A potential role of the heparan sulfate in the hepatitis C virus attachment.
Several putative cell surface receptors have been identified in the Hepatitis C virus (HCV) infection including CD81, low-density lipoprotein (LDL) receptor, scavenger receptor class B type I (SR-BI), and highly sulfated heparan sulfate (HS). In this study, we showed that the binding of soluble heparin to the envelope glycoprotein E2 (E2) of HCV was dependent on the dose and conformation of E2. On the other hand, the binding of E2 to the cell surface after treatment with soluble heparin was not markedly inhibited, what was different from other viruses utilizing cellular HS as the primary receptor. However, the enzymatic removal of HS from the cell surface led to a significant reduction in the binding of E2 to the cells. These facts imply that E2 was bound to cellular HS but might also have another route for cell attachment. Monoclonal antibodies with neutralizing activity against E2 did not completely block the binding of E2 to the cell surface, but their neutralization activity was greatly enhanced in the presence of soluble heparin. Taken together, the cellular HS could act as an alternative receptor for HCV and the interaction of E2 with HS could play a distinct role in escaping of HCV from the humoral immunity.


The diagnosis of early carcinoma of the prostate.
Careful palpation of the gland is a very important examination procedure in the detection of early carcinoma in the prostate. The finding of a suspicious area requires additional investigation, which must include histological examination of tissue from the suspected lesion. Adequate material for histological studies can usually be obtained by needle biopsy. The percutaneous perineal approach has been found satisfactory for this purpose. In those whose life expectancy is 10 years or more, prostatic carcinoma in its early stages should be treated by radical prostatectomy. For more advanced lesions or for patients whose life expectancy is less, hormonal therapy may be used.


High-sensitivity C-reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn's disease: a marker for patient classification?
C-reactive protein (CRP) is a traditional nonspecific marker of inflammation, with Crohn's disease (CD) being associated with a strong CRP response. Thus far, no clear cutoff values have been determined. The authors' aim was to investigate whether high-sensitivity (hs)-CRP is useful for the identification disease phenotype, active disease, and relapse during follow-up, using a classification based on the hs-CRP value at diagnosis. In all, 260 well-characterized, unrelated, consecutive CD patients (male/female: 120/140; duration: 7.0 ± 6.1 years), with a complete clinical follow-up, were included. Hs-CRP, clinical activity according to the Harvey-Bradshaw Index, and clinical data (disease phenotype according to the Montreal Classification, extraintestinal manifestations, smoking habits, medical therapy, and surgical events) were prospectively collected between January 1, 2008 and June 1, 2010. Medical records prior to the prospective follow-up period were analyzed retrospectively. In all, 32.3% of CD patients had normal hs-CRP at diagnosis. Elevated hs-CRP at diagnosis was associated with disease location (P = 0.002), noninflammatory disease behavior (P = 0.058), and a subsequent need for later azathioprine/biological therapy (P < 0.001 and P = 0.024), respectively. The accuracy of hs-CRP for identifying patients with active disease during prospective follow-up was good (area under the curve [AUC]: 0.82, cutoff: 10.7 mg/L). AUC was better in patients with an elevated hs-CRP at diagnosis (AUC: 0.92, cutoff: 10.3 mg/L). In Kaplan-Meier and Cox-regression analyses, hs-CRP was an independent predictor of 3- (P = 0.007) or 12-month (P = 0.001) clinical relapses for patients in remission who had elevated hs-CRP at diagnosis. In addition, perianal involvement (P = 0.01) was associated with the 12-month relapse frequency. Our data suggest that hs-CRP positivity at diagnosis is associated with disease location and behavior, and in patients who are hs-CRP positive at diagnosis, is an accurate marker of disease activity and a predictor of short- and medium-term clinical flare-ups during follow-up.


Comparison of Long-Term Effects between Chest Compression-Only CPR Training and Conventional CPR Training on CPR Skills among Police Officers.
Despite of the changes of out-of-hospital cardiac arrest (OHCA) survival rise when bystander CPR is provided, this was only conducted in about 23% of OHCA patients in Korea in 2018. Police officers acting as first responders have a high chance of witnessing situations requiring CPR. We investigated long-term effects on CPR quality between chest compression-only CPR training and conventional CPR training in police officers to find an efficient CPR training method in a prospective, randomized, controlled trial. Police officers underwent randomization and received different CPR training. With the Brayden Pro application, we compared the accuracy of CPR skills immediately after training and the one after 3 months. Right after training, the conventional CPR group presented the accuracy of the CPR skills (compression rate: 74.6%, compression depth: 66.0%, recoil: 78.0%, compression position: 96.1%) and chest compression-only CPR group presented the accuracy of the CPR skills (compression rate: 74.5%, compression depth: 71.6%, recoil: 79.2%, compression position: 99.0%). Overall, both groups showed the good quality of CPR skills and had no meaningful difference right after the training. However, three months after training, overall accuracy of CPR skills decreased, a significant difference between two groups was observed for compression position (conventional CPR: 80.0%, chest compression only CPR: 95.0%). In multiple linear regression analysis, three months after CPR training, chest compression-only CPR training made CPR skills accuracy 28.5% higher. In conclusion, police officers showed good-quality CPR right after CPR training in both groups. But three months later, chest compression-only CPR training group had better retention of CPR skills. Therefore, chest compression-only CPR training is better to be a standard training method for police officers as first responders.


Daily hassles, uplifts, and time use in individuals with bipolar disorder in remission.
Although life stress has been shown to trigger relapse in bipolar disorder, little is known about how bipolar patients perceive daily hassles or their positive counterparts, uplifts. We used the experience sampling method to investigate the daily experience of hassles and uplifts in 38 patients with remitted bipolar disorder and 38 healthy controls. Largely because of current unemployment, patients were more often alone and at home and spent less time working and more time in passive leisure activities. Contrary to expectations, the groups did not differ in total frequencies or appraisals of events. Within the patient group, however, those patients with current depressive symptoms and more previous depressive episodes experienced negative events as more stressful. These findings are consistent with hypothesized processes linking depressive symptoms to the generation of stressful conditions or to the reactivation of negative cognitive schemas.


Identifying Spurious Interactions in the Protein-Protein Interaction Networks Using Local Similarity Preserving Embedding.
In recent years, a remarkable amount of protein-protein interaction (PPI) data are being available owing to the advance made in experimental high-throughput technologies. However, the experimentally detected PPI data usually contain a large amount of spurious links, which could contaminate the analysis of the biological significance of protein links and lead to incorrect biological discoveries, thereby posing new challenges to both computational and biological scientists. In this paper, we develop a new embedding algorithm called local similarity preserving embedding (LSPE) to rank the interaction possibility of protein links. By going beyond limitations of current geometric embedding methods for network denoising and emphasizing the local information of PPI networks, LSPE can avoid the unstableness of previous methods. We demonstrate experimental results on benchmark PPI networks and show that LSPE was the overall leader, outperforming the state-of-the-art methods in topological false links elimination problems.


Occupation-related squatting, kneeling, and heavy lifting and the knee joint: a magnetic resonance imaging-based study in men.
We examined the relation between occupational exposures to frequent squatting/kneeling and/or heavy lifting with cartilage morphology, based on magnetic resonance imaging (MRI), at the tibiofemoral and patellofemoral joints in men and determined which compartments are most affected. We evaluated 192 men with symptomatic knee osteoarthritis (OA). The more symptomatic knee was imaged using MRI. Cartilage was scored using the Whole Organ MRI Score semiquantitative method at the medial and lateral tibiofemoral joint and patellofemoral joint. Occupational exposures to frequent squatting, kneeling, and/or heavy lifting were assessed using a validated questionnaire. Among the 192 men [mean (+/- standard deviation) age 69 +/- 9 yrs, body mass index (BMI) 30.8 +/- 4.7 kg/m(2)], those reporting occupational exposure to squatting/kneeling alone, heavy lifting alone, both squatting/kneeling and heavy lifting, or none of these activities numbered 7, 40, 47, and 98, respectively. Compared with men with no occupational exposure to these activities, and following adjustment for age, BMI, and history of knee injury or surgery, we found that men reporting occupational exposures to both squatting/kneeling and heavy lifting had a modest increased risk for worse cartilage morphology scores at the patellofemoral joint [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.1 to 3.2] and medial tibiofemoral joint (OR 1.6, 95% CI 0.9, 3.0), although the latter did not reach statistical significance. Men with frequent occupational squatting/kneeling and heavy lifting have a greater likelihood for worse cartilage morphology scores at the patellofemoral joint. These findings add support to the important role of biomechanical loading on the pathogenesis of knee OA, particularly patellofemoral OA.


Subtle Structural Changes in (CuIIL)2MnII Complexes To Induce Heterometallic Cooperative Catalytic Oxidase Activities on Phenolic Substrates (H2L = Salen Type Unsymmetrical Schiff Base).
A new Cu(II) complex of an asymmetrically dicondensed Schiff base (H2L = N-(2-hydroxyacetophenylidene)-N'-salicylidene-1,3-propanediamine) derived from 1,3-propanediamine, salicylaldehyde, and o-hydroxyacetophenone has been synthesized. Using this complex, [CuL] (1), as a metalloligand, two new trinuclear Cu-Mn complexes, [(CuL)2Mn(N3)(H2O)](ClO4)·H2O (2) and [(CuL)2Mn(NCS)2] (3), have been prepared. Single-crystal structural analyses reveal that complexes 2 and 3 both have the same bent trinuclear {(CuL)2Mn}2+ structural unit in which two terminal bidentate square-planar (CuL) units are chelated to the central octahedral Mn(II) ion. This structural similarity is also evident from the variable-temperature magnetic susceptibility measurements, which suggest that compounds 2 and 3 are both antiferromagnetically coupled with comparable exchange coupling constants (-21.8 and -22.3 cm-1, respectively). The only difference between 2 and 3 lies in the coordination around the central Mn(II) ion; in 3, two SCN- groups are coordinated to the Mn(II), leaving a neutral complex, but in 2, one N3- group and one H2O molecule are coordinated to give a positively charged species. The presence of such a labile H2O coligand makes 2 catalytically active in mimicking two well-known polynuclear copper proteins, catecholase and phenoxazinone synthase. The turnover numbers (kcat) for the aerial oxidation of 3,5-di-tert-butylcatechol and o-aminophenol are 1118 and 6581 h-1, respectively, values which reflect the facility of the heterometallic catalyst in terms of both efficiency and catalytic promiscuity for aerial dioxygen activation. The mechanisms of these biomimetic oxidase reactions are proposed for the first time involving any heterometallic catalyst on the basis of mass spectral analysis, EPR spectroscopy, and cyclic voltammetry. The evidence of the intermediates indicates possible heterometallic cooperative activity where the substrates bind to a Mn(II) center and Cu(II) plays the role of an electron carrier for transformation of the phenolic substrates to their respective products with the reduction of aerial dioxygen.


