Prenatal alcohol exposure and cognition at midlife: Evidence of fluid cognition deficits in two cohorts.
Prenatal alcohol exposure (PAE) impacts cognition in childhood and early adulthood. Here we evaluate the cognitive abilities of middle-aged adults with and without a history of PAE. Participants (N = 200) were recruited from longitudinal cohorts in the Atlanta and Seattle metropolitan areas and completed measures comprising the National Institutes of Health Toolbox's Fluid Cognition Composite. We found that individuals with PAE had lower Fluid Cognition Summary scores and lower Dimensional Change Card Sort and Flanker task subtest scores than non-PAE controls, after accounting for both potentially confounding demographic variables using propensity scores and the effects of study site. When we evaluated the effects of PAE with and without dysmorphic physical features, we found that middle-aged adults in both groups had lower fluid cognition scores than non-PAE controls. However, only the presence of PAE with dysmorphic features was associated with lower performance on the Dimensional Change Card Sort Test and Flanker tasks. While all participants with PAE had lower fluid cognition, those with PAE and dysmorphic features also exhibited specific deficits in their performance on measures of inhibition, attention, and cognitive flexibility. Thus, PAE is associated with ongoing cognitive deficits in middle adulthood, which can be observed most clearly among individuals with dysmorphic features.


Progressive development of pulmonary hypertension leading to right ventricular hypertrophy assessed by echocardiography in rats.
The present study aimed to evaluate the development of pulmonary hypertension by serial echocardiography, including measurements of pulmonary artery (PA) flow velocities, and correlate echocardiographic indices with pathological findings in rats administered monocrotaline (MCT). MCT (60 mg/kg body weight) or physiologic saline was administered to a total of 9 male Wistar rats at the age of 4 weeks (MCT group: n = 4, control group: n = 5, respectively). Echocardiography was performed serially until the age of 8 weeks. The ratio of right ventricular (RV) outflow tract dimensions to aortic dimensions increased progressively in the MCT group and became significantly greater than that of the control group after the age of 6 weeks. Peak PA velocity (Peak V) in the MCT group was significantly less than that of the control group at the ages of 7 and 8 weeks. The ratio of acceleration time to ejection time (AT/ET) in PA flow waveforms declined progressively and was significantly less than that of the control group after the age of 6 weeks. The ratio of RV weight to body weight (RVW/BW) in the MCT group was significantly greater than that of the control group. Both AT/ET ratio and Peak V were significantly inversely correlated with RVW/BW ratio. Furthermore, these echocardiographic findings were also significantly inversely correlated with the mean cross-sectional RV myocyte area. In conclusion, the progressive development of pulmonary hypertension leading to RV hypertrophy can be evaluated appropriately by echocardiography including PA flow Doppler indices in rats.


Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters.
More than 90% of all intravascular device-related septicaemias are due to central venous or arterial catheters. To assess the efficacy of cutaneous antisepsis to prevent catheter-associated infection, we prospectively studied three antiseptics for disinfection of patients' central venous and arterial catheter insertion sites in a surgical intensive care unit. 668 catheters were randomised to 10% povidone-iodine, 70% alcohol, or 2% aqueous chlorhexidine disinfection of the site before insertion and for site care every other day thereafter. Chlorhexidine was associated with the lowest incidence of local catheter-related infection (2.3 per 100 catheters vs 7.1 and 9.3 for alcohol and povidone-iodine, respectively, p = 0.02) and catheter-related bacteraemia (0.5 vs 2.3 and 2.6). Of the 14 infusion-related bacteraemias (4 due to contaminated infusate or catheter hub, 10 due to infected catheters), 1 was in the chlorhexidine group and 13 were in the other two groups (odds ratio 0.16, p = 0.04). We conclude that use of 2% chlorhexidine, rather than 10% povidone-iodine or 70% alcohol, for cutaneous disinfection before insertion of an intravascular device and for post-insertion site care can substantially reduce the incidence of device-related infection.


Clinical features of febrile seizures in children with COVID-19: an observational study from a tertiary care hospital in China.
Febrile seizures are a common neurologic manifestation in children with coronavirus disease 2019 (COVID-19). Compared to seasonal respiratory viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a pronounced neurological impact, with the result that febrile seizures with COVID-19 may exhibit unique clinical features. We conducted a retrospective study in a tertiary care hospital in China. We collected medical record information on febrile seizures with COVID-19, including demographic characteristics, clinical features, laboratory tests, and disease burden. Subsequently, the data were then analyzed descriptively. A total of 103 children diagnosed with febrile seizures and positive COVID-19 PCR results were included in our study. Among them, 81 (78.6%) were males and 22 (21.4%) were females. The age of onset of febrile seizures ranged from 14 to 57 months, with a mean age of 34.9 ± 6.24 months. Complex febrile seizures were observed in 34 (33%) cases. Antiseizure medications were administered to 24 (23.3%) patients. Laboratory tests showed a white blood cell count of (27.05 ± 8.20) × 103/µl, a neutrophil count of (20.09 ± 5.66) × 103/µl and a lymphocyte count of (6.44 ± 1.86) × 103/µl. A creatine kinase level was significantly elevated, with a mean value of (412.00 ± 158.96) U/L. The mean length of stay was 4.36 days. Twelve patients (11.7%) required intensive care services, but there were no deaths or patients remaining on antiseizure medications after discharge. In the post-epidemic era of COVID-19, pediatric clinicians should be aware of the changing clinical features of febrile seizures associated with COVID-19. The average age of onset has increased, with a higher proportion of males. Length of stay and hospitalization costs did not increase significantly. The prognosis remained favorable, although a small number of children required intensive care services during the acute phase.


Mucous Cell Prosoplasia in Oral Pathologies: A Brief Review.
One of the enigmas in cell differentiation process is prosoplasia, which is contemplated as forward differentiation. A well-known example of prosoplastic switch is mucous cell prosoplasia, which is the transformation of a simple squamous epithelial cell into mucous secreting cell. Numerous theories have been proposed for histogenesis of this phenomenon, which are comprehensively discussed in the present paper. Oral pathologies like odontogenic cysts and salivary gland tumours show mucous prosoplasia quite often; sometimes leading to diagnostic difficulties. In the present paper, efforts have been made to comprehensively discuss diverse aspects of mucous prosoplasia like histogenesis, theories and diagnostic importance in various oral pathologies.


A study on utilization and quality of coverage of antenatal care services at the subcentre level.
A community based cross-sectional study was done by interviewing a sample of 360 women of Anchuri Block in the district of Bankura, West Bengal to know the determinants of utilization and coverage quality of antenatal care services of subcentres using an appropriate scoring system for analysis. The study revealed underutilization of subcentres by the women and also sub-optimal performance of subcentres with regard to coverage quality of ANC services The main reason for under utilization of subcentres was found to be better service provision and easy accessibility of B.S. Medical College Hospital. Multiparous mothers were seen to be at a disadvantage both in terms of utilization of the source of choice as well as in terms of coverage of ANC services by subcentre ANMs.


Correlation of deglutition in subacute ischemic stroke patients with peripheral blood adaptive immunity: Essential amino acid improvement.
We aimed to document in stroke patients peripheral blood immune cell profiles, their relations with neuro-functional tests, and any possible influence of supplemented essential amino acids (EAAs) may have on both the immune system and the relationship of the latter with neuro-function.Forty-two dysphagic stroke patients (27 men; 71±9 years) underwent bio-humoral measurements, neuro-functional tests, including Functional Independence Measure (FIM) and Dysphagia Outcome and Severity Scale (DOSS), and were randomized to receive EAAs 8 g/d (EAA group) or isocaloric maltodextrin (placebo group).At discharge all measurements were repeated 38±1 days after randomization.At admission, total white cell (TWC), neutrophil (N), and lymphocyte (Lymph) counts were normal and the N/Lymph ratio was higher than normal values (<3.0). At discharge, both TWC and N decreased while Lymph increased significantly. As a result, the N/Lymph ratio significantly decreased (P <0.001) returning to normal levels. Absolute Lymph counts and Lymph % TWC correlated positively with DOSS (r = +0.235, P = 0.04 and r = +0.224, P = 0.05, respectively), negatively with C-reactive protein natural logarithm (ln CRP) (P = 0.02 and P = 0.0001, respectively), which is an inflammation marker. N correlated positively with ln CRP (P = 0.001) and had a slight negative association with FIM (P = 0.07). The N/Lymph ratio was inversely related to FIM (r = -0.262, P = 0.02) and DOSS (r = -0.279, P = 0.01). Finally, FIM correlated with DOSS (r = +0.35, P = 0.05).For the regression analysis, the overtime changes of Lymph % TWC correlated significantly with DOSS (P = 0.01). There was a positive correlation between Lymph % TWC and DOSS for the entire stroke population (P = 0.015). While this correlation was not important for the placebo group (P = 0.27), it was significant in the EAA subgroup (P = 0.018).In the sub-acute stroke stage, there may be slight alterations of peripheral blood immune cells. Lymph cells are associated with improved neuro-function tests with evidence that this association is enhanced by supplementing EAAs.


Teaching procedural skills to medical students: A pilot procedural skills lab.
Medical students have limited confidence in performing procedural skills. A pilot study was conducted to evaluate the effect of a multifaceted Procedural Skills Lab (PSL) on the confidence of medical students to perform procedural skills. Twelve 2nd year medical students were randomly selected to participate in a pilot PSL. The PSL students met with an instructor for 2 h once a week for 4 weeks. Students participated in a flipped classroom and spaced education program before laboratory sessions that included a cadaver laboratory. Procedural skills included a focused assessment with sonography in trauma (FAST) scan, cardiac echocardiogram, lumbar puncture, arthrocentesis, and insertion of intraosseous and intravenous catheters. Students in the PSL were asked to rank their confidence in performing procedural skills before and after completion of the laboratory sessions (Wilcoxon ranked-sum test). A web-based questionnaire was also emailed to all 2nd year medical students to establish a baseline frequency for observing, performing, and confidence performing procedural skills (Mann-Whitney U-test). Fifty-nine percent (n = 106) of 180 2nd year medical students (n = 12 PSL students [treatment group], n = 94 [control group]) completed the survey. Frequency of observation, performance, and confidence in performing procedural skills was similar between the control and treatment groups at baseline. There was an increased confidence level (p < 0.001) for performing all procedural skills for the treatment group after completion of the PSL. An innovative PSL may increase students' confidence to perform procedural skills. Future studies will examine competency after a PSL.


