Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus outbreak among healthcare workers in a long-term care facility.
We investigated an outbreak of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections that occurred among healthcare workers (HCWs) but not among residents of a long-term care facility (LTCF). Cases of S. aureus infection were sought by reviewing the medical records of residents and HCWs. In order to identify risk factors for the development of an S. aureus infection, an unmatched case-control study was conducted. Cases were all HCWs with a clinically compatible S. aureus infection; controls were HCWs with no history of a clinically compatible S. aureus infection. Cases and controls were interviewed and anterior nasal swabs were collected. Over a period of 14 months, a total of eight cases were identified among practice nurses, giving an attack rate of 10% for this category of profession. All isolates were identified as MRSA Panton-Valentine leukocidin (PVL)-producing SCCmec type IV. By multivariate analysis, working in a specific zone and being a practice nurse were found to be statistically significant risk factors for infection. The current outbreak indicates that HCWs may serve as vehicles for the entry of PVL-positive MRSA strains from the community into LTCFs, and that deficient hygiene practices and unrecognized carriage may facilitate spread. Given the increasing prevalence of PVL-positive MRSA infections worldwide, guidelines for the eradication of PVL-positive MRSA carriage within closed communities should be established and efforts to obtain cultures from compatible infections should be made.


Improving Anti-Cancer Potentiality and Bioavailability of Gallic Acid by Designing Polymeric Nanocomposite Formulation
Objective: In this study, we investigated the in vivo antitumor activity and pharmacokinetic characteristics of encapsulated GA-NC (gallic acid nanocomposite) in normal and hepatocellular carcinoma (HCC)-induced rats. Methods: Rats were distributed into 4 groups; negative control, HCC, gallic acid (GA), and GA-NC. Serum levels of alpha-fetoprotein (AFP), endoglin (ENG), heat shock protein-70 (HSP-70), pro-caspase 3, lipocalin-2 (LCN-2) and β-cell leukemia/lymphoma 2 (Bcl-2) were assayed by ELISA. The pharmacokinetic parameters for GA or GA-NC were determined by means of non-compartmental approach based on the serum– concentration profiles of free GA and GA-NC after oral administration. Also, histological procedures were used for examination of liver tissue sections. Results: Anaplastic changes in liver tissues were observed in untreated HCC group, as well as a significant increase in the serum AFP level. In addition, significant elevation in the serum ENG level as an angiogenic marker and the serum levels of the apoptotic mediators; HSP-70, Bcl-2 and pro-caspase 3 beside significant amplification in the serum inflammatory modulator, LCN-2 were recorded. Treatment with free GA or GA-NC markedly recovered the anaplastic changes in the rat liver tissues. In addition, they restored serum levels of AFP, ENG, HSP-70, Bcl-2, pro-caspase-3, and LCN-2. Pharmacokinetic analysis revealed that GA–NC displayed a characteristic sustained release profile with 4-fold increase in bioavailability in normal and HCC-induced rats. Conclusions: The results of this study suggest that encapsulation of GA into PLGA-CS-PEG enhances its oral bioavailability and anti-cancer activity. GA-NC may be a new therapeutic candidate for the mitigation of hepatocarcinogenesis.


Optimal management of neuromyelitis optica spectrum disorder with aquaporin-4 antibody by oral prednisolone maintenance therapy.
Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing neuroinflammatory disease associated with aquaporin-4 antibody. Since disabilities in patients with NMOSD accumulate with attacks, relapse prevention is crucially important for improving long-term outcomes. Corticosteroids are inexpensive and promising drugs for relapse prevention in NMOSD, but few studies have analysed the efficacy of corticosteroids in NMOSD, especially regarding the appropriate dosing and tapering regimens. A single-center, retrospective analysis of corticosteroid therapy in aquaporin-4 antibody-positive NMOSD patients fulfilling the 2015 international consensus diagnostic criteria was conducted. Medical records of a total of 89 Japanese patients with aquaporin-4 antibody-positive NMOSD seen at Department of Neurology, Tohoku University Hospital (2000~2016) were reviewed. At the last follow-up, 66% of the patients were treated with prednisolone (PSL) monotherapy, and the percentage of those receiving PSL monotherapy or a combination of PSL and other immunosuppressants increased from 17.5% in 2000 to 94.1% in 2016. On the other hand, annualised relapse rate (ARR) decreased from 0.78 (13 attacks in 200 person-months) in 2000 to 0.07 (5 attacks in 819 person-months) in 2016. Under PSL treatment, the mean ARR significantly decreased, and disabilities stabilized (PSL treatment vs no-medication; ARR: 0.21 vs 0.98, P < 0.01, Expanded Disability Status Scale score change: +0.02 vs +0.89, P < 0.01, observation periods: 60.1 vs 68.2 months, P=0.26). Using Kaplan-Meier curves, the 10-year relapse-free rate was 46.5% with PSL monotherapy and 7.1% with no medication (hazard ratio: 0.069, 95% confidence interval [CI] 0.024-0.199, P < 0.01). Rapid tapering of PSL (10 mg or less in one year and/or 5 mg or less in two years after clinical attacks) was associated with frequent relapses compared to gradual tapering (more than 10 mg in one year and more than 5 mg in two years after clinical attacks) (rapid vs gradual, 36.7% vs 17.7%, odds ratio 2.69, 95% CI 1.12-6.44, P = 0.02). However, even with PSL of 5 mg/day or less, the relapse rate was low after two years of acute treatment (before vs after, 53.8% vs 13.6%, odds ratio 0.12, 95% CI 0.03-0.50, P < 0.01). Nine patients needed additional immunosuppressants due to insufficient relapse prevention by PSL monotherapy. PSL monotherapy was generally well tolerated, but seven patients had severe adverse events, mainly bone fractures (5 with bone fracture, 1 with femoral capital necrosis and 1 with cerebral infarction). Our study suggests that PSL monotherapy is effective to prevent relapses in about half of patients with aquaporin-4 antibody-positive NMOSD if the doses are gradually reduced. Although it is important to have a treatment strategy tailored to each patient, this study provides evidence that PSL monotherapy can be an option for relapse prevention in some patients with NMOSD.


Improving the antifouling property of polysulfone ultrafiltration membrane by incorporation of isocyanate-treated graphene oxide.
In this paper, isocyanate-treated graphene oxide (iGO), which can be well dispersed in organic solvent, was prepared in a simple manner and showed excellent compatibility with polysulfone (PSF). iGO-PSF ultrafiltration membranes were prepared by the classical phase inversion method. The separation performance and the antifouling property of the prepared membranes were investigated in detail. The antifouling property of the prepared membranes was found to be greatly enhanced by the addition of iGO, and we attributed the enhanced antifouling property to the improved hydrophilicity, the more negative zeta potential and the improved smoothness of the membrane surface.


Perspective of patients referred to Yoga center in a tertiary neuropsychiatric hospital: A cross-sectional retrospective study.
Yoga has been extensively used as an alternative or complementary therapy in psychiatric disorders depending on the type and severity of the disorders. However, data related to perspective on yoga services and the benefits and adverse effects attributed to yoga by patients with major psychiatric disorders is lacking. The aim of the study was to assess feedback of the patients who attended yoga sessions at a Yoga center in a tertiary neuropsychiatric hospital. This was a cross-sectional retrospective study using a specific questionnaire to get feedback from patients referred to the NIMHANS Integrated Center for Yoga, at the end of their yoga training. Two hundred and one patients' data were included in this retrospective study. Most of the patients were referred by the doctors. The yoga module for schizophrenia was most commonly utilized, followed by depression. On an average, patients attended 13 sessions. Most of them practiced yoga for 1-2 weeks and had missed less than 2 sessions. The great majority of the patients reported that practicing yoga helped them. Spearman correlation analysis revealed positive associations between improvement attributed to yoga and variables affecting quality of yoga services at the center, including the quality of yoga sessions attended. Overall health and sleep improvement also positively correlated with improvement attributed to yoga. A minority of patients reported adverse effects, although these did not lead to discontinuation. In this retrospective study of patients referred to a Yoga center in a tertiary psychiatric facility, the majority of patients with major mental disorders were able to practice yoga under supervision and reported significant improvement in symptoms with minimal adverse effects.


Phosphates as Antibotulinal Agents in Cured Meats: A Review.
Phosphates have been suggested as potential substitutes for the currently used nitrite in cured meat products, yet relatively little research has been done on the antibotulinal effects of phosphates. Phosphate selection for use in the cured meat industry continues to be based upon achieving certain functional objectives rather than microbiological control (i.e., improved tenderness, moisture retention, reduced shrinking during cooking, pH adjustments, emulsification, sequestration of ions). Current federal regulations limit addition of phosphates to amounts needed to achieve functionality. One notable exception is shelf-stable pasteurized processed cheese, cheese foods and cheese spreads, in which addition of phosphates for emulsification purposes also appears to provide antimicrobial or antibotulinal protection. It is, therefore, becoming evident that phosphates have the potential under certain conditions, of enhancing microbial or botulinal safety and stability of certain foods, with certain phosphates [i.e. sodium acid pyrophosphate (SAPP)] or mixture of phosphates displaying more effectiveness than others.


A temporary antibiotic-loaded joint replacement system for management of complex infections involving the hip.
Management of the infected hip replacement associated with substantial loss of bone, especially segmental loss of the proximal femur, is a challenging problem. In this report, the authors outline the development of an immediate-fit, custom-made, antibiotic-selective replacement system for the hip and proximal femur, to help maintain limb length, joint stability, and mobility of the patient. Despite the initial relatively crude design, it was a valuable adjunct in the management of 15 consecutive cases. A more sophisticated and versatile system has since been developed for use in straightforward and complex cases.


Tuberculous pleural effusions: increased culture yield with bedside inoculation of pleural fluid and poor diagnostic value of adenosine deaminase.
A prospective study of 111 adult patients with a pleural effusion was carried out in an area with a high prevalence of tuberculosis to compare the yield of bedside with laboratory inoculation of pleural fluid, and the yield and speed of a radiometric mycobacterial culture system (BACTEC) with that of conventional culture. The use of adenosine deaminase activity in pleural fluid as a diagnostic test for tuberculosis was also evaluated. In the 62 cases of tuberculosis confirmed histologically or by culture, or both, the BACTEC system had the same culture yield as conventional mycobacterial culture (positive in 14 cases-23%), but was significantly faster (18 versus 33 days). Bedside inoculation had a culture yield significantly higher than laboratory inoculation in the 24 patients tested (11 versus four). The remaining three diagnostic categories were malignant (28), miscellaneous (10), and undiagnosed (11). Median adenosine deaminase activity was significantly higher in tuberculous effusions than in any of the other categories, but there was considerable overlap between the groups. It is concluded that the BACTEC system is significantly faster than conventional mycobacterial culture and that bedside inoculation of pleural fluid substantially increases culture yield. Adenosine deaminase does not provide as valuable a diagnostic test of pleural tuberculosis as has been suggested.