Microsporidian Nosema bombycis hijacks host vitellogenin and restructures ovariole cells for transovarial transmission.
Microsporidia are a group of obligate intracellular parasites that infect almost all animals, causing serious human diseases and major economic losses to the farming industry. Nosema bombycis is a typical microsporidium that infects multiple lepidopteran insects via fecal-oral and transovarial transmission (TOT); however, the underlying TOT processes and mechanisms remain unknown. Here, we characterized the TOT process and identified key factors enabling N. bombycis to invade the ovariole and oocyte of silkworm Bombyx mori. We found that the parasites commenced with TOT at the early pupal stage when ovarioles penetrated the ovary wall and were exposed to the hemolymph. Subsequently, the parasites in hemolymph and hemolymph cells firstly infiltrated the ovariole sheath, from where they invaded the oocyte via two routes: (I) infecting follicular cells, thereby penetrating oocytes after proliferation, and (II) infecting nurse cells, thus entering oocytes following replication. In follicle and nurse cells, the parasites restructured and built large vacuoles to deliver themselves into the oocyte. In the whole process, the parasites were coated with B. mori vitellogenin (BmVg) on their surfaces. To investigate the BmVg effects on TOT, we suppressed its expression and found a dramatic decrease of pathogen load in both ovarioles and eggs, suggesting that BmVg plays a crucial role in the TOT. Thereby, we identified the BmVg domains and parasite spore wall proteins (SWPs) mediating the interaction, and demonstrated that the von Willebrand domain (VWD) interacted with SWP12, SWP26 and SWP30, and the unknown function domain (DUF1943) bound with the SWP30. When disrupting these interactions, we found significant reductions of the pathogen load in both ovarioles and eggs, suggesting that the interplays between BmVg and SWPs were vital for the TOT. In conclusion, our study has elucidated key aspects about the microsporidian TOT and revealed the key factors for understanding the molecular mechanisms underlying this transmission.


Interleukin-8 and Its Receptors in Human Milk from Mothers of Full-Term and Premature Infants.
In addition to its nutritional benefits, human milk also has bioactive elements. Limited immunological functions of newborns are supported and altered by the immunological elements of mother milk. Chemokines are of importance among these immune factors. Interleukin-8 (IL-8) has been demonstrated in mother's milk, and its receptors, CXC chemokine receptors (CXCR)-1 and CXCR-2, were detected on cells, responsible for immunological reactions and mammary glandular cells. The soluble forms of these receptors are yet to be described in human milk. In this study, it was aimed to assess the IL-8 levels and the concentrations of its receptors in colostrum and mature mother's milk in regard to preterm and term delivery. The results of this study indicated a decline in IL-8 levels with the lactation stage, but no difference was observed between term and preterm mother's milk. Regarding the CXCR-1 and CXCR-2, the concentrations of these receptors were similar in both colostrum and mature milk. Furthermore, there was not any significant difference between term and preterm mother's milk. In conclusion, this is the first study to investigate the concentrations of CXCR-1 and CXCR-2 with the levels of IL-8 in colostrum and mature human milk of term and preterm newborns. The alterations in IL-8 levels were similar in some of the studies reported. CXCR-1 and CXCR-2 levels did not demonstrate any significant difference. Further studies are required to investigate the soluble forms of these receptors and their relation to IL-8 with larger cohort.


Clinical Perspectives of Multiple and Extensively Drug-Resistant Typhoid; result from a tertiary care hospital from Pakistan.
Typhoid fever remains a problem in developing countries, including Pakistan. The emergence of multidrug-resistant and, since 2016, of extensively drug-resistant cases is a continuous challenge for health care workers. The COVID-19 pandemic is making management more difficult. In the present study, a total of 52 confirmed cases of typhoid have been studied during 2019. Detailed clinical features, complications and, lab findings were studied. Typhoid culture and sensitivity were recorded and patients were treated accordingly. Patients were asked about risk factors to aim at informing prevention. Out of the 52 having blood culture positive for Salmonella Typhi 47 (90.4%) and Salmonella Paratyphi 5 (9.6%), 4 (7.7%) were sensitive to first-line (Non-resistant), 11 (21.2%) MDR and 37 (71.2%) patient were XDR. One case was resistant to azithromycin. Nausea, vomiting or, abdominal pain was present in 12 (23%), abdominal distension present in 9 (17.3%), abdominal tenderness in 8 (15.4%), hepatomegaly in 10 (19.2%) and, splenomegaly in 22 (42.3%).There were ultrasound abnormalities in 58% of patients and GI complications in 19% of patients. No significant difference was found in clinical findings and complications between resistant and non-resistant cases. Only 23-27% of patients were aware of typhoid prevention and vaccination measures. The increasing prevalence of resistance and higher degree of complications seen in typhoid fever raises the concern further about prevention and effective infection management in the community as well as clinical settings. Moreover, judicial use of antibiotics is much needed in developing countries like Pakistan.


Programmed cell death in the wing of Orgyia leucostigma (Lepidoptera: Lymantriidae).
Programmed cell death is an integral and ubiquitous phenomenon of development that is responsible for the reduction of wing size in female moths of Orgyia leucostigma (Lymantriidae). Throughout larval and pupal life, cells of the wing epithelium proliferate and interact to form normal imaginal discs and pupal wings in both sexes. But at the onset of adult development, most cells in female O. leucostigma wings degenerate over a brief, 2-day period. Lysosomes and autophagic vacuoles appear in cells of the wing epithelium shortly after it retracts from the pupal cuticle. Hemocytes actively participate in removing the resulting cellular debris. By contrast, epithelial cells in wings of developing adult males of O. leucostigma do not undergo massive cell death. Wing epithelium of female pupae transferred to male pupal hosts behaves autonomously in this foreign environment. By pupation, cells of the female wing apparently are committed to self-destruct even in a male pupal environment. Normal interactions among epithelial cells within the plane of a wing monolayer as well as between the upper and lower monolayers of the wing are disrupted in female O. leucostigma by massive cell degeneration. Despite this disruption, the remaining cells of the wing contribute to the formation of a diminutive, but reasonably proportioned, adult wing with scales and veins.


Mutations in the Bacillus thuringiensis Cry1Ca toxin demonstrate the role of domains II and III in specificity towards Spodoptera exigua larvae.
Several mutants of the Bacillus thuringiensis Cry1Ca toxin affected with regard to specific activity towards Spodoptera exigua were studied. Alanine was used to replace single residues in loops 2 and 3 of domain II (mutant pPB19) and to replace residues 541-544 in domain III (mutant pPB20). Additionally, a Cry1Ca mutant combining all mutations was constructed (mutant pPB21). Toxicity assays showed a marked decrease in toxicity against S. exigua for all mutants, while they retained their activity against Manduca sexta, confirming the importance of these residues in determining insect specificity. Parameters for binding to the specific receptors in BBMV (brush border membrane vesicles) of S. exigua were determined for all toxins. Compared with Cry1Ca, the affinity of mutant pPB19 was slightly affected (2-fold lower), whereas the affinity of the mutants with an altered domain III (pPB20 and pPB21) was approx. 8-fold lower. Activation of Cry1Ca protoxin by incubation with S. exigua or M. sexta BBMV revealed the transient formation of an oligomeric form of Cry1Ca. The presence of this oligomeric form was tested in the activation of the different Cry1Ca mutants, and we found that those mutated in domain II (pPB19 and pPB21) could not generate the oligomeric form when activated by S. exigua BBMV. In contrast, when oligomerization was tested using BBMV prepared from M. sexta, all of the Cry1Ca mutants showed the formation of a similar oligomeric form as did the wild-type toxin. Our results show how modification of insect specificity can be achieved by manipulation of different parts of the toxin structure involved in different steps of the mode of action of B. thuringiensis toxins.


Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.
The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke. We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT. Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13. 4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2. Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.


[Biopsies of the endoscopically normal colon].
The importance of biopsies of the endoscopically normal colonic mucosa is controversial. All patients who underwent total colonoscopy at St. Olav"s Hospital in 2004 were considered for inclusion if their colonoscopy was normal. Patients who were already enrolled in follow-up protocols were excluded. Biopsy practice and histological findings were recorded. Biopsies were taken in 266 of 738 normal colonoscopies (36%) The number of biopsies per colonoscopy varied from 1 to 16 (median 6). Biopsies from 8 of the 266 patients (3.0%) showed histological abnormalities of certain clinical significance. Seven of the 8 patients were investigated because of diarrhoea. In addition, histological abnormalities of limited clinical significance were found in biopsies from 13 of the patients (4.9%). Use of biopsy in the endoscopically normal colon varied considerably. Taking biopsies in patients without diarrhoea was of minor clinical importance. Guidelines for taking biopsies of the endoscopically normal colon are desirable.