Preoperative parameters and their prognostic value in amyotrophic lateral sclerosis patients undergoing implantation of a diaphragm pacing stimulation system.
Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease with devastating and fatal respiratory complications. Diaphragm pacing stimulation (DPS) is a treatment option in diaphragm insufficient ALS patients. Ventilatory insufficiency depending on diaphragmatic failure is treated by the present study aimed to investigate prognostic value of preoperative clinical and functional characteristics of ALS patients undergoing implantation of a DPS system and to determine appropriate indications for the DPS system. The study included 34 ALS patients implanted with DPS system. All patients underwent multidisciplinary and laboratory evaluations before the surgery. The laboratory examinations included pulmonary function tests and arterial blood gas analysis. Survival rates were recorded in a 2-year follow-up after the surgery. Twenty-eight of 34 patients with ALS survived after a 2-year follow-up. These patients were younger than those who died and had the disease for a longer time; however, the differences were not significant. Both right and left hemidiaghragms were thicker in the survived patients (P < 0.0001 for each). Pulmonary function tests revealed no significant differences between the patients who survived. Arterial blood gas analysis demonstrated lower partial pressure of carbon dioxide in the survived patients (P = 0.025). DPS implantation was more efficacious in ALS patients with mild respiratory failure and thicker diaphragm. Predictors of long-term effectiveness of DPS system are needed to be addressed by large-scale studies.


Effects of the COVID-19 pandemic on life expectancy at birth at the global, regional, and national levels: A joinpoint time-series analysis.
Current estimates indicate that coronavirus disease 2019 (COVID-19) caused 14.9 million excess deaths in 2020 and 2021. Thus, estimating the change in life expectancy at birth due to the COVID-19 pandemic could aid in understanding its impact and implementing public health initiatives. We collected data on the life expectancy at birth of the combined population between 1990 and 2021 at the global, regional, and national levels from the 2022 Revision of World Population Prospects. In this time series study, we estimated the trend segments, the change of trend years (joinpoints), the annual percentage change (APC) in life expectancy at birth within each trend segment, and the average APC (AAPC) in life expectancy at birth during the full study period using joinpoint regression analysis. The global life expectancy at birth decreased from 72.8 years in 2019 to 71.0 years in 2021, with an annual decrease of 1.2% (95% confidence interval (CI) = 1.0, 1.5) during the 2019-2021 period, despite an overall increasing trend during the entire period from 1990 to 2021 (AAPC = 0.3%; 95% CI = 0.3, 0.4). We observed a significantly increasing trend in life expectancy at birth in all regions and nearly 87.7% (207/236) of the world's countries and areas during the entire period (1990-2021). All continental regions except Africa and Oceania experienced a significant decreasing trend in life expectancy at birth in 2019-2021, with an APC of -1.2% (95% CI = -1.5, -0.9) for Asia, -2.1% (95% CI = -2.7, -1.6) for Latin America and the Caribbean, -1.1% (95% CI = -1.6, -0.6) for Northern America, and -1.4% (95% CI = -1.9, -0.9) for Europe. Among all countries and areas, 107 countries and areas (45.3%) experienced a significant decreasing trend in life expectancy at birth in the most recent time segment, with 77 countries and areas (32.6%) experiencing a significant decreasing trend during the 2019-2021 period. The world experienced a significant decreasing trend in life expectancy at birth in 2019-2021, with a decrease of 1.8 years; all continental regions except Africa and Oceania and 77 countries and areas experienced a significant decreasing trend in life expectancy at birth. These decreasing trends at global, regional, and national levels during the 2019-2021 period reflected the COVID-19 pandemic's direct and indirect adverse effects on life expectancy at birth.


Prevalence and antimicrobial resistance of Campylobacter species isolated from chicken carcasses during processing in Iran.
The objective of this study was to determine the prevalence and antimicrobial resistance of Campylobacter spp. isolated from chicken carcasses during different stages of broiler processing in a major commercial poultry processing plant in southwestern Iran. Overall, 84 chicken carcasses were sampled from 4 sites along the processing line during a total of 7 visits. In addition, 14 water samples from the chiller tank were taken. Using the cultural method, 186 of 336 (55.4%) carcasses were positive for Campylobacter. Campylobacter jejuni was more frequently isolated (89.4%) than Campylobacter coli (10.6%). The frequency of Campylobacter spp. on carcasses was 54.8% after defeathering, 51.2% after evisceration, 69.0% 20 min after the chilling period started, and 46.4% 24 h after the chilling period completed. Campylobacter was positive in 85.7% of the samples taken from the chilling water. The frequency of Campylobacter spp.-positive carcasses was reduced in complete chilled chickens but not during the slaughtering process. Susceptibilities of Campylobacter isolates were determined for 10 antimicrobial drugs using the disk diffusion method. Of the 198 Campylobacter isolates tested, 92.9% were resistant to one or more antimicrobial agents. Resistance to tetracycline was the most common finding (78.3%), followed by resistance to ciprofloxacin (62.1%), nalidixic acid (58.6%), and enrofloxacin (44.4%).


[Advances in the research of function of Merkel cells in tactile formation of skin].
Skin is the largest sense organ of human, with many mechanoreceptor cells under epidermis or dermis of skin and Merkel cell is one of them. It has been confirmed that Merkel cells play an important role in the process of mechanical transmission of mammalian soft tactile stimulation. Researches showed that Merkel cells had close relation to tactile formation and functioned by Merkel cell-neurite complexes and ion channels Piezo2. This article reviews Merkel cells and the function, problem and prospect of Merkel cells in tactile formation.


Cell interactions at the level of mature antibody producers: the properties of the bone marrow humoral factor stimulating antibody production.
The soluble factor recovered from supernatants of cultures of normal mouse bone marrow cells and previously isolated on Sephadex G-50 (n. w. 13,000 daltons), which stimulates antibody production when given at the peak of immune response, was further characterized in the present study. This stimulant of antibody producers (SAP) is active both in vitro and in vivo on PFC responses, and its effect does not show allogeneic or xenogeneic restriction. Using protein, RNA and DNA synthesis inhibitors, it was found that, in order to abolish the enhancing activity of treated bone marrow cells, protein synthesis must be inhibited by more than 80% and RNA synthesis by 20%, whereas inhibition of DNA synthesis by almost 100% did not interfere with the enhancing activity of treated cells. The stimulating activity of SAP was abolished by both RNase and pronase treatments, but heating at 100 degrees C for 10 min did not affect this activity. These properties indicate that SAP is a ribonucleoprotein complex. It is suggested that SAP mediates the regulatory function of bone marrow cells at the level of mature, differentiated cells of the B series.


[Analysis of the performance of the assessment battery related to psychosocial factors in Colombia].
The goal of this study is to analyze the performance of the three questionnaires and the file of general information that comprise the Set of Instruments for the Assessment of Psychosocial Factors in six companies from different economic sectors in Colombia, with regard to: (a) content of the instruments, (b) application methodology, and (c) the response from workers and employers. This research was performed through the study of multiple instances. It was based on the processing of: (1) the observation logs with regard to the application of the questionnaires, (2) workers' annotations about their questionnaires and (3) minutes of meetings with representatives of the workers. A reclassification into more specific subcategories was done taking into consideration some particular and common elements found between companies. Regarding the "Content" category, there are significant limitations in the questionnaires about both outside and inside-of-work factors. This is because some items cannot be applied under specific working conditions such as outsourcing or field work. In "Methodology" it was observed that some practices could decrease the reliability of the assessments, such as not having adequate schedules or locations. In the "Reception" category, it was found that even though this assessment is deemed desirable by most workers and employers, there are, however, some actions taken by companies that could affect this perception. It is positive to implement the assessment of psychosocial working conditions in companies of this country, even though this assessment, with a universal assessment tool, has difficulties in a changing and increasingly complex working world. It is advisable to complement these assessments with qualitative methods.


PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature.
Primary endometrial squamous cell carcinoma (PESCC) is a rare entity. As the clinicopathologic features and the immunophenotype have not been completely defined yet, here we report our experience and review of the literature on this topic. A 73-yr-old nulliparous woman presented with pelvic pain and vaginal bleeding. Endometrial biopsy showed a carcinoma with squamous differentiation infiltrating the myometrium. Total hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed. Definitive diagnosis was squamous carcinoma of the endometrium, with one lymph node metastasis (stage IIIC1). Immunohistochemistry evidenced immunoreactivity of the tumor cells for cytokeratin 5, p63, cytokeratin 7, PAX8, PTEN, and cyclin D1, aberrant p53 overexpression, and Ki-67 reactivity in ~70% of the tumor cells. Estrogen and progesterone receptor, PAX2, WT1, and p16 were negative. Our case was the first PAX8-positive PESCC in the literature, underlining the Mullerian system origin of this neoplasm. Abnormal p53 expression of this case confirmed its role in the pathogenesis of PESCC. Further studies on a large number of cases are needed to better understand the pathologic features and the immunophenotype of PESCC.


Effect of uncertainty-dependent residential mobility on loss aversion.
The current research aimed to examine the relationship between residential mobility and loss aversion, a ubiquitous decision-making bias conceptualized in prospect theory. Combining correlational, experimental, and electroencephalography approaches, we tested the hypothesis that residential mobility may increase loss aversion. The results revealed a positive correlation between residential mobility and loss aversion (Study 1). These effects were moderated by individuals' residential mobility/stability mindsets. Behaviorally, we observed a positive association between residential mobility history and loss aversion among individuals with a high (vs. low) subjective uncertainty after manipulating their residential mobility mindset by priming them with a mobile or stable lifestyle (Study 2). On the neural level, we found that the mindset of residential mobility (vs. stability) enhanced the differential feedback-related negativity (FRN) modulations between the large-win and large-loss conditions among Chinese participants with a high subjective uncertainty (Study 3). In conclusion, residential mobility elevated loss aversion by enhancing feelings of subjective uncertainty. Our findings provide novel insights into how changes in the socioecological environment shape individuals' decision-making bias.


