The aptitude-achievement test distinction: a study of unrelated children reared together.
Unrelated children reared together (N = 156) in 71 different families included in the Texas Adoption Project were compared for similarities on intelligence and achievement tests. The purpose was to see if a distinction between the two types of tests based on their heritabilities could be sustained. Results indicated no substantial differences in correlations for the two types of tests, and hence little or no support for the notion of an aptitude-achievement distinction based on differential heritabilities.


Parenteral immunization with IpaB/IpaD protects mice against lethal pulmonary infection by Shigella.
Shigellosis is an important diarrheal disease, especially among children in the developing world. About 90 million infections with Shigella spp are estimated to appear each year. We previously demonstrated that the type III secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens when administered intranasally using the mouse lethal pulmonary model. To simplify vaccine administration, we tested the parenteral route for IpaB and IpaD with several adjuvants and compared the immune response and protective efficacy via the intranasal route. We found that the intramuscular administration generated a response consisting of similar levels of serum IgG, a lack of IgA response and higher IL-17 secretion. Therefore, while parenteral administration yielded a unique pattern of immune responses, it retained the ability to protect mice in a lethal pulmonary challenge against S. flexneri when both proteins were used. Our results show the feasibility of generating protective parenteral vaccines against Shigella spp.


An empirical analysis of public and private medical practice in Australia.
The combination of public and private medical practice is widespread in many health systems and has important consequences for health care cost and quality. However, its forms and prevalence vary widely and are poorly understood. This paper examines factors associated with public and private sector work by medical specialists using a nationally representative sample of Australian doctors. We find considerable variations in the practice patterns, remuneration contracts and professional arrangements across doctors in different work sectors. Both specialists in mixed practice and private practice differ from public sector specialists with regard to their annual earnings, sources of income, maternity and other leave taken and number of practice locations. Public sector specialists are likely to be younger, to be international medical graduates, devote a higher percentage of time to education and research, and are more likely to do after hours and on-call work compared with private sector specialists. Gender and total hours worked do not differ between doctors across the different practice types.


Frequency of influenza-responsive cytolytic T-lymphocyte precursors in the thymus and spleen of unprimed mice.
Limiting dilution culture conditions were established which allowed the differentiation and quantitation of influenza-specific cytotoxic T-cell precursors (CTL.Ps) from naive mouse spleen and thymus. One in 49,000 nucleated spleen cells and 1 in 40,000 thymocytes responded to stimulation with influenza-infected, anti-Thy 1.2 and complement-treated spleen cells, in the presence of ConA-stimulated cell supernatant, with the production of cytotoxic effector cells. These frequencies are 4- to 15-fold higher than those for influenza-responsive B cells in the relevant lymphoid compartments, and it is argued that major quantitative discrepancies may exist in the sizes of the B- and CTL-receptor repertoires.


T lymphocyte participation in antibody-induced experimental glomerulonephritis.
Macrophage accumulation is a feature of some aggressive forms of human and experimental glomerulonephritis (GN). Both antibody Fc components and T cells may cause macrophage accumulation; however, there has been no previous demonstration of T cells at the site of injury in GN, although some indirect evidence of their possible participation has been reported. Specific monoclonal anti-rat T lymphocyte antibodies W3/13, W3/25, and Ox8 were used to demonstrate T cells within the glomeruli of rats with an augmented autologous anti-GBM GN, by indirect immunofluorescence. The injury in this model has been shown to be mediated by macrophages. The T cell infiltrate consisted mainly of T helper cells, was maximal 24 hr after induction of the disease and clearly preceded the peak influx of macrophages and glomerular damage. Suppression of T cell function using cyclosporin prevented T cell accumulation and the subsequent macrophage-induced injury. Glomerular T cells were not seen in passively induced GN. These studies support a role for cell-mediated immunity in attracting macrophages and initiating injury in experimental anti-GBM antibody-induced GN.


Newly synthesized dihydropyridine derivatives as modulators of P-glycoprotein-mediated multidrug resistance.
Newly synthesized 1,4-dihydropyridine derivatives possessing alkyl chains at the 4-position screened whether they could overcome P-glycoprotein-mediated multidrug resistance in cultured cancer cells and also leukemia-bearing animals. Of these derivatives, some could overcome drug resistance to doxorubicin and vincristine in multidrug resistant human cancer cell lines. Combined administration of vincristine and some of the derivatives significantly increased the life span of P-glycoprotein overexpressing multidrug-resistant P388 leukemia-bearing mice. The calcium antagonistic activities, an undesirable effects, were weaker than that of verapamil. These results suggested that the introduction of alkyl groups at the 4-position were effective for both overcoming multidrug resistance and reducing the calcium antagonistic activity.


Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited.
The transport of glucose across the blood-brain barrier (BBB) is mediated by the high molecular mass (55-kDa) isoform of the GLUT1 glucose transporter protein. In this study we have utilized the tritiated, impermeant photolabel 2-N-[4-(1 -azi-2,2,2-trifluoroethyl)[2-3H]propyl]-1,3-bis(D-mannose-4-ylo xy)-2-propylamine to develop a technique to specifically measure the concentration of GLUT1 glucose transporters on the luminal surface of the endothelial cells of the BBB. We have combined this methodology with measurements of BBB glucose transport and immunoblot analysis of isolated brain microvessels for labeled luminal GLUT1 and total GLUT1 to reevaluate the effects of chronic hypoglycemia and diabetic hyperglycemia on transendothelial glucose transport in the rat. Hypoglycemia was induced with continuous-release insulin pellets (6 U/day) for a 12- to 14-day duration; diabetes was induced by streptozotocin (65 mg/kg i.p.) for a 14- to 21-day duration. Hypoglycemia resulted in 25-45% increases in regional BBB permeability-surface area (PA) values for D-[14C]glucose uptake, when measured at identical glucose concentration using the in situ brain perfusion technique. Similarly, there was a 23+/-4% increase in total GLUT1/mg of microvessel protein and a 52+/-13% increase in luminal GLUT1 in hypoglycemic animals, suggesting that both increased GLUT1 synthesis and a redistribution to favor luminal transporters account for the enhanced uptake. A corresponding (twofold) increase in cortical GLUT1 mRNA was observed by in situ hybridization. In contrast, no significant changes were observed in regional brain glucose uptake PA, total microvessel 55-kDa GLUT1, or luminal GLUT1 concentrations in hyperglycemic rats. There was, however, a 30-40% increase in total cortical GLUT1 mRNA expression, with a 96% increase in the microvessels. Neither condition altered the levels of GLUT3 mRNA or protein expression. These results show that hypoglycemia, but not hyperglycemia, alters glucose transport activity at the BBB and that these changes in transport activity result from both an overall increase in total BBB GLUT1 and an increased transporter concentration at the luminal surface.


Argon laser photocoagulation for the treatment of polypoidal choroidal vasculopathy.
To evaluate the efficacy of conventional argon laser for the treatment of serosanguineous maculopathy secondary to polypoidal choroidal vasculopathy (PCV). A retrospective audit of patients who had argon laser photocoagulation to angiographically determined polypoidal lesions and subsequently followed up at 1, 3, 6, and 12 months post treatment. Twenty-one eyes (75%) had stable or improved vision at 12 months. Twenty-three eyes had extrafoveal, two eyes had juxtafoveal, and three eyes had subfoveal polyps. In the extrafoveal group, 18 eyes (78%) had stable or improved vision at 12 months. Eighteen eyes (64.3%) showed clinical or angiographic resolution of maculopathy. Three eyes (10.7%) had recurrence of polyps subfoveally, three eyes (10.7%) had subsequent choroidal neovascularisation, and four eyes (14.3%) had persistent leakage with neurosensory detachment. In our study, 18 of the 23 eyes which had extrafoveal polyps had stable or improved best-corrected visual acuity and showed complete resolution of maculopathy at 12 months follow-up. Argon laser photocoagulation would appear to be most beneficial for extrafoveal PCV. However, in view of the retrospective nature of this study, the true efficacy of argon laser treatment would have to be evaluated with a larger, prospective and randomised controlled trial.


Clinical validation of reduction in cocaine frequency level as an endpoint in clinical trials for cocaine use disorder.
Despite calls for non-abstinence endpoints in randomized clinical trials (RCTs) for cocaine use disorder, there is a lack of data validating non-abstinence endpoints. We conducted a clinical validation of reduction in cocaine frequency level as a non-abstinence endpoint in RCTs for cocaine use disorder (CUD). We utilized a pooled dataset (n = 716; 63.6 % male, 51.4 % non-Hispanic white) from seven RCTs for CUD. We specified three cocaine frequency levels at baseline and end of treatment (EOT): abstinence, low frequency (1-4 days/month), and high frequency (5+ days/month). Multiple regression analyses were conducted. Among the sample, 38.3 % had at least a one-level reduction from baseline to EOT, whereas 61.7 % did not change/increased frequency level. At least a one-level reduction in cocaine frequency level from baseline to EOT versus no change/increase was significantly associated with better functioning up to one year following treatment on measures of cocaine use, as well as psychological, employment, legal, and other drug use problem severity domains of the Addiction Severity Index (ASI). We also conducted analyses only among those at the high frequency level at baseline and found those who reduced to low frequency use at EOT had similar outcomes at follow-up as those who reduced to abstinence. At least a one-level reduction in cocaine frequency level from pretreatment to EOT can be a clinically meaningful endpoint given its relation to sustained clinical benefit up to one-year following treatment. These data parallel recent findings regarding reduction in drinking risk level among individuals with alcohol use disorder.


Ankylosing Spondylitis and Axial Spondyloarthritis in Patients With Long-term Inflammatory Bowel Disease: Results From 20 Years of Follow-up in the IBSEN Study.
Patients with inflammatory bowel disease [IBD] often suffer from rheumatic manifestations, including inflammatory back disorders. The prevalence of these disorders late in the course of IBD is poorly investigated. The aim of this study was to estimate the prevalence of inflammatory back disorders in patients with IBD 20 years after diagnosis, and to investigate possible associations with IBD severity, HLA-B27, and the NOD2 genotype. A population-based cohort [the IBSEN study] was followed prospectively for 20 years. Information covering IBD activity and rheumatic diseases was collected at the regular follow-ups. HLA-B27 and NOD2 were analysed as present or absent. At 20 years, 599 members of the original cohort were alive, of whom 470 [78.5%] were investigated [314 ulcerative colitis and 156 Crohn's disease patients]. Ankylosing spondylitis was diagnosed in 21 patients [4.5%], axial spondyloarthritis was diagnosed in 36 patients [7.7%], and inflammatory back pain was diagnosed in 54 patients [11.5%]. Chronic back pain [back pain > 3 months] was present in 220 patients [46.8%]. HLA-B27 was associated with ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain, whereas no significant association was found for NOD2. A more chronic IBD course was associated with axial spondyloarthritis. Our data revealed a high prevalence of ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain 20 years after the IBD diagnosis. HLA-B27 but not NOD-2 was a predisposing factor for the inflammatory back disorders in IBD patients. Axial spondyloarthritis was associated with a more chronic active IBD disease course.