Is the combination of sulfonylureas and metformin associated with an increased risk of cardiovascular disease or all-cause mortality?: a meta-analysis of observational studies.
Observational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the effects of combination therapy of sulfonylureas and metformin on the risk of all-cause mortality and cardiovascular disease (CVD) among people with type 2 diabetes. A MEDLINE search (January 1966-July 2007) was conducted to identify observational studies that examined the association between combination therapy of sulfonylureas and metformin on risk of CVD or all-cause mortality. From 299 relevant reports, 9 were included in the meta-analysis. In these studies, combination therapy of metformin and sulfonylurea was assessed, the risk of CVD and/or mortality was reported, and adjusted relative risk (RR) or equivalent (hazard ratio and odds ratio) and corresponding variance or equivalent was reported. The pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for CVD mortality, and 1.43 (1.10-1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events). The combination therapy of metformin and sulfonylurea significantly increased the RR of the composite end point of cardiovascular hospitalization or mortality (fatal and nonfatal events) irrespective of the reference group (diet therapy, metformin monotherapy, or sulfonylurea monotherapy); however, there were no significant effects of this combination therapy on either CVD mortality or all-cause mortality alone.


Tendinopathy--from basic science to treatment.
Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy.


The Effect of Japanese Herbal Medicines (Kampo) Goreisan and Saireito on the Prevention of Recurrent Chronic Subdural Hematoma: A Prospective Randomized Study.
Chronic subdural hematoma (CSDH) sometimes recurs after surgical treatment and requires reoperation. In Japan, Japanese herbal medicines (Kampo), such as Goreisan and Saireito, have been used as adjunctive therapies to prevent the recurrence of CSDH. However, no prospective randomized study has proven the efficacy of Kampo medicine in all patients. To investigate whether Goreisan and Saireito reduce the postoperative recurrence of CSDH in a prospective randomized study. Between April 2017 and July 2019, a total of 118 patients who underwent initial burr hole surgery for CSDH were randomly assigned to the following 3 groups: (1) Goreisan for 3 months (Group G), (2) Saireito for 3 months (Group S), and (3) no medication (Group N). The primary end point was symptomatic recurrence within 3 months postoperatively, and the secondary end point was complications associated with the administration of Kampo medicine. Among 118 patients, 114 (Group N, n = 39; Group G, n = 37; and Group S, n = 38) were included in our analysis. In this study, byakujutsu (containing Atractylodes rhizome ) Goreisan and Saireito were used, unlike other prospective randomized studies in which sojutsu (containing Atractylodes lancea rhizome) Goreisan was used. The overall recurrence rate was 11.4% (13/114: 10 for Group N, 2 for Group G, and 1 for Group S). The recurrence rate of Group G was significantly lower than that of Group N (5.4% vs 25.6%; P = .043). The recurrence rate of Group S was also significantly lower than that of Group N (2.6% vs 25.6%; P = .02). No patients developed complications associated with the administration of Kampo medicine. This is the first study to show that Kampo medicine reduced the recurrence rate of CSDH in an overall population. This study demonstrated that byakujutsu Goreisan and Saireito may have favorable effects, unlike other studies, because byakujutsu has stronger anti-inflammatory activity than sojutsu.


Staphylococcus protein A-based extracorporeal immunoadsorption and thalidomide in the treatment of skin manifestation of dermatomyositis: a case report.
Cutaneous involvement in dermatomyositis can be the prevalent component of disease, failing to respond to adequate therapies for myositis. In this case report, we describe a patient affected by dermatomyositis, characterized by prevalent skin involvement, successfully treated with Staphylococcus protein A-based extracorporeal immunoadsorption (Immunosorba, Fresenius Medical Care AG & Co. KGaA, Bad Homburg, Germany) and thalidomide. The patient showed panniculitic ulcerative lesions of the skin, difficult to treat because of side effects or ineffectiveness of various therapies. Skin manifestations rapidly improved after introduction of immunoadsorption; The association of thalidomide allowed a good maintenance of these results until the remission of skin lesions, despite several infective complications of some residual ulcers. Considering the difficulties in the management of our patient, combined therapy with Immunosorba and thalidomide has allowed a good clinical response. If confirmed, the observed beneficial effects suggest that protein A-based immunoadsorption and thalidomide can represent an alternative option in dermatomyositis, especially when cutaneous manifestations are predominant.


Altered miR-29 Expression in Type 2 Diabetes Influences Glucose and Lipid Metabolism in Skeletal Muscle.
MicroRNAs have emerged as important regulators of glucose and lipid metabolism in several tissues; however, their role in skeletal muscle remains poorly characterized. We determined the effects of the miR-29 family on glucose metabolism, lipid metabolism, and insulin responsiveness in skeletal muscle. We provide evidence that miR-29a and miR-29c are increased in skeletal muscle from patients with type 2 diabetes and are decreased following endurance training in healthy young men and in rats. In primary human skeletal muscle cells, inhibition and overexpression strategies demonstrate that miR-29a and miR-29c regulate glucose uptake and insulin-stimulated glucose metabolism. We identified that miR-29 overexpression attenuates insulin signaling and expression of insulin receptor substrate 1 and phosphoinositide 3-kinase. Moreover, miR-29 overexpression reduces hexokinase 2 expression and activity. Conversely, overexpression of miR-29 by electroporation of mouse tibialis anterior muscle decreased glucose uptake and glycogen content in vivo, concomitant with decreased abundance of GLUT4. We also provide evidence that fatty acid oxidation is negatively regulated by miR-29 overexpression, potentially through the regulation of peroxisome proliferator-activated receptor γ coactivator-1α expression. Collectively, we reveal that miR-29 acts as an important regulator of insulin-stimulated glucose metabolism and lipid oxidation, with relevance to human physiology and type 2 diabetes.


A coprological survey of parasites of wild mantled howling monkeys, Alouatta palliata palliata.
Fecal samples from 155 mantled howling monkeys (Alouatta palliata palliata) examined at Centro Ecologico La Pacifica, Guanacaste Province, Costa Rica, revealed 75 (48%) had parasitic infections. A sampling of nine howling monkeys from Santa Rosa National Park. Costa Rica indicated only one infected animal (11%). Only three of 19 (16%) spider monkeys (Ateles geoffroyi) also from Santa Rosa were infected. Controrchis biliophilus, Trypanoxyuris minutus, unidentified strongylid eggs and Isospora sp. oocysts were found. Three monkeys from La Pacifica died and were examined for adult helminths. They were infected with Ascaris lumbricoides, C. biliophilus and T. minutus.


Detection of Clostridium perfringens enterotoxin by tissue culture and double-gel diffusion methods.
Culture filtrates of four enterotoxin-producing strains of Clostridium perfringens type A produced morphological changes in cells of 10 of 12 established mammalian cell lines tested, and particularly Vero (African green-monkey kidney) and MDCK (dog kidney) cells. Double-gel diffusion and Vero-cell tests detected enterotoxin in culture filtrates of, respectively, 29 (28%) and 56 (54%) of 103 strains of C. perfringens tested. The feasibility of cell-culture assays for the routine detection of C. perfringens enterotoxin is indicated.


Are nursing theories holistic?
Nursing theories, while claiming to present models of holistic nursing care, do not deal adequately with human spirituality. This article reviews several nursing theories to find out which of them incorporate holism, and, if they do, whether the theorist's definition of holism includes spirituality.


Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice.
Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, and 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure.


[Multicentric ambulatory trial of Trolovol (D-penicillamine) in chronic polyarthritis].
Discontinuation of therapy and non-observance of the prescribed period required in the present evaluation to take the duration of treatment into account as an influential factor. However, due to the limited extent of the trial, it was not possible to process the time influence. Therefore, the conclusions gained are to be interpreted to the effect that they are statistically vertifiable for a selected patient group with a therapy period of 4 months or longer.


Vaccination with Prion Peptide-Displaying Polyomavirus-Like Particles Prolongs Incubation Time in Scrapie-Infected Mice.
Prion diseases like scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle or Creutzfeldt-Jakob disease (CJD) in humans are fatal neurodegenerative diseases characterized by the conformational conversion of the normal, mainly α-helical cellular prion protein (PrPC) into the abnormal β-sheet rich infectious isoform PrPSc. Various therapeutic or prophylactic approaches have been conducted, but no approved therapeutic treatment is available so far. Immunisation against prions is hampered by the self-tolerance to PrPC in mammalian species. One strategy to avoid this tolerance is presenting PrP variants in virus-like particles (VLPs). Therefore, we vaccinated C57/BL6 mice with nine prion peptide variants presented by hamster polyomavirus capsid protein VP1/VP2-derived VLPs. Mice were subsequently challenged intraperitoneally with the murine RML prion strain. Importantly, one group exhibited significantly increased mean survival time of 240 days post-inoculation compared with 202 days of the control group. These data show that immunisation with VLPs presenting PrP peptides may represent a promising strategy for an effective vaccination against transmissible spongiform encephalitis agents.


[Effects of gamma-oryzanol on the hypothalamo-pituitary axis in the rat].
The effects of gamma oryzanol (gamma-OZ), a ferulic acid of triterpene alcohol, on the synthesis and release of the growth hormone (GH) and prolactin (PRL) in vitro and turnover rates of hypothalamic catecholamines were investigated. A single subcutaneous injection of 20 mg/kg of gamma-OZ suppressed GH synthesis and PRL release 1 hour after the injection. gamma-OZ increased medial basal hypothalamic (MBH) dopamine (DA) content, and the DA content was decreased by a treatment of alpha-methyl-p-tyrosine (alpha MpT), a tyrosine hydroxylase inhibitor, indicating increased synthesis and release of DA in MBH by gamma-OZ. gamma-OZ did not alter norepinephrine (NE) content in MBH, while the NE content was significantly decreased, indicating unchanged synthesis and increased release of NE in MBH by gamma-OZ. These results may explain the previous data concerning the changes in serum levels of GH and PRL by gamma-OZ and also suggest that gamma-OZ can affect the synthesis and/or release of at least two hypothalamic neurotransmitters, DA and NE, resulting in the alterations of anterior pituitary hormone synthesis and/or release.


