Biochemical evidence for the local synthesis and retention of fibronectin in the tissue of human placenta.
1. Human chorionic tissues were incubated with [14C]leucine and/or [3H]glucosamine, and fibronectin synthesis was examined. 2. Radio-labeled fibronectin was detected in the tissue fraction of the incubation mixture, but not in the medium fraction, indicating that fibronectin is synthesized and retained in the tissue. 3. The glycopeptides derived from 3H-labeled fibronectin showed the lectin-binding characteristics similar to those from unlabeled placenta fibronectin, but different from those of plasma fibronectin.


High-frequency induction by 5-azacytidine of proline independence in CHO-K1 cells.
Proline independence in CHO-K1 Chinese hamster cells has in previous studies been characterized as an auxotrophic gene mutation. In the absence of direct proof, an alternative model must be considered, based on suppression of proline synthesis by DNA methylation changes at one or more loci concerned. This concept receives strong support from the present study, in which we show that treatment of CHO-K1 cells with 5-azacytidine induces a 10(5)-10(6) increase in background conversion to the proline-independent state. Revertants thus obtained, as well as those arising spontaneously or after treatment with ethyl methane sulfonate, are stable phenotypically in the presence or absence of proline. Proline independence in all variants examined was correlated with increased activity of pyrroline-5-carboxylate synthase. Four of five variants induced with 5-azacytidine showed simultaneous increases in activity of ornithine aminotransferase as well. Our data suggest that epigenetic, rather than genetic changes, underlie the transitions between proline dependence and independence in CHO-K1 cells.


Tumours of the spleen.
The spleen has been considered a 'forgotten organ' even if it is included and well demonstrated on every CT and MRI of the abdomen. Tumours of the spleen are rare; however, radiologists need to be aware of the main tumoral features and patterns in order to try to distinguish between benign and malignant masses often discovered incidentally. The principal tumoral masses, benign (cysts, haemangiomas, litteral cell angioma, lymphangioma) and malignant (lymphoma, metastases haemangiosarcoma), are described.


Evaluation of National Leprosy Eradication Program after Integration into General Health System in Rajkot District, Gujarat from 2003 to 2014.
National Leprosy Eradication Program (NLEP) was launched in 1983 with the goal of elimination of leprosy as a public health problem. To evaluate the NLEP performance after integration into general health system from April 2003 to March 2014. A retrospective record based study was conducted by obtaining data from Rajkot district leprosy center. Prevalence rate (PR), new case detection rate (NCDR), proportion of female cases, child cases, multibacillary (MB) cases, Grade II disability among new cases and release from treatment (RFT) cases were evaluated from April 2003 to March 2014 and analyzed by using Chi-square for trend analysis test. The PR of leprosy per 10,000 populations was significantly declined (P < 0.001) from 0.44 in 2003-2004 to 0.15 during March 2014. Reduction in NCDR trend was statistically significant (P < 0.001). The proportion of female cases among newly detected cases showed fluctuation from 36.23% in 2003-2004 to 37.10% in 2013-2014 (P > 0.05). The proportion of child cases also showed significantly declining trend from 12.08% in 2003-2004 to 6.70% in 2013-2014 (P < 0.05). Significant number of MB cases decreased from 122 (2003-2004) to 69 (2013-2014) (P < 0.001). Grade II disability proportion was 1.45% in the year 2003-2004, increased to 5.2% in 2009-2010 and then again decreased to 3.4% in 2013-2014 (P > 0.05). Proportion of patients RFT showed fluctuation from 66.66% (2003-2004) to 45.68% (2009-2010) and then 64.66% (2013-2014) (P < 0.001). The NLEP is having a favorable impact on the problem of leprosy by maintaining the elimination level of leprosy in Rajkot district over a decade.


