2 = 94%), failure rate (OR = 1.03; 95% CI, 0.21, 5.13; P = 0.97; I2 = 85%), and time to 2-needle cannulation (MD = -5.40; 95% CI, -38.88, 28.08; P = 0.75; I2 = 0%). However, a statistically significant difference was seen among the 2 groups for procedural time (MD = -54.25; 95% CI, -59.78, -48.71; P < 0.001; I2 = 98%), number of interventions needed to maintain patency (OR = 1.73; 95% CI, 1.22, 2.45; P < 0.01; I2 = 94%), and primary patency rate (OR = 0.34; 95% CI, 0.23,0.52; P < 0.001; I2 = 0%). The total number of studies included in this review was limited, with 3 of the 4 included studies being retrospective and only 1 being prospective. There was a lack of heterogeneity and randomization. Percutaneous fistula creation using Ellipsys or WavelinQ is a unique and safe alternative with outcomes comparable to surgery. Future studies are needed, including observational studies in current clinical practice, to evaluate the efficacy and outcomes of endovascular AVF creation in clinical populations.


Rat intestinal mast cell amines are released during nitric oxide synthase inhibition in vitro.
Inhibition of nitric oxide synthase increases microvascular permeability in rat small intestinal villi. To determine the mechanism(s) whereby this occurs we have perfused the vasculature of rat isolated small intestines with a gelatin-containing physiological salt solution. Inclusion of N-nitro-L-argintne methyl ester (L-NAME, 100 muM) or indomethacin (1 muM) in the perfusate increased leakage of injected colloidal carbon into microvessel walls. Pre-treatment with sodium nitroprusside (10 muM) significantly reduced the effects of both L-NAME and indomethacin, whereas carbacyclin (1 muM) only reduced the effects of indomethacin. PD151242 (1 muM) showed some antagonism towards the effects of L-NAME, but nordihydroguaiaretic acid (3 muM) was inactive. Pre-tment with cyproheptadine (10 muM) reduced the effects of both L-NAME and indomethacin, and also significantly reduced background (control) colloidal carbon leakage. Small intestines from polymixin B-treated rats showed significantly reduced colloidal carbon leakage in response to L-NAME. This suggests that the leakage-enhancing effects of both L-NAME and indomethacin in this preparation may be mediated by mast cell-derived amines.


Real-time forecasting of COVID-19 spread according to protective behavior and vaccination: autoregressive integrated moving average models.
Mathematical and statistical models are used to predict trends in epidemic spread and determine the effectiveness of control measures. Automatic regressive integrated moving average (ARIMA) models are used for time-series forecasting, but only few models of the 2019 coronavirus disease (COVID-19) pandemic have incorporated protective behaviors or vaccination, known to be effective for pandemic control. To improve the accuracy of prediction, we applied newly developed ARIMA models with predictors (mask wearing, avoiding going out, and vaccination) to forecast weekly COVID-19 case growth rates in Canada, France, Italy, and Israel between January 2021 and March 2022. The open-source data was sourced from the YouGov survey and Our World in Data. Prediction performance was evaluated using the root mean square error (RMSE) and the corrected Akaike information criterion (AICc). A model with mask wearing and vaccination variables performed best for the pandemic period in which the Alpha and Delta viral variants were predominant (before November 2021). A model using only past case growth rates as autoregressive predictors performed best for the Omicron period (after December 2021). The models suggested that protective behaviors and vaccination are associated with the reduction of COVID-19 case growth rates, with booster vaccine coverage playing a particularly vital role during the Omicron period. For example, each unit increase in mask wearing and avoiding going out significantly reduced the case growth rate during the Alpha/Delta period in Canada (-0.81 and -0.54, respectively; both p < 0.05). In the Omicron period, each unit increase in the number of booster doses resulted in a significant reduction of the case growth rate in Canada (-0.03), Israel (-0.12), Italy (-0.02), and France (-0.03); all p < 0.05. The key findings of this study are incorporating behavior and vaccination as predictors led to accurate predictions and highlighted their significant role in controlling the pandemic. These models are easily interpretable and can be embedded in a "real-time" schedule with weekly data updates. They can support timely decision making about policies to control dynamically changing epidemics.