[Cholecystokinin-peptides--new knowledge and possibilities for clinical use].
This issue comprises selected topics of CCK peptides. CCK peptides are linear peptides and were found within and outside the CNS. There is growing evidence that CCK peptides play a physiological role in food intake, contraction of gallbladder and regulation of motility of the gastrointestinal system. New aspects of the CCK research are concentrated on interaction with other transmitter systems especially with the dopamine and opioid system. The therapeutic action to improve clinical symptoms in human is unclear up to new. World-wide, the interest is focused to determine the potential of CCK peptides as an antipsychotic agent by controlled clinical studies.


Treatment adherence improves outcomes and manages costs.
Our experience with other chronic diseases, such as hypertension, diabetes, and asthma, has shown that adherence to treatment over time is about 50%. In HIV treatment, a significantly higher rate of adherence (i.e., 95% or greater) is required to achieve good outcomes. HAART is effective and cost-effective. Even with the high cost of antiretroviral drugs, the decrease in hospital utilization in addition to improved quality of life with HAART more than offsets the increased cost of drugs. This cost shifting from hospital utilization has been shown to result in a decrease of total monthly costs of care in many settings. In addition to decreased mortality and cost savings from decreased hospital utilization associated with HAART, the appropriate use of expensive antiretroviral drugs and the resultant reduction in antiretroviral resistance can save lives and money over the long term. However, we know that the performance of drugs in clinical trials is not always borne out in today's real world of ambulatory HIV care, underscoring the need for treatment adherence strategies in the HAART era. Our understanding of what improves adherence to antiretroviral treatment is still incomplete. However, there are a number of approaches that address the patient, the provider/multidisciplinary team, and the treatment regimen itself. The dedicated TAC, while not the only solution, has been shown to be an effective team member and a solution worth considering in managed care settings. When added to the costs of today's care, this team member should still prove cost-effective in the final analysis.


Multi-peak electromagnetically induced transparency (EIT)-like transmission from bull's-eye-shaped metamaterial.
We investigate the electromagnetic response of the concentric multi-ring, or the bull's eye, structure as an extension of the dual-ring metamaterial which exhibits electromagnetically-induced transparency (EIT)-like transmission characteristics. Our results show that adding inner rings produces additional EIT-like peaks, and widens the metamaterial's spectral range of operation. Analyses of the dispersion characteristics and induced current distribution further confirmed the peak's EIT-like nature. Impacts of structural and dielectric parameters are also investigated.


A novel indolocarbazole, ICP-1, abrogates DNA damage-induced cell cycle arrest and enhances cytotoxicity: similarities and differences to the cell cycle checkpoint abrogator UCN-01.
DNA damaging agents such as cisplatin arrest cell cycle progression at either G1, S, or G2 phase, although the G1 arrest is only seen in cells expressing the wild-type p53 tumor suppressor protein. We have reported that 7-hydroxystaurosporine (UCN-01) overcomes S and G2 phase arrest and enhances the cytotoxicity of cisplatin. Abrogation of arrest appears to be selective for cells defective in p53 and therefore provides a potential, tumor-targeted therapy. Unfortunately, UCN-01 binds avidly to human plasma proteins, limiting access to the tumor. A screen of related indolocarbazoles identified analogues with both beneficial and undesirable properties. This led to a synthetic program to develop a novel analogue rationally designed to overcome the obstacles observed with the other analogues. We report the synthesis and analysis of a novel analogue, ICP-1. This analogue abrogated S and G2 phase arrest and enhanced cytotoxicity induced by cisplatin only in p53 defective cells. ICP-1 also abrogated arrest and enhanced cell killing induced by the topoisomerase I inhibitor SN38. Analysis of proteins that regulate cell cycle arrest suggest both drugs inhibit checkpoint kinases Chk1 and/or Chk2. In contrast to UCN-01, checkpoint abrogation by ICP-1 was only slightly inhibited by human plasma. UCN-01 and ICP-1 differed significantly in other regards. UCN-01 potently enhanced the activity of 1-beta-D-arabinofuranosylcytosine in both p53 wild-type and mutant cells, whereas ICP-1 was inactive in this combination. This property of UCN-01 was independent of its ability to inhibit protein kinase C because more specific inhibitors of protein kinase C failed to enhance cell killing induced by 1-beta-D-arabinofuranosylcytosine. High concentrations of UCN-01 also inhibit C-TAK1 that results in S phase-arrested cells directly entering mitosis, but this property was not observed with ICP-1. Hence, ICP-1 appears to be a more selective inhibitor of the S and G2 cell cycle checkpoint than previously studied analogues and is worthy of study in preclinical tumor models.


Interpretation of the "positive" methacholine challenge.
A methacholine challenge may be used in confirming the diagnosis of asthma, occupational asthma, or reactive airways dysfunction syndrome (RADS) through identification of bronchial hyperreactivity (BHR). While sensitivity of the test in diagnosing clinically significant asthma is excellent, specificity of the test is poor. Since there are many conditions which have been associated with BHR, a positive test must be interpreted cautiously. This paper reviews potential causes of a positive methacholine challenge other than asthma or RADS which have been reported in the medical literature. Factors which may be associated with a positive methacholine test include test methodology, normal variation of BHR in the general population, and numerous medical conditions. In cases of inhalation exposure evaluations, alternative explanations must be considered when determining whether a causal association exists between the exposure and a positive methacholine test result.


Posterior malleolar fracture is often associated with spiral tibial diaphyseal fracture: a retrospective study.
It is known that posterior malleolar fracture is often associated with tibial diaphyseal fractures. However, in literature there are very few studies on tibial shaft fractures with respect to posterior malleolus fragment. We hypothesized that the incidence of posterior malleolar fracture is higher than in previous studies. A total of 74 closed tibial shaft fractures were treated with intramedullary nailing in Turku University Central Hospital between January 1994 and December 1998. There were 55 men and 19 women, with a mean age of 39 years (range, 16 to 58 years). Two cases were excluded and 72 tibial shaft fractures were analyzed retrospectively. Posterior malleolar fracture was observed in 18 cases (25.0%). Only 10 were observed preoperatively in plain films, seven were detected postoperatively and one was not detected at all during the treatment. Retrospectively, all 18 posterior malleolar fractures were detectable in preoperative plain films. A fracture of the posterior malleolus was involved in every fourth tibial diaphyseal fracture. The fractures of the posterior malleolus were always detected in preoperative plain films and should be suspected, especially in cases of low-energy spiral distal tibial diaphyseal fractures. We recommend additional plain films to be taken at the ankle region to better visualize these fractures.


Analysis of protein expression during oxidative stress in breast epithelial cells using a stable isotope labeled proteome internal standard.
Normal cells undergo a variety of molecular and physiological changes upon malignant transformation, including their responses to environmental factors that induce oxidative stress. Understanding the molecular pathways regulating these changes would facilitate the development of novel cancer treatments and chemoprevention strategies. Differences in the oxidative stress response were investigated between nonmalignant (S-1) and malignant (T4-2) cell lines (both derived from the HMT-3522 breast epithelial cells) using proteomic approaches. A modification of the stable isotope labeling of amino acids in cell culture (SILAC) approach was employed in which a [(13)C,(15)N]-labeled proteome was prepared from both cells. Relative quantification of the proteome derived from the S-1 cells and the T4-2 cells was then conducted using a [(13)C,(15)N]-labeled proteome as the internal standard. Differentially expressed proteins that changed in a similar manner in both cell lines were mainly stress response proteins, including heat shock proteins, peroxiredoxins, and redox proteins. Proteins that showed significant change in expression level in only one the cell lines included cytoskeleton proteins and proteins implicated in cell cycle and apoptosis regulation. Fortilin was found to be significantly up regulated in the transformed T4-2 cells after H(2)O(2) treatment but not in the parental S-1 cells. However, Ran/TC4 was up regulated by H(2)O(2) in the nonmalignant breast epithelial cells but not in the malignant cells. These results suggest that the malignant T4-2 cells have acquired more resistance to H(2)O(2)-induced apoptosis than the nonmalignant S-1 cells.


Integrated quantitative PIXE analysis and EDX spectroscopy using a laser-driven particle source.
Among the existing elemental characterization techniques, particle-induced x-ray emission (PIXE) and energy-dispersive x-ray (EDX) spectroscopy are two of the most widely used in different scientific and technological fields. Here, we present the first quantitative laser-driven PIXE and laser-driven EDX experimental investigation performed at the Centro de Láseres Pulsados in Salamanca. Thanks to their potential for compactness and portability, laser-driven particle sources are very appealing for materials science applications, especially for materials analysis techniques. We demonstrate the possibility to exploit the x-ray signal produced by the co-irradiation with both electrons and protons to identify the elements in the sample. We show that, using the proton beam only, we can successfully obtain quantitative information about the sample structure through laser-driven PIXE analysis. These results pave the way toward the development of a compact and multifunctional apparatus for the elemental analysis of materials based on a laser-driven particle source.


Investigation of activation markers demonstrates significant overexpression of the secretory component on salivary glands epithelial cells in Sjögren's syndrome.
Labial salivary glands biopsies (LSG) performed to support clinical anomalies suggestive of Sjögren's syndrome (SS) sometimes fail to confirm the diagnosis. Here we investigated whether epithelial activation markers could provide further information. Frozen cut sections of LSG from 40 patients, including 23 confirmed SS, were examined in immunofluorescence for the expression of HLA class II molecules, the protector of apoptosis bcl-2, the intercellular adhesion molecule 1 (ICAM-1) and secretory component (SC). Class II molecules were highly expressed on epithelial cells in SS patients (DR > DP > DQ). Bcl2 was expressed in infiltrating cells which were more numerous in the group of SS patients. ICAM-1 was present on endothelial and infiltrating cells of a few patients in both groups. Epithelial cells produced SC in 83% of SS patients samples vs four cases of non-SS patients (P = 0.0002). Investigation of the expression of SC on glandular epithelial cells could therefore be proposed as a marker of SS.