Leukocytosis, hypoalbuminemia, and the risk for chronic kidney disease in US adults.
Atherosclerosis and chronic kidney disease (CKD) share several common antecedents. However, the association between inflammatory markers and incident CKD is unknown. We determined risk for incident CKD, defined by treatment for kidney failure or death related to kidney disease, in 9,250 US adults aged 30 to 74 years who participated in the Second National Health and Nutrition Examination Survey (NHANES II), a nationally representative prospective cohort study with 17 years of follow-up. After adjusting for age, race, sex, blood pressure, smoking, and body mass index, there was a graded positive association with increasing total white blood cell (WBC) count and risk for CKD (P for trend < 0.001; relative hazard (RH) highest versus lowest quartile, 2.34; 95% confidence interval [CI], 1.30 to 4.19). This association remained statistically significant after adjusting further for the presence of diabetes and cardiovascular disease at baseline (RH, 2.01; 95% CI, 1.11 to 3.65). A similarly strong and graded association with incident CKD was observed for hypoalbuminemia after adjusting for age, race, sex, blood pressure, smoking, and body mass index (P for trend = 0.02; RH lowest versus highest quartile, 1.91; 95% CI, 0.89 to 4.07) and additionally adjusting for the presence of diabetes and cardiovascular disease at baseline (P for trend = 0.02; RH lowest versus highest, 2.05; 95% CI, 0.96 to 4.39). In a nationally representative sample of US adults, elevated WBC count and hypoalbuminemia were associated with future risk for CKD. These results support the hypothesis that systemic inflammation is an independent risk factor for CKD.


Surgery for femoroacetabular impingement using a minimally invasive anterolateral approach: analysis of 118 cases at 2.2-year follow-up.
Treatment of femoroacetabular impingement (FAI) has progressed over time from using long incisions and dislocation to using arthroscopic surgery. Minimally invasive treatment has rarely been evaluated and a minimally invasive, anterolateral approach has not been used up to now for this indication. A prospective, on-going study was performed to evaluate surgical treatment of FAI with a minimally invasive, anterolateral approach. Femoral neck, acetabulum and labrum abnormalities can be corrected without significant morbidity using a minimally invasive, anterolateral approach without dislocation. Treatment of 120 FAI cases (108 patients, 16 women, 92 men, 12 bilateral cases during one surgical session), average age: 34 years (18.9-63.5 years), was done prospectively and in an uninterrupted series. Two cases were lost to follow-up; 106 patients (118 FAI cases) were evaluated with a follow-up of at least 1 year. Assessments consisted of the Non-Arthritic Hip Score (NAHS), WOMAC, measurement of internal rotation with 90° flexion and the Nötzli alpha angle on an A/P radiograph in 45° of flexion, 45° abduction and 30° external rotation. Blood loss averaged 1.2g/dl (range 0.5 to 2.7g/dl) and the average operative time was 44.9 minutes (range 30 to 65). With an average follow-up of 2.2 years (range 12 to 54 months), the NAHS changed by 32.5 points (P<0.0001), internal rotation by 19.0° (P<0.0001) and the alpha angle by -24.9° (P<0.0001). Eight surgical revisions were required (6.8%) (four haematomas, two capsular debridement, two additional procedures on the acetabulum) and these had a good outcome; there were no nerve-related or infection-related complications. Four failures (3.5%) were revised by arthroplasty (two patients experienced residual pain and two patients rapidly progressed to osteoarthritis). Eighteen cases progressed by only one Tönnis stage. Brooker stage II and III ossification were observed in 12 cases (10.2%) but these did not affect the functional score and range of motion improvement. This approach, which can be learned and performed quickly, does not require any specific materials and yields a reliable surgical procedure without major complications. This short-term study, where the central cartilaginous compartment was not explored and the labrum was not sutured, comprised a consecutive, non-selected series of patients (independent of age, weight, osteoarthritis stage) and had encouraging results. Level III, prospective study, no control group.


Surgical treatment of AO type C distal humeral fractures: internal fixation with a Y-shaped reconstruction (Lambda) plate.
Although surgical repair is considered the standard treatment for intraarticular distal humeral fractures, most investigators have assessed its results using dual-plate fixation in 2 planes. The purpose of this study was to determine the functional outcome of open reduction and internal fixation of these complex fractures using Y-shaped reconstruction plates. We identified 17 patients who had operative treatment for Arbeitsgemeinschaft Für Osteosynthesefragen (AO) type 1, 3-C fractures using a Y-shaped Lambda plate (Zimmer, Warsaw, IN). Patients were recalled for follow-up that included recording of a complete history, physical examination, radiographic evaluation, and completion of a limb-specific questionnaire. The mean duration of follow-up was 37.3 months. The average loss of extension was 13 degrees , and the average arc of flexion-extension was 112 degrees . As determined by the Mayo Elbow Performance Index, 6 were graded excellent; 8, good; 3, fair; and none, poor. Surgical repair of intraarticular distal humeral fractures by open reduction and internal fixation with a Lambda plate is an effective procedure that allows for stable osteosynthesis without loss of reduction or fixation as a basis for good functional outcome.


Metabolism and Colorectal Cancer.
Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal of cellular waste in nutrient-poor environments. Intestinal stem cells (ISCs), the primary cell of origin for CRCs, must adapt their metabolism along the adenoma-carcinoma sequence to the unique features of their complex microenvironment that include interactions with intestinal epithelial cells, immune cells, stromal cells, commensal microbes, and dietary components. Emerging evidence implicates modifiable risk factors related to the environment, such as diet, as important in CRC pathogenesis. Here, we focus on describing the metabolism of ISCs, diets that influence CRC initiation, CRC genetics and metabolism, and the tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, and the tumor microenvironment in enhancing or supporting CRC tumorigenesis are becoming better understood. Thus, greater knowledge of CRC metabolism holds promise for improved prevention and treatment.


The impact of EPLINα (Epithelial protein lost in neoplasm) on endothelial cells, angiogenesis and tumorigenesis.
EPLIN (epithelial protein lost in neoplasm) is a cytoskeletal associated protein involved in the regulation of actin dynamics and subsequently in cell motility. EPLIN expression is frequently reduced in a variety of cancer cells and tissues and this loss may account for increased invasive traits in cancer cells. The current study aimed to assess the role of EPLIN in endothelial cells and the angiogenic process. EPLINα expression was enhanced in HECV endothelial cells through transfection with a pEF6 expression plasmid containing the full coding sequence of EPLINα. The impact of EPLINα on HECV cells was then assessed using a range of in vitro and in vivo models. transfection and over-expression of HECV cells with EPLINα expression plasmid resulted in a significant reduction in cell-matrix adhesion (P = 0.003), the rate of migration (P = 0.009) and tubule formation (P = 0.007) and also enhanced paxillin staining compared to transfection controls. Additionally, MDA-MB-231 breast cancer cells co-injected with HECV(EPLIN exp) cells developed at a slower rate than those co-injected with HECV(pEF6) cells (day 26, P = 0.05; day 33, P = 0.065, overall deviation over time P < 0.001). Treatment of HECV(EPLIN exp) cells with ERK inhibitor could rescue HECV cells from the inhibitory effect of EPLINα over-expression on tubule formation, returning these cells to control levels. EPLINα over-expression can regulate HECV cell motility, matrix adhesion and tubule formation in vitro and slow in vivo tumour formation, suggesting an anti-angiogenic role for EPLINα. Extracellular signal-regulated kinase (ERK) also appears to be linked to the ability of EPLINα to inhibit tubule formation in vitro.


Protein A-based antibody immobilization onto polymeric microdevices for enhanced sensitivity of enzyme-linked immunosorbent assay.
Highly efficient antibody immobilization is extremely crucial for the development of high-performance polymeric microdevices for enzyme-linked immunosorbent assay (ELISA). In this article, a site-selective tyrosinase (TR)-catalyzed protein A strategy for antibody immobilization was developed to enhance the sensitivity of ELISA in poly-(methyl methacrylate) (PMMA) microchannels for interferon-gamma (IFN-gamma) assay. To effectively immobilize the target antibodies, oxygen plasma was first used to activate the inert PMMA. This is followed by poly(ethyleneimine) (PEI) coating, an amine-containing functional polymer. For comparison, protein A was also immobilized through the commonly used amine-glutaraldehyde (GA) chemistry. Oxygen plasma treatment effectively increased the amount of PEI attachment and subsequent binding efficiency of the primary antibody. The antibody immobilized via TR-catalyzed protein A was able to provide much better specific antigen capture efficiency than GA chemistry due to the optimal spacing and orientation. Consequently, by using this new method, the detection signal and the signal-to-noise ratio of the ELISA immunoassay in microdevices were all significantly improved. In comparison to the standard assay carried out in the 96-well microtiter plate, the treated microchannels exhibited a broader detection range and a shorter detection time. And the detection limit was also decreased to 20 pg/mL, much lower than that obtained in other microdevices.


[Effect of fluocortin butylester (0.75%) as an ointment in the pyrexal erythema test on human skin (author's transl)].
The antiinflammatory efficacy of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) as a 0,75% ointment was tested in comparison with 1% hydrocortisone acetate ointment in the model of the pyrexal erythema. Fluocortin butylester appeared to be significantly superior to hydrocortisone acetate.