MicroRNA-145 targets the metalloprotease ADAM17 and is suppressed in renal cell carcinoma patients.
A disintegrin and metalloproteinase 17 (ADAM17) is a metalloprotease that is overexpressed in many cancer types, including renal cancers. However, the regulatory mechanisms of ADAM17 in cancer development and progression are poorly understood. In the present work, we provide evidence using overexpression and inhibition of microRNA 145 (miR-145) that miR-145 negatively regulates ADAM17 expression. Furthermore, we show that ADAM17 negatively regulates miR-145 through tumor necrosis factor-α, resulting in a reciprocal negative feedback loop. In this study, the expression of ADAM17 and miR-145 correlated negatively in renal cancer tumor tissues and cell lines, suggesting an important regulatory mechanism. Additionally, we showed that the regulation of ADAM17 is partly involved in the effects of miR-145 on proliferation and migration, whereas no involvement in chemosensitivity was observed. Importantly, in the healthy kidney, miR-145 was detected in different cell types including tubular cells, which are considered the origin of renal cancer. In renal cancer cell lines, miR-145 expression was strongly suppressed by methylation. In summary, miR-145 is downregulated in renal cancer patients, which leads to the up-regulation of ADAM17 in renal cancer. Importantly, miR-145 and ADAM17 are regulated in a reciprocal negative feedback loop.


Decreasing perinatal mortality: unchanged infantile spasm morbidity.
The present study examined whether changes in the incidence of infantile spasms could be used to evaluate changes in the quality of pre- and perinatal care over time. 107 children in 1960 to 1976, and 102 in 1977 to 1991, developed infantile spasms in southern Finland. The number of small-for-gestational age (SGA) infants and infants with neonatal hypoglycaemia decreased significantly. Brain malformations, malformation syndromes and patients with tuberous sclerosis increased; this probably reflects the development of more refined neuroradiological screening methods. SGA infants are probably more apt to develop infantile spasms than preterm infants appropriate for gestational age. Early prenatal factors seem to play a major role in the genesis of infantile spasms. Little can be done to reduce the incidence of infantile spasms, but every effort should be made to reduce the number of SGA infants by good prenatal care. Treatment of hypoglycaemia is important because infantile spasms might be preventable in these infants.


Response of adrenal cells to parathyroid hormone stimulation.
Dispersed adrenal cells of avian and bovine origin were incubated with human (h) 1-34 parathyroid hormone (PTH(1-34)), bovine (b) PTH(1-84), bPTH(3-34), avian (a) PTH, and with ACTH. Kidney tubular cells, the established target cells for PTH, were used for comparison. Cyclic AMP (cAMP) accumulation and steroid hormone (aldosterone and corticosterone) secretion were measured in response to the hormones. In the bovine adrenocortical cells PTH of both bovine and avian origin stimulated cAMP production, but the aPTH action was more pronounced. The maximal cAMP response of avian adrenocortical cells to aPTH was 15-fold greater than that of ACTH, but a 20-times higher concentration of aPTH was required to reach half-maximal response. Avian PTH stimulated steroid hormone secretion in the chick adrenocortical cells, but the induced secretion was similar to that induced by ACTH, despite the difference in cAMP accumulation. Human PTH(1-34) and bPTH(1-84), which stimulated cAMP production in kidney cells, and the conventional antagonist bPTH(3-34) inhibited aPTH stimulation of cAMP accumulation in avian adrenocortical cells, but did not interfere with ACTH action. Furthermore, cAMP stimulation by aPTH and ACTH in avian adrenal cells was additive. The results establish the adrenal as a target organ for PTH, and suggest that the PTH acts through specific receptors, distinct from those for ACTH.


[Toxic megacolon with colonic perforation complicating Campylobacter jejuni ileo-colitis].
Campylobacter jejuni is an enteropathogen with invasive ability which may be responsible for acute colitis. We report the case of a 38-year-old woman who was hospitalized for severe acute colitis. Stool specimen examination revealed Campylobacter jejuni. A laparotomy was performed due to clinical deterioration and toxic megacolon. Colic perforations were observed. The examination of the colectomy specimen revealed ulcerative pancolitis. This is the first published case of Campylobacter jejuni infection complicated by toxic megacolon and perforation.


Acute non-A non-B aortic dissection: incidence, treatment and outcome.
Our aim was to report outcome of patients with acute non-A non-B aortic dissection involving the aortic arch but not the ascending aorta. Dissection extension and entry location were analysed in patients with acute aortic dissection admitted between 2001 and 2016 at a tertiary centre. Non-A non-B dissection was classified as descending-entry type with entry distal to the left subclavian artery and dissection extending into the aortic arch, and arch-entry type with entry between the innominate and left subclavian arteries. We compared these 2 groups' clinical presentation, treatment and outcome. Among 396 acute aortic dissection patients, 43 (median age 60 ± 12 years, 81% males) had non-A non-B dissection (descending-entry n = 21, arch-entry n = 22). The overwhelming majority of aortic segments were not dilated in all these patients. The 2 groups' cardiovascular risk profiles did not differ. Emergency open or endovascular aortic repair were necessary due to malperfusion or aortic rupture in 29% descending-entry and 36% arch-entry (in-hospital mortality was 1/6 and 3/8, respectively). Aortic repair within 2 weeks due to new organ malperfusion, rapid aortic growth, aortic rupture or persisting pain was performed in 43% descending-entry and 36% arch-entry patients (0% in-hospital mortality). All others (except for 1 diagnosed in 2014) required aortic repair for aneurysm at follow-up. Acute non-A non-B aortic dissection frequently requires emergency aortic repair due to organ malperfusion or aortic rupture. Most descending-entry and arch-entry non-A non-B dissection patients undergo aortic repair within 2 weeks after dissection onset.


Chemical matricectomy with sodium hydroxide: long-term follow-up results.
Chemical matricectomy with sodium hydroxide is a method being used successfully in the treatment of ingrown toenail. In this study, it was aimed to evaluate long-term recurrence rates after chemical matricectomy using sodium hydroxide application of different durations. Two hundred two patients with ingrown nail edges were treated with either 1-minute (Group 1) or 2-minute (Group 2) applications of sodium hydroxide matricectomy. All patients were followed for at least 2 years. Chemical matricectomy with sodium hydroxide was applied to a total of 585 nail edges of 202 cases. The overall recurrence rates in Group 1 and Group 2 were 6.4% and 7.1%, respectively, during the average 7.5-year follow-up period. No statistically significant differences were detected in terms of recurrence between the 2 groups (p = .73). Chemical matricectomy with sodium hydroxide is an easy method in the treatment of ingrown nails, with low morbidity and high success rates. There was no difference between 1-minute and 2-minute applications in terms of recurrence during the long-term follow-up. Chemical matricectomy with 1-minute application of sodium hydroxide showed high success in terms of long-term follow-up results.


Clinicopathological and immunohistological correlation of malignant lymphomas of the skin.
The study utilised monoclonal antibodies for T and B cells to study the immunophenotype in our lymphomas and to correlate with the clinicopathological aspects of eight cases of malignant lymphomas, of which four are cutaneous T cell lymphoma and four malignant lymphomas. The method used was immunohistochemical staining of tissue section by the alkaline phosphatase anti-alkaline phosphatase (APAAP) procedure. For four cases of cutaneous T cell lymphoma, three were in stage 1 and one in stage 2. The immunophenotypes were typical of mycosis fungoides-type cutaneous T cell lymphoma. They were predominantly T cells with many mature T cells. The CD4 to CD8 ratio fell within the normal range. There was no specific loss of CD7. For four cases of malignant lymphoma, T cell type, the pattern was again T cell phenotype with all of CD2, CD5, CD7 and CD4. The CD4 to CD8 ratios fell within the normal range except for one case, which showed a reversal of CD4/CD8, and this patient perished. His T suppressor cells were increased and had several cycles of malignant flare-up. One case showed mycosis fungoides, converting to lymphoma. This study demonstrates that monitoring of the progress is possible and can detect downgrading of malignant lymphomas.


Surgery for Velopharyngeal Insufficiency Following Cleft Palate Repair: An Audit of Contemporary Practice and Proposed Schema of Techniques and Variations.
Surgical treatment of velopharyngeal insufficiency (VPI) includes a wide array of procedures. The purpose of this study was to develop a classification for VPI procedures and to describe variations in how they are performed.Design/participants/setting/outcomes: We completed an in-depth review of the literature to develop a preliminary schema that encompassed existing VPI procedures. Forty-one cleft surgeons from twelve hospitals across the USA and Canada reviewed the schema and either confirmed that it encompassed all VPI procedures they performed or requested additions. Two surgeons then observed the conduct of the procedures by surgeons at each hospital. Standardized reports were completed with each visit to further explore the literature, refine the schema, and delineate the common and unique aspects of each surgeon's technique. Procedures were divided into three groups: palate-based surgery; pharynx-based surgery; and augmentation. Palate-based operations included straight line mucosal incision with intravelar veloplasty, double-opposing Z-plasty, and palate lengthening with buccal myomucosal flaps. Many surgeons blended maneuvers from these three techniques, so a more descriptive schema was developed classifying the maneuvers employed on the oral mucosa, nasal mucosa, and muscle. Pharynx-based surgery included pharyngeal flap and sphincter pharyngoplasty, with variations in design for each. Augmentation procedures included palate and posterior wall augmentation. A comprehensive schema for VPI procedures was developed incorporating intentional adaptations in technique. There was substantial variation amongst surgeons in how each procedure was performed. The schema may enable more specific evaluations of surgical outcomes and exploration of the mechanisms through which these procedures improve speech.