Variation in the temporal expression of overlapping baculovirus transcripts.
To investigate gene expression from the Autographa californica nuclear polyhydrolysis virus genome (AcNPV), complementary DNA (cDNA) was synthesized from polyadenylated RNA transcribed at 2 h and 10 h postinfection (p.i.) and then cloned into Escherichia coli using plasmid pUC-9. Eighteen 2 h cDNA plasmids were homologous to five distinct regions of the viral genome, while forty-nine 10 h cDNA plasmids were homologous to 15 regions including the five regions transcribed at 2 h. Temporal expression of polyadenylated RNA transcribed from diverse regions of the genome was examined using Northern blot hybridization with the above 2 and 10 h cDNA probes. All regions displayed overlapping sets of RNAs. In addition to HindIII-I/EcoRI-F (IF) and HindIII-B2/EcoRI-H (B2H), several, but not all, regions showed a sequential appearance of higher molecular weight RNAs as the infection progressed. Each overlapping set of RNAs exhibited unique characteristics including variations in the number of overlapping transcripts, their temporal regulation, and their relative abundance during the course of infection.


Influence of solvents on the variety of crystalline forms of erythromycin.
The influence of the organic solvents widely used in the pharmaceutical industry (acetone, methylethylketone, ethanol, and isopropanol) both in the presence and in the absence of water on the crystallization behavior of erythromycin (Em), a clinically relevant antibiotic of the macrolide group, was investigated. It was observed that despite a high preference for water as a guest molecule, Em rather easily forms solvates with the organic solvents studied. Consequently, 4 distinct solvates of Em have been isolated by recrystallization: acetonate, methylethylketonate, ethanolate, and isopropanolate. It was established that in a pure organic solvent, or 1:9 or 1:1 water-organic solvent mixtures, the corresponding solvate is always crystallized. However, the recrystallization of erythromycin from 2:1 water-organic solvent (excluding methylethylketone) mixture results in the formation of a crystal hydrate form. X-ray powder diffraction revealed the isostructurality of the solvates with acetone and methylethylketone. Thermogravimetric analysis showed that the loss of volatiles by all of the solvated crystals is nonstoichiometric. The desolvation behavior of the solvates with the organic solvents studied by means of variable-temperature x-ray powder diffraction indicates that in contrast to erythromycin dihydrate, they belong to a different class of solvates--those that produce an amorphous material upon desolvation.


Predictive Warning of Nociceptive Temperature during Prosthetic Hand Prehension.
Grasping hot objects may be harmful, and a warning of nociceptive temperature should be provided to prevent prosthetic hands from damage. This study developed a fast algorithm to predict the steady state temperature of grasped objects based on a thermoresistant sensor, and verified a bi-state sensory encoding strategy to inform either contact force or nociceptive temperature at prosthetic finger. Below the threshold, a buzz percept was used to encode fingertip force, and above the threshold, a tingling pain sensation was induced to warn harmful temperature. This sensory encoding mechanism was tested in one able-bodied subject with a psychophysical experimental paradigm. Results indicated that fast identification of the steady state temperature could be achieved in 0.75±0.00 s with an error of 8.3±6.0%. The subject was able to recognize whether the object temperature was above or below the threshold of nociceptive temperature with an average success rate of 98.2% and 97.0%, respectively. The action to release the tube could be executed in 0.80±0.32 s. The reaction time of successful identification and execution was 1.55 ± 0.32 s. The probability that a release reaction was triggered at the threshold of 60.0°C was calculated with tube temperatures varying from 30.0°C to 80.0°C. The 50% percentile point on the fitted stimulus-response curve corresponded to a temperature of 59.5°C, nearly identical to the internally set threshold. The psychophysical behavior test verified the sensory function to recognize and notify unsafe temperatures in real time.Clinical Relevance-The method of identifying and alerting nociceptive temperatures may restore the sensory ability of amputees to avoid potential damage of grasping hot objects with a prosthetic hand in activities of daily life.


Crystallographic snapshots of Tom20-mitochondrial presequence interactions with disulfide-stabilized peptides.
Most mitochondrial proteins are synthesized in the cytosol and imported into mitochondria. The Tom20 protein, residing on the mitochondrial surface, recognizes the N-terminal presequences of precursor proteins. We previously determined the crystal structures of the Tom20-presequence complex. The successful crystallization involved tethering the presequence to Tom20 through an intermolecular disulfide bond with an optimized linker. In this work, we assessed the tethering method. The intermolecular disulfide bond was cleaved in crystal with a reducing agent. The pose (i.e., conformation and position) of the presequence was identical to the previously determined pose. In another experiment, a longer linker than the optimized length was used for the tethering. The perturbation of the tether changed the pose slightly, but the interaction mode was preserved. These results argue against the forced interaction of the presequence by its covalent attachment to Tom20. Second, as an alternative method referred to as "molecular stiffening", we introduced a disulfide bond within the presequence peptide to restrict the freedom of the peptide in the unbound states. One presequence analogue exhibited over 100-fold higher affinity than its linear counterpart and generated cocrystals with Tom20. One of the two crystallographic snapshots revealed a known pose previously determined by the tethering method, and the other snapshot depicted a new pose. These results confirmed and extended the dynamic, multiple bound state model of the Tom20-presequence interactions and also demonstrated the validity of the molecular tethering and stiffening techniques in studies of transient protein-peptide interactions.


Bilateral ostial coronary stenosis and rheumatic aortic valve stenosis.
A 49-year-old patient presented with angina pectoris and clinical findings of aortic valve stenosis and regurgitation. Rheumatic aortic valve stenosis and regurgitation was diagnosed on echocardiography. Coronary angiography findings showed severe calcification in the aorta root with right coronary ostial occlusion, and were suggestive of left main ostial stenosis and proximal main stem stenosis, which was confirmed on CT angiography. Curvilinear calcification of the aorta was present on CT angiography. The findings suggested syphilitic aortitis. Syphilis serology was positive (RPR titre 1/16). The angina was caused by severe coronary ostial disease likely due to syphilitic aortitis and exacerbated by the rheumatic aortic valve stenosis and regurgitation.


Laparoscopic Complete Mesocolic Excision versus Open Complete Mesocolic Excision for Transverse Colon Cancer: Long-Term Survival Results of a Prospective Single Centre Non-Randomized Study.
Laparoscopic complete mesocolic excision (CME) used in the treatment of transverse colon cancer has been questioned on the basis of the technical challenges. The aim of this study was to evaluate the medium- and long-term clinical and survival outcomes after laparoscopic and open CME for transverse colon cancer and to compare the 2 approaches. This study was a retrospective non-randomized study of patients with prospectively registered data on open and laparoscopic CME for transverse colon cancer tumour-node-metastasis stages I-III operated on between 2007 and 2014. This was a single-centre study in a community teaching hospital. A total of 56 patients with transverse colon cancer were included, excluding those with tumours in the colonic flexures. The outcome aims were 4-year time to recurrence (TTR) and cancer-specific survival (CSS). Morbidity was also measured. The 4-year TTR was 93.9% in the laparoscopic group and 91.3% in the open group (p = 0.71). The 4-year CSS was 97.0% in the laparoscopic group and 91.3% in the open group (p = 0.42). This was a prospective single-institution study with a small sample size. Results of the study suggest that the laparoscopic CME approach might be the preferred approach for transverse colon cancer, especially regarding its benefits in terms of short-term morbidity, length of stay and oncological outcome.


Subnuclear localization of protein kinase C delta in beta cells.
Our laboratory has previously shown that beta cells express multiple isoforms of protein kinase C (PKC) and that some isoforms are located to multiple pools within the cell, including the cytoskeletal elements. In this study we analyzed the localization of the delta, epsilon, zeta, beta, and alpha isoforms of PKC to the nucleus. Nuclei were isolated from insulinoma beta cells and fractionated by centrifugation to give the nuclear soluble fraction, nuclear membrane fraction, and the insoluble matrix. The nuclear pellet was enriched in DNA and contained less than 5% of the total cellular nucleotidase activity. The nuclear membrane contained less than 2% of the total cellular nucleotidase activity, suggesting negligible plasma membrane contamination. Analysis of cellular fractions by immunoblotting with isoform-specific anti-PKC antibodies showed that PKC alpha, beta, zeta, and epsilon could be detected in the soluble fraction of the cell but could not be detected in the nucleus. Only PKC delta could be detected in the nucleus and was mostly present in the nuclear membrane fraction. There was light staining in the nucleocytosol and the nuclear matrix but the enzyme in the nuclear membrane represented approximately 76% of the total nuclear enzyme. Nuclear PKC delta constituted approximately 9% of the total cellular enzyme. Phorbol ester (1 microM, 15 min) increased the levels associated with the nuclear membrane approximately threefold but not to the nuclear matrix or nucleocytosol. Inhibition of PKC with MDL 29152 increased levels of preproinsulin mRNA relative to beta-actin mRNA levels, while chronic phorbol ester treatment led to a slight decrease. Taken together, these data suggest that PKC is constitutively active in the nucleus and may be important in modulating preproinsulin mRNA levels.


Protein translocation and retro-translocation across the endoplasmic reticulum are crucial to inflammatory effector CD4+ T cell function.
Effector CD4+ T cells can be classified by the cytokines they secrete, with T helper 1 (Th1) cells generating interferon (IFN)γ and Th17 cells secreting interleukin (IL)-17. Both Th1 and Th17 cells are strongly implicated in the initiation and chronicity of autoimmune diseases such as multiple sclerosis. The endoplasmic reticulum (ER) has been implicated as a potentially crucial site in regulating CD4+ T cell function. Secretory and transmembrane proteins are shuttled into the ER via the Sec61 translocon, where they undergo appropriate folding; misfolded proteins are retro-translocated from the ER in a p97-dependent manner. Here, we provide evidence that both processes are crucial to the secretion of inflammatory cytokines from effector CD4+ T cells. The pan-ER inhibitor eeeyarestatin-1 (ESI), which interferes with both Sec61 translocation and p97 retro-translocation, inhibited secretion of interferon (IFN)γ, interleukin (IL)-2 and tumor necrosis factor (TNF)α from Th1 cells in a dose-dependent manner. Selective inhibition of Sec61 by Apratoxin A (ApraA) revealed that ER translocation is crucial for Th1 cytokine secretion, while inhibition of p97 by NMS-873 also inhibited Th1 function, albeit to a lesser degree. By contrast, none of ESI, ApraA or NMS-873 could significantly reduce IL-17 secretion from Th17 cells. ApraA, but not NMS-873, reduced phosphorylation of Stat1 in Th1 cells, indicating the involvement of ER translocation in Th1 differentiation pathways. ApraA had modest effects on activation of the Th17 transcription factor Stat3, while NMS-873 had no effect. Interestingly, NMS-873 was able to reduce disease severity in CD4+ T cell-driven experimental autoimmune encephalomyelitis (EAE). Together, our data indicate that CD4+ T cell function, and Th1 cell function in particular, is dependent on protein translocation and dislocation across the ER.