Modulation of long chain fatty acid unsaturation by dietary copper.
Research over the past 20 years into the effect of copper on fatty acid profiles in several species suggests that copper has a unique effect on long chain fatty acid metabolism. Copper supplementation in the pig and rat and copper deficiency in the rat, mouse and human indicates that inadequate copper intake (or genetic copper deficiency in the brindled mouse and in Menke's disease) impairs the ability to monounsaturate long chain saturated fatty acids and that, conversely, copper supplementation (greater than 150 mg/kg diet) usually increases monounsaturated fatty acids. Several recent studies of copper deficiency in the rat suggest that our interpretation of these effects needs to be more refined since membrane fatty acid profiles do not appear as sensitive to the effects of copper depletion as triglyceride fatty acid profiles. This suggests that changes in long chain fatty acid metabolism other than desaturation may also be affected by copper.


Multiple sclerosis and breast cancer.
Multiple sclerosis (MS) and breast cancer (BC) share common features; most notably, both are more frequent in women than in men. In addition to the involvement of sex hormones, a number of genetic and pharmacological studies support a possible relationship between these two diseases. However, there are no conclusive epidemiological findings related to MS and BC worldwide, and there are no recent data for the US population. We conducted a case-control study using a hospital inpatient discharge dataset (21,536 cases and two control series totaling 59,581 controls) from the Texas Health Care Information Collection. We assessed occurrence of MS in BC cases and in two control series: diabetes mellitus type II, and open wounds. After controlling for age, race-ethnicity, and health insurance status, a statistically-significant protective association was detected: BC cases were 45% less likely than diabetic controls to have MS (OR=0.55, 95% CI=0.37-0.81), and 63% less likely than open wound controls to have MS (OR=0.37, 95% CI=0.21-0.66). Our study presented here is the only current assessment of the association between MS and BC in the USA and suggests a protective effect of MS on BC in the hospitalized population.


Anhedonia in Eating Disorders.
Anhedonia is frequently observed among individuals with eating disorders (ED), though its relevance to ED pathology and clinical outcomes remain poorly understood. This chapter will present the latest findings regarding anhedonia in ED, with the majority of data available for anorexia nervosa (AN) and bulimia nervosa (BN). We consider anhedonia from the mechanistic lens of altered reward processing, with attention given to subjective experience, neurotransmitter function, neural correlates, and cognitive performance corresponding to distinct components of reward (i.e., liking, wanting, and learning). Findings from animal models are also highlighted. The chapter concludes with a discussion of implications for treatment and future directions aimed at better understanding anhedonia in ED.


Unilateral leg swelling in a newborn.
A female neonate was born with asymmetric lower limbs, the right leg appearing enlarged, with thickened, reddish-purple skin and ectasic superficial reticulum (figure 1A,B). Limb pulses were present and symmetrical. The girl's family history and prenatal scans were unremarkable. Laboratory findings were within the normal range, except for a mild thrombocytopenia (90 000/μL), which spontaneously resolved during the next few days. A leg X-ray and the Doppler analysis ruled out the presence of calcifications and venous varices, respectively. Ultrasound showed significant skin thickening, with marked dermal hypertrophy and hyperechogenicity. Magnetic resonance showed circumferential thickening of the derma, with mild hypertrophy of some perforating vessels (figure 2). A biopsy of the right thigh showed capillary malformations on histology.


Those famous red pills-Deliberations and hesitations. Ethics of placebo use in therapeutic and research settings.
Placebo fascinates and mystifies. Even with today's medical science we still do not know how and if it works. The use of placebo both in therapy and in research evokes ethical problems that are not easily resolved either. Placebo is intrinsically linked to deception, while veracity is a basic tenet in today's thinking of a doctor-patient relationship. In research ethics placebo, though considered the golden control condition, leads to the question of the therapeutic obligation. This narrative review presents an overview of these ethical questions and offers considerations that are of relevance to daily medical and research practice both in psychiatry and elsewhere.


Absence of center of mass control for leg abduction in long-term weightlessness in humans.
The present investigation describes for the first time leg lateral abduction performance during long-term microgravity exposure. Two astronauts took part in the experiments, starting 2 weeks into the mission and lasting for 5 months. Results on joint angles kinematics confirm previous investigations on parabolic flights, showing good task fulfillment for both subjects. Special interest was focused on whole body center of mass (CM) positioning. As in short-term microgravity, no initial CM lateral shift toward the 'supporting' leg was observed. In contrast with short-term microgravity and ground-based experiments, no stabilization of the CM medio-lateral position was found but a significant shift of CM toward the moving leg was observed. This suggests that the adaptation to sustained weightlessness might have led to a microgravity-specific motor strategy for leg abduction, which was not focused on CM strategy.


Exosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma and can discriminate patients from those with malignancies of other histological types.
microRNAs (miRNAs) stably exist in circulating blood encapsulated in extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve as novel cancer biomarkers. New diagnostic markers to detect high grade serous ovarian cancer (HGSOC) are urgently needed. The aim of this study was to identify miRNAs specific to HGSOC and analyze whether serum miRNA can discriminate HGSOC patients from healthy controls or patients with ovarian malignancies of other histological types. Exosomes from ovarian cancer cell lines were collected and exosomal miRNAs extracted. miRNA microarray analysis revealed several elevated miRNAs specific to HGSOC. Among these, we focused on miR-1290. Sera from 70 ovarian cancer patients and 13 healthy controls were gathered and its expression levels detected by quantitative real-time polymerase chain reaction. In HGSOC patients, serum miR-1290 was significantly overexpressed compared to in healthy controls (3.52 fold; P = 0.03), unlike in patients with ovarian cancers of other histological types. The relative expression of miR-1290 was higher in advanced stages of HGSOC than in early stages (4.23 vs. 1.58; P = 0.23). Its expression significantly decreased after operation (5.87 to 1.17; P < 0.01), indicating that this miRNA reflects tumor burden. A receiver operating characteristic curve analysis showed that at the cut-off of 1.20, the sensitivity and specificity were 63% and 85% respectively for discriminating patients with HGSOC (area under the curve [AUC] = 0.71) from healthy controls, and at the cut-off of 1.55, the sensitivity and specificity were 47% and 85% respectively for discriminating patients with HGSOC (AUC = 0.76) from those with malignancies of other histological types. Serum miR-1290 is significantly elevated in patients with HGSOC and can be used to discriminate these patients from those with malignancies of other histological types; it is a new potential diagnostic biomarker for HGSOC.


[Study on the technological process of extraction and clathration for Rhizoma Atractylodis Macrocephalae oil with beta-cyclodextrin].
To study the optimal extraction and clathration technology of Rhizoma Atractylodis Macrocephalae oil in Heweilichang Pill. Orthogonal test was employed for selecting the optimum of extraction technology of Rhizoma Atractylodis Macrocephalae oil and the oil extraction rate were used as a index. The optimum including technology was chosen by determining the oil-bearing rate and extract ratio of inclusion compound. The inclusion compound were identified with thin chromatogram. The extraction technology was 10 volumes of water, extracted 6h with thick granula of Rhizoma Atractylodis Macrocephalae. The optimum preparation conditions for clathrate were established as beta-CD: oil was 6: 1, 3. 5 times of water, triturated for 75 minutes. The process is feasible and the method can be used for production.


Segmental multicystic dysplastic kidney in children: clinical presentation, imaging finding, management, and outcome.
The aim of the study was to assess the presentation, imaging findings, management, and outcome of segmental multicystic dysplastic kidney (MCDK) in children. Six patients with segmental MCDK were diagnosed and observed at our hospital. We reviewed the medical records to collect data on initial symptoms, results of imaging studies, associated urinary tract anomalies, operation, and outcome. Three patients had abnormal prenatal ultrasound and were diagnosed by further postnatal imaging; they were asymptomatic after birth. The other 3 children presented with a renal mass, recurrent urinary tract infection, or urinary incontinence. Five patients had associated ipsilateral or contralateral urinary tract abnormalities, including vesicoureteral reflux, ureterocele, duplex collecting system, ureteropelvic junction stenosis, and ectopic ureter. Lower tract reconstruction was performed in 3, and open biopsy was done in 1 child. None underwent partial or total nephrectomy, and all had involution of the cysts for a mean of 40 months. Most of the cases occur in the upper pole of a duplex kidney and often involute spontaneously without significant complication. The clinical presentation and imaging findings depend on the associated anomalies and complications. Although the latter may require surgery to resolve, segmental MCDK itself rarely requires resection.


Neurofibromatosis pseudogene amplification underlies euchromatic cytogenetic duplications and triplications of proximal 15q.
Cytogenetically visible interstitial duplications of proximal 15q, which lack the Prader-Willi Angelman critical region (PWACR) frequently segregate in families without phenotypic effect, but the nature of the extra euchromatin has remained unclear. We used comparative genome hybridisation to confirm that the extra material in a cytogenetic triplication originated from proximal 15q. A PAC clone containing sequences specific for the type-1 neurofibromatosis (NF-1) pseudogenes, which map to 15q11.2, hybridised along the length of the enlarged region between the PWACR and the centromere. Computerised measurement of the fluorescent signal from the enlarged and normal chromosomes gave an average ratio of 9.85:1, consistent with amplification. In a second family, an amplified P1-4 signal co-segregated with a cytogenetic duplication and the average ratio between amplified and normal signals in the proband was 8.22:1. Ratios in noncarrier family members and control individuals were close to unity in most cases, but significantly greater than one in at least one instance. Our results provide a novel explanation for cytogenetic variation in 15q11.2. They also suggest that NF-1 pseudogene copy number may be polymorphic in the normal population, and that high copy numbers can produce G bands which do not reflect those of the normal constitutional karyotype.