Cellular uptake of antisense oligonucleotides after complexing or conjugation with cell-penetrating model peptides.
The uptake by mammalian cells of phosphorothioate oligonucleotides was compared with that of their respective complexes or conjugates with cationic, cell-penetrating model peptides of varying helix-forming propensity and amphipathicity. An HPLC-based protocol for the synthesis and purification of disulfide bridged conjugates in the 10-100 nmol range was developed. Confocal laser scanning microscopy (CLSM) in combination with gel-capillary electrophoresis and laser induced fluorescence detection (GCE-LIF) revealed cytoplasmic and nuclear accumulationin all cases. The uptake differences between naked oligonucleotides and their respective peptide complexes or conjugates were generally confined to one order of magnitude. No significant influence of the structural properties of the peptide components upon cellular uptake was found. Our results question the common belief that the increased biological activity of oligonucleotides after derivatization with membrane permeable peptides may be primarily due to improved membrane translocation.


Mitral valve replacement in children.
Rheumatic fever leading to advanced valvular heart disease, in adults and children, is still frequently seen in developing countries. In the period 1981-87, 1137 patients underwent open heart surgery for either repair (489 patients), or replacement (639 patients) of defective cardiac valves. The experience with 75 children who underwent mitral valve replacement among this group is reviewed. The aetiology of mitral valve disease was rheumatic in 71, and infective endocarditis in four; 85% of the children were in NYHA functional class III, and 15% in class IV. Seven children had intra-operative findings of rheumatic activity. Pure mitral regurgitation was seen in 41, while mixed mitral valve disease was observed in 34 children. Twenty-seven children underwent mitral valve replacement with Ionescu-Shiley bovine pericardial valves, and 48 with mechanical Bi-leaflet valves. The operative mortality was 9.3%, and the actuarial survival rate, calculated by the Cutler and Ederers method, was 87% at 5 years.


Stretching DNA with optical tweezers.
Force-extension (F-x) relationships were measured for single molecules of DNA under a variety of buffer conditions, using an optical trapping interferometer modified to incorporate feedback control. One end of a single DNA molecule was fixed to a coverglass surface by means of a stalled RNA polymerase complex. The other end was linked to a microscopic bead, which was captured and held in an optical trap. The DNA was subsequently stretched by moving the coverglass with respect to the trap using a piezo-driven stage, while the position of the bead was recorded at nanometer-scale resolution. An electronic feedback circuit was activated to prevent bead movement beyond a preset clamping point by modulating the light intensity, altering the trap stiffness dynamically. This arrangement permits rapid determination of the F-x relationship for individual DNA molecules as short as -1 micron with unprecedented accuracy, subjected to both low (approximately 0.1 pN) and high (approximately 50 pN) loads: complete data sets are acquired in under a minute. Experimental F-x relationships were fit over much of their range by entropic elasticity theories based on worm-like chain models. Fits yielded a persistence length, Lp, of approximately 47 nm in a buffer containing 10 mM Na1. Multivalent cations, such as Mg2+ or spermidine 3+, reduced Lp to approximately 40 nm. Although multivalent ions shield most of the negative charges on the DNA backbone, they did not further reduce Lp significantly, suggesting that the intrinsic persistence length remains close to 40 nm. An elasticity theory incorporating both enthalpic and entropic contributions to stiffness fit the experimental results extremely well throughout the full range of extensions and returned an elastic modulus of approximately 1100 pN.


Deletion of chloroplast NADPH-dependent thioredoxin reductase results in inability to regulate starch synthesis and causes stunted growth under short-day photoperiods.
Plastid-localized NADPH-dependent thioredoxin reductase C (NTRC) is a unique NTR enzyme containing both reductase and thioredoxin domains in a single polypeptide. Arabidopsis thaliana NTRC knockout lines (ntrc) show retarded growth, especially under short-day (SD) photoperiods. This study identified chloroplast processes that accounted for growth reduction in SD-acclimated ntrc. The strongest reduction in ntrc growth occurred under photoperiods with nights longer than 14 h, whereas knockout of the NTRC gene did not alter the circadian-clock-controlled growth of Arabidopsis. Lack of NTRC modulated chloroplast reactive oxygen species (ROS) metabolism, but oxidative stress was not the primary cause of retarded growth of SD-acclimated ntrc. Scarcity of starch accumulation made ntrc leaves particularly vulnerable to photoperiods with long nights. Direct interaction of NTRC and ADP-glucose pyrophosphorylase, a key enzyme in starch synthesis, was confirmed by yeast two-hybrid analysis. The ntrc line was not able to maximize starch synthesis during the light period, which was particularly detrimental under SD conditions. Acclimation of Arabidopsis to SD conditions also involved an inductive rise of ROS production in illuminated chloroplasts that was not counterbalanced by the activation of plastidial anti-oxidative systems. It is proposed that knockout of NTRC challenges redox regulation of starch synthesis, resulting in stunted growth of the mutant lines acclimated to the SD photoperiod.


Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions.
Improvements in the control of inflammation in rheumatoid arthritis (RA) by conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) have led to a substantial change in the clinical outcomes of patients during the last 30 years. Current treatment can lead to sustained remission in some patients raising questions about the optimal management strategies in this subgroup of patients. Today, tapering of DMARDs and even their discontinuation appears as an interesting concept for achieving a more tailored and dynamic treatment approach of RA, especially in patients, who achieved full disease control by DMARD treatment. In this review article, current developments of DMARD tapering are discussed. The article provides an overview of existing studies on this topic and addresses new strategies to reach drug-free remission. Furthermore, concepts for defining patients eligible for DMARD tapering are described and potential future strategies in using biomarkers in predicting the risk for disease relapse after initiation of DMARD tapering are addressed. These findings are finally considered in light of the vision to achieve cure as an ultimate goal in patients with RA achieving full control of inflammation.


Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation.
Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL. In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes. Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs. These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients.


Discovery of altered protein profiles in epithelial ovarian carcinogenesis by SELDI mass spectrometry.
Identification of proteomic alterations in epithelial ovarian tumorigenesis may facilitate the understanding of progression of this disease. Specific protein peak patterns were identified in 20 microdissected epithelial ovarian tumors (13 epithelial ovarian cancers (EOCs) and 7 low malignant potential (LMP) tumors), as well as in the matched normal cells. Protein profiles were generated by surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) from all the different types of cells. Among seven protein peaks from EOC cells, six were significantly increased while one was decreased compared with normal cells, and three peaks from LMP cells were markedly increased while one was decreased compared with normal cells. The combination of SELDI and laser capture microdissection (LCM) is effective in finding the key molecules in ovarian tumorigenesis. Further identification of these protein peaks is important and these malignant protein signatures lend themselves to identification of populations at high-risk for EOC and for monitoring response to EOC chemopreventive agents.


Health care utilization related to the introduction of designated GPs at care homes in Denmark: a register-based study.
To investigate the correlation between having designated general practitioners (GPs) in residential care homes and the residents' number of contacts with primary care, number of hospital admissions and mortality. A retrospective register-based longitudinal study. Forty-two care homes in Aarhus Municipality, Denmark. A total of 2376 care home residents in the period from 1 September 2016 to 31 December 2018. We used two models to calculate the incidence risk ratio (IRR) for primary care contacts, hospital admission or dying. Model 1 compared the residents' risk time before with their risk time after implementation of the designated GP model. Model 2 included only risk time after implementation and was based on calculations of successful (rate ≥60%) implementation. Weighted by time at risk, the proportion of females across the two models ranged from 64% to 68%. The largest group was aged '85-94' years. In Model 1, the mere implementation of the model did not correlate with changes in primary care contacts, hospital admissions, or mortality. Contrarily, in Model 2, residents living in care homes with successful implementation had fewer email contacts (IRR = 0.81, 95%CI: 0.68;0.96), fewer telephone contacts (IRR = 0.78, 95%CI: 0.68;0.90) and fewer hospital admissions (IRR = 0.85, 95%CI: 0.73;0.99), but more home visits (IRR = 1.70, 95%CI: 1.29;2.25) than residents living in care homes with lower implementation rates. The designated GP model seems promising, as a high implementation degree of the model correlated with a reduced the number of acute admissions, short-term admissions and readmissions. Future studies should focus on gaining deeper insight into the mechanisms of the designated GP model to further optimize the model.Key pointsA new care model was introduced in Denmark in 2017, designating dedicated GPs to residential care homes for the elderly.Successful implementation correlated with significantly fewer hospital admissions, specifically for acute admissions, but also with fewer short-term admissions and readmissions.The implementation of the model correlated significantly with fewer e-mail and telephone contacts and with more home visits.Future studies should gain more insight into the mechanisms of the designated GP model to further optimize the model.


[Estrogen receptors and breast cancer].
Activation of oestrogen receptor has a promoting effect in early steps of mammary carcinogenesis. Loss of oestrogen receptor, or of its functionality is associated to more aggressive and hormone unresponsive breast cancers. Anti-oestrogens are antiproliferative agents inhibiting oestrogens and growth factors action by binding to the oestrogen receptor. Assay of oestrogen and progesterone receptors, in the cytosol of primary breast cancer provides information on the differentiation and prognosis of the tumour and on the efficacy of endocrine treatment. Several oestrogen receptor variants have been detected in breast cancer, but their significance remains hypothetical. They could act in a positive constitutive fashion (e.g. anomaly of the hormone binding site with conservation of the DNA binding site) or be nonfunctional (e.g. anomaly of the DNA binding domain and or transactivation). They are often associated in the tumor with normal wild type receptors and could decrease their activity by forming nonfunctional heterodimers.


A novel leukemia cell line, MR-87, with positive Philadelphia chromosome and negative breakpoint cluster region rearrangement coexpressing myeloid and early B-cell markers.
We developed a Philadelphia chromosome (Ph) positive cell line, designated MR-87, from a 4-year-old boy with Ph+-acute leukemia. MR-87 cells grew in single cell suspensions with a doubling time of 120 to 144 hours. Both MR-87 and original leukemia cells were positive for myeloperoxidase (MPO) and myeloid antigen CD13. These cells exhibited the early B-cell phenotype, ie, terminal deoxynucleotidyl transferase+, Ia+, CD19+, and CD10+. Rearrangement of the immunoglobulin heavy chain was confirmed in both. Approximately 80% of MR-87 cells coexpressed CD13 and lymphoid antigens CD10 or CD19, as confirmed by a two-color analysis. Simultaneous expression of MPO and CD19 on a single MR-87 cell was demonstrated at ultrastructural level. Thus, MR-87 is a Ph+ leukemia cell line exhibiting a hybrid phenotype. The breakpoint cluster region (bcr) was not rearranged in the MR-87 cells and subsequent analysis using antisera revealed that these cells expressed a novel protein, P190c-abl, which was immunoprecipitated with anti-abl and anti-phosphotyrosine antibodies. The MR-87 line will be most useful for investigating the biology and pathogenesis of Ph+ bcr- acute leukemia.