Isolation of the 5'-flanking region of genes by thermal asymmetric interlaced polymerase chain reaction.
Isolation of the 5'-flanking region of gene segments adjacent to known sequences is a tedious task. Thermal asymmetric interlaced (TAIL)-PCR developed in 1995 uses nested sequence-specific primers together with a shorter arbitrary degenerate primer so that the relative amplification efficiencies of specific and nonspecific products can be thermally controlled. In the present study, we modified the TAIL-PCR method to isolate the 5'-flanking region of two human genes, human natriuretic peptide receptor type A (NPRA) and type B (NPRB) genes. We improved upon the original TAIL-PCR method in some aspects: three different series of eight AD primers were used simultaneously; a high denaturing temperature was used; and a Taq DNA polymerase developed for long and accurate PCR was used. We succeeded in isolating the 5'-flanking region of the NPRA and NPRB genes directly from human genomic DNA. Our TAIL-PCR method is applicable not only to be human genome but also to the genome of other life forms.


Significance of mucin stain in uterine cervical cancers.
Histopathological examination of 140 cases of cervical cancer was supplemented with staining for the presence of mucin. Secretion of mucin was detected in 27 cases. Fourteen cases of large cell non-keratinizing (LCNK) squamous cell carcinoma were reclassified, 12 as squamous cell carcinoma with mucin secretion and two as adeno-squamous carcinoma. One case of undifferentiated carcinoma was labelled as adenocarcinoma on the basis of mucin stain. None of the keratinizing squamous cell carcinomas were positive for mucin. The results indicate that mucin expression should be looked for even in those carcinomas where no obvious gland formation is seen.


Effect of Ti: Sapphire and Nd: YAG Lasers on Shear Bond Strength at the Zirconia - Veneering Ceramic Juncture.
Introduction: This study was conducted to assess the impact of nanosecond and femtosecond lasers on shear bond strength at the zirconia - veneering ceramic juncture. Materials and Methods: The first 60 samples of partially sintered zirconia cylindrical discs measuring 7 mm diameter and 4 mm height were milled and sintered. Then they were randomly divided into three groups namely group C (control, n=10), group N (Nd: YAG laser, n=10), and group T (Ti: sapphire laser n=40) which was further divided based on the duration of laser irradiation, into 4 subgroups (n=10 each) which were 30 seconds, 1 minute, 2 minutes and 3 minutes. Surface treatment was done on sintered zirconia discs based on the group. Following the treatment, the discs were ultrasonically cleaned followed by liner application (IPS Emax Zirliner, Ivoclar-Vivadent) and veneer ceramic layering (IPS e.max Ceram, Ivoclar-Vivadent) of 1.5 mm height. Each sample underwent shear stress in the universal test machine on the mounting jig, and bond strength was evaluated. Data were assessed using ANOVA followed by Tukey's post hoc multiple comparison analyses. Results: According to one-way ANOVA, there was a significant difference in shear bond strength between the groups. Tukey's post hoc pair wise comparison test showed a significant difference (P value = 0.001) in shear bond strength of all pairs except group C and group N. The results of repeated measures, ANOVA (related and dependent groups) and Tukey's multiple pair wise comparison test showed that there was a significant difference (P value = 0.001) in shear bond strength at 30 seconds and all other groups. Conclusion: Ti: sapphire laser irradiation for 30 seconds can be used as potential surface treatment to increase shear bond strength at the zirconia-veneering ceramic juncture.


Effects of different light intensities during the daytime on circadian rhythm of core temperature in humans.
The present study was to determine the effects of bright light exposure during the daytime on core temperature rhythm. Eight female students participated as subjects. They were exposed to bright light of 5000 lux or dim light of 200 lux for 13 hours (06:30-19:30) for two consecutive days. Except the sleep period (22:30-06:30) and during the bright light exposure, light intensity was controlled at 200 lux. Rectal temperature data were collected every 10 min throughout the whole experimental period. The mean level of rectal temperature was not significantly different between the bright and the dim light conditions. However, the evening fall and the morning rise of rectal temperature were significantly greater in the bright light conditions on Day 2 compared to the dim. Furthermore, cosinor analysis showed that the acrophase of rectal temperature rhythm was earlier on Day 2 in the bright light conditions than the dim, and was significantly delayed on Day 2 compared to Day 1 in the dim light conditions. These results suggest that low intensity during the daytime for two consecutive days may induce a phase delay of core temperature rhythm rather than the bright light exposure at least in normally entrained female subjects.


Clinical Issues-February 2022.
Performing systematic reviews Key words: systematic review protocol, nurse researcher, literature search strategy, scoping review, methodology. Sequential application of patient skin antiseptic solution Key words: sequential antisepsis, surgical site preparation, skin antiseptic, instructions for use (IFU), preoperative. Patient radiology shielding Key words: radiation safety officer (RSO), gonadal shielding, radiosensitive organs, as low as reasonably achievable (ALARA), radiological exposure. Patient hair removal for neurosurgery Key words: patient hair removal, surgical site infection, neurosurgical procedures, patient satisfaction, disposable clipper system.


Three years of experience of the congenital hypothyroidism National Register.
Mental retardation caused by congenital deficiency of thyroid hormones can be prevented by early diagnosis and therapy which are assured by neonatal thyroid screening. Congenital hypothyroidism screening is performed in Italy by regional centres which in 1989 have screened more than 82% of neonatal population. Since 1987 a National Register of children affected by CH has been instituted. The results of the analysis of data collected in the first three years are reported.


[Chemical constituents from the roots of Angelica polymorpha Maxim].
Angelica polymorpha Maxim. is a plant of the Angelica genus (Umbelliferae). The root and stem of this plant is a folk medicine known to have the actions of relieving rheumatism and cold and subsiding swelling and pains. To investigate the chemical constituents in the root of A. polymorpha Maxim., seven compounds were isolated from an 80% ethanol extract by column chromatography. Their structures were elucidated according to the spectroscopic analysis. Compound 1 is a new sesquiterpene, named as bisabolactone. Its absolute configuration was determined by 1D NOESY and CD analysis. The others were identified as 5-hydroxymethylfurfural (2), hycandinic acid ester 1 (3), ferulic acid (4), isooxypeucedanin (5), noreugenin (6) and cimifugin (7). Compound 2 and 3 were isolated from this genus for the first time and compound 4 was isolated from this plant for the first time.


Persistence of antibody responses to COVID-19 vaccines among participants in the COVID-19 Community Research Partnership.
High levels of immunity to SARS-CoV-2 in the community correlate with protection from COVID-19 illness. Measuring COVID-19 antibody seroprevalence and persistence may elucidate the level and length of protection afforded by vaccination and infection within a population. We measured the duration of detectable anti-spike antibodies following COVID-19 vaccination in a multistate, longitudinal cohort study of almost 13,000 adults who completed daily surveys and submitted monthly dried blood spots collected at home. Overall, anti-spike antibodies persisted up to 284 days of follow-up with seroreversion occurring in only 2.4% of the study population. In adjusted analyses, risk of seroreversion increased with age (adults aged 55-64: adjusted hazard ratio [aHR] 2.19 [95% confidence interval (CI): 1.22, 3.92] and adults aged > 65: aHR 3.59 [95% CI: 2.07, 6.20] compared to adults aged 18-39). Adults with diabetes had a higher risk of seroreversion versus nondiabetics (aHR 1.77 [95% CI: 1.29, 2.44]). Decreased risk of seroreversion was shown for non-Hispanic Black versus non-Hispanic White (aHR 0.32 [95% CI: 0.13, 0.79]); college degree earners versus no college degree (aHR 0.61 [95% CI: 0.46, 0.81]); and those who received Moderna mRNA-1273 vaccine versus Pfizer-BioNTech BNT162b2 (aHR 0.35 [95% CI: 0.26, 0.47]). An interaction between healthcare worker occupation and sex was detected, with seroreversion increased among male, non-healthcare workers. We established that a remote, longitudinal, multi-site study can reliably detect antibody durability following COVID-19 vaccination. The survey platform and measurement of antibody response using at-home collection at convenient intervals allowed us to explore sociodemographic factors and comorbidities and identify predictors of antibody persistence, which has been demonstrated to correlate with protection against disease. Our findings may help inform public health interventions and policies to protect those at highest risk for severe illness and assist in determining the optimal timing of booster doses.Clinical trials registry: NCT04342884.


Intravenous injection of a D1 protein of the Smith proteins postpones murine lupus and induces type 1 regulatory T cells.
T cells that recognize nucleoproteins are required for the production of anti-dsDNA Abs involved in lupus development. SmD1 83-119 (a D1 protein of the Smith (Sm) proteins, part of small nuclear ribonucleoprotein) was recently shown to provide T cell help to anti-dsDNA Abs in the NZB/NZW model of lupus. Using this model in the present study, we showed that high dose tolerance to SmD1 (600-1000 microg i.v. of SmD1(83-119) peptide/mo) delays the production of autoantibodies, postpones the onset of lupus nephritis as confirmed by histology, and prolongs survival. Tolerance to SmD1 83-119 was adoptively transferred by CD90+ T cells, which also reduce T cell help for autoreactive B cells in vitro. One week after SmD1 83-119 tolerance induction in prenephritic mice, we detected cytokine changes in cultures of CD90+ T and B220+ B cells with decreased IFN-gamma and IL-4 expression and an increase in TGFbeta. Increased frequencies of regulatory IFN-gamma+ and IL10+ CD4+ T cells were later detected. Such regulatory IL-10+/IFN-gamma+ type 1 regulatory T cells prevented autoantibody generation and anti-CD3-induced proliferation of naive T cells. In conclusion, these results indicate that SmD1 83-119 peptide may play a dominant role in the activation of helper and regulatory T cells that influence autoantibody generation and murine lupus.


Enzymes of sucrose and hexose metabolism in developing kernels of two inbreds of maize.
Tissue distribution and activity of enzymes involved in sucrose and hexose metabolism were examined in kernels of two inbreds of maize (Zea mays L.) at progressive stages of development. Levels of sugars and starch were also quantitated throughout development. Enzyme activities studied were: ATP-linked fructokinase, UTP-linked fructokinase, ATP-linked glucokinase, sucrose synthase, UDP-Glc pyrophosphorylase, UDP-Glc dehydrogenase, PPi-linked phosphofructokinase, ATP-linked phosphofructokinase, NAD-dependent sorbitol dehydrogenase, NADP-dependent 6-P-gluconate dehydrogenase, NADP-dependent Glc-6-P dehydrogenase, aldolase, phosphoglucoisomerase, and phosphoglucomutase. Distribution of invertase activity was examined histochemically. Hexokinase and ATP-linked phosphofructokinase activities were the lowest among these enzymes and it is likely that these enzymes may regulate the utilization of sucrose in developing maize kernels. Most of the hexokinase activity was found in the endosperm, but the embryo had high activity on a dry weight basis. The endosperm, which stores primarily starch, contained high PPi-linked phosphofructokinase and low ATP-linked phosphofructokinase activities, whereas the embryo, which stores primarily lipids, had much higher ATP-linked phosphofructokinase activity than did the endosperm. It is suggested that PPi required by UDP-Glc pyrophosphorylase and PPi-linked phosphofructokinase in the endosperm may be supplied by starch synthesis. Sorbitol dehydrogenase activity was largely restricted to the endosperm, whereas 6-P-gluconate and Glc-6-P dehydrogenase activities were highest in the base and pericarp. A possible metabolic pathway by which sucrose is converted into starch is proposed.