Surgery for large primary liver cancer more than 10 cm in diameter.
Large primary liver cancer (PLC) more than 10 cm in diameter is not infrequently encountered in clinical practice. This study evaluated the clinicopathological features and long-term results after surgery for large PLC. Comparison of clinicopathological data between patients with PLC >/=10 cm ( n=1,227) and PLC <10 cm ( n=2,349) during the same period. In comparison with patients with PLC <10 cm, patients with PLC >/=10 cm were significantly younger ( P<0.01), had a lower incidence of asymptomatic tumors (9.1% vs 39.5%, P<0.001), higher alpha-fetoprotein levels ( >400 ng/ml, 78.3% vs 49.2%, P<0.001), higher gamma-glutamyl transpeptidase levels ( >6U, 87.7% vs 70.5%, P<0.001), a lower incidence of a history of hepatitis (45.0% vs 61.4%, P<0.001) and associated macronodular cirrhosis (cirrhotic nodules >/=0.3 cm, 59.8% vs 66.6%, P<0.001), poor differentiation of tumor cells (Edmondson grade 3-4, 24.3% vs 19.7%, P<0.01), a lower percentage of single nodule tumors (59.9% vs 75.4%, P<0.001) and well-encapsulated tumors (28.5% vs 62.1%, P<0.001), a higher proportion of tumor emboli in the portal vein (20.5% vs 9.0%, P<0.001), a lower resection rate (50.6% vs 86.8%, P<0.001), a lower curative resection rate (54.8% vs 78.3%, P<0.001), a higher operative mortality rate (4.5% vs 2.3%, P<0.001), and less local resection (52.5% vs 80.2%, P<0.001). The 5- and 10-year survival rates after resection were 26.2% and 17.5%, respectively, for patients with PLC >/=10 cm ( n=621), and 54.3% and 39.5%, respectively, for patients with PLC <10 cm ( n=2039) ( P<0.01). Large PLC had specific clinicopathological features. Surgery is the first choice of treatment. In selected patients, resection is safe and offers the chance of long-term survival. Large PLC does not exclude the possibility of cure.


Treatment of iron deficiency conditions in blood donors: controlled study of iron sulphate versus iron protein succinylate.
Iron protein succinylate is a new iron preparation for oral administration. In a controlled study versus iron sulphate in 40 blood donors with low levels of stored iron, treatment for 30 days with iron protein succinylate resulted in greater iron absorption compared to the reference drug. Serum iron concentration significantly increased compared with baseline values only in patients given iron protein succinylate. The amount of stored iron, evaluated by serum ferritin levels, significantly increased in both treatment groups.


Calanus Oil Supplementation Does Not Further Improve Short-Term Memory or Brain-Derived Neurotrophic Factor in Older Women Who Underwent Exercise Training.
In our study, we examined changes in short-term episodic memory and brain-derived neurotrophic factor (BDNF) in women after an exercise program alone or in combination with omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation. Fifty-five healthy elderly women (65-80 years) were randomly split into two groups: in the first group were women attending an exercise program while taking wax esters-rich oil (Calanus) supplementation (n = 28) and in the other group were women undergoing the same exercise program while taking placebo (n = 27). The 16-week exercise program consisted of functional circuit training (twice a week) and Nordic walking lessons (once a week). Short-term episodic memory was evaluated by the Czech screening Test "Pojmenování OBrázků A jejich Vybavení" (POBAV) baseline and after the program lasting 16 weeks. Our results show that short-term memory significantly improved following the exercise program, but there was no added value in using n-3 PUFA supplements. BDNF values did not differ between baseline and follow-up in either group. However, there was a statistically significant positive relationship between relative change (%) in the POBAV test and VO2peak in the placebo group (r = 0.49). Despite the added value of n-3 PUFA supplementation not being proven, our results may strengthen the importance of physical activity in averting age-related memory decline and dementia.


A possible high molecular weight precursor to vasoactive intestinal polypeptide sequestered into pheochromocytoma chromaffin granules.
Chromaffin granules, the catecholamine storage granules of pheochromocytoma were isolated from five human pheochromocytoma tumors. Vasoactive intestinal polypeptide (VIP) immunoreactivity was detected in all chromaffin granule preparations, paralleling the synthetic VIP antibody binding curve over a range of serial dilutions. In addition, gel filtration revealed an immunoreactive peptide peak coeluting with VIP. However, high molecular weight immunoreactive material was also detected on the column. This high molecular weight material was further characterized by sodium dodecyl sulfate gel electrophoresis, followed by electroblotting onto nitrocellulose paper and detection by anti-VIP antibodies with a secondary antibody conjugated to horseradish peroxidase. A 70 000 dalton immunoreactive band was identified, in which reactivity with anti-VIP antibody was inhibited by VIP; this band did not cross react with non-related antibodies. This 70 000 dalton protein may be an intermediate molecule in the biosynthesis and processing of VIP.


Immunohistochemical localization of Y hapten and the structurally related H type-2 blood-group antigen on large-bowel tumours and normal adult tissues.
The monoclonal antibody C14/1/46/10 which defines the Y hapten carbohydrate antigen (Brown et al., 1983) was shown, by the indirect immunoperoxidase technique, to stain tissue sections of 96% of colo-rectal adenocarcinomas and 100% of colo-rectal adenomas. In contrast, a monoclonal antibody defining the related H type-2 blood-group antigen was found to stain 86% of adenocarcinomas and 32% of adenomas. In adenocarcinomas the percentage of cells stained for both antigens was, on average, greater in group O than in group A patients. In adenomas a focal pattern of expression was observed, for both Y hapten and H type-2 antigen, that was characteristic of group A but not group O adenocarcinomas. In the normal mucosa of the distal colon, whilst H type-2 antigen was absent, Y hapten was found in the immature cells of the crypt bases. A comparison of the cellular phenotypes present in adenocarcinomas, adenomas and normal mucosa of the distal colon supports the adenoma-carcinoma sequence hypothesis for the genesis of colo-rectal carcinomas. In normal adult tissues Y hapten was predominantly found on epithelial cells whilst nervous tissues, muscles and connective tissues were negative. The expression of Y hapten in several positive tissues was dependent upon secretor status. A comparison of the expression of Y hapten and H type 2 antigen on normal adult tissues revealed that all of the permutations of expression of these two structurally related antigens were possible.


Hypertension in obesity: is leptin the culprit?
The number of obese or overweight humans continues to increase worldwide. Hypertension is a serious disease that often develops in obesity, but it is not clear how obesity increases the risk of hypertension. However, both obesity and hypertension increase the risk of cardiovascular diseases (CVD). In this review, we examine how obesity may increase the risk of developing hypertension. Specifically, we discuss how the adipose-derived hormone leptin influences the sympathetic nervous system (SNS), through actions in the brain to elevate energy expenditure (EE) while also contributing to hypertension in obesity.


Clock-drawing test performance in the normal elderly and its dependence on age and education.
The main objective was to assess the relative frequency and types of errors on the clock-drawing test (CDT) in normal elderly subjects, and the dependence of their CDT performance upon their age and education. The CDT performance of 242 normal elderly subjects, stratified according to age and education, was analyzed using both an absolute error count and a modified scoring sheet derived from 2 scales. Normal elderly subjects (average age: 73.4 +/- 8.4 years; mean Mini-Mental State Examination score: 27.7 +/- 1.6) often have problems placing figures on the clock face and differentiating the clock hands correctly. The absolute number of errors increases with age and decreases with formal school education. A cumulative effect of both high age and a low level of school education yields substantially inferior scores, on the modified scale used, in comparison with younger subjects and those with higher levels of education. The frequent errors made by normal elderly subjects, and a combined negative influence of high age and low education level, suggest caution when interpreting the significance of CDT performance in the elderly.


Combined effect of silica fume and fly ash as cementitious material on strength characteristics, embodied carbon, and cost of autoclave aerated concrete.
Aerated concrete (AAC) or lightweight concrete is primarily used for non-load bearing structures in construction work. Generally, it is produced with cement as a main binding ingredient, and the production of cement is blamed to contribute 7 to 8% of CO2 emission in the environment. In addition, the dumping of industrial wastes is also a great environmental concern. This research is an attempt to produce low-cost and sustainable aerated concrete utilizing silica fume and fly ash as partial substitution to cement without compromising the fundamental properties of aerated concrete. The current study was divided into two phases: in the first phase, the silica fume was substituted up to 20% with a variation of 5% in each mix. In the second phase, the fly ash was replaced with cement in three variations, i.e., 10%, 20%, and 30% containing an optimum proportion of silica fume obtained in phase 1. The aluminum powder was added at 0.4% by weight of binder to introduce aeration in concrete. Before testing, samples of aerated concrete were cured with steam in an autoclaving machine for 9 h at a pressure and temperature of 1.5 bars and 127 °C respectively and oven-dried at a temperature of 105 °C for 24 h after steam curing. From the experimental results, the highest compressive and split tensile strength of AAC was recorded when 15% of the cement was replaced with silica fume and 30% of the cement was replaced with fly ash combined. At this proportion the least density was also recorded which showed the lightweight of AAC without compromising the strength characteristics. In addition, the reduction of 42.64% and 32.4% of embodied carbon and cost was observed respectively.


Pupillary responses on the visual backward masking task reflect general cognitive ability.
Cognitive processing efficiency requires both an ability to attend to task-relevant stimuli with quickness and accuracy, also while filtering distracting or task-irrelevant stimuli. This study investigated cognitive processing efficiency by using pupillary responses as an index of attentional allocation to relevant target and irrelevant masks on a visual backward masking task. The relationship between attentional allocation on this task and general cognitive ability on the scholastic aptitude test (SAT) was examined in college students (n=67). A principle components analysis of the pupillary response waveform isolated a late component that appeared to index the attentional demands associated with processing masks on the backward masking task. This pupillary response index of wasteful resource allocation to the mask accounted for significant variance in SAT scores over and above that accounted for by socio-economic status and target detection accuracy scores. Consistent with the neural efficiency hypothesis, individuals who allocated more resources to processing irrelevant information performed more poorly on cognitive ability tests.


On methylene-bridged cysteine and lysine residues in proteins.
Cysteine residues ubiquitously stabilize tertiary and quaternary protein structure by formation of disulfide bridges. Here we investigate another linking interaction that involves sulfhydryl groups of cysteines, namely intra- and intermolecular methylene-bridges between cysteine and lysine residues. A number of crystal structures possessing such a linkage were identified in the Protein Data Bank. Inspection of the electron density maps and re-refinement of the nominated structures unequivocally confirmed the presence of Lys-CH2 -Cys bonds in several cases.