Whole-exome sequencing identified a novel homozygous ASPH frameshift variant causing Traboulsi syndrome in a Chinese family.
Traboulsi syndrome is a rare disorder characterized by ectopia lentis and facial dysmorphism (large beaked nose), which was only reported in 18 individuals to date. It is caused by homozygous/compound heterozygous variants in the aspartate/asparagine-β-hydroxylase (ASPH) gene, which hydroxylates the aspartic acid and asparagine in epidermal growth factor-like domains of various proteins. Whole-exome and Sanger sequencing were used to identify the disease-causing gene of the patient in a consanguineous Chinese family. Domain analysis was applied to predict the impact of the variant on ASPH protein. Through exome and Sanger sequencing, we identified a novel homozygous ASPH variant (NM_004318.4:c.1910del/NP_004309.2: p.(Asn637MetfsTer15)) in the patient, which may lead to blockage of the ASPH function through truncating the AspH oxygenase domain of the ASPH protein and/or nonsense-mediated decay of the ASPH transcript. This is the first report of Traboulsi syndrome in a Chinese patient who was combined with ventricular septal defect, lung bullae, and recurrent spontaneous pneumothorax. Our results revealed the clinical characteristics of the first Chinese patient with Traboulsi syndrome. Additionally, our study expands the mutational spectrum of Traboulsi syndrome and provides information for clinical genetic counseling to this family.


Maternal contact differentially modulates central and peripheral oxytocin in rat pups during a brief regime of mother-pup interaction that induces a filial huddling preference.
Central oxytocin mediates the acquisition of a filial preference for maternal odour in rat pups, manifested by their huddling preferences. The present study was designed to examine whether maternal care modulates oxytocin concentrations in rat pups and, if so, how different types of maternal contact are associated with the pups' oxytocin concentrations. Pairs of 14-day-old littermates were removed from their home cage for 1 h and then placed with a lactating foster mother for 2 h, or they remained isolated at room temperature. Enzyme immunoassays revealed that maternal care and maternal separation can differentially modulate pups' oxytocin concentrations. Both hypothalamic and serum oxytocin increased during the 1-h separation. Pups placed with a foster mother after the separation maintained the same concentrations in the hypothalamus and serum through the fostering period. By contrast, pups placed with no mother showed a further increase in hypothalamic oxytocin but serum oxytocin decreased. Behavioural analyses revealed that skin-to-skin contact with the mother, but not simple physical contact or maternal licking/grooming, was positively correlated with the pups' hypothalamic oxytocin concentrations. These neuroendocrine data match previous findings showing that skin-to-skin contact with mother facilitates the acquisition of the pups' huddling preference for a maternally-associated odour. Taken together, the present study suggests that maternal skin-to-skin contact stimulates pups' central oxytocin, at the same time as creating the conditions for inducing a preference for maternal odour and establishing a social affiliation in rat pups; the natural schedule of maternal separation and reunion may modulate pups' oxytocin concentrations, providing scaffolding for the acquisition of their filial huddling preference.


Hypothalamic-pituitary-adrenal axis dysfunction in non-clinical psychosis.
While studies have examined psychosocial stress in non-clinical psychosis (NCP), it is unclear if the elevated cortisol seen in schizophrenia also occurs in this group. Cortisol was sampled in High- and Low-NCP groups, and findings of elevated resting cortisol in the former suggest that hypothalamic-pituitary-adrenal-axis dysfunction underlies a psychosis continuum.


Case report 808: Avulsion fracture of the greater trochanter.
The differential diagnosis of unexplained hip pain after trauma in patients with normal radiographs includes both soft tissue and bony abnormalities. We have presented a case of an isolated fracture of the greater trochanter in an adult with normal radiographs where the diagnosis was made by MRI.