Fluctuation properties of an effective nonlinear system subject to Poisson noise.
We study the work fluctuations of a particle, confined to a moving harmonic potential, under the influence of friction and external asymmetric Poissonian shot noise. This type of noise generalizes the usual Gaussian noise and induces an effective interaction between the noise and the potential, leading to an effectively nonlinear system with singular features. On the basis of an analytic solution we investigate the roles of time scales, symmetries, and singularities in the context of nonequilibrium fluctuations. Our results highlight the nonuniversality of the steady-state fluctuation theorem in stochastic systems.


Anti-control of chaos of single time-scale brushless DC motor.
Anti-control of chaos of single time-scale brushless DC motors is studied in this paper. In order to analyse a variety of periodic and chaotic phenomena, we employ several numerical techniques such as phase portraits, bifurcation diagrams and Lyapunov exponents. Anti-control of chaos can be achieved by adding an external constant term or an external periodic term.


The role of interferon-alpha in the treatment of myeloproliferative disorders.
The interferons are cytokines with a wide array of biological properties. In hematological malignancies the most used IFN class is -alpha; it has been used for thirty years but the mode of action is still not absolutely clear. Nevertheless, the benefits of IFN-alpha for the treatment of CMD have been described in particular for CML and less for PV, ET and MMM. IFN-alpha is presently considered the golden standard of therapy for CML patients not eligible for SCT; the antileukemic effect has been well documented by hematological and cytogenetic response. The survival advantage for IFN treated patients is remarkable in comparison with patients treated with conventional chemotherapy. Recently, the combination IFN-alpha plus Ara-C has demonstrated to increase the rate of major cytogenetic response and to prolong survival. To date, there is not a generally accepted treatment for ET, PV and MMM, which can reduce the risk of thromboembolism and/or hemorragic events. In several subsets of ET and PV patients, IFN-alpha can be considered as first line therapy. IFN-alpha is usually associated with the development of early and later side effects, that reduce the enthusiasm for its use. In the future PEG-IFN-alpha would improve the quality of life of IFN-treated CMD patients.


Preoperative staging of rectal carcinoma using transrectal ultrasonography (Trus): experience with 30 Nigerians.
Colorectal cancer is the second most common malignancy; accounting for approximately 155,000 new diagnosed cases each year in the United States. It is about the commonest Gastrointestinal Malignancy in Nigeria. For cancers specifically located in the rectum, various therapeutic options are available including local excision, total mesorectal excision, preoperative radiotherapy etc. These treatment modalities vary in morbidity and chance for cure. The choice of surgery as well as possible outcome largely depends on the depth of tumour infiltration of the rectal wall as well as extent of perirectal tissue involvement. The aim of this study was to assess local fixity clinically and also to assess the ability of transrectal ultrasound (TRUS) to fulfil staging requirements in patients with rectal cancer. The results of these findings were compared with findings at operation and subsequent findings at pathological examination. This is with the aim of evaluating the usefulness of transrectal ultrasound in selecting patients for surgical intervention especially with respect to resectability. Thirty consecutive patients with histologically confirmed rectal carcinoma at UITH, Ilorin from January 1998 to December 2002 who underwent preoperative TRUS were prospectively studied. After clinical examination including digital rectal examination they all had TRUS, proctoscopy and sigmoidoscopy. Result of findings on clinical examination, TRUS, findings at surgery and histological findings were compared and analysed using SPSS 10.0. There were 30 patients reviewed. Twenty per cent of patients who were thought to have fixation of the tumour on clinical examination were not confirmed on TRUS and at surgery. All the patients that TRUS diagnosed as fixed and therefore not resectable were confirmed at surgery and histopathology. Digital Rectal Examination (DRE) identified four patients with peri-rectal lymph nodes but TRUS picked six; though only five were histologically positive. TRUS is a useful preoperative imaging technique especially where CT and MRI are not readily available. This can assist the surgeon in preoperative decision taking as to the resectability of the tumour and possible prognosis.


Epilepsy and seizure classification in 63 dogs: a reappraisal of veterinary epilepsy terminology.
The human definitions of epilepsy and seizure classification were applied rigidly to epileptic dogs to investigate whether the distribution of the seizure types and epilepsies of dogs is comparable to that of human beings. Sixty-three dogs were referred because of recurrent (> 2) epileptic seizures. Only dogs without previous or ongoing antiepileptic treatment were included. All dogs had a physical and neurologic examination and blood work that included a CBC and a biochemical profile. All owners were asked to complete a questionnaire, focusing on seizure development. In addition, video recordings of suspected seizure episodes were analyzed if available. In the majority of dogs where an intracranial lesion was suspected, a computerized tomography scan was performed. Sixty-five percent of the dogs experienced partial seizures with or without secondary generalization and 32% exhibited primary generalized seizures; in 3% of the dogs the seizures could not be classified. Twenty-five percent of these cases were classified as idiopathic, 16% as symptomatic, and 45% as cryptogenic epilepsy; in 14% of these a classification was not possible. Applying human definitions, the distribution of seizure types and epilepsy classifications in these dogs differed widely from those in previous reports of canine epilepsy, where generalized seizures and idiopathic epilepsy were most frequently reported. However, our findings are consistent with the results of several large studies of human epilepsy patients. In dogs with epilepsy, closer attention must be given to the detection of a partial onset of seizures. In this study, detailed questioning of the owners and when possible analysis of video recorded seizures, proved to be sufficient for diagnosing seizures with a partial onset in a significant number of dogs. Partial onset of seizures may be an indication of underlying cerebral pathology. Some adjustments of veterinary epilepsy terminology are suggested.


Comparison of Management and Outcomes of Symptomatic Urolithiasis During the COVID-19 Pandemic to a Comparative Cohort.
To analyze the clinical presentation and outcomes for patients who presented with symptomatic urolithiasis during the initial months of the COVID-19 pandemic. We retrospectively reviewed Emergency Department (ED) presentations from a Philadelphia healthcare system for symptomatic urolithiasis between March and June 2020 and compared these with presentations for the same time period from the year prior. Patient demographics, stone characteristics, management, and clinical outcomes were compared between the 2 years. One hundred and thirty-nine patients presented during 2020 compared to 269 in 2019. There were fewer patients who presented during the initial COVID-19 pandemic surge who had obesity (37.41% vs 49.44%, P = .024), hyperlipidemia (18.71% vs 31.60, P = .006), and asthma (5.76% vs 16.73%, P = .002). Although overall stone characteristics did not differ between the 2 groups, a larger proportion of patients in 2020 presented with an obstructing stone (81.16% vs 64.1%, P = .001). Patients who presented during the COVID-19 pandemic did not have higher rates of infection, acute kidney injury, or complications. Rates of surgical modalities, emergent procedures, and discharges from the ED were similar between the 2 years. The COVID-19 pandemic initial surge resulted in fewer ED presentations for symptomatic urolithiasis; however, patients who did present were more likely to have obstructing stones, perhaps due to delaying presentation to avoid COVID-19 exposure in the ED. Despite higher rates of obstruction, clinical outcomes and morbidity were similar.


Effect of human growth hormone-releasing factor and(or) thyrotropin-releasing factor on growth, carcass composition, diet digestibility, nutrient balance, and plasma constituents in dairy calves.
Sixty male dairy grain-fed calves, raised from 70 to 223 kg BW in individual crates, were used in a 2 X 2 factorial arrangement to determine the effect of administration of human growth hormone-releasing factor (1-29)NH2 (GRF) and(or) thyrotropin-releasing factor (TRF). Calves received twice-daily s.c. injections of .9% NaCl (control), GRF (5 micrograms/kg BW), TRF (1 micrograms/kg BW) or GRF (5 micrograms/kg BW) plus TRF (1 micrograms/kg GTRF). Average daily gain and days on feed were not affected by treatments, but TRF treatment increased (P less than .05) total intake of dry matter (DM) and feed conversion ratio: 3.00, 3.02, 3.08, and 3.22 kg DM/kg weight gain for control, GRF, TRF, and GTRF, respectively. During two 7-d periods, after 66 and 75 d of treatment, feces and urine were collected from 40 calves (5 per treatment per period). Treatment with GRF increased (P less than .05) digestibility of DM, nitrogen (N), and energy and tended (P less than .20) to increase N retention. At slaughter, withers height was increased (P = .05) by GRF and carcass length was increased (P less than .05) by TRF. Pituitary and liver weights were increased (P less than .05) by TRF. The combination of GRF and TRF slightly increased (P less than .10) protein content and decreased (P less than .05) fat content of the 9-10-11th rib section. After d 1, GRF treatment chronically increased (P less than .05) insulin concentrations and also increased (P less than .10) IGF-I concentrations on d 29 and 57. In summary, chronic treatment with GRF and(or) TRF did not improve growth or efficiency, although GRF increased digestibility of DM, N, and energy and the GRF plus TRF combination resulted in slightly leaner carcasses.


Functional Metabolomics Analysis Elucidating the Metabolic Biomarker and Key Pathway Change Associated With the Chronic Glomerulonephritis and Revealing Action Mechanism of Rhein.
Chronic glomerulonephritis (CGN) as the culprit of kidney failure can increase the mortality of critically ill patients and seriously threatens people's health all over the world. This study using metabolomics strategy is to reveal the potential therapeutic mechanism-related targets to evaluate the effects of rhein (RH) on CGN rats. Changes of serum metabolites and pathways were analyzed by non-targeted metabolomic method based on liquid chromatography-mass spectrometry (LC-MS) combined with ingenuity pathway analysis. In addition, the levels of biochemical indicators were also detected. A total of 25 potential biomarkers were identified to express serum metabolic turbulence in CGN animal model, and then 16 biomarkers were regulated by RH trending to the normal states. From metabolite enrichment and pathway analysis, pharmacological activity of RH on CGN were mainly involved in six vital metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, tricarboxylic acid cycle (TCA cycle), alanine, aspartate, and glutamate metabolism, arginine and proline metabolism. It suggested CGN treatment with RH, which may be mediated via interference with metabolic pathway such as amino acid metabolism, arachidonic acid metabolism, and TCA cycle to regulating inflammation, oxidation response and immune regulation against CGN. It showed that metabolomics method offer deeply insight into the therapeutic mechanisms of natural product.