Clinical Characteristics and Lesions Responsible for Swallowing Hesitation After Acute Cerebral Infarction.
Some stroke patients with a unilateral lesion demonstrate acute dysphagia characterized by a markedly prolonged swallowing time, making us think they are reluctant to swallow. In order to clarify the clinical characteristics and causative lesions of delayed swallowing, we conducted a retrospective analysis of 20 right-handed patients without a history of swallowing dysfunction who underwent videofluorography on suspicion of dysphagia after a first ischemic stroke. The oral processing time plus the postfaucial aggregation time required to swallow jelly for patients classified as having delayed swallowing was over 10 s. The time required for swallowing jelly was significantly longer than that without the hesitation (median value, 24.1 vs. 8.9 s, P < 0.001). The oral processing time plus the postfaucial aggregation time required for patients with delayed swallowing to swallow thickened water was largely over 5 s and significantly longer than that of patients without swallowing hesitation (median value, 10.2 vs. 3.3 s, P < 0.001). Swallowing hesitation caused by acute unilateral infarction could be separated into two different patterns. Because four of the five patients with a rippling tongue movement in the swallowing hesitation pattern had a lesion in the left primary motor cortex, which induces some kinds of apraxia, swallowing hesitation with a rippling tongue movement seems to be a representative characteristic of apraxia. The patients with swallowing hesitation with a temporary stasis of the tongue in this study tended to have broad lesions in the frontal lobe, especially in the middle frontal gyrus, which is thought to be involved in higher cognition.


The influence of pre-sleep cognitive arousal on sleep onset processes.
Cognitive hyperarousal, resulting in enhanced cognitive activation, has been cited as an important contributor to the development and preservation of insomnia. To further understand this process, our study examined the effects of acutely-induced pre-sleep cognitive hyperarousal on sleep onset processes in healthy volunteers. Following an adaptation night, 15 subjects slept two nights in our sleep laboratory: one reference night and another one with cognitive arousal induction, in a counterbalanced order. In the cognitive arousal condition, subjects worked through half an hour of cognitive tasks without interference of an emotional component prior to retiring to bed. Objective sleep onset latency was significantly prolonged in the cognitive arousal condition compared to the reference condition. Significantly more high frequency activity was recorded during the first and second deep-sleep period. Moreover, differences in heart rate and proximal temperature during and after sleep onset were observed in the nights after the cognitive induction. Pre-sleep cognitive activation successfully induced a significant cognitive load and activation in our subjects to influence subsequent sleep (onset) processes.


Providing comprehensive health care to children with chronic illness.
To test whether a program of outreach and comprehensive health care for children with chronic disorders provides more complete care and reduces unmet health needs compared with traditional care. A pretest-posttest randomized control trial. An inner-city municipal teaching hospital. Two hundred nineteen systematically enrolled mothers of children with diverse chronic physical health conditions. A comprehensive outreach program, Pediatric Home Care (PHC), contrasted with Standard Care. Nine elements of comprehensive care established in the literature as components of a basic package of care for those with chronic conditions. The PHC intervention addressed gaps in services and improved both the acquisition and maintenance of elements of comprehensive care. These data suggest mechanisms through which comprehensive care programs may contribute to the improvement in psychological and social outcomes previously reported for those in the PHC intervention.


Medical 3D Printing: Tools and Techniques, Today and Tomorrow.
Three-dimensional printing is a still-emerging technology with high impact for the medical community, particularly in the development of tissues for the clinic. Many types of printers are under development, including extrusion, droplet, melt, and light-curing technologies. Herein we discuss the various types of 3D printers and their strengths and weaknesses concerning tissue engineering. Despite the advantages of 3D printing, challenges remain in the development of large, clinically relevant tissues. Advancements in bioink development, printer technology, tissue vascularization, and cellular sourcing/expansion are discussed, alongside future opportunities for the field. Trends regarding in situ printing, personalized medicine, and whole organ development are highlighted.


Intermediate levels of neuronal palmitoyl-protein Delta-9 desaturase in heterozygotes for murine Batten disease.
We recently demonstrated reduced activity of a novel palmitoyl-protein Delta-9 desaturase in neuronal tissues from mice with the cln3 Juvenile Neuronal Ceroid-Lipofuscinosis (Batten disease) gene ablated. In this follow-up study we have been able to obtain tissues from heterozygous cln3 mice and report that the enzyme activity in brain and pancreas from the heterozygotes is intermediate at 40% of the wild-type activity and consistent with recessive inheritance. Neuronal tissues from the CLN1 knock-out mouse demonstrated normal enzymatic activity pointing to the specificity of the desaturase function to CLN3. Non-neuronal tissues did not have measurable desaturase activity in wild-type or knock-out mice using this assay system. This may be due to lack of sensitivity of our assay system in these tissues or failure to activate the enzyme in these tissues. This is the first report of a heterozygous abnormality in Batten disease and provides important confirmation that this is the function of the CLN3 protein in neuronal tissues.


Retracted: Rural Architectural Planning and Landscape Optimization Design under the Background of Ecological Environment Protection.
[This retracts the article DOI: 10.1155/2022/5901718.].


Paramagnetic gold nanostructures for dual modal bioimaging and phototherapy of cancer cells.
Paramagnetic gold nanostructures were synthesized by combining the paramagnetism of gadolinium with the plasmonic properties of gold nanoparticles and used for dual modal (MRI and optical) imaging and phototherapy of breast cancer cells.


Accessing Methyl Groups in Proteins via 1H-detected MAS Solid-state NMR Spectroscopy Employing Random Protonation.
We recently introduced RAP (reduced adjoining protonation) labelling as an easy to implement and cost-effective strategy to yield selectively methyl protonated protein samples. We show here that even though the amount of H2O employed in the bacterial growth medium is rather low, the intensities obtained in MAS solid-state NMR 1H,13C correlation spectra are comparable to spectra obtained for samples in which α-ketoisovalerate was employed as precursor. In addition to correlations for Leu and Val residues, RAP labelled samples yield also resonances for all methyl containing side chains. The labelling scheme has been employed to quantify order parameters, together with the respective asymmetry parameters. We obtain a very good correlation between the order parameters measured using a GlcRAP (glucose carbon source) and a α-ketoisovalerate labelled sample. The labelling scheme holds the potential to be very useful for the collection of long-range distance restraints among side chain atoms. Experiments are demonstrated using RAP and α-ketoisovalerate labelled samples of the α-spectrin SH3 domain, and are applied to fibrils formed from the Alzheimer's disease Aβ1-40 peptide.


Phosphorylation of polyoma T antigens.
The T antigens of polyoma virus have been examined for phosphorylation in vivo and associated protein kinase activities in vitro. The 100K "large" T antigen is the major phosphoprotein among the T antigen species in vivo as determined by labeling virus-infected cells with 32P-orthophosphate. Hr-t mutants show normal phosphorylation of their 100K T antigens. The wild-type 56K plasma membrane-associated "middle" T antigen is also phosphorylated in the cell, but to a lesser extent than the 100K; this low level phosphorylation is also observed in the presumably altered 56K protein induced by hr-t mutant NG59 and in the 50K truncated "middle" T of hr-t mutant SD15. Addition of dibutyryl cyclic AMP to the medium does not affect labeling of either large or middle T antigens in wild-type- or mutant-infected cells. Thus no differences are observed in T antigen phosphorylation in vivo between wild-type virus and hr-t mutants. Hr-t mutants are defective in a protein kinase activity assayed in vitro by adding gamma-32P-ATP to T antigen immunoprecipitates. In the case of wild-type virus, the 56K protein is the major phosphate acceptor in the in vitro kinase reaction, with a somewhat lower level of phosphorylation observed in the 100K band. Hr-t mutants NG59 and SD15 show no labeling of the altered 56K or 50K, respectively, but do show detectable levels of 32P in the 100K bands. A wild-type virus carrying a small deletion affecting the 100K and 56k bands shows a normal level of kinase activity associated with the truncated T antigens. Ts-a mutants appear to be normal with respect to the middle T antigen-associated kinase. Photoaffinity labeling of infected cell extracts with 8-azido cyclic AMP shows that the two major classes of regulatory subunits of cyclic AMP-dependent protein kinases are present in the immunoprecipitates. Phosphorylation of histone H1 occurs when this substrate is added to immunoprecipitates of either mock-infected or virus-infected cells, again demonstrating the presence of cellular kinases. Further experiments will be required to determine whether the middle T antigen of polyoma virus is itself a protein kinase or simply a substrate for one or more cellular kinases.


The lasting effects of historical racial divides in nursing education: A case study examining holistic admission policies development.
Historically, in the United States, nursing programs reflected practices that systematically discriminated against Black students and nurses. The authors investigated historical nursing school admission policies to determine if racist practices existed that impeded Black students' ability to access formal nurse training programs. This study further examined whether those historical discriminating practices continue to exist in schools of nursing today and if admission policies in a Southern School of Nursing contributed to inequitable admission of students. Current recommendations for increasing diversity, equity and inclusion in nursing schools will be addressed. This study combines social-historical archival research with a case study of the racial breakdown of applied versus admitted nursing students at a Southern university. School of Nursing admission data (2019-2021) demonstrate discrepancies in the distribution of admitted students by race, reflecting the ongoing effects of systematic discrimination. In the United States, the nursing profession is pursuing strategies to promote diversity, equity, and inclusion. However, the lingering effects of policies that systematically built barriers keeping underrepresented groups from earning a nursing education persist. Holistic admission is one way that nursing programs can address this inequity.


Successful salvage treatment of steroid-refractory bronchiolar COP with low-dose macrolides.
Cryptogenic organizing pneumonia (COP) is an idiopathic interstitial pneumonia characterized by fibroblastic tissues that occupy the lumina of alveoli and alveolar ducts or respiratory bronchioles. Although adequate doses and durations of glucocorticoids can improve its condition, COP is sometimes resistant to glucocorticoid therapy and is often lethal.Herein, a very rare case of 'bronchiolar COP' that was confined to the respiratory bronchioles is reported. This case indicates that macrolides may act as anti-inflammatory agents in patients with COP. Timely and precise pathological diagnosis may corroborate clinician diagnoses and eventually improve chances to overcome the disease.


Correlates of dental visits in children with hearing loss: An application of the theory of planned behaviour.
Maintenance of oral health of children with special needs requires the involvement of caregivers who are also responsible for ensuring adherence to professional recommendations, including dental visits. This study aimed at exploring the correlates of dental visits of children with hearing loss (CWHL) in Indonesia using the theory of planned behaviour (TPB). This cross-sectional study involved purposive sampling methods, conducted via an online survey administered to mothers of CWHL who were aged 5-12 years. Constructs of the TPB model were collected, including the mother's attitudes, subjective norms, perceived behaviour control (PBC) and intention towards dental visits for CWHL. Dental visits were measured by asking whether their children had a dental visit within the last 12 months. Data were analysed using SPSS for descriptive and bivariate analyses. The significance level was set as p < .05. Partial least square structural equation modelling (PLS-SEM) was used to analyse measurement and structural TPB models. A total of 254 mothers participated in this study. The final TPB model explained 35.4% and 9.2% of the variance in mothers' intention and behaviour towards their children's dental visits, respectively. Of all the included constructs from the TPB model, only PBC was significantly associated with intention and behaviour (p < .05). The mother's attitude and subjective norms did not significantly predict intention (p > .05). Intention did not significantly predict the mother's behaviour towards children's dental visits (p > .05). The TPB model revealed a construct associated with dental visit intention and behaviour in CWHL. This study suggested that effective promotion intervention should focus on the mother's PBC to increase parents' adherence to preventive dental visits in CWHL in Indonesia.