The frequency of a common anti-DNA antibody idiotype (16/6) in different populations of patients with systemic lupus erythematosus.
The 16/6 anti-DNA idiotype (id) is a pathogenic idiotype first identified on a human hybridoma antibody derived from a patient with systemic lupus erythematosus (SLE). The SA-1 anti-DNA, which antibody was established in a similar fashion from a patient with polymyositis, also carries the 16/6 id, although it has a greater reactivity with dsDNA. The presence of the 16/6 id as defined by anti-16/6 and anti-SA-1 was determined in 3 distinct populations of patients with SLE: 502 Mexicans, 98 English (including Caucasians, West Indians, Chinese, Asians) and 93 Israelis. A similar prevalence (around 20%) of the 2 idiotypes was found, with a significant overlap. The latter finding was supported by a significant correlation noted between the prevalence of the 2 idiotypes (r = 0.58 p less than 0.001). Despite the fact that 16/6 antibody is most probably encoded by a germline gene, thus being genetically determined, no distinction in the prevalence of the ids could be detected between completely different populations of patients with SLE. This finding may support the independent pathogenic role ascribed to the 16/6 id.


3-Monochloropropane-1,2-diol reduced bioaccessibility of sn-2 palmitate via bounding with pancreatic lipase in infant formula during gastrointestinal digestion.
Infant formula contains 3-monochloropropane-1,2-diol esters which are formed during the deodorization step of vegetable oils refining. European Food Safety Authority stated that 3-monochloropropane-1,2-diol esters can be hydrolyzed in the gastrointestinal tract to free-form 3-monochloropropane-1,2-diol, which has potential toxicity and can be rapidly absorbed. Evaluating the effect of 3-monochloropropane-1,2-diol on nutrition absorption is a prerequisite for establishing effective management strategies. A total of 66 crucial lipid molecules associated with 3-monochloropropane-1,2-diol were identified based on Debiased Sparse Partial Correlation analysis. 3-Monochloropropane-1,2-diol affected triglyceride hydrolyzation and increased the concentration of undigested sn-2 palmitate (9.57 to 17.06 mg kg-1). 3-Monochloropropane-1,2-diol reduced the bioaccessibility of fatty acids and more short- (31.42 to 58.02 mg kg-1) and medium-chain fatty acids (17.03 to 26.43 mg kg-1) remained unabsorbed. Lipidomics profiles of infant formula models spiked with different 3-MCPDE levels were investigated and the results were consistent with the experiments with the commercial formula indicating lipid alteration was mainly affected by the digestive 3-MCPD. The formation of 3-monochloropropane-1,2-diol ester-pancreatic lipase with the binding energy of -4.9 kcal mol-1 was more stable than triglyceride-pancreatic lipase (-4.0 kcal mol-1), affecting triglyceride hydrolyzation. 3-Monochloropropane-1,2-diol was bound to Glu13 and Asp331 residues of the pancreatic lipase via hydrogen bonds, which resulted in a conformational change of pancreatic lipase and spatial shielding effect. The existence of the spatial shielding effect reduced the accessibility of pancreatic lipase and further affected triglyceride hydrolyzation. These findings indicated that 3-monochloropropane-1,2-diol obstructed nutrient acquisition and laid the foundation for the subsequent nutrition enhancement design.


Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism.
Stromal cell-derived factor 1 (SDF-1) plays a major role in the migration, recruitment, and retention of endothelial progenitor cells to sites of ischemic injury and contributes to neovascularization. We provide direct evidence demonstrating an important role for heme oxygenase 1 (HO-1) in mediating the proangiogenic effects of SDF-1. Nanomolar concentrations of SDF-1 induced HO-1 in endothelial cells through a protein kinase C zeta-dependent and vascular endothelial growth factor-independent mechanism. SDF-1-induced endothelial tube formation and migration was impaired in HO-1-deficient cells. Aortic rings from HO-1(-/-) mice were unable to form capillary sprouts in response to SDF-1, a defect reversed by CO, a byproduct of the HO-1 reaction. Phosphorylation of vasodilator-stimulated phosphoprotein was impaired in HO-1(-/-) cells, an event that was restored by CO. The functional significance of HO-1 in the proangiogenic effects of SDF-1 was confirmed in Matrigel plug, wound healing, and retinal ischemia models in vivo. The absence of HO-1 was associated with impaired wound healing. Intravitreal adoptive transfer of HO-1-deficient endothelial precursors showed defective homing and reendothelialization of the retinal vasculature compared with HO-1 wild-type cells following ischemia. These findings demonstrate a mechanistic role for HO-1 in SDF-1-mediated angiogenesis and provide new avenues for therapeutic approaches in vascular repair.


Changes in the Risk Perception of Food Safety between 2004 and 2018.
To afford the future agenda of risk communication through an evaluation of the past, we examined the changes in risk perception in the food safety sector over the 15 years (2004-2018) since the establishment of the Food Safety Commission of Japan (FSCJ) in 2003 by analyzing the data of the food safety monitor survey. Hazards such as contaminants including cadmium, methylmercury and arsenic, and pesticide residues caused high levels of concern among the public in 2004. In contrast, hazards such as food poisoning by harmful microorganisms and so-called "Health foods" have been ranked high among concerns since 2008 and 2014, respectively. Scoring of concern levels showed that concern related to food additives and pesticide residues intentionally added to foods and controlled has gradually decreased in a time-dependent manner. These concern scores were considerably lower in male monitors than in female ones; the scores were also lower for individuals with professional experience in the food sector than without the experience. The concern scores for contaminants were lower for males with professional experience. The concern scores related to food poisoning and health foods were not decreased and were remained high in recent years. These scores did not show clear dependence on job experience or gender of the monitors. A gap between food specialists and other attributes in the basic recognition of risk seems to make it difficult to communicate effectively and constructively among various interested individuals. To improve the quality of risk communication in the food safety field, it will be necessary to provide scientific knowledge and information regarding food safety management mechanisms for individuals without professional experience in the food sector, taking into account the changes in information media and influence on risk perception.


High-Dose Betahistine Improves Cognitive Function in Patients With Schizophrenia: A Randomized Double-Blind Placebo-Controlled Trial.
Background: There is currently no effective treatment for cognitive impairment associated with schizophrenia (CIAS). Recent studies have shown that increased histamine levels in the brain may help to improve CIAS symptoms. Betahistine is an H1-receptor agonist and H3-receptor antagonist. This study evaluated the effect of high-dose betahistine on cognitive function as well as its safety in Chinese Han patients with schizophrenia. Methods: This randomized double-blind, placebo-controlled trial enrolled 89 patients with schizophrenia who were randomly administered betahistine (72 mg/d) or placebo for 12 weeks. At baseline and at 4, 8, and 12 weeks after commencing the intervention, we measured changes in cognitive function and clinical symptoms using the MATRICS Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. Furthermore, we used the Treatment Emergent Symptom Scale (TESS) to assess the adverse effects of the patients' medications. Results: Compared to the placebo group, the betahistine group showed significant improvements in the MCCB composite score after 12 weeks of treatment (p = 0.003) as well as improvements in MCCB verbal learning (p = 0.02) and visual learning (p = 0.001) domain scores. However, there were no significant improvements in the PANSS total scores or subscores (p > 0.05). Generally, high-dose betahistine treatment was considered safe in patients with schizophrenia. Conclusions: Additional use of high-dose betahistine can effectively improve cognitive function but not psychiatric symptoms in patients with schizophrenia. Betahistine (72 mg/d) is well tolerated by Chinese Han patients with schizophrenia. Trial Registration: chictr.org.cn, identifier: ChiCTR1900021078. http://www.chictr.org.cn/edit.aspx?pid=35484&htm=4.


Small Bowel Obstruction Caused by Aloe vera Bezoars: A Case Report.
Small bowel obstruction is a clinical condition commonly caused by postoperative adhesion, volvulus, intussusceptions, and hernia. Small bowel obstruction due to bezoars is clinically uncommon, accounting for approximately 2-4% of all obstructions. Computed tomography (CT) is a useful method in diagnosing the cause of small bowel obstruction. However, small bowel obstruction caused by bezoars may not be detected by an abdominal CT examination. Herein, we report a rare case of small bowel obstruction by Aloe vera bezoars, which were undetected by an abdominal CT. Phytobezoars should be included in the differential diagnosis of small bowel obstruction in patients with predisposing factors, such as excessive consumption of high-fiber food and diabetes.