BDNF levels are increased by aminoindan and rasagiline in a double lesion model of Parkinson׳s disease.
The anti-Parkinsonian drug rasagiline is a selective, irreversible inhibitor of monoamine oxidase and is used in the treatment of Parkinson׳s disease (PD). Its postulated neuroprotective effects may be attributed to MAO inhibition, or to its propargylamine moiety. The major metabolite of rasagiline, aminoindan, has shown promising neuroprotective properties in vitro but there is a paucity of studies investigating in vivo effects of this compound. Therefore, we examined neuroprotective effects of rasagiline and its metabolite aminoindan in a double lesion model of PD. Male Fisher 344 rats received i.p. injections of the noradrenergic neurotoxin DSP-4 and intra-striatal stereotaxic microinjections of the dopamine neurotoxin 6-OHDA. Saline, rasagiline or aminoindan (3mg/kg/day s.c.) were delivered via Alzet minipumps for 4 weeks. Rats were then tested for spontaneous locomotion and a novel object recognition task. Following behavioral testing, brain tissue was processed for ELISA measurements of growth factors and immunohistochemistry. Double-lesioned rats treated with rasagiline or aminoindan had reduced behavioral deficits, both in motor and cognitive tasks compared to saline-treated double-lesioned rats. BDNF levels were significantly increased in the hippocampus and striatum of the rasagiline- and aminoindan-lesioned groups compared to the saline-treated lesioned group. Double-lesioned rats treated with rasagiline or aminoindan exhibited a sparing in the mitochondrial marker Hsp60, suggesting mitochondrial involvement in neuroprotection. Tyrosine hydroxylase (TH) immunohistochemistry revealed a sparing of TH-immunoreactive terminals in double-lesioned rats treated with rasagiline or aminoindan in the striatum, hippocampus, and substantia nigra. These data provide evidence of neuroprotection by aminoindan and rasagiline via their ability to enhance BDNF levels.


Dietary fucoidan from a brown marine algae (Ecklonia cava) attenuates lipid accumulation in differentiated 3T3-L1 cells and alleviates high-fat diet-induced obesity in mice.
Fucoidan from marine algae is used as a functional ingredient in the food. Here, we purified fucoidan fractions from a crude polysaccharide obtained after the crude polysaccharide of celluclast-assisted hydrolysate from Ecklonia cava (ECC). We evaluated the effect of ECC on lipid accumulation in differentiated 3T3-L1 adipocytes and investigated its anti-obesity effects in vivo in high-fat diet (HFD)-induced obese mice. In vitro Oil Red O staining revealed that treatment with ECC and its purified fucoidan fractions of celluclast assisted hydrolysate from Ecklonia cava (ECFs) remarkably reduced lipid accumulation in 3T3-L1 cells. ECF3 contained the highest contents of polysaccharides and sulfate compared with other fucoidan fractions. ECF3 treatment significantly reduced lipid accumulation in 3T3-L1 cells. Oral administration of ECC significantly reduced body weight, body weight gain, serum lipid content, and total white adipose tissue mass. Histological analysis revealed that ECC reduced lipid accumulation in EAT and liver tissues. Our findings suggest that the anti-obesity effects of ECC are associated with suppressing lipid accumulation in white adipose tissues and increased energy expenditure by upregulating the expression of thermogenic UCP1 and UCP3 in BAT. These results indicate that ECC and its ECFs possess anti-obesity properties and can be used in food and nutraceutical industries.


MMN to natural Arabic CV syllables: 2 - cross language study.
Mismatch negativity response parameters; latency, amplitude, and duration - to natural Arabic and natural English CV syllables - were obtained from normal-hearing adult Egyptians, in two experiments. In the first experiment, MMN was obtained in response to English CV syllable paradigms (Ba-Wa) and (Ga-Da) differing in formant duration and start of third formant, respectively. In the second experiment, MMN response for Arabic paradigm (Baa-Waa), English paradigm (Ba-Wa), and for Arabic-English paradigm (Waa-Wa) was obtained. Results revealed that the three levels of speech representation; acoustic, phonetic and phonologic could be probed preattentatively by MMN. The acoustic properties of speech signal are processed earlier than the phonetic and phonologic properties.


The efficacy and safety of mirabegron for adult and child patients with neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.
We aimed to investigate the effectiveness and safety of mirabegron for adult and child patients with neurogenic lower urinary tract dysfunction (NLUTD). A comprehensive search for articles about mirabegron treatment of NLUTD patients was conducted in PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov databases. Retrospective studies and randomized-controlled studies were included if they met the inclusion criteria and were evaluated by different quality evaluation methods according to study types. Mean difference (MD) and 95% confidence intervals (CIs) were calculated using fixed-effects models or random models depending on heterogeneity. Clinical and urodynamic parameters were pooled to evaluate the efficacy, and safety was measured by adverse events rate. A total of 10 studies with 314 participants were finally included. Four retrospective and six prospective studies containing two randomized-control trials met the inclusion criteria with moderate and high evidence levels. Compared to the baseline date, the pooled results suggested that patients who underwent mirabegron treatment presented less urinary frequency (MD = -0.70; 95% CI: -1.08 to -0.32; p < 0.01) and less incontinence (MD = -1.62; 95% CI: -2.20 to -1.03; p < 0.01), showed conspicuous improvements in adult and child patients' urodynamic parameters, while the incidence of adverse events (10.0% on average, 0%-31.25%) also demonstrated the safety of mirabegron. Mirabegron can significantly improve urodynamic parameters and quality of life in adult and child patients with NLUTD, and increase patient compliance with a smaller complication rate.