Commissioning post-registration education programmes for health professionals.
Many of the post-registration education programmes provided by the universities for health professionals are commissioned on behalf of NHS employers by the Workforce Development Confederations. (Workforce Development Confederations were formed from their predecessor organizations, Education Consortia, from 1 April 2001.) This study describes a review of the post-registration education contracts held by the North and East Yorkshire Confederation, together with a survey of post-registration contracting across England. A recurrent theme was that contracting arrangements did not easily allow the purchasers of education to measure value for money. Other key issues were found to be the relevance of courses to clinical practice and their accessibility in view of difficulties in releasing staff. A new form of contract will be introduced by this Confederation, basing payment on the academic credit of courses, which will facilitate cost comparisons with other providers. At the same time a greater level of partnership with providers will be fostered and the risks inherent in the contracting mechanism will be shared between the commissioner and the providers. The review also highlighted issues that must be addressed by NHS employers if Confederations are to be able to commission effectively on their behalf.


Discapseudes holthuisi (Crustacea: Tanaidacea) as an intermediate host of Caballerorhynchus lamothei (Acanthocephala: Cavisomidae).
The intermediate host of the acanthocephalan Caballerorhynchus lamothei Salgado-Maldonado, 1977, is reported for the first time. Cystacanths of C. lamothei were found in the hemocoel of the tanaid shrimp Discapseudes holthuisi Bacescu and Gutu, 1975, in Alvarado and Sontecomapan lagoons, Veracruz, Mexico. This is the first report of a palaeacanthocephalan using a tanaid shrimp as an intermediate host. Prevalence by locality, shrimp length, sex and developmental stage, and an analysis of the distribution of number of cystacanths per host are presented. A higher prevalence, and percentage of multiple infections and larger host size were found in Alvarado Lagoon.


Review of the investigation and surgical management of resectable ampullary adenocarcinoma.
Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with significant mortality and morbidity. Some recent publications have advocated the use of endoscopic papillectomy for the treatment of early ampullary adenocarcinoma. This article reviews investigations and surgical treatment options of ampullary tumours. A systematic review of English-language articles was carried out using an electronic search of the Ovid MEDLINE (from 1996 onwards), PubMed and Cochrane Database of Systematic Reviews databases to identify studies related to the investigation and management of ampullary tumours. Distinguishing between ampullary adenoma and adenocarcinoma is challenging given the inaccuracy of endoscopic biopsy, for which high false negative rates of 25-50% have been reported. Endoscopic ultrasound is the most accurate method for local staging of ampullary lesions, but distinguishing between T1 and T2 adenocarcinomas is difficult. Lymph node metastasis occurs early in the disease process; it is lowest for T1 tumours, but the risk is still high at 8-45%. Case reports of successful endoscopic resection and transduodenal ampullectomy of T1 adenocarcinomas have been published, but their duration of follow-up is limited. Optimal staging should be used to distinguish between ampullary adenoma and adenocarcinoma. Pancreaticoduodenectomy remains the treatment of choice for all ampullary adenocarcinomas.


Role of Viral Infections in Testicular Cancer Etiology: Evidence From a Systematic Review and Meta-Analysis.
The most represented histotype of testicular cancer is the testicular germ-cell tumor (TGCT), both seminoma and non-seminoma. The pathogenesis of this cancer is poorly known. A possible causal relationship between viral infections and TGCTs was firstly evoked almost 40 years ago and is still a subject of debate. In the recent past, different authors have argued about a possible role of specific viruses in the development of TGCTs including human papillomavirus (HPV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), Parvovirus B-19, and human immunodeficiency virus (HIV). The aim of this present review was to summarize, for each virus considered, the available evidence on the impact of viral infections on the risk of developing TGCTs. The review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all observational studies reported in English evaluating the correlations between viral infections (HPV, CMV, EBV, Parvovirus B19, and HIV) and TGCTs. The methodological quality of studies included in the meta-analysis was evaluated using a modified version of the "Newcastle-Ottawa Scale." Meta-analyses were conducted using the "Generic inverse variance" method, where a pooled odds ratio (OR) was determined from the natural logarithm (LN) of the studies' individual OR [LN (OR)] and the 95% CI. A total of 20 studies (on 265,057 patients) were included in the review. Meta-analysis showed an association with TGCTs only for some of the explored viruses. In particular, no association was found for HPV, CMV, and Parvovirus B-19 infection (p = ns). Conversely, EBV and HIV infections were significantly associated with higher risk of developing TGCTs (OR 7.38, 95% CI 1.89-28.75, p = 0.004; OR 1.71, 95% CI 1.51-1.93, p < 0.00001). In conclusion, we found adequate evidence supporting an oncogenic effect of HIV and EBV on the human testis. Conversely, available data on HPV and TGCTs risk are conflicting and further studies are needed to draw firm conclusions. Finally, current evidence does not support an effect of CMV and Parvovirus B-19 on testicular carcinogenesis.


Outpatient clinic waiting time, provider communication styles and satisfaction with healthcare in India.
Purpose - The purpose of this paper is to evaluate the impact of extended waiting time on patients' perceptions of provider communication skills and in-clinic satisfaction, in three major cities in India. Design/methodology/approach - In total, 625 patients were interviewed. The multivariate general linear model was used to determine the causality and relationship between the independent and the dependent variable. A moderation analysis was also conducted to assess waiting time role as a potential moderator in doctor-patient communication. Findings - Results show that patients with higher waiting time were less satisfied with health care quality. Male patients and patients of male providers were more affected by extended waiting time than female patients and patients of female providers. The advanced regression analysis, however, suggests weak support for waiting time and its effect on overall satisfaction with clinic quality. Waiting time did not moderate the relationship between satisfaction with dominant communication style, and overall satisfaction at the outpatient clinic. Research limitations/implications - A cross-sectional study does not easily lend itself to explaining causality with certainty. Thus, sophisticated techniques, such as structural equation modelling may also be utilized to assess the influence of extended waiting time on satisfaction with healthcare at outpatient clinics. Practical implications - Findings are relevant for providers as the onus is on them to ensure patient satisfaction. They should initiate a workable waiting time assessment model at the operational level. Originality/value - There has been a relatively lesser focus on patient waiting time in patient-provider satisfaction studies. In India, this aspect is still vastly unexplored especially in the context of outpatient clinics. Gender wise pattern of patient satisfaction and waiting time is also missing in most studies.


Comprehensive bioinformatics analysis reveals the crosstalk genes and immune relationship between the systemic lupus erythematosus and venous thromboembolism.
It is well known that patients with systemic lupus erythematosus (SLE) had a high risk of venous thromboembolism (VTE). This study aimed to identify the crosstalk genes between SLE and VTE and explored their clinical value and molecular mechanism initially. We downloaded microarray datasets of SLE and VTE from the Gene Expression Omnibus (GEO) dataset. Differential expression analysis was applied to identify the crosstalk genes (CGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the shared genes. The shared diagnostic biomarkers of the two diseases were further screened from CGs using least absolute shrinkage and selection operator (Lasso) regression. Two risk scores for SLE and VTE were constructed separately to predict the likelihood of illness according to the diagnostic biomarkers using a logical regression algorithm. The immune infiltration levels of SEL and VTE were estimated via the CIBERSORT algorithm and the relationship of CGs with immune cell infiltration was investigated. Finally, we explored potential phenotype subgroups in SLE and VTE based on the expression level of CGs through the consensus clustering method and studied immune cell infiltration in different subtypes. A total of 171 CGs were obtained by the intersection of differentially expressed genes (DEGs) between SLE and VTE cohorts. The functional enrichment shown these CGs were mainly related to immune pathways. After screening by lasso regression, we found that three hub CGs (RSAD2, HSP90AB1, and FPR2) were the optimal shared diagnostic biomarkers for SLE and VTE. Based on the expression level of RSAD2 and HSP90AB1, two risk prediction models for SLE and VTE were built by multifactor logistic regression and systemically validated in internal and external validation datasets. The immune infiltration results revealed that CGs were highly correlated with multiple infiltrated immunocytes. Consensus clustering was used to respectively regroup SLE and VTE patients into C1 and C2 clusters based on the CGs expression profile. The levels of immune cell infiltration and immune activation were higher in C1 than in C2 subtypes. In our study, we further screen out diagnostic biomarkers from crosstalk genes SLE and VTE and built two risk scores. Our findings reveal a close relationship between CGs and the immune microenvironment of diseases. This provides clues for further exploring the common mechanism and interaction between the two diseases.


Current irrigation practices in the central United States reduce drought and extreme heat impacts for maize and soybean, but not for wheat.
In this study, we assessed the adaptive effects of irrigation on climatic risks for three crops (maize, soybean, and wheat) at the regional scale from 1981 to 2012 in the Central US. Based on yields of 183 counties for maize, 121 for soybean and 101 for wheat, statistical models were developed for irrigated, rainfed and county-level yields. Results show that irrigation has a statistically significant effect on abating detrimental climate impacts, specifically drought and extreme heat, in maize and soybean but not in wheat. On average, irrigation reduces the negative influences of extreme heat by around 7.2% for maize and 5.0% for soybean yields for each additional 10 degree-days above the optimal temperature for each crop. This is approximately two-thirds of the negative effects of extreme heat under rainfed management. The remaining third of the yield reduction is caused by heat damage that cannot be alleviated by irrigation. No significant differences were detected between county yields and irrigated yields for maize and soybean, suggesting that the existing irrigation practices were reasonably efficient. Efforts to mitigate future climate risks for these two crops should focus on improving the heat sensitivity contributing to the yield losses from heat damage. In contrast, the existing irrigation does not improve the resilience of wheat to climate risks. Both increased temperature and drought were critical to wheat production, which was potentially caused by relatively poor irrigation supplies for wheat. Further enhancement of wheat yield may be possible through improved irrigation management.