The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation.
The first intracellular loop (ICL1) of G protein-coupled receptors (GPCRs) has received little attention, although there is evidence that, with the 8th helix (H8), it is involved in early conformational changes following receptor activation as well as contacting the G protein β subunit. In class B1 GPCRs, the distal part of ICL1 contains a conserved R12.48KLRCxR2.46b motif that extends into the base of the second transmembrane helix; this is weakly conserved as a [R/H]12.48KL[R/H] motif in class A GPCRs. In the current study, the role of ICL1 and H8 in signaling through cAMP, iCa2+ and ERK1/2 has been examined in two class B1 GPCRs, using mutagenesis and molecular dynamics. Mutations throughout ICL1 can either enhance or disrupt cAMP production by CGRP at the CGRP receptor. Alanine mutagenesis identified subtle differences with regard elevation of iCa2+, with the distal end of the loop being particularly sensitive. ERK1/2 activation displayed little sensitivity to ICL1 mutation. A broadly similar pattern was observed with the glucagon receptor, although there were differences in significance of individual residues. Extending the study revealed that at the CRF1 receptor, an insertion in ICL1 switched signaling bias between iCa2+ and cAMP. Molecular dynamics suggested that changes in ICL1 altered the conformation of ICL2 and the H8/TM7 junction (ICL4). For H8, alanine mutagenesis showed the importance of E3908.49b for all three signal transduction pathways, for the CGRP receptor, but mutations of other residues largely just altered ERK1/2 activation. Thus, ICL1 may modulate GPCR bias via interactions with ICL2, ICL4 and the Gβ subunit.


Increased TNF-alpha and PGI(2), but not NO release from macrophages in 18-month-old rats.
TNF-alpha is an important pro-inflammatory mediator that influences host defense against infection and cancer. Previous examinations of TNF-alpha release and synthesis within the context of age have provided conflicting data, as both increased and decreased TNF-alpha synthesis have been described in aged populations. The present study was designed to reevaluate TNF-alpha production and synthesis in primary cultured peritoneal macrophages of young and 18-month-old rats. We were also interested in the link between the production of this cytokine and other important mediators, such as prostaglandin I(2) (PGI(2)) and nitric oxide (NO) in these rats. Primary cultured peritoneal macrophages of rat were stimulated with 1.0 microg/ml of lipopolysaccharide (LPS) for 12 h. The level of TNF-alpha protein in culture supernatant was measured by enzyme-linked-immunosorbent-assay (ELISA), and TNF-alpha mRNA production was assessed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). At the same time, the levels of NO and PGI(2) were measured. Macrophages from 18-month-old rats produced more TNF-alpha protein, PGI(2) and TNF-alpha mRNA than those from the young rats (2 month). There was no difference in NO production of macrophages between 18-month-old and young rats. The results demonstrate that TNF-alpha and PGI(2) production by rat macrophages increase with age. The results also suggest that NO might not contribute to the increased TNF-alpha production in 18-month-old rat macrophages.


Distribution of various neurochemicals within the zona incerta: an immunocytochemical and histochemical study.
To gain insight into the cellular organisation of the zona incerta, we have examined the chemoarchitectonic properties of this "uncertain zone". The brains of Sprague-Dawley rats and common cats were processed for immunocytochemistry or NADPH-diaphorase histochemistry using standard methods. For the immunocytochemistry, antibodies to y-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD), parvalbumin, calbindin, tyrosine hydroxylase, somatostatin, serotonin and glutamate were used. Two general patterns of distribution in the zona incerta were seen. First, labelled cells were restricted largely to one of the cytoarchitectonically defined sectors of the zona incerta. For instance, GABA, GAD and parvalbumin-immunoreactive cells were found principally within the ventral sector, NADPH-diaphorase and glutamate-immunoreactive cells within the dorsal sector and tyrosine hydroxylase- and somatostatin-immunoreactive cells within the rostral sector. Second, labelled cells were scattered somewhat across all incertal sectors, with no clear region of concentration. This pattern included the calbindin- and serotonin-immunoreactive cell groups. These results indicate that the zona incerta is made up of many neurochemically distinct cell groups, some of which respect the well-defined cytoarchitectonic boundaries of the nucleus, whilst others do not. This rich neurochemical diversity in the zona incerta suggests that this nucleus may have differential effects on the different structures that it projects to.


Methyldopa. Mechanisms and treatment 25 years later.
Methyldopa, an adrenergic-inhibiting compound, has been used for over 25 years as a safe and effective antihypertensive agent. The postulated mechanisms for the antihypertensive action of this compound have been varied and parallel our broadening knowledge of the role of the adrenergic nervous system in controlling arterial pressure. This review outlines the mechanisms of adrenergic control of the circulation and how the proposed mechanisms of action of methyldopa (ie, dopa decarboxylation, false neurotransmission, inhibition of renin release, and stimulation of alpha receptor sites in the brain) seem to account for the depressor action of the drug. Physiologic effects as well as immunologic and other clinical effects are also discussed.


Lung Ultrasound in the COVID-19 Pandemic.
Lung ultrasound (LUS) is one of the most important and innovative applications in emergency and critical care medicine for the management of critically ill patients. Ultrasound has been widely used in the COVID-19 pandemic as an extremely reliable technique and has proved to have a key role in the diagnosis and monitoring of patients with acute respiratory failure. The diagnostic accuracy of LUS is higher than chest X-ray and similar to computed tomography, which is considered the gold standard. COVID-19 pneumonia has some distinctive ultrasonographic signs but not pathognomonic, and LUS significantly improves the management of COVID-19 patients speeding up the diagnostic path. The examination is bedside; reduces the risk of contamination, avoiding mobilization of the patients; cuts down the amount of radioactive exposure; and gives real-time answers to many diagnostic and therapeutic doubts. Finally, the instruments are small and the scanner and the probes can be protected from contamination easily.


Effects of atomoxetine on attention and impulsivity in the five-choice serial reaction time task in rats with lesions of dorsal noradrenergic ascending bundle.
Atomoxetine, a noradrenaline reuptake inhibitor (NRI), which is a non-stimulating medicine that is used for the treatment of patients with attention deficit hyperactivity disorder (ADHD), has been found to be effective in reducing behavioral impulsivity in rodents, but its efficacy in a dorsal noradrenergic ascending bundle (DNAB)-lesioned condition has not been examined. The present study aimed to investigate the effects of DNAB lesions on attention and impulsive control in the five-choice serial reaction time task (5-CSRTT) in rats treated with atomoxetine. The drug-induced changes in noradrenaline efflux in the medial prefrontal cortex were also measured. 5-CSRTT-trained rats were included in one of the following groups: N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)/Atomoxetine, Sham/Atomoxetine, DSP-4/Saline, or Sham/Saline. Acute atomoxetine (0.3 mg/kg) was administered 14 days after the DSP-4 regime. The behavioral testing included manipulations of the inter-trial interval (ITI), stimulation duration and food satiety. In vivo microdialysis of the noradrenaline efflux in the medial prefrontal cortex and the expression of the noradrenaline transporter (NAT) in the DNAB areas were examined. Atomoxetine reduced impulsivity and perseveration in the long-ITI condition with no effects on any other variables. This phenomenon was not influenced by DSP-4 pre-treatment. The DNAB-lesioned rats had lower noradrenaline efflux in the medial prefrontal cortex. DSP-4 caused no change in NAT expression in the DNAB areas. These findings suggested that noradrenaline reuptake may not be exclusively responsible for the atomoxetine effects in adjusting impulsivity. The role of DNAB should also be considered, particularly in conditions requiring greater behavioral inhibition.


Generic dynamic scaling in kinetic roughening
We study the dynamic scaling hypothesis in invariant surface growth. We show that the existence of power-law scaling of the correlation functions (scale invariance) does not determine a unique dynamic scaling form of the correlation functions, which leads to the different anomalous forms of scaling recently observed in growth models. We derive all the existing forms of anomalous dynamic scaling from a new generic scaling ansatz. The different scaling forms are subclasses of this generic scaling ansatz associated with bounds on the roughness exponent values. The existence of a new class of anomalous dynamic scaling is predicted and compared with simulations.


Vaccination and blood sampling acceptability during Ramadan fasting month: A cross-sectional study in Conakry, Guinea.
There are few data on the acceptability of vaccination or blood sampling during Ramadan fasting month in Muslim countries. This could impact vaccination campaigns, clinical trials or healthcare during Ramadan. Using a semi-structured questionnaire, we conducted a cross-sectional study on 201 practising Muslims and 10 religious leaders in Conakry, Guinea in the wake of the recent epidemic Ebola epidemic. Acceptability of vaccination and blood sampling during Ramadan were investigated as well as reasons for refusal. Vaccination was judged acceptable during Ramadan by 46% (93/201, 95% CI 0.40-0.53) of practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) of religious leaders (p=0.11). Blood sampling was judged acceptable during Ramadan by 54% (108/201, 95% CI 0.47-0.60) of practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) of religious leaders (p=0.19). The percentage of participants that judged both blood sampling and vaccination acceptable during Ramadan was 40% (81/201, 95% CI 0.34-0.47) for practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) for religious leaders (p=0.048). The most common reasons for refusal of vaccination or blood sampling were that nothing should enter or leave the body during Ramadan (43%), that adverse events could lead to breaking the fast (32%), that blood should not be seen during Ramadan (9%) and that the Quran explicitly forbids it (9%). Although most Muslims leaders and scientists consider that injections including immunization and blood sampling should be authorized during Ramadan, many Muslims in our study judged vaccination or blood sampling unacceptable when fasting. Widely available recommendations on healthcare during Ramadan would be useful to inform Muslims.


Religious Beliefs and Depression: Psychosocial Factors Affecting HIV Treatment Outcomes in South Africa.
Analyzing factors associated with virological failure (VF) may improve antiretroviral therapy (ART) outcomes for individuals living with HIV. The Risk Factors for Virological Failure (RFVF) study compared 158 cases with VF (viral load, VL, >1,000 copies/mL) and 300 controls with virological suppression (VL ≤1,000 copies/mL) after ≥5 months on their first ART regimen at McCord Hospital in Durban, South Africa between October 2010 and June 2012. RFVF participants completed a battery of various psychosocial measures. Using multivariate logistic regression stratified for gender, the association of various psychosocial factors with VF was assessed. It was found that not all factors were equally significant for both genders. The factors that were significantly associated with VF for both genders were younger age, shorter treatment duration and reporting depressive symptoms. The factors associated with VF that differed by gender were religious inactivity, having HIV+ family members, and status disclosure to friends.