Influence of 4'-6'-diamidino-2-phenylindole on the secondary structure and template activities of DNA and polydeoxynucleotides.
The interaction between 4'-6-Diamidino-2-Phenylindole-hydrochloride (DAPI) and a variety of DNAs and synthetic polydeoxynucleotides was investigated in order to delineate the nucleic acid structural features necessary for binding. The spectra of DAPI-DNA complexes, measured at various DAPI:DNA molar ratios (r), are hypochromic relative to DNA in the region of its maximum absorption. All the curves pass through an isosbestic point at 268 nm. A new maxima appears in the region of 380-392 nm for DAPI-DNA COMplexes. The magnitude of the peaks in the region are directly proportional to the amount of drug present in the complex. Studies with various DNA types and synthetic polydeoxynucleotides indicate that the drug preferentially binds to dAT-rich regions of DNA. This was also confirmed by enzymatic studies. The inhibition of template action by DAPI in a purified DNA-polymerase reaction was dependent on the dAT-content of the template. The implication of these data to explain a selective binding of DAPI to mitochondrial DNA have been discussed.


Elevated serum levels of soluble vascular cell adhesion molecule-1 in NIDDM patients with proliferative diabetic retinopathy.
We studied 68 Japanese NIDDM patients (38 men and 30 women), aged 56.9+/-1.2 years (range 33-75 years), with a BMI of 23.1+/-0.5 kg/m2 without hypertension, dyslipidemia, and diabetic macroangiopathy for evaluating the relationship between serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and the severity of diabetic retinopathy. Fundus examination was performed by an ophthalmologist using an ophthalmoscope, and the findings were graded as: (1) no signs of diabetic retinopathy (NDR), (2) background diabetic retinopathy (BDR), or (3) proliferative diabetic retinopathy (PDR). Serum sVCAM-1 levels were measured in duplicate by enzyme-linked immunosorbent assay using the soluble VCAM-1 KIT (R&D Systems Ltd., Ablingdon, Oxfordshire, UK). There was no difference in serum sVCAM-1 levels between patients with BDR (n = 17) and patients with NDR (n = 40) (1035.3+/-104.4 and 978.8+/-48.9 ng/ml, respectively, P = 0.8), but patients with PDR (n = 11) showed a significant increase of serum sVCAM-1 levels compared with patients with NDR (1281.8+/-166.3 and 978.8+/-48.9 ng/ml, respectively, P = 0.02). Although serum sVCAM-1 levels were correlated, not only with age but also with the known diabetic duration (r = 0.39, P = 0.001, and r = 0.40, P = 0.0007, respectively), age-adjusted sVCAM-1 levels were still significantly higher in the PDR group than in the NDR group. In contrast. serum sVCAM-1 levels were not related to the presence of diabetic nephropathy or HbA1c levels. Our results suggest that sVCAM-1 might be implicated in the development of the diabetic retinopathy, and measurement of serum sVCAM-1 levels in NIDDM patients maybe clinically useful for assessing the severity and possibly the activity of diabetic retinopathy.


Gingipain adhesin domains mediate Porphyromonas gingivalis adherence to epithelial cells.
Porphyromonas gingivalis, a Gram-negative oral anaerobe, interacts with epithelium lining the gingival sulcus. Continuing our studies on the role of gingipain cysteine proteinases in P. gingivalis adherence to epithelial cells, we showed that antibody raised to the recombinant adhesin domain of arg-gingipain A blocked bacterial attachment, providing new additional evidence that P. gingivalis adherence to epithelial cells is mediated by gingipain adhesin peptides.