Role of neurotransmitters and teratogens on palate development.
Neurotransmitters regulate palate shelf reorientation. Acetylcholine and serotonin stimulate, whereas GABA inhibits reorientation. Serotonin stimulates cell movement in an in vitro chemotactic system. Diazepam may cause cleft palate by mimicking GABA. Diazepam sensitivity may be caused by genotypic differences in a GABA-ergic system in the embryo.


Why are diabetes, stomach cancer and circulatory diseases more common in Northern Sweden?
Why does a greater proportion of the population of northern Sweden suffer from such diseases as diabetes, stomach cancer and those of the circulatory system than people living in the southern part of the country? Are there any environmental factors that can explain these circumstances? It can be concluded from this study that the regional mortality pattern displayed here cannot be disregarded. The consistency of the finding is supported by the joint analysis of several data sources. The analyses in this study indicate that dietary habits, water hardness, and seasonal variations--rather than smoking habits or alcohol abuse--could be causal explanations for the regional mortality pattern in circulatory diseases. Diet and genetic factors may explain the regional variations in diabetes, while there is so far no evidence for associations between stomach cancer and any environmental factors. Thus, there is no correlation between stomach cancer and waterborne nitrate level in the 24 Swedish counties. This calls for further studies on the connections between stomach cancer and intake of salt, vitamins or trace elements. The preparation of foods could also have some impact on the incidence of stomach cancer.


[The arsenal of extracorporeal circulation systems in pediatric cardiosurgery].
The paper presents the arsenal of extracorporeal circulation systems used in the surgical treatment congenital cardiac diseases. It provides some experience in using the extracorporeal circulation systems, indications for and contraindications for their use, and a working classification of extracorporeal circulatory techniques. Their methodological features, criteria for the adequate use of extracorcopreal techniques, and the results of their application are described.


Patient safety in primary health care: a systematic review.
The aim of this study was to identify methodologies to evaluate incidents in primary health care, types of incidents, contributing factors, and solutions to make primary care safer. A systematic literature review was performed in the following databases: PubMed, Scopus, LILACS, SciELO, and Capes, from 2007 to 2012, in Portuguese, English, and Spanish. Thirty-three articles were selected: 26% on retrospective studies, 44% on prospective studies, including focus groups, questionnaires, and interviews, and 30% on cross-sectional studies. The most frequently used method was incident analysis from incident reporting systems (45%). The most frequent types of incidents in primary care were related to medication and diagnosis. The most relevant contributing factors were communication failures among member of the healthcare team. Research methods on patient safety in primary care are adequate and replicable, and they will likely be used more widely, thereby providing better knowledge on safety in this setting.


Characterization of rabbit ileal receptors for Clostridium difficile toxin A. Evidence for a receptor-coupled G protein.
The purpose of this study was to characterize the surface receptor for toxin A, the enterotoxin from Clostridium difficile, on rabbit intestinal brush borders (BB) and on rat basophilic leukemia (RBL) cells. Purified toxin A was radiolabeled using a modified Bolton-Hunter method to sp act 2 microCi/micrograms, with retention of full biologic activity. 3H-Toxin A bound specifically to a single class of receptors on rabbit BB and on RBL cells with dissociation constants of 5.4 x 10(-8) and 3.5 x 10(-8) M, respectively. RBL cells were highly sensitive to toxin A (cell rounding) and had 180,000 specific binding sites per cell, whereas IMR-90 fibroblasts were far less sensitive to toxin A and lacked detectable specific binding sites. Exposure of BB to trypsin or chymotrypsin significantly reduced 3H-toxin A specific binding. Preincubation of BB with Bandeirea simplicifolia (BS-1) lectin also reduced specific binding, and CHAPS-solubilized receptors could be immobilized with WGA-agarose. The addition of 100 nM toxin A accelerated the association of 35S-GTP gamma S with rabbit ileal BB, and preincubation of BB with the GTP analogues GTP gamma S or Gpp(NH)p, significantly reduced 3H-toxin A specific binding. Our data indicate that the membrane receptor for toxin A is a galactose and N-acetyl-glucosamine-containing glycoprotein which appears to be coupled to a G protein.


Characterization of CpSte11, a MAPKKK gene of Cryphonectria parasitica, and initial evidence of its involvement in the pheromone response pathway.
The gene CpSte11 of Cryphonectria parasitica, which encodes a yeast Ste11 homologue, was cloned and characterized. Gene replacement analysis revealed a high frequency of CpSte11 null mutants. When compared with the wild-type parent strain, CpSte11 null mutants showed no difference in terms of growth rate or pigmentation. However, CpSte11 null mutants showed a marked decrease in both the number and size of stromal pustules on chestnut twigs. The virulence test showed that, in comparison with those of the wild-type and virus-infected hypovirulent strains, CpSte11 null mutants produced necrotic areas of intermediate size. Disruption of the CpSte11 gene also resulted in defects in female fertility. Down-regulation of transcripts for the mating pheromone precursor gene, Mf2/2, and mating response transcription factors, such as cpst12 and pro1, was observed in CpSte11 null mutants. The down-regulation of Mf2/2, cpst12 and pro1 was also observed in the mutant phenotype of Cpmk2, a mating response Fus3-like mitogen-activated protein kinase (MAPK) gene, but not in the mutant of Cpmk1, a high-osmolarity glycerol Hog1-like MAPK gene. These results indicate that the cloned CpSte11 gene is functionally involved in the mating response pathway and acts through downstream targets, including Cpmk2, cpst12, pro1 and Mf2/2. However, the characteristics of the CpSte11 null mutant were fully phenocopied only in the cpst12 null mutant, but not in other studied null mutants of components of the putative mating response pathway.


C-reactive protein-associated genetic variants and cancer risk: findings from FINRISK 1992, FINRISK 1997 and Health 2000 studies.
Evidence from prospective observational studies suggests that elevated circulating C-reactive protein (CRP) concentrations are associated with cancer risk, but it is unclear whether this association is causal. In order to examine this, we investigated whether genetic variants that are associated with circulating CRP concentrations are associated with cancer risk. We pooled data from three population-based prospective Finnish studies: FINRISK 1992 (n = 5289), FINRISK 1997 (n = 7160) and Health 2000 (n = 6299). Cancer cases were identified from cancer registrations. Thirteen CRP-associated SNPs, identified from genome-wide association studies, were genotyped. We examined the associations of the SNPs and cancer risk using Cox, probit and instrumented probit regression models. Compared to common allele homozygotes, individuals carrying one or two variant T alleles at rs1892534 had 1.05-fold (95% confidence interval (CI): 0.90, 1.23) and 1.2-fold (95% CI: 1.01, 1.42) increased overall cancer risk, respectively. Individuals with one or two variant A alleles at rs1169300 or rs2464196 had approximately 1.5- and 2-fold increased risk of lung cancer, respectively (p trend for both: 0.007). CRP SNPs were not associated with colorectal, prostate or breast cancer risk nor was CRP-associated with the probability of developing cancer in the instrumented probit analyses. We found some evidence for an association of a small number of CRP-associated SNPs with the overall cancer risk and lung cancer risk. Our instrumental variable analyses provided no clear evidence for a causal association of CRP and cancer. These findings suggest that circulating CRP concentrations are unlikely to have a causal role in cancer.


[Hydatoid cysts of liver--diagnostic and therapeutic problem].
In the Department of General Surgery of Medical University 11 patients with hydatid cysts of liver were operated. Ultrasonography and computer tomography allowed to define exact localization, size and contents of the cysts, what made possible planning of operating procedure. In 2 cases nonanatomic resection of liver parenchyma was performed, in 2 ones with coexisting stomach neoplasm just excision of the frontal wall of the cyst and emptying of the interior. In all the other cases the cysts were removed with surrounding liver tissue. Late results of surgical treatment with albendazol therapy are good. Diagnosis of echinococcic desease should be precised, considering with possibility of co-existing foci in other organs.


The effectiveness of quality protein maize in improving the nutritional status of young children in the Ethiopian highlands.
Undernutrition is a persistent problem in Africa, especially in rural areas where the poor largely depend on staples and have limited access to a diverse diet. Quality protein maize (QPM) consists of maize varieties biofortified with increased lysine and tryptophan levels. Several studies in controlled settings have indicated the positive impact of QPM on the nutritional status of children. Two 1-year, randomized, controlled studies were undertaken to measure the effect of QPM on the nutritional status of children consuming typical maize-based diets when QPM was cultivated by their households in the western Ethiopian highlands. The first study used a cluster-randomized design with 151 children aged 5 to 29 months; the second study used a completely randomized design with 211 children aged 7 to 56 months. In both studies, half of the households were provided with QPM seed and the other half with seed of an improved conventional maize variety. Undernutrition was pervasive, and maize was the dominant food in the children's complementary diets. In the first study a positive effect of QPM was observed for weight but not height, with children in the QPM group recovering from a drop in weight-for-height. In the second study, children consuming conventional maize progressively faltered in their growth, whereas children consuming QPM did not change significantly in height-for-age and had a marginal increase in weight-for-age. These studies indicate that in major maize-producing and -consuming areas of Africa, home cultivation and use of QPM in children's diets could reduce or prevent growth faltering and may in some cases support catch-up growth in weight.


Epitaxial Crystallization Behavior of Poly(butylene adipate) on Orientated Poly(butylene succinate) Substrate.
The crystallization behavior of poly(butylene adipate) (PBA) in the sheared PBS/PBA blend, as well as on highly orientated poly(butylene succinate) (PBS) substrate, was studied by means of DSC, POM, Raman microscopy, and XRD. The results showed that the pre-existing orientated PBS crystals exhibit a very strong nucleation ability toward PBA as reflected by the increased crystallization temperature and the occurrence of heteroepitaxy and transcrystallization of PBA on the PBS substrate. The epitaxial crystallization of PBA on the PBS substrate results in the formation of α-form PBA crystals in any crystallization conditions.