3D free-standing porous scaffolds made of graphene oxide as substrates for neural cell growth.
The absence of efficient therapies for the treatment of lesions affecting the central nervous system encourages scientists to explore new materials in an attempt to enhance neural tissue regeneration while preventing inhibitory fibroglial scars. In recent years, the superlative properties of graphene-based materials have provided a strong incentive for their application in biomedicine. Nonetheless, a few attempts to date have envisioned the use of graphene for the fabrication of three-dimensional (3D) substrates for neural repair, but none of these involve graphene oxide (GOx) despite some attractive features such as higher hydrophilicity and versatility of functionalization. In this paper, we report novel, free-standing, porous and flexible 3D GOx-based scaffolds, produced by the biocompatible freeze-casting procedure named ISISA, with potential utility in neural tissue regeneration. The resulting materials were thoroughly characterized by Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopies and scanning electron microscopy, as well as flexibility testing. Embryonic neural progenitor cells were then used to investigate adhesion, morphology, viability, and neuronal/glial differentiation. Highly viable and interconnected neural networks were formed on these 3D scaffolds, containing both neurons and glial cells and rich in dendrites, axons and synaptic connections, and the results are in agreement with those obtained in initial studies performed with two-dimensional GOx films. These results encourage further investigation in vivo on the use of these scaffolds as guide substrates to promote the repair of neural injuries.


Pyrethroid resistance and mechanisms of resistance in field strains of Helicoverpa armigera (Lepidoptera: Noctuidae).
Pyrethroid resistance was found in 54 field strains of Helicoverpa armigera collected between 1995 and 1999 from 23 districts in seven states of India. LD50 values of the field strains ranged from 0.06 to 72.2 microg/larva with slopes of 0.5-3.1. Resistance was highest in regions where pyrethroid use was frequent (four to eight applications per season). Resistance to deltamethrin was exceptionally high with resistance ratios of 13,570 and 27,160 in two strains collected during February 1998 in central India. Resistance to cypermethrin, fenvalerate and cyhalothrin also was high with resistance ratios of >1,000 in four strains collected from central and southern India. Resistance ratios were below 100 in >50% of the strains tested. Pyrethroid resistance was high in strains collected from the districts in Andhra Pradesh where a majority of the cotton farmer suicide cases in India were reported. Resistance to pyrethroids appeared to have increased over 1995-1998 in most of the areas surveyed. Studies carried out through estimation of detoxification enzyme activity and synergists indicated that enhanced cytochrome p450 and esterase activities were probably important mechanisms for pyrethroid resistance in field strains. Pyrethroid nerve insensitivity also was found to be a major mechanism in some parts of the country where the use of pyrethroids was high. The information presented illustrates the importance of proper insect management programs to avoid the consequences associated with improper insecticide use.


Association of Interferon-γ Receptor-1 Gene Polymorphism with Nontuberculous Mycobacterial Lung Infection among Iranian Patients with Pulmonary Disease.
Nontuberculous mycobacteria (NTM) cause significant pulmonary infections in humans. Researchers have reported an association between interferon-gamma receptor-1 (IFN-γR1 or IFNGR1) deficiency and susceptibility to NTM, but the relevance of polymorphism within these genes is not yet clear. In this study, a single nucleotide polymorphism (SNP), T to C, at position-56 in NTM patients with pulmonary disease was investigated. Molecular identification of Mycobacterium isolates was performed with hsp65 genes using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Then, the host genomic DNA from confirmed NTM patients (N = 80) and control subjects (N = 80) were screened for SNPs of IFNGR1 (T-56C) by PCR-RFLP. The results indicated that NTM patients had higher TC (26/80; 32.5%) or CC (46/80; 57.5%) genotypes in comparison with control groups (TC genotypes [22/80, 27.5%]; CC genotypes [6/80, 7.5%]) (P < 0.05). In this regard, all the patients infected with rapid-growing Mycobacterium (RGM, i.e., Mycobacterium chelonae and Mycobacterium fortuitum) had CC genotypes (100%). In contrary, only 50.7% (35/69) of infected patients with slow-growing Mycobacterium (i.e., Mycobacterium simiae, Mycobacterium kansasii, and Mycobacterium avium-intracellulare) had CC genotypes. Thus, patients with CC mutation in IFNGR1 at position-56 are more likely to develop RGM infection. In overall, there is a significant association between SNP of IFNGR1 at position-56 and susceptibility to NTM infection. Based on these data, we propose SNP of IFNGR1 at position-56 as a suitable "biomarker" for identifying populations at higher risk of infection.


Vitamin A intake and status in populations facing economic stress.
Dietary quality and diversity reflect adequacy of vitamin A. Both can deteriorate in response to economic crises. Although the nutritional consequences of the 2008 world food price crisis remain unclear, past studies of diet, status, and socioeconomic standing under usual (deprived) and unusually disruptive times suggest dietary quality and vitamin A status decline in mothers and young children. This is presumably the result of shifting diets to include less preformed vitamin A-rich animal source foods and, to a lesser extent, vegetables and fruits. Cross-sectional assessments of diet, deficiency, and socioeconomic status in a number of countries and surveillance data collected during the Indonesian economic crisis of 1997-8 indicate that the prevalence of vitamin A deficiency, night blindness, and other related disorders (e.g., anemia) may have increased during the 2008 crisis, and that it might not have necessarily recovered once food prices waned later in 2008. Lost employment may be a factor in slow nutritional recovery, despite some easing of food prices. Vitamin A deficiency should still be preventable amid economic instabilities through breast feeding promotion, vitamin A supplementation, fortification of foods targeted to the poor, and homestead food production that can bolster income and diversify the diet.


Association between Receipt of Intrapartum Magnesium Sulfate and Postpartum Hemorrhage.
Objective The aim of the study is to investigate the association between intrapartum administration of magnesium sulfate in women with hypertensive disorders of pregnancy and postpartum hemorrhage. Study Design This was a retrospective cohort study of women diagnosed with a hypertensive disorder of pregnancy who delivered singleton gestations >32 weeks at a single, large volume tertiary care center between January 2006 and February 2015. Women who received intrapartum magnesium sulfate for seizure prophylaxis were compared with women who did not receive intrapartum magnesium sulfate. The primary outcome was frequency of postpartum hemorrhage. Secondary outcomes included estimated blood loss, uterine atony, and transfusion of packed red blood cells. Bivariable analyses were used to compare the frequencies of each outcome. Multivariable logistic regression models examined the independent associations of magnesium sulfate with outcomes. Results Of 2,970 women who met inclusion criteria, 1,072 (36%) received intrapartum magnesium sulfate. Women who received magnesium sulfate were more likely to be nulliparous, publicly insured, of minority race or ethnicity, earlier gestational age at delivery, and undergo labor induction. The frequency of postpartum hemorrhage was significantly higher among women who received magnesium sulfate compared with those who did not (12.4 vs. 9.3%, p = 0.008), which persisted after controlling for potential confounders. Of secondary outcomes, there was no difference in estimated blood loss between women who did and did not receive magnesium sulfate (250 mL [interquartile range 250-750] vs. 250 mL [interquartile range 250-750], p = 0.446). However, compared with women who did not receive magnesium sulfate, women who received magnesium sulfate had a greater frequency of uterine atony (8.9 vs 4.9%, p < 0.001) and transfusion of packed red blood cells (2.0 vs. 0.8%, p = 0.008). These differences persisted after controlling for potential confounders. Conclusion Intrapartum magnesium sulfate administration to women with hypertensive disorders of pregnancy is associated with increased odds of postpartum hemorrhage, uterine atony, and red blood cell transfusion.


A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease.
To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab' fragment of anti-tumor necrosis factor, CDP870) in Crohn's disease. In a placebo-controlled, phase II study, 292 patients with moderate to severe Crohn's disease received subcutaneous certolizumab 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. The primary end point was the percentage of patients with a clinical response at week 12 (a Crohn's Disease Activity Index decrease of > or = 100 points or remission [Crohn's Disease Activity Index < or = 150 points]) in the intent-to-treat population. All certolizumab doses produced significant clinical benefit over placebo at week 2 (placebo, 15.1%; certolizumab 100 mg, 29.7% [P = .033]; 200 mg, 30.6% [P = .026]; 400 mg, 33.3% [P = .010]). At all time points, the clinical response rates were highest for certolizumab 400 mg, greatest at week 10 (certolizumab 400 mg, 52.8%; placebo, 30.1%; P = .006) but not significant at week 12 (certolizumab 400 mg, 44.4%; placebo, 35.6%; P = .278). Patients with baseline C-reactive protein levels of 10 mg/L or greater (n = 119) showed clearer separation between active treatment and placebo (week 12 clinical response: certolizumab 400 mg, 53.1%; placebo, 17.9%; P = .005; post hoc analysis) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups. Certolizumab 400 mg may be effective and is well tolerated in patients with active Crohn's disease. High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo. Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab.


Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging.
The p63 gene regulates thymic epithelial cell (TEC) proliferation, whereas FoxN1 regulates their differentiation. However, their collaborative role in the regulation of TEC homeostasis during thymic aging is largely unknown. In murine models, the proportion of TAp63(+), but not ΔNp63(+), TECs was increased with age, which was associated with an age-related increase in senescent cell clusters, characterized by SA-β-Gal(+) and p21(+) cells. Intrathymic infusion of exogenous TAp63 cDNA into young wild-type (WT) mice led to an increase in senescent cell clusters. Blockade of TEC differentiation via conditional FoxN1 gene knockout accelerated the appearance of this phenotype to early middle age, whereas intrathymic infusion of exogenous FoxN1 cDNA into aged WT mice brought only a modest reduction in the proportion of TAp63(+) TECs, but an increase in ΔNp63(+) TECs in the partially rejuvenated thymus. Meanwhile, we found that the increased TAp63(+) population contained a high proportion of phosphorylated-p53 TECs, which may be involved in the induction of cellular senescence. Thus, TAp63 levels are positively correlated with TEC senescence but inversely correlated with expression of FoxN1 and FoxN1-regulated TEC differentiation. Thereby, the p63-FoxN1 regulatory axis in regulation of postnatal TEC homeostasis has been revealed.