Simulation technology for resuscitation training: a systematic review and meta-analysis.
To summarize current available data on simulation-based training in resuscitation for health care professionals. MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Web of Science, Scopus and reference lists of published reviews. Published studies of any language or date that enrolled health professions' learners to investigate the use of technology-enhanced simulation to teach resuscitation in comparison with no intervention or alternative training. Data were abstracted in duplicate. We identified themes examining different approaches to curriculum design. We pooled results using random effects meta-analysis. 182 studies were identified involving 16,636 participants. Overall, simulation-based training of resuscitation skills, in comparison to no intervention, appears effective regardless of assessed outcome, level of learner, study design, or specific task trained. In comparison to no intervention, simulation training improved outcomes of knowledge (Hedges' g) 1.05 (95% confidence interval, 0.81-1.29), process skill 1.13 (0.99-1.27), product skill 1.92 (1.26-2.60), time skill 1.77 (1.13-2.42) and patient outcomes 0.26 (0.047-0.48). In comparison with non-simulation intervention, learner satisfaction 0.79 (0.27-1.31) and process skill 0.35 (0.12-0.59) outcomes favored simulation. Studies investigating how to optimize simulation training found higher process skill outcomes in courses employing "booster" practice 0.13 (0.03-0.22), team/group dynamics 0.51 (0.06-0.97), distraction 1.76 (1.02-2.50) and integrated feedback 0.49 (0.17-0.80) compared to courses without these features. Most analyses reflected high between-study inconsistency (I(2) values >50%). Simulation-based training for resuscitation is highly effective. Design features of "booster" practice, team/group dynamics, distraction and integrated feedback improve effectiveness.


Acoustic and electrical pattern analysis of consonant perceptual cues used by cochlear implant users.
It is hypothesized that for postlingually deafened adult cochlear implant (CI) users, a significant source of their perceptual performance variability is attributable to differences in their ability to discriminate the basic perceptual cues that are important in speech recognition. Previous research on 'electric hearing' has identified consistent perceptual cues for vowel recognition. However, the results on consonant perception by CI users are less clear. The primary purpose of this study is to present a quantitative method of evaluating potential 'electric cues' used by CI users in consonant identification. Since the actual input signals to the auditory periphery of CI users are electric in nature, we elected to measure the CI electric discharge patterns in addition to the original acoustic waveforms. The characteristics of the electric discharge patterns in response to intervocalic consonants were quantified and correlated with the dimensions of CI patients' perceptual spaces, which were computed from multidimensional scaling analyses of their consonant confusion matrices. The results agree with most, but not all, commonly accepted acoustic cues used by normal-hearing listeners. The correlation findings also suggest that CI users employ different sets of 'electric cues' in perceiving consonants that differ in their manner of articulation. Specifically, spectral and temporal cues associated with slowly changing formant structures and transitions, and features associated with frication and high-frequency noise, are all highly correlated with the perceptual dimensions of all CI users. However, rapidly changing formant transitions, such as those present in stop consonants, did not appear to play a significant role in consonant recognition by more poorly performing CI subjects. The perceptual results were consistent with our physical findings that the SPEAK coding strategy partially degraded the rapidly changing formant transitions.


Conditional Survival in Prostate Cancer in the Nordic Countries Elucidates the Timing of Improvements.
The incidence of prostate cancer (PC) increased vastly as a result of prostate-specific antigen (PSA) testing. Survival in PC improved in the PSA-testing era, but changes in clinical presentation have hampered the interpretation of the underlying causes. We analyzed survival trends in PC using data from the NORDCAN database for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) by analyzing 1-, 5- and 10-year relative survival and conditional relative survival over the course of 50 years (1971-2020). In the pre-PSA era, survival improved in FI and SE and improved marginally in NO but not in DK. PSA testing began toward the end of the 1980s; 5-year survival increased by approximately 30%, and 10-year survival improved even more. Conditional survival from years 6 to 10 (5 years) was better than conditional survival from years 2 to 5 (4 years), but by 2010, this difference disappeared in countries other than DK. Survival in the first year after diagnosis approached 100%; by year 5, it was 95%; and by year 10, it was 90% in the best countries, NO and SE. In spite of advances in diagnostics and treatment, further attention is required to improve PC survival.