Association between cannabis and the eyelids: A comprehensive review.
Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients. There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug. These include ptosis induction, an "eyelid tremor" appearance and blepharospasm attenuation. Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors. Fourteen articles report eyelid tremors in intoxicated drivers and ptosis as a secondary effect in cannabinoid animal experimental models. The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear. Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis.


Ligand-Dependent Effects of Methionine-8 Oxidation in Parathyroid Hormone Peptide Analogues.
LA-PTH is a long-acting parathyroid hormone (PTH) peptide analogue in preclinical development for hypoparathyroidism (HP). Like native PTH, LA-PTH contains a methionine at position 8 (Met8) that is predicted to be critical for function. We assessed the impact of Met oxidation on the functional properties of LA-PTH and control PTH ligands. Oxidation of PTH(1-34) resulted in marked (~20-fold) reductions in binding affinity on the PTH receptor-1 (PTHR1) in cell membranes, similarly diminished potency for 3',5'-cyclic AMP signaling in osteoblastic cell lines (SaOS-2 and UMR106), and impaired efficacy for raising blood calcium in mice. Surprisingly, oxidation of LA-PTH resulted in little or no change in these functional responses. The signaling potency of oxidized-LA-PTH was, however, reduced approximately 40-fold compared to LA-PTH in cells expressing a PTHR1 construct that lacks the N-terminal extracellular domain (ECD). Molecular modeling revealed that while Met8 of both LA-PTH and PTH(1-34) is situated within the orthosteric ligand-binding pocket of the receptor's transmembrane domain bundle (TMD), the Met8 sidechain position is shifted for the 2 ligands so that on Met8 oxidation of PTH(1-34), steric clashes occur that are not seen with oxidized LA-PTH. The findings suggest that LA-PTH and PTH(1-34) engage the receptor differently in the Met8-interaction environment of the TMD bundle, and that this interaction environment can be allosterically influenced by the ECD component of the ligand-receptor complex. The findings should be useful for the future development of novel PTH-based peptide therapeutics for diseases of bone and mineral ion metabolism.


MicroRNA-140-5p shuttled by microglia-derived extracellular vesicles attenuates subarachnoid hemorrhage-induced microglia activation and inflammatory response via MMD downregulation.
It is documented that microglia-secreted extracellular vesicles (microglia-EVs) exert neuroprotection which is important following subarachnoid hemorrhage (SAH). Herein, we focused on the mechanism of microglia-EVs harboring microRNA-140-5p (miR-140-5p) in SAH development. After the successful establishment of SAH rats, neurological function was evaluated, and behaviors were observed. Serum inflammatory factors (IL-1β and TNF-α) were quantified by ELISA, followed by the detection of microglial polarization by immunofluorescence. The relationship between miR-140-5p and monocyte to macrophage differentiation-associated (MMD) was evaluated using luciferase assay. Following the extraction of microglia and microglia-EVs, the transferring of miR-140-5p by microglia-EVs was assessed by co-culture experiments. SAH rats were treated with the EVs sourced from microglia overexpressing miR-140-5p (microglia-EVs-miR-140-5p) or EVs sourced from miR-140-5p-deficient microglia (microglia-EVs-miR-140-5p inhibitor) for in vivo effect assessment. Microglia-EVs inhibited microglia activation and secretion of TNF-α and IL-1β by delivering miR-140-5p. Microglia-EVs could transmit miR-140-5p into microglia. Furthermore, microglia-EVs-miR-140-5p reduced the expression of its target MMD, resulting in blocked inflammatory response and activation of microglia in SAH rats by disrupting the PI3K/AKT and Erk1/2 signaling. In summary, microglia-EVs transmitted miR-140-5p into microglia to downregulate MMD and finally contributed to neuroprotection in SAH rats.


Parametric optimisation for the design of gravity energy storage system using Taguchi method.
Gravitational energy storage systems are among the proper methods that can be used with renewable energy. However, these systems are highly affected by their design parameters. This paper presents a novel investigation of different design features of gravity energy storage systems. A theoretical model was developed using MATLAB SIMULINK to simulate the performance of the gravitational energy storage system while changing its design parameters. A parametric optimization study was also conducted using Taguchi and analysis of variance (ANOVA) techniques for optimizing the energy storage rate. Six parameters were studied; three are related to the piston design (diameter, height, and material density). The other parameters are the return pipe diameter, length, and charging/discharging time. Results revealed that the piston diameter and height are the two most significant parameters for the system performance compared to the other parameters, as they contributed by 35.11% and 30.28%, respectively. The optimization results indicated that the optimal piston diameter, height, and return pipe diameter were 0.25, 0.5, and 0.01 of the container height. The outcomes of this paper can significantly improve energy storage and power generation from renewable energy systems as it provides a reliable, economical, sustainable, and durable energy storage system.


Cell signaling and estrogens in female rat osteoblasts: a possible involvement of unconventional nonnuclear receptors.
Estrogen deficiency is associated with bone loss, and estrogen replacement is an effective treatment of this osteoporotic process. This study examines the early (5-120 s) effects of 17 beta-estradiol on the intracellular calcium and phospholipid metabolism in confluent female rat osteoblasts. The cytosolic free Ca2+ concentration ([Ca2+]i) was determined using fura-2/AM as Ca2+ probe. Cells were labeled with myo-[2-3H]inositol or [14C]arachidonic acid for inositol or lipid determination. Inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) production were determined by either mass measurement or anion-exchange chromatography or by thin-layer chromatography, respectively. 17 beta-Estradiol (1 pM to 1 nM) increased [Ca2+]i in a biphasic manner within 10 s via Ca2+ influx from the extracellular milieu, as shown by the effects of the calcium chelator EGTA and the Ca2+ channel blockers nifedipine and verapamil, and via Ca2+ mobilization from the endoplasmic reticulum (ER), as shown by the effects of thapsigargin. 17 beta-Estradiol (1 pM to 1 nM) induced a biphasic and concomitant increase in IP3 and DAG formation. Estradiol immobilized on bovine serum albumin (BSA) [E-(O-carboxymethyl)oxime BSA] and its derivative (O-carboxymethyl)oxime rapidly increased ([Ca2+]i, IP3, and DAG and were full agonists, although they were less potent than the free estradiol. They had the same action time course and acted via Ca2+ influx and Ca2+ mobilization from ER. Tamoxifen, a potent inhibitor of genomic steroid responses, did not block the rapid increase in Ca2+, IP3, and DAG induced by estradiol. Finally, inhibitor of phospholipase C (neomycin) and pertussis toxin abolished the effects of 17 beta-estradiol on IP3 and DAG formation. These results suggest that female rat osteoblasts bear non-genomic unconventional cell surface receptors for estradiol, belonging to the class of the membrane receptors coupled to a phospholipase C via a pertussis toxin-sensitive G protein.


Compliance during sessions and homework in exposure-based treatment of agoraphobia.
The relationship between compliance with cognitive-behavioral treatment instructions and outcome was examined for 56 agoraphobic clients treated with in vivo exposure and training in anxiety management strategies. Clients who complied more often with anxiety management instructions during treatment sessions tended to improve more on a behavioral avoidance test than those who were less compliant, but did not differ on three other outcome variables. Compliance with instructions for self-directed exposure between sessions was examined in a subset of 28 of these Ss. Clients who spent more time doing homework reported significantly greater decrements in fear of fear than less compliant clients and also tended to report larger changes on avoidance behavior. However, a quasi-experimental comparison of homework vs no-homework treatment protocols yielded no difference in outcome. Less compliant clients were more symptomatic pretreatment and rated their therapists as less caring and less self-confident.


The aetiology and treatment of needle phobia in the young patient--a review.
This Paper reviews current concepts regarding the aetiology and treatment of needle phobias in young patients.


The endogenous progesterone metabolite, 5a-pregnane-3,20-dione, decreases cell-substrate attachment, adhesion plaques, vinculin expression, and polymerized F-actin in MCF-7 breast cancer cells.
Tumorous human breast tissue readily converts progesterone to 5alpha-pregnane-3,20-dione (5alphaP), and this metabolite has been shown to stimulate proliferation and to decrease adhesion of MCF-7 breast cancer cells. To determine the mechanisms of action of 5alphaP on cell adhesion, MCF-7 cells were grown without or with 5alphaP (10(-9)-10(-5) M), and the effects on cell and nuclear morphology, adhesion plaques, vinculin and actin expression, actin polymerization, and microfilament distribution were examined by immunohistochemistry, morphometry (using confocal microscopy and digital computer imaging analysis), and Western blotting. Treatment of cells with 10(-9)-10(-6) M 5alphaP resulted in dose-dependent decreases in cell area, cell-to-cell contacts, and attachment to the substratum, and increases in variation in nuclear area. These changes in the 5alphaP-treated cells were accompanied by decreases in vinculin-containing adhesion plaques, vinculin expression, polymerized actin stress fibers, and decreases in insoluble and increases in soluble actin fractions. The results suggest that the observed decreases in adhesion and increases in cell proliferation following 5alphaP treatment may be owing to depolymerization of actin and decreased expression of actin and vinculin. We conclude that the endogenous progesterone metabolite, 5alphaP, may be involved in promoting breast neoplasia and metastasis by affecting adhesion and cytoskeletal molecules.