The effects of community pluralism on press coverage of health risks from local environmental contamination.
Based on the conflict/consensus model of Tichenor, Donohue and Olien, we proposed that mass mediated information signalling that local agents are contaminating the local environment and posing health risks is conflict-generating information and, therefore, will be controlled in the interest of community stability. We expected such control to vary by community structure. A content analysis of nine months of coverage by 19 newspapers supported the hypothesis that papers in more pluralistic communities were more likely than papers in less pluralistic communities to link contamination from local agents to threats to human health in the community and to frame such stories as problems. Newspapers in less pluralistic communities were more likely to frame local contamination in the context of solutions to the problem and were more likely to link contamination to health risks if the contamination were in a distant community.


"yl"-Oxygen exchange in uranyl(VI) ion: a mechanism involving (UO2)2(μ-OH)2(2+) via U-O(yl)-U bridge formation.
Szabó and Grenthe (Inorg. Chem. 2007, 46, 9372-9378) suggested from NMR spectroscopy that the "yl"-oxygen exchange in dioxo uranium(VI) ion in acidic solution occurs via an OH-bridged binuclear complex (UO(2))(2)(μ-OH)(2)(2+). Here, an "yl"-oxygen exchange pathway involving the (UO(2))(2)(μ-OH)(2)(2+) is studied by B3LYP density functional theory calculations. The oxygen exchange takes place via an intramolecular proton shuttle between the oxygen atoms in (UO(2))(2)(μ-OH)(2)(H(2)O)(6)(2+). The direct proton transfer from the hydroxo bridge or from the coordinating water to the "yl"-oxygen in (UO(2))(2)(μ-OH)(2)(H(2)O)(6)(2+) appears to be negligible because of an exceedingly high activation barrier (∼170 kJ mol(-1)). The exchange mechanism in (UO(2))(2)(μ-OH)(2)(H(2)O)(6)(2+) can be described by a multistep pathway that leads to the formation of an oxo bridge between two uranyl(VI) centers (U-O(yl)-U bridge). The activation enthalpy Δ(‡)H of the reaction obtained at the B3LYP level is 94.7 kJ mol(-1) and is somewhat larger than the experimental value of 80 ± 14 kJ mol(-1). However, the discrepancy between theory and experiment is at the acceptable level. The formation of an oxo bridge between the two uranyl(VI) centers was found to be the key step in proton shuttling, indicating that uranyl(VI) complexes with a stable oxo bridge (such as trinuclear (UO(2))(3)(μ(3)-O)(OH)(3)(+)) may have even faster "yl"-oxygen exchange rates than (UO(2))(2)(μ-OH)(2)(2+).


[Relationship between cortisol and testosterone during resting conditions, after acute stress and hormone stimulation in steers].
In this study the relationship between peripheral concentrations of cortisol and testosterone was investigated in 7 adult bulls under resting conditions as well as after sexual and hormonal stimulation. The animals were kept under natural photoperiods of 16L:8D and for hormone determinations blood was withdrawn from an indwelling jugular vein catheter every 30 minutes for 24 and 48 h, respectively. Evaluation of the hormonal profiles revealed that both steroids are secreted episodically characterized by irregular, short term fluctuations with high individual variability. A clear circadian rhythm with high levels in the morning and during the day and low concentrations in the evening and during night was observed for cortisol only. Concentrations of both steroidal hormones were not significantly correlated with each other. Intense sexual stimulation (mounting several times with ejaculation) during 30 minutes caused a rapid increase of cortisol without affecting testosterone secretion. After intravenous application of 1500 IU hCG and 0.5 mg GnRH a sharp rise of testosterone concentrations occurred with high values remaining for several hours but leaving the circadian cortisol pattern unchanged. The intravenous injection of 5 mg PGF2 alpha stimulated both the cortisol and testosterone secretion. Results from this investigation show that cortisol and testosterone are secreted episodically without any interrelationship under resting conditions. Sexual stress induced an increase of cortisol which did not inhibit testosterone secretion and high testosterone levels did neither influence the cortisol pattern. The concomitant increase of cortisol and testosterone after PGF2 alpha suggests a central (hypothalamus/hypophysis) action for prostaglandin.


[Myoclonus in the adult: diagnostic approach].
Myoclonus, defined as shock-like involuntary movement, may be physiological or caused by a very wide variety of hereditary and acquired conditions. Because myoclonus can originate from different disorders and lesions affecting quite varied levels of the central and peripheral nervous systems, it represents from many points of view a diagnostic challenge. Moreover, new entities have been recently individualized, such as cortical tremor, which deserve renewed attention. The aim of this review is to propose a rationale for a diagnostic approach based on clinical and electrophysiological grounds. In this setting, we successively address 1) the clinical features allowing a positive diagnosis of myoclonus; 2) the clinical clues to the etiology; 3) the relevance of the clinical context to the diagnosis; and 4) the contribution of neurophysiology. Differentiating myoclonus from tics, spasm, chorea and dystonia can be difficult, and a careful reappraisal of clinical features allowing precise identification is presented. Moreover, the topographical distribution of myoclonus, the temporal pattern of muscle recruitment, the condition of occurrence and the rhythm of the event, may provide clinical clues relevant to the diagnosis. Myoclonus without associated epilepsy, myoclonus with epilepsy, myoclonus with encephalopathy, parkinsonism and/or dementia represent overlapping clinical categories, although they remain useful for the diagnostic approach. Using electrophysiology (including back-averaging EEG, MEG, SEP, C-reflex studies) to determine the origin of myoclonus may not allow us to focus on the underlying condition. Indeed, in many instances, the myoclonus is cortical in origin, but the pathology is found elsewhere.


Analysis of sampling strategies for pulse loads of SARS-CoV-2: implications for wastewater-based epidemiology.
A faecal transport model was applied to a 11.3 km2 wastewater servicing area in Toronto, Ontario, Canada to explore the role that different wastewater sampling campaigns have on estimating the prevalence of SARS-CoV-2 in a population of 60,000. A stochastic wastewater and water quality model was used to evaluate the effectiveness of 11 sampling campaigns during periods of high and low COVID-19 infection among the population, tested using virtual sampling during dry-weather flow. The virtual sampling campaigns were based on the most common automatic sampler programming capabilities and widely used wastewater-based epidemiology (WBE) sampling campaigns reported in the literature. Sampling campaigns differ in weighting method (time, volume, or flow-weighted sampling), sample count, collection period, or sample time. Results suggest that grab samples should be avoided and/or that sampling campaigns with the greatest sample counts and durations are the most robust at capturing COVID-19 infection among the population. Most surprisingly, changes to the weighting method were negligible indicating that a greater number of samples, and larger sample volumes are preferred. This work suggests that investment in flow monitoring equipment for flow- or volume-weighted sampling will not improve WBE results, and that standard time based sampling is sufficient.


S-Adenosylmethionine May Mitigate Obstructive Sleep Apnea in an Adult with Down Syndrome: A Case Report.
Obstructive sleep apnea (OSA) is common in individuals with Down syndrome (DS). These patients are characterized by reduced levels of S-adenosylmethionine (SAMe) due to a depression of mitochondrial methylation capacity, and its implementation may improve cognitive performance. Based on the above, it is likely a beneficial effect in the treatment with SAMe also on the quality of the sleep. We report the case of an adult male with DS who received benefit of SAMe administration during OSA treatment with CPAP. We observed a significant improvement of apnea/hypopnea index (AHI), which has never been previously reported in Down individuals. AHI dropped from 51.2 to 17.2 from 0 to 49 months.


[Studies on immunoregulation of polysaccharides-la from Radix Cynanchi Bungei].
To study the effects of PRCB1a (one component of polysaccharides from Radix Cynanchi Bungei) on transformation of T lymphocytes of rabbit in vitro and immune function in mice. Three doses of PRCB1a (2,4,6 g x L(-1)) were respectively put in bottle with PHA and blood of rabbit. The effect of PRCB1a on immunity in vitro was studied by observing transformation of T lymphocytes; The dosage of PRCB1a (50,100,150 mg x kg(-1) x d(-1)) was given orally for seven days. The effects on immune function were investigated in mice. Three doses of PRCB1a could significantly promote (P < 0.01) the ability of T lymphocytes proliferation; PRCB1a could improve the mouse thymus and spleen index, the celiac macrophage ability of engulfing CRBC, the delayed type hypersensitivity ability and the macrophage engulfing carbon granula ability. The results indicate PRCB1a can enhance nonspectific and specific cellular immune function.


Pupae of the Nearctic species of Culicoides Latreille subgenus Monoculicoides Khalaf (Diptera: Ceratopogonidae).
There are 160 valid species of Culicoides Latreille described from the Nearctic Region, but many are unknown as immatures or, although partially described, cannot be readily identified. We provide pupal diagnoses, descriptions, and a key to all seven known species of Culicoides subgenus Monoculicoides Khalaf occurring in the Nearctic biogeographic region. A diagnosis of several characters unique to this subgenus is provided to allow for the recognition of the included species from those of other subgeneric groupings. Microphotography of important morphological characters for both the key and descriptions are provided. This study highlights the usefulness of examining the pupae of Culicoides as a tool for species identification. The pupae of Culicoides grandensis Grogan Phillips, C. occidentalis Wirth Jones, and C. shemanchuki Grogan Lysyk are newly described and those of C. riethi Kieffer, C. stigma (Meigen), and C. variipennis Wirth Jones are redescribed in detail. The seventh species, C. sonorensis, was fully described recently.


Prevalence of Soil-Transmitted Helminth Infection Among School-Aged Children of Ethiopia: A Systematic Review and Meta-Analysis.
Soil-transmitted helminths (STH) are still major health problems in resource-poor countries. Despite several epidemiological studies were available in Ethiopia, summarized data on the prevalence of STH among school-aged children (SAC) is lacking in the country. This study was aimed to summarize the existing published studies of STH among SAC children in Ethiopia. The search was carried out in open access databases such as Science Direct, Scopus, and PubMed Central which reported STH in Ethiopia. Open access articles published between 2000 and 2019 were included in this meta-analysis. The pooled prevalence was determined using a random-effect model while heterogeneities between studies were evaluated by I 2 test. A total of 46 338 children (Male = 23 374 and Female = 22 964) were included in the 70 eligible studies for this meta-analysis. The pooled prevalence of STH among SAC was 33.4%; 95% CI, 29.3% to 37.7% in Ethiopia. Ascaris lumbricoides (19.9%; 95% CI, 17.2%-22.6%) was the most prevalent STH followed by Trichuris trichiura (12.4%; 95% CI, 10.6%-14.1%), and hookworm (7.9%; 95% CI, 6.9%-8.9%) infection in the country. High prevalence of STH was observed in Oromia (42.5%; 95% CI, 31.6%-53.4%) followed by SNNPR (38.3%; 95% CI, 27.7%-48.8%) and Amhara (32.9%; 95% CI, 27.0%-38.8%) regional states. High heterogeneity on the prevalence of STH was observed across studies within and among regions (I 2 > 96% and P < .001). This review showed that more than one-third of the Ethiopian SAC were infected with STH. The high prevalence of STH observed in this review highlight the needs of improved control and prevention strategies in Ethiopia.