Core protein: A pleiotropic keystone in the HBV lifecycle.
Hepatitis B Virus (HBV) is a small virus whose genome has only four open reading frames. We argue that the simplicity of the virion correlates with a complexity of functions for viral proteins. We focus on the HBV core protein (Cp), a small (183 residue) protein that self-assembles to form the viral capsid. However, its functions are a little more complicated than that. In an infected cell Cp modulates almost every step of the viral lifecycle. Cp is bound to nuclear viral DNA and affects its epigenetics. Cp correlates with RNA specificity. Cp assembles specifically on a reverse transcriptase-viral RNA complex or, apparently, nothing at all. Indeed Cp has been one of the model systems for investigation of virus self-assembly. Cp participates in regulation of reverse transcription. Cp signals completion of reverse transcription to support virus secretion. Cp carries both nuclear localization signals and HBV surface antigen (HBsAg) binding sites; both of these functions appear to be regulated by contents of the capsid. Cp can be targeted by antivirals - while self-assembly is the most accessible of Cp activities, we argue that it makes sense to engage the broader spectrum of Cp function. This article forms part of a symposium in Antiviral Research on "From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B: an unfinished story."


Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in vitro.
Phenotypic screening of high quality compound library is one of the most effective strategy to obtain novel bioactive compounds. Recently, our group have constructed a Wogonin-scaffold library with substituents diversity and successfully obtained a series of potent compounds. Herein, we reported the synthesis of these compounds and evaluated the in vitro antitumor activity against a panel of human tumor cell lines. Most of them showed good activity with a broad spectrum and preliminary structure-activity relationship for the substitutions were obtained. Further biological assays showed that the most potent compounds 18n and 20b could significantly enhance the intracellular ROS level and induce the cell apoptosis at low micromole level. Through similarity searching, CDK9 was identified as the potential target for 20b, which could be a start point for next structure-based drug design.


A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus.
An S678P substitution in Fks1p, the major subunit of glucan synthase, was sufficient to confer echinocandin resistance in Aspergillus fumigatus. The equivalent mutation in Candida spp. has been implicated in echinocandin resistance. This work demonstrates that modification of Fks1p is a conserved mechanism for echinocandin resistance in pathogenic fungi.


Potential cerebrovascular accident signal for risankizumab: A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS).
The interleukin-23 (IL-23) inhibitor risankizumab was recently approved for the treatment of moderate-to-severe plaque psoriasis in the United States. Low rates of cerebrovascular accident (CVA) were observed in risankizumab-treated patients during clinical trials. The aim of this study was to determine whether risankizumab may be associated with CVA in a real-world setting. A retrospective disproportionality analysis was conducted utilizing postmarketing adverse event reports submitted to the US Food and Drug Administration Adverse Event Reporting System (FAERS) through the fourth quarter of 2021. A custom query consisting of 22 CVA-related Medical Dictionary for Regulatory Activities (MedDRA) preferred terms previously reported in clinical trials of plaque psoriasis medications was used to identify cases. Disproportionality was measured by calculating reporting odds ratios (ROR) and 95% confidence intervals (CI), whereby the lower limit of a 95% CI >1.0 and ≥ three cases was considered a signal. Risankizumab was associated with significantly disproportionate CVA reporting compared to all other drugs in FAERS (ROR 2.48; 95% CI 2.14-2.88) as well as 11 alternative plaque psoriasis therapeutics across five pharmacologic classes. The largest disproportionality signals for risankizumab were identified relative to apremilast (ROR 9.07; 95% CI 7.56-10.89), ixekizumab (ROR 6.75; 95% CI 5.14-8.86), guselkumab (ROR 6.74; 95% CI 4.68-9.71), certolizumab (ROR 5.70; 95% CI 4.74-6.85) and etanercept (ROR 4.91; 95% CI 4.21-5.73). This study detected a previously unreported signal of disproportionate CVA reporting with the real-world use of risankizumab. Further long-term observational data will be necessary to better characterize this unconfirmed potential safety signal.


Flagellin domain that affects H antigenicity of Escherichia coli K-12.
Escherichia coli K-12 mutants with altered flagellum antigenicity were isolated by introducing random deletions into the flagellin gene. The deletions were identified in the central region of the gene. It is suggested that this region corresponds to the flagellin domain molecule which affects flagellum antigenicity.