Effects of anticoagulant and antiplatelet drugs on the risk for hospital admission for traumatic injuries: a case-control and population-based study.
The current cardiovascular literature advocates an overall beneficial balance between the advantages of oral anticoagulants and antiplatelet drugs in preventing and treating thromboembolic events and their disadvantages in promoting hemorrhage. However, traumatic injuries have usually received little attention despite several studies from the surgical literature showing worse outcomes in anticoagulated trauma registry patients. To quantify at population level too this seemingly deleterious impact, we investigated the effects of anticoagulants and antiplatelet use on the risk for hospital admission for acute traumatic causes. A population-based, case-control study in an Italian region with 4.5 million inhabitants was conducted. Cases were all the 59,348 adult residents admitted to the hospital for traumatic injuries in the years 2010 and 2011. Controls were age- and sex-matched residents selected by incidence density sampling. By conditional logistic regression adjusted for comorbidities, we estimated the risk for traumatic hospital admission while on anticoagulant, antiplatelet, and combined medications. The odds ratios (ORs) for anticoagulation and combined medications were 1.21 (95% confidence interval [CI], 1.15-1.28) and 1.39 (95% CI, 1.21-1.62). These effects were generally consistent across subgroups of demographic and clinical characteristics and particularly important in the head injured (e.g., OR for anticoagulation, 2.00; 95% CI, 1.77-12.27). Antiplatelets alone had no overall effect (OR, 1.02; 95% CI, 0.99-1.05). The number-needed-to-harm of anticoagulation was 595. Oral anticoagulation increased the population risk for traumatic hospital admission, with a further increase in case of concurrent antiplatelet use. Because this effect is most likely to derive from the prohemorrhagic properties of these drugs, injured patients should be included in the future evaluations of the cost-benefit profiles of these medications. Epidemiologic/prognostic study, level III.


Optimism as modifier of escalation of commitment.
To study whether optimism-pessimism modifies escalation of commitment, 52 undergraduates were told that they had made an unsuccessful investment, then they chose to continue or discontinue this investment. Optimism about future returns was induced in one group by varying the probability of a successful outcome from an initial low to medium, pessimism was induced in another group by varying this probability from an initial high to medium. Supporting the assumption of the manipulation, the results showed that optimistic participants preferred to continue investments whereas pessimistic participants preferred not to. As predicted, when the sunk cost increased, optimism led to escalation of commitment, whereas pessimism led to de-escalation of commitment. These effects were strengthened when probability of a successful outcome was ambiguous.


Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients.
This study examined the binding to cortical serotonin 5-HT2A receptors of conventional doses of the typical neuroleptic chlorpromazine in comparison with clozapine, the prototype atypical antipsychotic, and amisulpride, a specific dopamine D2-D3 blocker. Seventeen schizophrenic patients treated with chlorpromazine (75-700 mg/day), four treated with clozapine (200-600 mg/day), and five treated with amisulpride (200-1200 mg/day) were studied. Cortical 5-HT2A binding was estimated by reference to the values for 14 antipsychotic-free schizophrenic subjects with the use of positron emission tomography and [18F]setoperone, a high-affinity radioligand for cortical 5-HT2A receptors. A dose-dependent decrease in the number of available cortical binding sites for [18F] setoperone was demonstrated in the chlorpromazine group; for the highest dose, there was a virtual lack of sites available for binding. A very low percentage of available binding sites was also observed in the clozapine-treated patients at all doses. This suggests a high level of 5-HT2A blockade with both clozapine and high doses of chlorpromazine. No significant binding of amisulpride to 5-HT2A receptors was detected. A high level of 5-HT2A receptor blockade does not appear specific to clozapine in comparison with high doses of chlorpromazine, suggesting that the distinct clinical profiles of both drugs are unrelated to 5-HT2A blockade itself.


Effects of Solution Structure on the Folding of Lysozyme Ions in the Gas Phase.
The fidelity between the structures of proteins in solution and protein ions in the gas phase is critical to experiments that use gas-phase measurements to infer structures in solution. Here we generate ions of lysozyme, a 129-residue protein whose native tertiary structure contains four internal disulfide bonds, from three solutions that preserve varying extents of the original native structure. We then use cation-to-anion proton-transfer reactions (CAPTR) to reduce the charge states of those ions in the gas phase and ion mobility to probe their structures. The collision cross section (Ω) distributions of each CAPTR product depends to varying extents on the original solution, the charge state of the product, and the charge state of the precursor. For example, the Ω distributions of the 6+ ions depend strongly on the original solutions conditions and to a lesser extent on the charge state of the precursor. Energy-dependent experiments suggest that very different structures are accessible to disulfide-reduced and disulfide-intact ions, but similar Ω distributions are formed at high energy for disulfide-intact ions from denaturing and from aqueous conditions. The Ω distributions of the 3+ ions are all similar but exhibit subtle differences that depend more strongly on the original solutions conditions than other factors. More generally, these results suggest that specific CAPTR products may be especially sensitive to specific elements of structure in solution.


Tuning the solvation of indigo in aqueous deep eutectics.
The solubility of synthetic indigo dye was measured at room temperature in three deep eutectic solvents (DESs)-1:3 choline chloride:1,4-butanediol, 1:3 tetrabutylammonium bromide:1,4-butanediol, and 1:2 choline chloride:p-cresol-to test the hypothesis that the structure of DESs can be systematically altered, to induce specific DES-solute interactions, and, thus, tune solubility. DESs were designed starting from the well-known cholinium chloride salt mixed with the partially amphiphilic 1,4-butanediol hydrogen bond donor (HBD), and then, the effect of increasing salt hydrophobicity (tetrabutylammonium bromide) and HBD hydrophobicity (p-cresol) was explored. Measurements were made between 2.5 and 25 wt. % H2O, as a reasonable range representing atmospherically absorbed water, and molecular dynamics simulations were used for structural analysis. The choline chloride:1,4-butanediol DES had the lowest indigo solubility, with only the hydrophobic character of the alcohol alkyl spacers. Solubility was highest for indigo in the tetrabutylammonium bromide:1,4-butanediol DES with 2.5 wt. % H2O due to interactions of indigo with the hydrophobic cation, but further addition of water caused this to reduce in line with the added water mole fraction, as water solvated the cation and reduced the extent of the hydrophobic region. The ChCl:p-cresol DES did not have the highest solubility at 2.5 wt. % H2O, but did at 25 wt. % H2O. Radial distribution functions, coordination numbers, and spatial distribution functions demonstrate that this is due to strong indigo-HBD interactions, which allow this system to resist the higher mole fraction of water molecules and retain its solubility. The DES is, therefore, a host to local-composition effects in solvation, where its hydrophobic moieties concentrate around the hydrophobic solute, illustrating the versatility of DES as solvents.


Near-Infrared-Triggered Photodynamic Therapy with Multitasking Upconversion Nanoparticles in Combination with Checkpoint Blockade for Immunotherapy of Colorectal Cancer.
While immunotherapy has become a highly promising paradigm for cancer treatment in recent years, it has long been recognized that photodynamic therapy (PDT) has the ability to trigger antitumor immune responses. However, conventional PDT triggered by visible light has limited penetration depth, and its generated immune responses may not be robust enough to eliminate tumors. Herein, upconversion nanoparticles (UCNPs) are simultaneously loaded with chlorin e6 (Ce6), a photosensitizer, and imiquimod (R837), a Toll-like-receptor-7 agonist. The obtained multitasking UCNP-Ce6-R837 nanoparticles under near-infrared (NIR) irradiation with enhanced tissue penetration depth would enable effective photodynamic destruction of tumors to generate a pool of tumor-associated antigens, which in the presence of those R837-containing nanoparticles as the adjuvant are able to promote strong antitumor immune responses. More significantly, PDT with UCNP-Ce6-R837 in combination with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade not only shows excellent efficacy in eliminating tumors exposed to the NIR laser but also results in strong antitumor immunities to inhibit the growth of distant tumors left behind after PDT treatment. Furthermore, such a cancer immunotherapy strategy has a long-term immune memory function to protect treated mice from tumor cell rechallenge. This work presents an immune-stimulating UCNP-based PDT strategy in combination with CTLA-4 checkpoint blockade to effectively destroy primary tumors under light exposure, inhibit distant tumors that can hardly be reached by light, and prevent tumor reoccurrence via the immune memory effect.


Physical Activity and Social Comparison: The Importance of Group Composition in an Employee Fitbit Intervention.
This study examined the impact of group composition of a 6-week group-based employee Fitbit intervention on daily physical activity steps. Group composition comprised heterogenous and homogeneous groupings based on variations in baseline high, medium, and low steppers. The intervention included weekly step leaderboard information, motivational and informative messages, and the ability to participate in group step challenges. Repeated measures analysis of variance (ANOVA) examined differences in change of steps across time, step-level groups (low, medium, and high), and group composition (low/high, similar, and mixed), and replicated with a subgroup of participants who participated in group step challenges. While group and step level did not emerge as significant interactions in the overall sample, when focused within the group step challenge subsample, relationships among time, the group composition, and participant step-level categories emerged. Overall, the greatest increases in steps occurred at the mid-point time period, among lower steppers, and within the low/high comparison group. This study provides evidence of the importance of group composition in physical activity interventions as well as the fidelity of intervention design in facilitating group comparisons.


[Spontaneous rupture of nylon sutures in the cornea spontaneously (author's transl)].
In 8 patients rupture of nylon sutures in the cornea occurred spontaneously. This happened four times after a corneal cataract extraction, three times after a perforating keratoplasty and once after a perforating corneal injury. The rupture appeared three times 6 1/2 to 7 months after the operation, once after 1 1/2 months. In the other 4 cases the time of rupture is not known. The examination of the nylon sutures with a microscope showed a lamellar-concentric reduction in the straight parts of the sutures and superficial and deep sagittal in the curved parts of the sutures.