Efficacy of human beta-casein fragment (54-59) and its synthetic analogue compound 89/215 against Leishmania donovani in hamsters.
The characteristic feature of visceral leishmaniasis (VL) is the profound impairment of immune system of the infected host, which contributes significantly to the partial success of antileishmanial chemotherapy. Since in VL, cure is the combinatorial effect of drug and immune status of the host, the rationale approach towards antileishmanial chemotherapy would be to potentiate the immune functioning of the host to extract desired results. Towards this direction several rationally designed analogues of human beta-casein fragment (54-59) were evaluated for their ability to stimulate the non-specific resistance in hamsters against Leishmania donovani infection. By virtue of being derived from the food protein casein derivatives may be devoid of unwanted side effects associated with the substances of microbial origin, e.g. muramyl dipeptide (MDP). Out of this one peptide Val-Glu-Gly-Ile-Pro-Tyr (compound 89/215) had been reported to have such activity. In this communication, the prophylactic and therapeutic efficacy of the peptide along with its natural sequence has been evaluated in detail against experimental VL in hamsters. Their use as an adjunct to chemotherapy was also explored. Human beta-casein fragment, compound 89/215 and MDP were tested in vivo at various dose levels wherein compound 89/215 showed superiority over MDP at 3 mg/kg x 2 given intraperitoneally (i.p.). Compound 89/215 sensitized peritoneal macrophages acquired considerable resistance and only 24% of the cells were found infected in comparison to control peritoneal macrophages where 76.4% of the cells were found infected. Similarly, the efficacy of sodium antimony gluconate (SAG) in hamsters pretreated with compound 89/215 enhanced significantly (P < 0.001). This peptide also exhibited considerably good therapeutic efficacy when evaluated either alone or in combination with SAG in established infection of L. donovani.


Root reconstructed with mineral trioxide aggregate and guided tissue regeneration in apical surgery: a 5-year follow-up.
Apical surgery should be considered as the last treatment option and employed when conventional endodontic treatment does not provide the expected result. In teeth undergoing apical surgery, the type of retrograde filling material is one of the factors interfering with the repair of periapical tissues. The material in intimate contact with the periapical tissues plays a fundamental role in the repair process. Several materials have been studied and indicated for use in apical surgery procedures, but the mineral trioxide aggregate (MTA) is still the most frequently used one. Guided tissue regeneration (GTR) techniques have been proposed as an adjunct to apical surgery to enhance bone healing. Here is reported a clinical case in which apical surgery was performed in conjunction with MTA-based root reconstruction of the maxillary right second incisor. After the apical surgery, a root-end cavity was prepared at the vestibular face of the involved tooth and filled with MTA. A bovine bone graft and a cortical collagen membrane were placed on the bone defect. After 5 years, clinical and radiographic assessments showed that the treatment was successful. It may be concluded that MTA presents favorable characteristics in adverse conditions and can be used in conjunction with GTR in cases involving root reconstruction.


Adenovirus-mediated E2F-1 gene transfer in nonsmall-cell lung cancer induces cell growth arrest and apoptosis.
Since overexpression of E2F-1 has been shown to induce apoptosis, the ability of adenovirus-mediated transfer of E2F-1 to inhibit tumour growth in nonsmall-cell lung cancer cell lines was investigated. Three cell lines with various genomic status were infected with AdE2F. Cell proliferation and viability were determined by trypan blue exclusion. Apoptosis induction was assessed by flow cytometry and poly-adenosine diphosphate-ribose-polymerase cleavage assay. In vivo, the effect of E2F-1 on tumour growth was determined in severe combined immunodeficiency (SCID) mice. The current experiments showed that overexpression of E2F-1 suppressed tumour cell growth. The population of apoptotic cells was dramatically increased 96 h after infection with AdE2F. Inhibition of cell growth and induction of apoptosis was not dependent on genomic status. Moreover, treatment of implanted tumours in SCID mice with AdE2F inhibited tumour growth. These data suggest that adenovirus-mediated E2F-1 gene therapy may be effective in the treatment of nonsmall-cell lung cancer.


Dorsal Anterior Cingulate Cortex: A Bottom-Up View.
The dorsal anterior cingulate cortex (dACC) has attracted great interest from neuroscientists because it is associated with so many important cognitive functions. Despite, or perhaps because of, its rich functional repertoire, we lack a single comprehensive view of its function. Most research has approached this puzzle from the top down, using aggregate measures such as neuroimaging. We provide a view from the bottom up, with a focus on single-unit responses and anatomy. We summarize the strengths and weaknesses of the three major approaches to characterizing the dACC: as a monitor, as a controller, and as an economic structure. We argue that neurons in the dACC are specialized for representing contexts, or task-state variables relevant for behavior, and strategies, or aspects of future plans. We propose that dACC neurons link contexts with strategies by integrating diverse task-relevant information to create a rich representation of task space and exert high-level and abstract control over decision and action.


Combined Fontana-Masson/Perls' staining.
A procedure that allows successive staining of tissue sections with the Fontana-Masson technique for melanin and Perls' technique for hemosiderin is described.


Efficacy Analysis of In Situ Synthesis of Nanogold via Copper/Iodonium/Amine/Gold System under a Visible Light.
This article presents, for the first time, the kinetics and the general features of a photopolymerization system (under visible light), copper-complex/Iodonium/triethylamine/gold-chloride (orA/B/N/G), with initial concentrations of A0, B0, N0 and G0, based on the proposed mechanism of Tar et al. Analytic formulas were developed to explore the new features, including: (i) both free radical photopolymerization (FRP) efficacy and the production of nanogold (NG), which are proportional to the relative concentration ratios of (A0 + B0 + N0)/G0 and may be optimized for maximum efficacy; (ii) the two competing procedures of NG production and the efficacy of FRP, which can be tailored for an optimal system with nanogold in the polymer matrix; (iii) the FRP efficacy, which is contributed by three components given by the excited state of copper complex (T), and the radicals (R and S) produced by iodonium and amine, respectively; (iv) NG production, which is contributed by the coupling of T and radical (S) with gold ion; and (v) NG production, which has a transient state proportional to the light intensity and the concentration ratio A0/G0) + (N0/(K'M0), but also a steady-state independent of the light intensity.


More than Enzymes That Make or Break Cyclic Di-GMP-Local Signaling in the Interactome of GGDEF/EAL Domain Proteins of Escherichia coli.
The bacterial second messenger bis-(3'-5')-cyclic diguanosine monophosphate (c-di-GMP) ubiquitously promotes bacterial biofilm formation. Intracellular pools of c-di-GMP seem to be dynamically negotiated by diguanylate cyclases (DGCs, with GGDEF domains) and specific phosphodiesterases (PDEs, with EAL or HD-GYP domains). Most bacterial species possess multiple DGCs and PDEs, often with surprisingly distinct and specific output functions. One explanation for such specificity is "local" c-di-GMP signaling, which is believed to involve direct interactions between specific DGC/PDE pairs and c-di-GMP-binding effector/target systems. Here we present a systematic analysis of direct protein interactions among all 29 GGDEF/EAL domain proteins of Escherichia coli Since the effects of interactions depend on coexpression and stoichiometries, cellular levels of all GGDEF/EAL domain proteins were also quantified and found to vary dynamically along the growth cycle. Instead of detecting specific pairs of interacting DGCs and PDEs, we discovered a tightly interconnected protein network of a specific subset or "supermodule" of DGCs and PDEs with a coregulated core of five hyperconnected hub proteins. These include the DGC/PDE proteins representing the c-di-GMP switch that turns on biofilm matrix production in E. coli Mutants lacking these core hub proteins show drastic biofilm-related phenotypes but no changes in cellular c-di-GMP levels. Overall, our results provide the basis for a novel model of local c-di-GMP signaling in which a single strongly expressed master PDE, PdeH, dynamically eradicates global effects of several DGCs by strongly draining the global c-di-GMP pool and thereby restricting these DGCs to serving as local c-di-GMP sources that activate specific colocalized effector/target systems.IMPORTANCE c-di-GMP signaling in bacteria is believed to occur via changes in cellular c-di-GMP levels controlled by antagonistic and potentially interacting pairs of diguanylate cyclases (DGCs) and c-di-GMP phosphodiesterases (PDEs). Our systematic analysis of protein-protein interaction patterns of all 29 GGDEF/EAL domain proteins of E. coli, together with our measurements of cellular c-di-GMP levels, challenges both aspects of this current concept. Knocking out distinct DGCs and PDEs has drastic effects on E. coli biofilm formation without changing the cellular c-di-GMP level. In addition, rather than generally coming in interacting DGC/PDE pairs, a subset of DGCs and PDEs operates as central interaction hubs in a larger "supermodule," with other DGCs and PDEs behaving as "lonely players" without contacts to other c-di-GMP-related enzymes. On the basis of these data, we propose a novel concept of "local" c-di-GMP signaling in bacteria with multiple enzymes that make or break the second messenger c-di-GMP.


Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.
The cerebral folate receptor alpha (FRα) transports 5-methyltetrahydrofolate (5-MTHF) into the brain; low 5-MTHF in the brain causes cerebral folate deficiency (CFD). CFD has been associated with autism spectrum disorders (ASD) and is treated with d,l-leucovorin (folinic acid). One cause of CFD is an autoantibody that interferes with the function of the FRα. FRα autoantibodies (FRAAs) have been reported in ASD. A systematic review was performed to identify studies reporting FRAAs in association with ASD, or the use of d,l-leucovorin in the treatment of ASD. A meta-analysis examined the prevalence of FRAAs in ASD. The pooled prevalence of ASD in individuals with CFD was 44%, while the pooled prevalence of CFD in ASD was 38% (with a significant variation across studies due to heterogeneity). The etiology of CFD in ASD was attributed to FRAAs in 83% of the cases (with consistency across studies) and mitochondrial dysfunction in 43%. A significant inverse correlation was found between higher FRAA serum titers and lower 5-MTHF CSF concentrations in two studies. The prevalence of FRAA in ASD was 71% without significant variation across studies. Children with ASD were 19.03-fold more likely to be positive for a FRAA compared to typically developing children without an ASD sibling. For individuals with ASD and CFD, meta-analysis also found improvements with d,l-leucovorin in overall ASD symptoms (67%), irritability (58%), ataxia (88%), pyramidal signs (76%), movement disorders (47%), and epilepsy (75%). Twenty-one studies (including four placebo-controlled and three prospective, controlled) treated individuals with ASD using d,l-leucovorin. d,l-Leucovorin was found to significantly improve communication with medium-to-large effect sizes and have a positive effect on core ASD symptoms and associated behaviors (attention and stereotypy) in individual studies with large effect sizes. Significant adverse effects across studies were generally mild but the most common were aggression (9.5%), excitement or agitation (11.7%), headache (4.9%), insomnia (8.5%), and increased tantrums (6.2%). Taken together, d,l-leucovorin is associated with improvements in core and associated symptoms of ASD and appears safe and generally well-tolerated, with the strongest evidence coming from the blinded, placebo-controlled studies. Further studies would be helpful to confirm and expand on these findings.