Isolation and characterization of an antifreeze protein from the longhorn sculpin, Myoxocephalus octodecimspinosis.
A new type of antifreeze protein was isolated from the serum of the longhorn sculpin, Myoxocephalus octodecimspinosis, by gel filtration and high-performance liquid chromatography. This protein (LS-12) exhibits freezing point depression activity (thermal hysteresis) and ice crystal modification properties similar to those seen for other types of fish antifreeze polypeptide, except that ice crystals grow as hexagonal trapezohedra in the presence of LS-12, rather than hexagonal bipyramids usually seen. Ice crystal etching studies demonstrate that LS-12 does not bind to the hexagonal bipyramidal or secondary prism surfaces reported for the antifreeze polypeptides from winter flounder and shorthorn sculpin, respectively. Circular dichroism studies indicate that LS-12 has an alpha-helix content of about 60% at 1 degreesC, which is in good agreement with a value of about 70% predicted from the amino acid sequence. Limited proteolysis studies and further analysis of the amino acid sequence suggest that LS-12 consists of four amphipathic alpha-helices of similar length which are folded into a four-helix bundle. Based on its size (Mr=12299) and predicted tertiary structure, LS-12 can be regarded as the first example of a new class (type IV) of fish antifreeze protein.


Neuronal birth and death.
Neurogenesis and cell death occur predominantly during the postnatal period in the dentate gyrus of the rat. Recent studies have shown that mitosis and apoptosis in this system are regulated by adrenal steroids, possibly through excitatory amino acids. Studies performed in other systems have identified genes that mediate cell birth and death, which may also participate in the development and maintenance of the dentate gyrus.


Clinical evaluation of a chlorhexidine intravascular catheter gel dressing on short-term central venous catheters.
A major source of microbial colonization of short-term central venous catheters (CVC) is the patients' endogenous skin microorganisms located at the CVC insertion site. The aim of this study was to determine if a transparent film dressing incorporating a 2% (weight/weight) chlorhexidine gluconate (CHG) gel decreases CVC and insertion site microbial colonization compared with a nonantimicrobial dressing in adult patients in critical care. On CVC removal, samples for microbiological investigation were taken from both the skin surrounding the CVC insertion site and also from sutures securing the CVC. The sutures and intradermal and tip sections of the CVC were also collected for microbiological investigation. Microorganisms recovered from the samples were subsequently tested for susceptibility to CHG. There was a significant reduction in the number of microorganisms recovered from the CVC insertion site, suture site, sutures, and catheter surface in the CHG dressing group (n = 136) compared with the nonantimicrobial dressing group (n = 137). There was no significant difference in susceptibility to CHG between the microorganisms isolated from the CHG and standard dressing study patients. A film dressing incorporating a CHG gel pad significantly reduced the number of microorganisms at the CVC insertion and suture sites with concomitant reduced catheter colonization.


Winter ecology of nonmigratory Alpine red deer.
In winter, red deer (Cervus elaphus hippelaphus) that are not receiving supplementary feeding emphasize and rely on energy-saving strategies. In severe winters with deep snow, they select a home-range habitat-windblown alpine pastures above the timberline-that meets the requirements of this strategy: a much lower sinking depth and good forage availability are due to patchy snow distribution, while the open area provides higher radiation, permits group formation and thus sociobiological wellbeing. The energy costs of thermoregulation are minimized by selecting slopes with south to south-west exposures, seeking thermal shelter from strong winds, while high flight distances and horizontal flight routes reduce the energy costs of fleeing. In years with little winter snowfall non-supplemented red deer prefer the greater security of forested habitats in lower areas and obtain higher food intake from slightly more nutritious meadows in the valley bottom. The food-supplemented herd has much more constant and predictable habitat use, combining an energy-saving strategy-choosing alpine pastures as low-cost winter home range-with high energy income at the feeding station.


Hematological alterations can often be observed during rheumatic diseases. The effects can be clinically severe, ranging from anemia of different grades of severity, through increased risk of hemorrhage due to thrombocytopenia up to severe infections as a result of high-grade leukocytopenia. The clinical sequelae for patients are predominantly determined by the extent of cytopenia. The underlying disease itself can initially be considered as the cause. Examples are anemia as a result of chronic inflammation, antibody-mediated thrombocytopenia as in systemic lupus erythematosus (SLE) or granulocytopenia within the framework of Felty's syndrome. Immunosuppressive treatment also often leads to alterations in the blood constituents. Although some substances, such as cyclophosphamide can suppress all three cell types, there are also selective effects, such as isolated thrombocytopenia under treatment with tocilizumab and JAK inhibitors. The differential diagnostic clarification of cytopenia can be difficult and necessitates a systematic work-up of the course of the disease and the subsequent treatment. The reviews of anemia, leukocytopenia and thrombocytopenia presented here summarize the most important components of the differentiation of hematological alterations in patients with rheumatic diseases.