Circulation of a type 1 recombinant vaccine-derived poliovirus strain in a limited area in Romania.
After intensive immunisation campaigns with the oral polio vaccine (OPV) as part of the Global Polio Eradication Initiative, poliomyelitis due to wild viruses has disappeared from most parts of the world, including Europe. Here, we report the characterization of a serotype 1 vaccine-derived poliovirus (VDPV) isolated from one acute flaccid paralysis (AFP) case with tetraplegia and eight healthy contacts belonging to the same small socio-cultural group having a low vaccine coverage living in a small town in Romania. The genomes of the isolated strains appeared to be tripartite type 1/type 2/type 1 vaccine intertypic recombinant genomes derived from a common ancestor strain. The presence of 1.2% nucleotide substitutions in the VP1 capsid protein coding region of most of the strains indicated a circulation time of about 14 months. These VDPVs were thermoresistant and, in transgenic mice expressing the human poliovirus receptor, appeared to have lost the attenuated phenotype. These results suggest that small populations with low vaccine coverage living in globally well-vaccinated countries can be the origin of VDPV emergence and circulation. These results reaffirm the importance of active surveillance for acute flaccid paralysis and poliovirus in both polio-free and polio-endemic countries.


Occult blood and fecal leukocytes as screening tests in childhood infectious diarrhea: an old problem revisited.
During a 24-month period 446 children with diarrhea and 16 controls had examination of their stools for leukocytes and for occult blood. Fecal leukocytes were found in 36, 16 and 18% of children with Salmonella-Shigella-Campylobacter, rotavirus or enterotoxigenic Escherichia coli, or cryptosporidial diarrhea, respectively. Similarly 43, 39 and 38% of these groups, respectively, as well as 13% of controls had occult blood. Notably 70% of 10 Shigella cases had fecal leukocytes. In 166 children with mixed pathogens leukocytes were seen in 27 and 8% of children with Salmonella-Shigella-Campylobacter or noninvasive pathogen, respectively. Likewise 44 and 18% of these groups had occult blood. Agreement between both tests being positive was poor, the highest result being 50% for Shigella. Dysentery combined with both tests positive was associated with 15 (88%) cases of invasive agents present in stool cultures, and combination of dysentery with fecal leukocytes was associated with 21 (72%) cases of invasive agents recovered. The results of these tests should be interpreted in the context of the clinical situation. A combined clinical-epidemiologic and screening tests-based approach to infectious diarrhea of childhood is suggested.


Neural processing of eye gaze and threat-related emotional facial expressions in infancy.
Combined with emotional expressions, eye gaze can provide essential information to indicate threat in the environment. The current study assessed the effects of eye gaze direction on infants' neural processing of fearful and angry faces. Event-related potentials were recorded from thirteen 7-month-old infants. Two face-sensitive posterior components, the N290 and P400, as well as a frontocentral negative component (Nc), indicating attentional arousal, were sensitive to eye gaze direction and emotion. A larger Nc was observed for angry faces with direct compared to averted eye gaze. Fearful faces elicited a larger N290 than angry faces, whereas angry faces elicited a more prominent P400 regardless of eye gaze direction. The findings are discussed in terms of early social cognitive and neural development.


Overexpression, purification, and characterization of the cloned metallo-beta-lactamase L1 from Stenotrophomonas maltophilia.
The metallo-beta-lactamase L1 from Stenotrophomonas maltophilia was cloned, overexpressed, and characterized by spectrometric and biochemical techniques. Results of metal analyses were consistent with the cloned enzyme having 2 mol of tightly bound Zn(II) per monomer. Gel filtration chromatography demonstrated that the cloned enzyme exists as a tightly held tetramer with a molecular mass of ca. 115 kDa, and matrix-assisted laser desorption ionization and time-of-flight mass spectrometry indicated a monomeric molecular mass of 28.8 kDa. Steady-state kinetic studies with a number of diverse penicillin and cephalosporin antibiotics demonstrated that L1 effectively hydrolyzes all tested compounds, with k(cat)/Km values ranging between 0.002 and 5.5 microM(-1) s(-1). These characteristics of the recombinant enzyme are contrasted to those previously reported for metallo-beta-lactamases isolated directly from S. maltophilia.


Synthesis of Aromatic Thiolate-Protected Gold Nanomolecules by Core Conversion: The Case of Au36(SPh-tBu)24.
Ultrasmall nanomolecules (<2 nm) such as Au25(SCH2CH2Ph)18, Au38(SCH2CH2Ph)24, and Au144(SCH2CH2Ph)60 are well studied and can be prepared using established synthetic procedures. No such synthetic protocols that result in high yield products from commercially available starting materials exist for Au36(SPh-X)24. Here, we report a synthetic procedure for the large-scale synthesis of highly stable Au36(SPh-X)24 with a yield of ∼42%. Au36(SPh-X)24 was conveniently synthesized by using tert-butylbenzenethiol (HSPh-tBu, TBBT) as the ligand, giving a more stable product with better shelf life and higher yield than previously reported for making Au36(SPh)24 from thiophenol (PhSH). The choice of thiol, solvent, and reaction conditions were modified for the optimization of the synthetic procedure. The purposes of this work are to (1) optimize the existing procedure to obtain stable product with better yield, (2) develop a scalable synthetic procedure, (3) demonstrate the superior stability of Au36(SPh-tBu)24 when compared to Au36(SPh)24, and (4) demonstrate the reproducibility and robustness of the optimized synthetic procedure.


Frames of reference for saccadic command tested by saccade collision in the supplementary eye field.
In what frame of reference does the supplementary eye field (SEF) encode saccadic eye movements? In this study, the "saccade collision" test was used to determine whether a saccade electrically evoked in the monkey's SEF is programmed to reach an oculocentric goal or a nonoculocentric (e.g., head or body-centered) goal. If the eyes start moving just before or when an oculocentric goal is imposed by electrical stimulation, the trajectory of the saccade to that goal should compensate for the ongoing movement. Conversely, if the goal imposed by electrical stimulation is nonoculocentric, the trajectory of the evoked saccade should not be altered. In head-fixed experiments, we mapped the trajectories of evoked saccades while the monkey fixated at each of 25 positions 10 degrees apart in a 40 x 40 degrees grid. For each studied SEF site, we calculated convergences indices and found that "convergent" and "nonconvergent" sites were separately clustered: nonconvergent rostral to convergent. Then, the "saccade collision" test was systematically applied. We found compensation at sites where saccades were of the nonconvergent type and practically no compensation at sites where saccades were of the convergent type. The results indicate that the SEF can encode saccade goals in at least two frames of reference and suggest a rostrocaudal segregation in the representation of these two modes.


Genome-Wide Association Study of Anthracnose Resistance in Andean Beans (Phaseolus vulgaris).
Anthracnose is a seed-borne disease of common bean (Phaseolus vulgaris L.) caused by the fungus Colletotrichum lindemuthianum, and the pathogen is cosmopolitan in distribution. The objectives of this study were to identify new sources of anthracnose resistance in a diverse panel of 230 Andean beans comprised of multiple seed types and market classes from the Americas, Africa, and Europe, and explore the genetic basis of this resistance using genome-wide association mapping analysis (GWAS). Twenty-eight of the 230 lines tested were resistant to six out of the eight races screened, but only one cultivar Uyole98 was resistant to all eight races (7, 39, 55, 65, 73, 109, 2047, and 3481) included in the study. Outputs from the GWAS indicated major quantitative trait loci (QTL) for resistance on chromosomes, Pv01, Pv02, and Pv04 and two minor QTL on Pv10 and Pv11. Candidate genes associated with the significant SNPs were detected on all five chromosomes. An independent QTL study was conducted to confirm the physical location of the Co-1 locus identified on Pv01 in an F4:6 recombinant inbred line (RIL) population. Resistance was determined to be conditioned by the single dominant gene Co-1 that mapped between 50.16 and 50.30 Mb on Pv01, and an InDel marker (NDSU_IND_1_50.2219) tightly linked to the gene was developed. The information reported will provide breeders with new and diverse sources of resistance and genomic regions to target in the development of anthracnose resistance in Andean beans.


Somatic symptoms and internalizing problems in urban youth: a cross-cultural comparison of Czech and Russian adolescents.
Although the association between somatic complaints and internalizing problems (anxiety, somatic anxiety and depression) is well established, it remains unclear whether the pattern of this relationship differs by gender and in different cultures. The aim of this study was to examine cross-cultural and gender-specific differences in the association between somatic complaints and internalizing problems in youth from the Czech Republic and Russia. The Social and Health Assessment, a self-report survey, was completed by representative community samples of adolescents, age 12-17 years, from the Czech Republic (N = 4770) and Russia (N = 2728). A strong association was observed between somatic complaints and internalizing psychopathology. Although the levels of internalizing problems differed by country and gender, they increased together with and largely in a similar way to somatic complaints for boys and girls in both countries. The association between somatic symptoms and internalizing problems seems to be similar for boys and girls across cultures.


Molecular Diagnostics Update for the Emerging (If Not Already Widespread) Sexually Transmitted Infection Agent Mycoplasma genitalium: Just About Ready for Prime Time.
Mycoplasma genitalium is an important and emerging agent of sexually transmitted infection in females and males, carrying the potential for postinfection genital tract sequelae. Past efforts to identify this organism on a routine basis, which were problematic due to the fastidious nature of the bacterium and its antigenic intricacies, have recently become supplemented by molecular diagnostics. A number of these assays are available commercially. This minireview describes the format and performance indices of a number of M. genitalium DNA- and RNA-based amplification assays; many of these assays have contributed to an improved clinical and epidemiologic understanding of this organism.


Severity of alcohol dependence and social/occupational problems: relationship to clinical and familial history.
We examined the relationship of major depression, aspects of antisocial personality disorder, family history of alcoholism, treatment history, and onset of alcohol problems to the severity of alcohol dependence and severity of social/occupational problems due to alcohol. Subjects were 111 randomly sampled patients in alcohol rehabilitation. The predictor variables formed different patterns of relationships with alcohol dependence and with social/occupational problems. Implications of the findings for future research are discussed.