Diagnostic imaging of ankle impingement syndromes in athletes.
The chronic ankle pain is a very frequent clinical problem, which is often characterized by a painful mechanical limitation of full-range ankle movement. A large amount of causes are involved in its pathogenesis, but the most common forms are secondary to an osseous or soft tissue abnormality. Especially for professional athletes, impingement lesions are the most important causes of chronic pain; however, this symptomatology can also affect ordinary people, mostly in those who work in environments that cause severe mechanical stress on the joints. This group of pathologies is characterized by a joint conflict secondary to an abnormal contact among bone surfaces or between bones and soft tissues. Diagnosis is mainly clinic and secondly supported by imaging in order to localize the critical area of impingement and determine the organic cause responsible for the joint conflict. Treatments for different forms of impingement are similar. Usually, the first step is a conservative approach (rest, physiotherapy, ankle bracing, shoe modification and local injection of corticosteroids), and only in case of unsuccessful response, the second step is the operative treatment with open and arthroscopic techniques. The aim of the study is to describe different MR imaging patterns, comparing our data with those reported in the literature, in order to identify the best accurate diagnostic protocol.


Mapping hospital antimicrobial stewardship programmes in the Gulf Cooperation Council states against international standards: a systematic review.
While there is evidence of implementation of antimicrobial stewardship programmes (ASPs) in the Gulf Cooperation Council (GCC) states, there has been limited benchmarking and mapping to international standards and frameworks. To critically appraise and synthesize the evidence of ASP implementation in GCC hospitals with reference to the framework of the Centers for Disease Control and Prevention (CDC), identifying key facilitators and barriers. A systematic review protocol was developed based on Preferred Reporting Items for Systematic Reviews and Meta-analyses for Protocols guidelines. Five electronic databases were searched for studies published in English from 2010 onwards. Study selection, quality assessment and data extraction were performed independently by two reviewers. A narrative synthesis was conducted with ASP interventions mapped to CDC core elements. Seventeen studies were identified, most of which (N=11) were from Saudi Arabia. Mapping to the CDC framework identified key areas of strengths and weaknesses in reporting implementation. Studies more commonly reported core elements of pharmacy expertise, selected aspects of implementation actions, tracking, antibiotic use and resistance, and education. Little emphasis was placed on the reporting of leadership and accountability. Key implementation facilitators were physician and organization support, information systems and education, and barriers were dedicated staff, workload and funding. There is a need to enhance the reporting of ASP implementation in GCC hospitals. The CDC framework should be used as a guide during the development, implementation and reporting of ASP interventions. Action is required to identify facilitators and overcome barriers, where possible.


Novel immune subtypes identification of HER2-positive breast cancer based on immunogenomic landscape.
HER2 positive BC is heterogeneous. But few studies discussed the classification of HER2-positive BC based on immune-related signatures. Using three publicly BC genomics datasets, we classified HER2 positive BC based on 33 immune-related signatures and used unsupervised machine learning methods to predict and perform the classification. We grouped three HER2-positive BC subtypes that we called Immune-High (IM-H), Immune-Medium (IM-M), and Immune-Low (IM-L), and manifested this categorization was predictable, duplicable and reliable by analyzing another dataset. Compared to other subtypes, IM-H had a higher immune cell infiltration level and stronger anti-tumor immune activities, as well as better clinical survival outcome. Besides these signatures, there were some cancer-related pathways which were hyperactivated in IM-H, including cytokine-cytokine receptor interactions, antigen processing and presentation pathways, natural killer cell-mediated cytotoxicity, Th1 and Th2 cell differentiation, chemokine signaling pathway, Th17 cell differentiation, B and T cell receptor signaling, NF-kappa B signaling, PD-L1 expression and PD-1 checkpoint pathway in cancer, TNF signaling, IL-17 signaling, NOD-like receptor signaling and Toll-like receptor signaling. By contrast, IM-L showed depressed immune-related signatures and enhanced activation of lycosylphosphatidylinositol-anchor biosynthesis and mismatch repair. Moreover, we discovered a gene co-expression network focused on eight transcription factor genes (EOMES, TBX21, GFI1, IRF4, POU2AF1, CIITA, FOXP3 and TOX) and one tumor suppress gene (PRF1), which were closely related with tumor immune. We identified three HER2-positive BC subtypes based on immune-related signatures, which had potential clinical implications and promoted the optimal stratification of HER2-positive BC responsive to immunotherapy.


Mortality and neurodevelopmental outcomes of infants with spontaneous intestinal perforation: a systematic review and meta-analysis.
There is limited information about the mortality and neurodevelopmental outcomes of very preterm infants (<32 weeks) with spontaneous intestinal perforation (SIP). To explore the association between SIP and neurodevelopmental outcomes and mortality in very preterm infants. Medline, EMBASE, Cochrane Library, EMCARE and MedNar. Databases were searched until September 2021. Studies comparing outcomes of 'SIP' versus 'no SIP or necrotising enterocolitis (NEC)' were included. Neurodevelopmental outcomes at ≥1 year corrected age were extracted as the main outcome measure. Data were pooled separately for adjusted and unadjusted ORs using the random-effects model. The evidence level was assessed using the GRADE (Grading of Recommendations, Assessments, Development and Evaluations) framework. Eighteen cohort studies (13 606 infants) were included. Meta-analysis of unadjusted ORs showed that SIP was significantly associated with increased odds of mortality, cerebral palsy, composite outcome of death or disability, visual impairment and hearing impairment. However, pooling of adjusted ORs (aOR) found significant associations only for mortality (aOR (95% CI) 2.27 (2.07 to 2.49); I2: 0%; four studies (n=10 695)), severe disability (aOR (95% CI) 2.06 (1.38 to 3.08); I2: 0%; two studies (n=321)) and composite outcome of 'death or disability' (aOR (95% CI) 2.18 (1.55 to 3.06); I2: 0%; two studies (n=321)). The level of evidence was 'low' or 'very low'. Lack of information on aORs from many studies. SIP in very preterm infants is associated with higher odds of mortality, severe disability, and death or disability.


Crafting the magnonic and spintronic response of BiFeO3 films by epitaxial strain.
Multiferroics are compounds that show ferroelectricity and magnetism. BiFeO3, by far the most studied, has outstanding ferroelectric properties, a cycloidal magnetic order in the bulk, and many unexpected virtues such as conductive domain walls or a low bandgap of interest for photovoltaics. Although this flurry of properties makes BiFeO3 a paradigmatic multifunctional material, most are related to its ferroelectric character, and its other ferroic property--antiferromagnetism--has not been investigated extensively, especially in thin films. Here we bring insight into the rich spin physics of BiFeO3 in a detailed study of the static and dynamic magnetic response of strain-engineered films. Using Mössbauer and Raman spectroscopies combined with Landau-Ginzburg theory and effective Hamiltonian calculations, we show that the bulk-like cycloidal spin modulation that exists at low compressive strain is driven towards pseudo-collinear antiferromagnetism at high strain, both tensile and compressive. For moderate tensile strain we also predict and observe indications of a new cycloid. Accordingly, we find that the magnonic response is entirely modified, with low-energy magnon modes being suppressed as strain increases. Finally, we reveal that strain progressively drives the average spin angle from in-plane to out-of-plane, a property we use to tune the exchange bias and giant-magnetoresistive response of spin valves.


De novo neuromuscular junction formation on human muscle fibres cultured in monolayer and innervated by foetal rat spinal cord: ultrastructural and ultrastructural--cytochemical studies.
Ultrastructural features of neuromuscular junction formation and transverse tubule development were studied utilizing a newly developed model in which human muscle fibres cultured in monolayer are innervated by foetal rat spinal cord with dorsal root ganglia attached. At early innervation (7-10 days), when distinct 'boutons' are contacting muscle fibres, the contacts of nerve terminals with the muscle fibres are, ultrastructurally, superficial and unorganized, and there is no basal lamina-like material between nerve terminals and muscle fibres. A bouton consists, ultrastructurally, of a cluster of small nerve terminals contacting the muscle fibre. At 2-3 weeks of innervation, shallow 'beds' are formed on the muscle fibre just beneath nerve terminals, and occasionally there are irregular and miniscule fragments of basal lamina-like material in the cleft. There is no Schwann cell apposing the nerve terminal at this stage of innervation. After 4-5 weeks of innervation there is more definite basal lamina material in the cleft and suggestive postsynaptic plasmalemmal densities and invaginations. However, there is no Schwann cell apposing the nerve terminal at this stage. At 6-8 weeks of innervation, deep postsynaptic folds are present, a Schwann cell apposes the nerve terminal, and basal lamina surrounds the entire muscle fibre. At all four stages of innervation examined, ultrastructural cytochemistry of alpha-bungarotoxin binding reveals that nicotinic ACh receptors are located exclusively at the neuromuscular junctions. After 1-2 weeks of innervation, very few lanthanum-positive transverse tubules are observed and only in close proximity to the surface membrane. After 3 weeks of innervation, more lanthanum-positive tubules are present, and they are located deeper within the muscle fibre. Five weeks after innervation, somewhat more elaborated tubules (but no lateral sacs) appear, and honeycomb structures are often present. After 6-7 weeks of innervation the tubular system is very elaborate and lateral sacs are present. Hence, this study describes consecutive stages of the formation of neuromuscular junctions and transverse tubules in innervated cultured human muscle, and provides an important basis to which similar studies related to the diseased human muscle can be compared.


Walking the walk: Advice for anti-racist academic leaders.
The importance of advancing anti-racism within research has gained recent attention. Academic medical organizations have attempted to increase diversity while seeking structural reforms to advance equity. However, efforts remain constrained while persons from racialized groups continue to experience discrimination. Mental health research is not immune to the experience of inequity. There is ample evidence that mental health research is underfunded compared to other types of health research. In addition, many racialized researchers and research staff have experienced different forms of implicit, explicit, and structural racism and are finding the courage to share their stories. Such experiences of racial trauma have a disastrous impact on the well-being of mental health researchers and adversely influence our overall mission. In this commentary, we also provide tangible and practical suggestions for academic leaders in the field. First, leaders must name racism and resist fragility and defensive reactions when the topic of racism in research is broached. Second, leaders should seek to foster a culture of belonging on teams where feedback from all is welcomed and encouraged. Third, leaders should seek structural change to ensure that teams are diverse and the adverse influence of systemic forms of racial discrimination on research our mitigated. Fourth, leaders must center the voices and perspective of those impacted by racial discrimination when developing, implementing, and evaluating their anti-racism work.


Optimizing Safety for Surgical Patients Undergoing Interhospital Transfer.
Interhospital transfers play a key role in ensuring that patients receive necessary care. However, patients who are transferred between hospitals are a vulnerable population, and outcomes of transferred patients are suboptimal. Despite the critical nature of interhospital transfers, only limited effort has been dedicated to standardization and improvement of the transfer process. Studying and adapting quality improvement efforts directed at other transitions of care, particularly those that cross between different facilities and care teams "such as the transition from hospital to home or extended care facilities" may improve the care of surgical patients transferred between acute care institutions.