Prognostic significance of the skeletal muscle index and an inflammation biomarker in patients with breast cancer who underwent postoperative adjuvant radiotherapy.
Given the growing evidence that sarcopenia and inflammation influence the survival of patients with cancer, we evaluated the prognostic significance of the skeletal muscle index (SMI) combined with an inflammation marker in patients with breast cancer who underwent postoperative adjuvant radiotherapy. We conducted a retrospective analysis of 301 patients with breast cancer who received postoperative adjuvant radiotherapy between 2010 and 2012. The SMI was measured using preradiotherapy computed tomography (CT) simulation images at the level of the fourth thoracic vertebra (T4). Receiver operating characteristic curve analyses were used to determine the optimal cutoff values for the SMI and inflammatory marker. Patients were divided into 2 groups (high SMI and low SMI), based on the SMI cutoff of 10.57 cm2/m2. Patients in the high-SMI group had a median overall survival (OS) of 62.4 months, which was significantly shorter than those in the low-SMI group, with a median OS of 68.5 months (P = 0.025). Patients in the high-SMI group had a median recurrence-free survival (RFS) of 62.3 months, which was shorter but not significantly than the median RFS of 65.2 months of the low-SMI group (P = 0.159). Univariate and multivariate survival analyses revealed SMI was an independent predictor of OS (P = 0.044). The SMI-MLR combination was found to be an independent predictor of OS (P = 0.006) and RFS (P = 0.009). The current findings support the SMI as a promising indicator for predicting clinical outcomes in patients with breast cancer receiving postoperative adjuvant radiotherapy. A high SMI accompanied by systemic inflammation was significantly associated with reduced OS and RFS.


Genome-wide identification and expression of SAUR gene family in peanut (Arachis hypogaea L.) and functional identification of AhSAUR3 in drought tolerance.
Small auxin-upregulated RNAs (SAURs) gene family plays important roles in plant growth, development, and stress responses. However, the function of few SAUR genes is known in the peanut (Arachis hypogaea L.), one of the world's major food legume crops. This study aimed to perform a comprehensive identification of the SAUR gene family from the peanut genome. The genome-wide analysis revealed that a total of 162 SAUR genes were identified in the peanut genome. The phylogenetic analysis indicated that the SAUR proteins were classified into eight subfamilies. The SAUR gene family experienced a remarkable expansion after tetraploidization, which contributed to the tandem duplication events first occurring in subgenome A and then segmental duplication events occurring between A and B subgenomes. The expression profiles based on transcriptomic data showed that SAUR genes were dominantly expressed in the leaves, pistils, perianth, and peg tips, and were widely involved in tolerance against abiotic stresses. A total of 18 AhSAUR genes selected from different subfamilies randomly presented 4 major expression patterns according to their expression characteristics in response to indole-3-acetic acid. The members from the same subfamily showed a similar expression pattern. Furthermore, the functional analysis revealed that AhSAUR3 played a negative role in response to drought tolerance. This study provided insights into the evolution and function of the SAUR gene family and may serve as a resource for further functional research on AhSAUR genes.


Single spin asymmetries in charged pion production from semi-inclusive deep inelastic scattering on a transversely polarized 3He Target at Q2 = 1.4-2.7 GeV2.
We report the first measurement of target single spin asymmetries in the semi-inclusive (3)He(e,e'π(±))X reaction on a transversely polarized target. The experiment, conducted at Jefferson Lab using a 5.9 GeV electron beam, covers a range of 0.16 < x < 0.35 with 1.4 < Q(2) < 2.7 GeV(2). The Collins and Sivers moments were extracted from the azimuthal angular dependence of the measured asymmetries. The π(±) Collins moments for (3)He are consistent with zero, except for the π(+) moment at x = 0.35, which deviates from zero by 2.3σ. While the π(-) Sivers moments are consistent with zero, the π(+) Sivers moments favor negative values. The neutron results were extracted using the nucleon effective polarization and measured cross section ratios of proton to (3)He, and are largely consistent with the predictions of phenomenological fits and quark model calculations.