Population structuring of Glossina palpalis gambiensis (Diptera: Glossinidae) according to landscape fragmentation in the Mouhoun river, Burkina Faso.
The impact of landscape fragmentation due to human and climatic mediated factors on the structure of a population of Glossina palpalis gambiensis Vanderplank (Diptera: Glossinidae) was investigated in the Mouhoun river basin, Burkina Faso. Allele frequencies at five microsatellite loci, and metric properties based on 11 wing landmarks, were compared between four populations. The populations originated from the Mouhoun river and one of its tributaries. The average distance between samples was 72 km with the two most widely spaced populations being 216 km apart. The sampling points traversed an ecological cline in terms of rainfall and riverine forest ecotype, along a river enlarging from downstream to upstream and oriented south to north. Microsatellite DNA comparison demonstrated structuring between the populations, but not complete isolation, with an overall Fst = 0.012 (P < 0.001). Wing geometry revealed significant centroid size and shape differences between populations, especially between the two most distant populations. There was no significant correlation between gene flow and geographic distance at this scale, but there was a positive correlation in females between metric distances (wing shape differences) and geographic distances that might be attributed to the cline of environmental conditions. The impact of the fragmentation of riparian landscapes on tsetse population structure is discussed in the context of control campaigns currently promoted by Pan African Tsetse and Trypanosomosis Eradication Campaign.


Identification of a novel Anaplasma marginale appendage-associated protein that localizes with actin filaments during intraerythrocytic infection.
The rickettsial pathogen Anaplasma marginale assembles an actin filament bundle during intracellular infection. Unlike other bacterial pathogens that generate actin filament tails, A. marginale infects mature erythrocytes, and the F-actin appendages are assembled on the cytoplasmic surface of a vacuole containing several organisms. To identify A. marginale molecules associated with these filaments, two complementary approaches were used: matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and tandem mass spectrometry of A. marginale proteins identified with an appendage-specific monoclonal antibody and expression screening of an A. marginale phage library. Amino acid and nucleotide sequences were mapped to a full-length gene in the genome of the St. Maries strain of A. marginale; the correct identification was confirmed by expression of full-length recombinant protein and its reactivity with appendage-specific antibodies. Interestingly, there is marked variation in the abilities of diverse A. marginale strains to assemble the F-actin appendages. Comparison of four strains, the Florida, Illinois, St. Maries, and Virginia strains, revealed substantial polymorphism in the gene encoding the appendage-associated protein, with amino acid sequence identity of as low as 34% among strains. However, this variation does not underlie the differences in expression, as there is no specific polymorphism associated with loss of ability to assemble actin appendages. In contrast, the ability to assemble an actin filament bundle reflected dramatic strain-specific differences in the expression level of the appendage-associated protein. Understanding how this protein influences the cycle of invasion, replication, and egress in the host cell may provide new insights into pathogen-host interactions.


The fear-avoidance model: helping patients to cope with disfigurement.
Last week's article established that body disfigurement affects a considerable number of people and causes them significant distress. It also explored how a cognitive behavioural model of psychological disturbance might inform our understanding of the difficulties faced by people with disfigurement. This week's article examines the practical application of the fear-avoidance model and discusses how it can be used by nurses as a means of providing general advice and more specialist intervention.


Detection and Quantification of Pythium tracheiphilum in Soil by Multiplex Real-Time qPCR.
In Canada, head lettuce (Lactuca sativa capitata) is extensively produced in the muck soils of southwestern Québec. However, yields are increasingly affected by various soilborne pathogens, including Pythium spp., which cause wilt and damping off. In a survey conducted in Québec muck soils in 2010 and 2011, Pythium tracheiphilum Matta was identified as the predominant Pythium sp. in the root of head lettuce showing Pythium stunt symptoms. Therefore, to improve risk assessment and help further understanding of disease epidemiology, a specific and sensitive real-time quantitative polymerase chain reaction (qPCR) assay based on TaqMan-minor groove binder (MGB) technology was developed for P. tracheiphilum. The PCR primers along with a TaqMan-MGB probe were designed from the ribosomal internal transcribed spacer 2 region. A 100-bp product was amplified by PCR from all P. tracheiphilum isolates tested while no PCR product was obtained from 38 other Pythium spp. or from a selection of additional lettuce pathogens tested. In addition to P. tracheiphilum, the assay was multiplexed with an internal control allowing for the individual validation of each PCR. In artificially infested soils, the sensitivity of the qPCR assay was established as 10 oospores/g of dry soil. P. tracheiphilum was not detected in soils in which lettuce has never been grown; however, inoculum ranged from 0 to more than 200,000 oospores/g of dry soil in commercial lettuce fields. Also, disease incidence was positively correlated with inoculum concentration (r = 0.764). The results suggest that inoculum concentration should be considered when making Pythium stunt management decisions. The developed qPCR assay will facilitate reliable detection and quantification of P. tracheiphilum from field soil.


Contribution of upper limb muscles to two different gripping styles in elite indoor tug of war athletes.
To investigate characteristic upper limb muscle use between two common tug of war (TOW) gripping styles, 20 elite athletes from two high school TOW teams were recruited. Under conditioned attack pulling (with 90% maximal force) on a tug machine, participants used their own habitual gripping style to pull for five 15-s trials. Force and kinematic measurements showed a significantly better force performance and higher centre-of-gravity tilting angle with the gripping style one than with the gripping style two (GS2) (both p < 0.05). However, an overall higher and more symmetrical muscle activation detected by normalised surface electromyography signal amplitude was found in the GS2 group (both p < 0.05). In both groups, the distal and flexor muscles were more activated than the proximal and extensor muscles, respectively (p < 0.05). Higher co-contraction ratio was found in the wrist joints of the latter arm in both groups (p < 0.05). As higher muscle activation level and co-contraction indicate higher muscle and joint injury incidences, we suggest that gripping style factors should be considered in training to prevent muscle and joint injury. Future study concerning segmental kinematics, ground reaction force, moment arm and muscle endurance during the defence phase are warranted.


Surgical palliation for recurrent rectal cancers ulcerating in the perineum.
This report describes a unique palliative approach of radical surgical debridement for uncontrollable, recurrent pelvic tumors ulcerating through the perineum. All conservative treatment attempts with radiotherapy and chemotherapy had failed. Seven patients have been treated with resection of the tumor including a portion of the sacrum to obtain all but the deep margins clear of tumor. Coverage was obtained with myocutaneous flaps. All patients were significantly relieved of pain, requiring little or no subsequent analgesics. Three patients returned to work and the remainder led a relatively comfortable existence at home until their demise. At the time of death, four patients had no visible perineal disease. When conservative attempts at chemotherapy and radiotherapy have failed in this situation, the authors believe that palliative surgery prolongs both quantity and, more importantly, quality of life.


N-acetylcysteine administration does not improve patient outcome after liver resection.
Post-operative hepatic dysfunction is a major cause of concern when undertaking a liver resection. The generation of reactive oxygen species (ROS) as a result of hepatic ischaemia/reperfusion (I/R) injury can result in hepatocellular injury. Experimental evidence suggests that N-acetylcysteine may ameliorate ROS-mediated liver injury. A cohort of 44 patients who had undergone a liver resection and receiving peri-operative N-acetylcysteine (NAC) were compared with a further cohort of 44 patients who did not. Liver function tests were compared on post-operative days 1, 3 and 5. Peri-operative outcome data were retrieved from a prospectively maintained database within our unit. Administration of NAC was associated with a prolonged prothrombin time on the third post-operative day (18.4 versus 16.4 s; P = 0.002). The incidence of grades B and C liver failure was lower in the NAC group although this difference did not reach statistical significance (6.9% versus 14%; P = 0.287). The overall complication rate was similar between groups (32% versus 25%; P = ns). There were two peri-operative deaths in the NAC group and one in the control group (P = NS). In spite of promising experimental evidence, this study was not able to demonstrate any advantage in the routine administration of peri-operative NAC in patients undergoing a liver resection.


A Guideline for Effectively Synthesizing and Characterizing Magnetic Nanoparticles for Advancing Nanobiotechnology: A Review.
The remarkable multimodal functionalities of magnetic nanoparticles, conferred by their size and morphology, are very important in resolving challenges slowing the progression of nanobiotechnology. The rapid and revolutionary expansion of magnetic nanoparticles in nanobiotechnology, especially in nanomedicine and therapeutics, demands an overview of the current state of the art for synthesizing and characterizing magnetic nanoparticles. In this review, we explain the synthesis routes for tailoring the size, morphology, composition, and magnetic properties of the magnetic nanoparticles. The pros and cons of the most popularly used characterization techniques for determining the aforementioned parameters, with particular focus on nanomedicine and biosensing applications, are discussed. Moreover, we provide numerous biomedical applications and highlight their challenges and requirements that must be met using the magnetic nanoparticles to achieve the most effective outcomes. Finally, we conclude this review by providing an insight towards resolving the persisting challenges and the future directions. This review should be an excellent source of information for beginners in this field who are looking for a groundbreaking start but they have been overwhelmed by the volume of literature.


Proteins that interact with facilitative glucose transporters: implication for function.
The cellular uptake of glucose catalysed by the facilitated glucose transporter (GLUT) family is further regulated by metabolites and hormones, most importantly by insulin. All of the six isoforms known in this family possess a large cytoplasmic domain of divergent amino acid sequence. A body of evidence indicates that this domain is important for GLUT regulation. Exactly how this domain participates in the regulation, however, is not known. A likely possibility is that a specific cellular protein interacts with GLUT at this domain, and thus modulates the function. This putative, glucose transporter binding protein (GTBP) may be an enzyme, or a non-enzymic adaptor or docking protein. Indeed, we have identified several cellular proteins that bind to the cytoplasmic domain of GLUT proteins; these include glyceraldehyde-3-phosphate dehydrogenase, glucokinase, GTBP70, GTBP85, GTBP28 and L-3-hydroxyacyl-CoA dehydrogenase. Some of these GLUT-GTPB interactions are functionally coupled. Whether any of these interactions actually participates in the insulin-induced GLUT regulation is yet to be determined.