A meta-analysis of excess cardiac mortality on Monday.
Available evidence suggests a peak in the incidence of cardiovascular events on Mondays compared to other days of the week. The exact magnitude of the excess risk and the role of age and gender, however, remain unclear. To quantify the excess risk associated with the Monday peak in cardiovascular mortality and to explore the role of age and gender. A meta-analysis of available published studies reporting on weekly patterns in incidence of myocardial infarction and sudden cardiac death was performed. Reports based on routinely collected data from population statistics (n = 5) generally reported a lower odds ratio (OR) of an event on Monday than studies with a confirmed diagnosis (n = 16). The pooled OR estimate based on population statistics was 1.04 (95%CI: 1.03; 1.05), whereas the pooled OR estimate based on confirmed diagnoses was 1.19 (95%CI: 1.17; 1.21). Subgroup analysis yielded an OR of 1.19 (95%CI: 1.07; 1.31) for men and 1.15 (95%CI: 0.99; 1.32) for women. Odds ratios for patients younger than 65 years of age and 65 or older were 1.22 (95%CI: 1.09; 1.36) and 1.16 (95%CI: 1.07; 1.27), respectively. The differences between subgroup odds ratios were not statistically significant. The incidence of sudden cardiac death is markedly increased on Monday, similar for men and women, and for subjects below and above 65 years of age.


Effect of hydraulic retention time on anaerobic hydrogenesis in CSTR.
The objective of this work was to evaluate the production of hydrogen in a continuous system as a function of hydraulic retention time (HRT). The intermediates accumulated and other parameters of pH, oxidation-reduction potential were quantified. The heat treatment (103 degrees C for 24 h) of the compost from a cattle dung composting facility was able to select H2-producing spores; this product was used as a seed for continuous systems. The brewery waste was used as substrate. For the eight runs with combinations of five HRTs and four pHs, the results indicate that at pH=5.5, a maximum H2 production of 47% H2 concentration, 43 ml H2/g COD(added), and 3.1 l H2/l reactor d was achieved at HRT=18 h. Nevertheless, at HRT=18 h, pH 5.5 was also the optimum pH for the maximum H2 production among four pHs evaluated from 5 to 6.5. There was a significant accumulation of volatile acid and alcohols during the entire study.


A simple, accurate, and sensitive assay method of dehydroepiandrosterone sulfate: application for quantitative determination in human breast cyst and duct fluids.
Radioimmunoassay (RIA) is the most prevalent method for measuring small amounts of hormones, peptides, and other compounds in human body fluids. The method, however, has several problems, such as cross reactions or non-specific reactions of the antibody used. In order to establish an improved method for assaying dehydroepiandrosterone sulfate (DHEAS) and cholesterol, which are the largest components of human breast cyst and duct fluids, we describe a simple, accurate, and sensitive method using high-performance liquid chromatography (HPLC). The samples were treated with cholesterol oxidase for quantitation of dehydroepiandrosterone (DHEA) and free cholesterol, and the respective oxidized substances, 4-androstene-3,17-dione and 4-cholesten-3-one, were extracted with n-hexane. The extracts were analyzed by straight phase HPLC. Effluents were monitored by measuring absorption at 240 nm, where a newly introduced chromophoric group, an alpha,beta-unsaturated ketone, showed intense absorption (epsilon = 16,000). When the total amount of DHEA (DHEAS plus DHEA) was measured, the sample had been solvolyzed by sulfatase beforehand. The amounts of DHEAS were quantified by comparing the amounts of DHEA before and after solvolysis. Levels of free cholesterol, DHEAS, and DHEA in human breast cyst fluids (n = 30) were 1.77 +/- 1.12 mmol/dl, 8.27 +/- 10.24 micromol/dl, and 0.02 +/- 0.02 micromol/dl (means +/- SD), respectively. The levels of sterol and steroid measured in breast duct fluids that were turbid, brown, dark green, or milky in color (n = 9) (mean levels, 3.20 +/- 2.97 mmol/dl for free cholesterol and 14.77 +/- 13.75 micromol/dl for DHEAS) were significantly (P < 0.01) higher than the levels in clear or serous breast fluids (n = 21) (mean levels, 0.14 +/- 0.13 mmol/dl for free cholesterol and 0.04 +/- 0.07 micromol/dl for DHEAS).


Patients From Appalachia Have Reduced Access to Liver Transplantation After Wait-Listing.
The Appalachian region is medically underserved and characterized by high morbidity and mortality. We investigated disparities among patients listed for liver transplantation (LT) in wait-list outcomes, according to residence in the Appalachian region. Data on adult patients listed for LT were obtained from the United Network for Organ Sharing for July 2013 to December 2015. Wait-list outcomes were compared using cause-specific hazard models by region of residence (Appalachian vs non-Appalachian) among patients listed at centers serving Appalachia. Posttransplant patient and graft survival were also compared. The study included 1835 LT candidates from Appalachia and 5200 from non-Appalachian regions, of whom 1016 patients experienced wait-list mortality or were delisted; 3505 received liver transplants. In multivariable analyses, patients from Appalachia were less likely to receive LT (hazard ratio [HR] = 0.86; 95% confidence interval [CI]: 0.79-0.93; P < .001), but Appalachian residence was not associated with wait-list mortality or delisting (HR = 1.03; 95% CI: 0.89-1.18; P = .696). Among liver transplant recipients, patient and graft survival did not differ by Appalachian versus non-Appalachian residence. Appalachian residence was associated with lower access to transplantation after listing for LT. This geographic disparity should be addressed in the current debate over reforming donor liver allocation and patient priority for LT.


Serum progranulin levels are elevated in patients with chronic hepatitis B virus infection, reflecting viral load.
Progranulin (PGRN) is implicated in infection, immunity and host defense, but its role in the pathogenesis of HBV infection remains unknown. Here we investigated whether there is dysregulated production and the clinical significance of circulating PGRN in patients with chronic HBV infection. Serum concentrations of PGRN were analyzed by enzyme-linked immunosorbent assay. Serum PGRN levels were significantly higher in patients with chronic HBV infection than healthy subjects. PGRN levels were significantly associated with HBV-DNA levels, but did not correlate with the concentrations of alanine aminotransferase and aspartate aminotransferase. This study demonstrates increased circulating PGRN production and association between PGRN levels and viral loads in patients with chronic HBV infection, suggesting a functional role of PGRN in the pathogenesis of HBV infection.


An insight into source apportionment of metals in superficial sediments from the Tien Hai nature reserve of the Red River delta, Vietnam.
In the present study, concentrations of 23 metallic elements (Al, Fe, K, Mg, Ti, Mn, V, Cr, Co, Ni, Cu, Zn, Ga, As, Sr, Zr, Mo, Cd, Ba, W, Hg, Pb and U) were determined in superficial sediments from 20 sites within the Tien Hai nature reserve of the Red River delta. An integrated approach including correlation analysis (CA), principal components analysis (PCA) and positive matrix factorization (PMF) was combined to identify and quantify the sources of these metals. The results indicated that the correlation analysis was able to identify both allochthonous and authigenous origin of metals while the remaining methods were unable to identify these origins. With the help of CA, the PMF model performed better at the source identification of metals than the PCA. The results of PMF demonstrated that weathering products formed on different parent rocks were the biggest contributor to natural sources of metals in the superficial sediments, while agricultural activities were regarded as the major contributor to anthropogenic sources of metals. These findings could provide a scientific basis for environmental protection authority to prevent and control the sediment metal pollution. Accordingly, application of organic amendments and reduction of inorganic fertilizer should be encouraged to minimize metal accumulation in sediments.


Green Metal-Free Photochemical Hydroacylation of Unactivated Olefins.
Direct alkylation of C(sp2 )-H bonds to convert an aldehyde into a ketone is a notorious transformation, due to the laborious challenge of the formation of ketyl or acyl radicals. Herein, we report a green, cheap, metal-free and efficient method for the hydroacylation of olefins in water. This photochemical protocol utilizes phenylglyoxylic acid, a commercially available small organic molecule, as the photoinitiator, water as the solvent and household fluorescent lamps as the irradiation source, leading to a broad substrate scope of products in moderate to good yields. A wide range of aromatic and aliphatic aldehydes, terminal and non-terminal alkenes and pharmaceutically relevant molecules can be employed, without the need of directing groups and additives or metal catalysts.


Loss of CB1 receptors leads to decreased cathepsin D levels and accelerated lipofuscin accumulation in the hippocampus.
Early onset of age-related changes in the brain of cannabinoid 1 receptor knockout (Cnr1(-/-)) mice suggests that cannabinoid 1 (CB1) receptor activity significantly influences the progression of brain aging. In the present study we show that lack of CB1 receptors leads to a significant increase in lipofuscin accumulation and a reduced expression and activity of cathepsin D, lysosomal protease implicated in the degradation of damaged macromolecules, in the hippocampus of 12-month-old mice. The impaired clearance of damaged macromolecules due to the low cathepsin D levels and not enhanced oxidative stress may be responsible for the lipofuscin accumulation because macromolecule oxidation levels were comparable between the genotypes within the same age group. The altered levels of autophagy markers p62 and LC3-II suggest that autophagy is upregulated in CB1 knockout mice. Increased autophagic flux in the absence of CB1 receptors is probably a compensatory mechanism to partially counteract decreased lysosomal degradation capacity. Together, these results suggest that CB1 receptor activity affects lysosomal activity, degradation of damaged macromolecules and thus it may influence the course and onset of brain aging.


Eigenstress model for electrochemistry of solid surfaces.
Thermodynamic analysis and molecular dynamics simulations were conducted to systematically study the size-dependent electrochemical response of solids. By combining the generalized Young-Laplace equation with the popular Butler-Volmer formulation, the direct influence of surface stress on solid film electrochemical reactions was isolated. A series of thermodynamic formulas were developed to describe the size-dependent electrochemical properties of the solid surface. These formulas include intrinsic surface elastic parameters, such as surface eigenstress and surface elastic modulus. Metallic films of Au, Pt, Ni, Cu and Fe were studied as examples. The anodic current density of the metal film increased, while the equilibrium potential decreased with increasing solid film thickness.