Aligned Scaffolds with Biomolecular Gradients for Regenerative Medicine.
Aligned topography and biomolecular gradients exist in various native tissues and play pivotal roles in a set of biological processes. Scaffolds that recapitulate the complex structure and microenvironment show great potential in promoting tissue regeneration and repair. We begin with a discussion on the fabrication of aligned scaffolds, followed by how biomolecular gradients can be immobilized on aligned scaffolds. In particular, we emphasize how electrospinning, freeze drying, and 3D printing technology can accomplish aligned topography and biomolecular gradients flexibly and robustly. We then highlight several applications of aligned scaffolds and biomolecular gradients in regenerative medicine including nerve, tendon/ligament, and tendon/ligament-to-bone insertion regeneration. Finally, we finish with conclusions and future perspectives on the use of aligned scaffolds with biomolecular gradients in regenerative medicine.


Empyema Tube or No Tube?
We report the case of a 36-year-old man with cirrhosis who presented with recurrent infection of his right-sided hepatic hydrothorax in the form of fever, dyspnea, and cough. The pleural fluid analysis showed transudative fluid with normal pH, lactic acid dehydrogenase, and glucose, but with Escherichia coli growth. An uncommon diagnosis of high mortality, spontaneous bacterial empyema was made. Criteria for chest tube drainage were met, but he was managed without one. He developed hospital-acquired pneumonia during his stay, but his pleural fluid showed the same characteristics. His empyema and pneumonia were managed with antibiotics and other supportive measures. On follow-up, he was readmitted on three other occasions with similar complaints and succumbed to upper gastrointestinal bleed during the fifth admission. A chest tube is not indicated in patients with spontaneous bacterial empyema unless frank pus is present.


Design, Properties and Recent Application of Macrocycles in Medicinal Chemistry.
Macrocyclic compounds have recently received increasing attention in drug discovery as these compounds offer the potential to modulate difficult targets and to access novel chemotypes. Approaches towards libraries of macrocyclic compounds based on modular organic synthesis and applications of these technology platforms to find and improve biologically active compounds are introduced in this minireview. Alternatively, lead compounds may be obtained by truncation and modification of macrocyclic natural products. Selected medicinal chemistry programs are discussed, illustrating a macrocyclization approach toward ligands with improved properties. The design of such ligands is often informed by X-ray crystal structures of protein-ligand complexes. Efforts to understand cellular permeability and oral bioavailability of cyclic peptides and non-peptidic macrocycles are summarized.


Dance Wherever You Are: The Evolution of Multimodal Delivery for Social Inclusion of Rural Older Adults.
Older adult social inclusion involves meaningful participation that is increasingly mediated by information communication technology and in rural areas requires an understanding of older adults' experiences in the context of the digital divide. This article examines how the multimodal streaming (live, prerecorded, blended in-person) of the Sharing Dance Older Adults program developed by Canada's National Ballet School and Baycrest influenced social inclusion processes and outcomes in rural settings. Data were collected from on-site observations of dance sessions, research team reflections, focus groups, and interviews with older adult participants and their carers in pilot studies in the Peterborough region of Ontario and the Westman region of Manitoba, Canada (2017-2019). There were 289 participants including older adults, people living with dementia, family carers, long-term care staff, community facilitators, and volunteers. Analytic themes were framed in the context of rural older adult social exclusion. Remote delivery addressed barriers of physical distance by providing access to the arts-based program and enhancing opportunities for participation. Constraints were introduced by the use of technology in rural areas and mitigated by in-person facilitators and different streaming options. Meaningful engagement in dynamic interactions in the dance was achieved by involving local staff and volunteers in facilitation of and feedback on the program and its delivery. Different streaming technologies influenced social inclusion in different ways: live-stream enhanced connectedness, but constrained technical challenges; prerecorded was reliable, but less social; blended delivery provided options, but personalization was unsustainable. Understanding different participants' experiences of different technologies will contribute to more effective remote delivery of arts-based programs with options to use technology in various contexts depending on individual and organizational capacities.


Predictors of feminist activism among sexual-minority and heterosexual college women.
Engagement in activism is related to several aspects of social development in adolescence and emerging adulthood. Therefore, it is important to examine the correlates of different forms of activism, such as feminist collective action, among all youth. However, previous research has not investigated young sexual-minority women's engagement with feminist collective action. This study examined predictors of college-aged heterosexual and sexual-minority women's commitment to and participation in feminist activism. Sexual orientation, number of years in college, social support, experiences with discrimination, and gender identity were tested as predictors of commitment to and participation in feminist activism with a sample of 280 college-aged women (173 heterosexuals and 107 sexual minorities). Similar predictors were related to both commitment to and participation in feminist activism. However, for sexual-minority women, but not heterosexual women, the number of years in college was correlated with participation in feminist activism. Young sexual-minority women reported more participation in feminist activism than did heterosexual women, even after controlling for social support, discrimination, and gender identity.


Photobiomodulation (λ=808nm) and Platelet-Rich Plasma (PRP) for the Treatment of Acute Rheumatoid Arthritis in Wistar Rats.
Introduction: Rheumatoid arthritis (RA) causes inflammation, pain, edema, and articular degradation and its treatment can be based on anti-inflammatory drugs, photobiomodulation (PBM) and/or platelet-rich plasma (PRP) that can decrease cell flow and promote local healing. In the present study, we evaluate the effects of PBM and PRP on acute arthritis in Wistar rats through inflammatory and oxidative stress parameters. Methods: Thirty female Wistar rats were assigned to five groups (n=6, each group): Control, Sham, PRP, Laser, and PRP+Laser. For arthritis induction, all animals of groups Sham, PRP, Laser and PRP+Laser received an intraarticular injection of Zymosan® (200µg) in the right knee. Twenty-four hours post-arthritis induction, PRP was prepared and injected (8 × 105 of platelets) in animals of PRP and PRP+Laser groups. PBM was performed in Laser and PRP+Laser groups by single-dose therapy with the GaAlAs laser (λ=808 nm, P=25 mW, fluence=30 J/cm2, beam area=0.02 mm2, t=33 seconds, E=0.825 J, punctual application). After seven days of induction, serum samples were collected and thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) and catalase activity were analysed. Morphological parameters were measured for inflammation areas, cartilage thickness, and C3 protein expression in knee samples. Statistical analysis was performed with an ANOVA test and Tukey's post-hoc test with a significance level of 5% (P<0.05). Results: NO was lower in the treated groups compared to the Sham group, and TBARS did not show any differences, while catalase showed greater activity between PRP+Laser versus PRP (P<0.05). Inflammatory areas and cartilage thickness were lower in the treated groups compared to Sham (P<0.05), while no differences in C3 protein expression was observed. Conclusion: PBM associated with PRP is better for anti-inflammatory and joint preservation by morphological aspects and NO levels that concern a potential clinical application.


Dactylitis in patients with seronegative spondylarthropathy. Assessment by ultrasonography and magnetic resonance imaging.
To establish by means of ultrasound and magnetic resonance imaging (MRI) the role of tenosynovitis and arthritis in determining the "sausage-like" aspect of finger dactylitis and to compare the results of the 2 examinations. Twelve dactylitic fingers and their corresponding normal contralateral fingers belonging to 10 patients who met the Amor criteria for the diagnosis of seronegative spondylarthropathy (SpA) were studied by ultrasonography and MRI. MRI revealed a significant increase in the volar bone-to-skin distance in dactylitic fingers with respect to that of the normal contralateral fingers (P < 0.001). This increase was due to distension of the flexor synovial sheaths (P < 0.00001) by fluid collection. Peritendinous soft tissues were not involved, since these were found to be significantly thicker in the normal fingers (P < 0.05). Of the 36 joints of the 12 dactylitic fingers, only 1 showed capsule distension. Using MRI as the "gold standard," ultrasonography showed a 100% sensitivity and specificity for flexor tenosynovitis, but lacked sensitivity for joint involvement because it failed to reveal joint capsule distension in the only joint involved. Similarly, physical examination showed a 100% sensitivity and specificity for flexor sheath involvement. Dactylitis is due to flexor tenosynovitis. Enlargement of the finger joint capsule is not an indispensable condition for the "sausage-like" feature. Physical examination is a sufficient method for the diagnosis of dactylitis.


Three RNases in Senescent and Nonsenescent Wheat Leaves : Characterization by Activity Staining in Sodium Dodecyl Sulfate-Polyacrylamide Gels.
We have described three RNases in wheat leaves (Triticum aestivum L. cv Chinese Spring) and developed assays for measuring each RNase individually in crude leaf extracts. We initially used activity staining in sodium dodecyl sulfate-polyacrylamide gels to characterize RNases in extracts of primary and flag leaves. We thus identified acid RNase (EC 22.214.171.124, here designated RNase WL(A)), and two apparently novel enzymes, designated RNases WL(B) and WL(C). RNase WL(B) activity displays a distinctive isozyme pattern, a molecular mass of 26 kilodaltons (major species), a broad pH range with an optimum near neutrality, insensitivity to EDTA, and stimulation by moderate concentrations of KCl and by MgCl(2). RNase WL(C) activity exhibits a molecular mass of 27 kilodaltons, a neutral pH optimum, insensitivity to EDTA, and inhibition by KCl, MgCl(2), and tri-(hydroxymethyl)aminomethane. Based on distinctive catalytic properties established in gels, we designed conventional solution assays for selective quantitation of each RNase activity. We used the assays to monitor the individual RNases after gel filtration chromatography and native gel electrophoresis of extracts. In accompanying work, we used the assays to monitor RNases WL(A), WL(B), and WL(C), which are present in senescent and nonsenescent leaves, during the course of leaf senescence.