The mechanism of injury in a steatotic liver graft during cold preservation.
Fatty livers are more prone to primary nonfunction after transplantation. It is known that cell injury is strongly associated with alterations in the content and composition of membrane lipids. We assumed that plasma membrane (PM) fluidity, which is the most important property of the membrane, differed between fatty and normal livers. The livers from obese and lean Zucker rats were flushed with cold Ringer's lactate and University of Wisconsin (UW) solution via the portal vein and preserved in cold UW solution for 24 hr. Histological examinations of electron microscopy were performed to investigate of sinusoidal lining cells (SLCs). PMs were isolated using a discontinuous density gradient of Percoll, and the lipid compositions were determined by chromatography. SLCs of fatty livers were markedly injured compared with control livers even after short preservation time. Moreover, many blebs were observed in the obese rats even after short preservation time. As for PM lipid composition, the cholesterol/phospholipid (PL) ratio of total PM was 0.14+/-0.03 in the obese rats and 0.21+/-0.03 in the lean rats (P<0.05). The relative proportions of polyunsaturated fatty acids among PLs in PM were 35.7+/-1.2% vs. 45.9+/-1.5% (P<0.0001). These results indicated that the fluidity of the PM in the obese rats is decreased after exposure to low temperatures. Our results suggest that steatotic livers from obese donors are more susceptible to cold preservation injury than livers without steatosis because of the severe deterioration of SLCs, and it is associated with PM fluidity even after short-term cold preservation.


CYP21 pseudogene transcripts are much less abundant than those from the active gene in normal human adrenocortical cells under various conditions in culture.
The human steroid 21-hydroxylase pseudogene (CYP21P, also termed CYP21A) is transcribed in the adrenal cortex, but the relative abundance of transcripts from CYP21P and from the active CYP21 gene (also termed CYP21B) is not well established. In the present experiments we cultured primary human adrenocortical cells in defined medium and used RNase protection assays to examine whether there might be a selective increase in the relative abundance of CYP21P transcripts under any of the various regulatory factors known to affect expression of 21-hydroxylase. Differences between the sequences of intron 2 in CYP21P and CYP21 allowed the synthesis of gene-specific probes spanning exon 3 and parts of the adjacent introns. CYP21- and CYP21P-specific probes spanning the site of the start of transcription were also synthesized. CYP21 transcripts were readily detectable. In agreement with previous observations on 21-hydroxylase mRNA and enzyme activity in primary cultures of human adrenocortical cells, the abundance of CYP21 transcripts was increased by cyclic AMP analogues (N6-monobutyryl cyclic AMP and 8-bromo cyclic AMP), insulin, IGF-I and tetradecanoyl phorbol acetate (TPA). However, CYP21P transcripts were not detected in the presence of any of the various regulatory factors known to affect expression of 21-hydroxylase.


Structural and thermodynamic insights into the recognition of native proteins by anti-peptide antibodies.
The mechanism by which antibodies elicited against protein-derived peptides achieve cross-reactivity with their cognate proteins remains unknown. To address this question, we have carried out the complete thermodynamic characterization of the association of a monoclonal antibody (260.33.12) raised against a peptide (SNpep) derived from staphylococcal nuclease (SNase) with both eliciting peptide and cognate protein. Although both ligands bind with similar affinity (Kd=0.42 μM and 0.30 μM for protein and peptide, respectively), protein and peptide binding have highly different thermodynamic signatures: peptide binding is characterized by a large enthalpic contribution (ΔH=-7.7 kcal/mol) whereas protein binding is dominated by a large entropic contribution (-TΔS=-7.2 kcal/mol). The structure of the SNpep:Fab complex, determined by X-ray diffraction, reveals that the bound conformation of the peptide differs from the conformation of the corresponding loop region in crystal structures of free SNase. The energy difference, estimated by molecular dynamics simulations between native SNase and a model in which the Ω-loop is built in the conformation of the Fab-bound peptide, shows that the energetic cost of adopting this conformation is compatible with the enthalpic cost of binding the protein vis-à-vis the peptide. These results are compatible with a mechanism by which the anti-peptide antibody recognizes the cognate protein: high affinity is maintained upon binding a non-native conformation by offsetting enthalpic penalties with reduced entropic losses. These findings provide potentially useful guidelines for the identification of linear epitopes within protein sequences that are well suited for the development of synthetic peptide vaccines.


Knowledge, attitude and practice among Chinese acupuncturists receiving sham and/or placebo acupuncture: a cross-sectional survey.
Placebo and sham acupuncture are common control strategies in acupuncture studies. However, the perception and practice of these approaches in acupuncturists are poorly documented. To investigate knowledge of, attitude towards and practice of sham and/or placebo acupuncture among Chinese acupuncturists. A cross-sectional survey conducted in six different tertiary care hospitals of traditional Chinese medicine in Beijing, China. A total of 92 licensed acupuncturists were asked to complete a predesigned and structured questionnaire on-site. A response rate of 92.4% (n=85) was achieved. Almost all participants (99%, n=84) had moderate knowledge about sham and/or placebo acupuncture, but only a minority (27%, n=23) reported an excellent understanding. The general attitude towards sham and/or placebo acupuncture was positive. Most respondents (99%, n=84) thought such controls were necessary and the majority (81%, n=69) believed they were feasible in acupuncture research. More than two-thirds of participants (71%, n=60) had applied sham and/or placebo acupuncture, but only a few (8%, 5/60) used it as the most common control strategy in clinical trials. The result of our survey suggests that Chinese acupuncturists have a moderate knowledge of, and a positive attitude towards, sham and/or placebo acupuncture. Research into sham and/or placebo acupuncture is limited in comparison with other control strategies. Therefore, an in-service education programme for acupuncturists and standardisation of sham and/or placebo acupuncture need to be developed.


[Analysis of a scale for the assessment of attention deficit disorder with hyperactivity in Chilean children].
Epidemiologic studies may be used as a starting point to improve interventions and improve diagnosis, with instruments that are both reliable and adequate. To analyze the psychometric properties of the Attention Deficit Disorder Evaluation Scale (ADDES) in Chilean primary and high school students. The ADDES was applied by 142 teachers to 254 students. Attention Defcit Disorder was already diagnosed in 144 students. Explanatory and confirmatory factorial analyses were carried out. Confirmatory Factorial Analysis (CFA) proved that the model suggested by the authors could not be replicated in the Chilean sample. Exploratory Factorial Analysis (EFA) showed that three new factors came out of the analysis. CFA was applied to the new model and modification indexes suggested the introduction of new saturations. Based on the model with the best goodness-of-fit, psychometric characteristics were evaluated. The ADDES adapted to the Chilean context has a high reliability and a strong discrimination ability, allowing the evaluation of behavior disorders, hyperactivity/impulsivity and attention deficit.


Phosphate utilization and constitutive synthesis of phosphatases in Thermoactinomyces vulgaris Tsilinsky.
Thermoactinomyces vulgaris utilized both organic and inorganic phosphates with equal efficiency for its growth. The specific activities of the thermophilic acid and alkaline phosphatases were found to be maximum at 1 mM concentration of each phosphate source. All the phosphatase isoenzymes (three alkaline and one acidic) were observed irrespective of the substrate source and concentration, suggesting constitutive synthesis of the enzymes. During growth and differentiation, both acid and alkaline phosphatases exhibited uniformly stable patterns of isoenzymes with slight variations in their specific activities.


Managing home enteral tube feeding for children.
There is a growing awareness of the long-term consequences of undernutrition in childhood. Consequently, an ever-increasing number of children are receiving nutritional support using an enteral tube. While most of the children will commence artificial feeding in hospital, a significant proportion will continue to be artificially fed on discharge into the community. This article discusses the various routes of enteral tube feeding, their indications and contraindications and problem-solving procedures. The article also discusses the issues of cooperation and coordination between acute and community services, and offers some guidance on effective discharge planning for these children.


Profile and essentiality of Nursing in the context of the COVID-19 pandemic.
The present study aims to describe the sociodemographic and health profile of nursing professionals in the context of the COVID-19 pandemic and propose a reflective analysis on the essentiality of the category facing the intrinsic demands of patients and the Brazilian health system, especially in the context of the public health emergency triggered by the exponential advance of the SARS-CoV-2 virus. This study reveals the relationship between historical injustices and the different types of inequality that impacted and caused the vulnerability of the profession, with an emphasis on the presentation of potential perspectives arising from this historical process and recent events.


Effects of ultrasonic pretreatment on quantity and composition of bacterial DNA recovered from granular activated carbon used for drinking water treatment.
Effects of ultrasonic pretreatment on bacterial DNA recovery from granular activated carbon (GAC) were investigated. GAC (Calgon F400), biologically activated, was sampled from an actual drinking water plant. Different ultrasonic energy densities (0-400 J·cm(-3)) were applied with agitation (250 rpm for 30 min), and recovered bacterial DNA was quantified using quantitative PCR. Energy density was linearly correlated with the concentration of carbon fines produced from GAC during ultrasonication. Ultrasonication alone had no effect on DNA recovery at ≤60 J·cm(-3), but a strongly adverse effect at >67 J·cm(-3) due to the produced carbon fines. Agitation along with ultrasonication strongly enhanced the bacterial DNA recovery when ≤40 J·cm(-3) was applied, although it did not affect the production of carbon fines. Ribosomal tag pyrosequencing was used to compare recovered bacterial communities (0, 20 and 30 J·cm(-3) with or without agitation). Ultrasonication allowed for obtaining a more diverse and richer bacterial community from GAC, compared with the control. Agitation did not show a positive effect on community organization (richness and diversity). Consistently, canonical correspondence analysis indicated that the energy density was associated with the relative abundances of particular bacterial members (P < 0.05), while agitation did not. Correspondence analysis revealed that the recovered bacterial communities were grouped according to the applied energy densities. In conclusion, ultrasonication and agitation influence the recovered DNA in quality and quantity, respectively, and carbon fines as a by-product by ultrasonication interfere with the DNA recovery.