Heterogeneously vancomycin-resistant Staphylococcus epidermidis strain causing recurrent peritonitis in a dialysis patient during vancomycin therapy.
Methicillin-resistant Staphylococcus epidermidis (MRSE) was recovered over a 2-month period from the dialysis fluid of a peritoneal dialysis (PD) patient who experienced recurrent episodes of peritonitis during therapeutic and prophylactic use of vancomycin. Characterization of five consecutive MRSE isolates by molecular and microbiological methods showed that they were representatives of a single strain, had reduced susceptibility to vancomycin, did not react with DNA probes specific for the enterococcal vanA or vanB gene, and showed characteristics reminiscent of the properties of a recently described vancomycin-resistant laboratory mutant of Staphylococcus aureus. Cultures of these MRSE isolates were heterogeneous: they contained-with a frequency of 10(-4) to 10(-5)-bacteria for which vancomycin MICs were high (25 to 50 microg/ml) which could easily be selected to "take over" the cultures by using vancomycin selection in the laboratory. In contrast, the five consecutive MRSE isolates recovered from the PD patient during virtually continuous vancomycin therapy showed no indication for a similar enrichment of more resistant subpopulations, suggesting the existence of an "occult" infection site in the patient (presumably at the catheter exit site) which was not accessible to the antibiotic.


[Mild cognitive deficit in the elderly. Results of a gerontologic study].
The term "mild cognitive impairment" refers to cognitive deficits which exceed normal physiological aging processes, but do not fulfill the criteria for dementia. The prevalence rates of four current concepts were compared in a sample of 202 healthy 60-64 year-old participants recruited from the interdisciplinary longitudinal study on adult development and aging (ILSE). Furthermore, the relationships between cognitive deficits and psychological and sociodemographic variables were examined. The following prevalence rates were determined: 13.5% for age-associated memory impairment, 6.5% for age-consistent memory impairment, 1.5% for late-life forgetfulness and 23.5% for aging-associated cognitive decline. Subjective cognitive complaints did not correlate with results obtained from neuropsychological tests. Significant correlations were however found between subjective cognitive complaints and higher scores on depression and neuroticism scales. Significant correlations were also found between a reduced test performance and a lower educational level and socioeconomic status. Longitudinal studies are warranted to further elucidate the predictive value of these diagnostic concepts.


The indicators for early blood transfusion in patients with placental abruption with intrauterine fetal death: a retrospective review.
Placental abruption (PA) with intrauterine fetal death (IUFD) is associated with a high risk of postpartum hemorrhage (PPH) resulting from severe disseminated intravascular coagulation (DIC). Therefore, blood products that are sufficient for coagulation factor replacement must be prepared, and delivery should occur at referral medical institutions that are equipped with sufficient blood products and emergency transfusion protocols. We retrospectively reviewed the records of patients with PA and IUFD (PA-IUFD) to identify possible factors that may indicate the need for early blood transfusion and investigated whether the Japanese scoring system for PPH can be applied in such cases. We used a database of 16,058 pregnant patients who delivered at Yokohama City University Medical Center between January 2000 and February 2016. Thirty-three patients were diagnosed with PA-IUFD before delivery and categorized into two groups-blood transfusion and non-transfusion-to compare the maternal characteristics and pregnancy outcomes. In patients with PA-IUFD, the transfusion group exhibited significantly more blood loss; lower fibrinogen levels and platelet counts; higher levels of fibrin degradation products (FDP), D-dimer, and prothrombin time; and a tendency for tachycardia on admission, compared to the non-transfusion group. Many patients in the transfusion group had normal fibrinogen levels on admission but later displayed markedly decreased fibrinogen levels. The Japan Society of Obstetrics and Gynecology (JSOG) DIC score was significantly higher in the transfusion than in the non-transfusion group. In PA-IUFD, the fibrinogen level, platelet count, D-dimer, FDP, heart rate, and JSOG DIC score on admission may indicate the need for blood transfusion. However, even with normal fibrinogen levels on admission, continuous monitoring is indispensable for identifying progressive fibrinogen reductions in patients with PA-IUFD.


The influence of digital learning on health sciences students' competence development- A qualitative study.
Health care experts need high levels of competence, yet there is little evidence on the influence of digital learning on health science students' competence development. This study aims to describe health sciences students' experiences of the development of their competence and the influences of digital learning upon their competence. A qualitative descriptive research. A total of 15 health sciences students were interviewed. The data was collected by using individual semi-structured interviews during the spring of 2021. The data was analyzed using content analysis. The health sciences students felt that their expertise encompasses motivation for future career development, understanding the social and professional influences on their career development, versatile expertise in various aspects of health sciences, and developing competence in different learning environments. The students recognized that digital learning requires the active participation, digitalization is a part of a successful learning environment, and digital learning challenges social interactions. The students' digital learning facilitated competence development, which broadened their understanding of skills relevant to health sciences; however, these benefits could only be obtained when including adequate support. The results hold social value for the development of health sciences education as policy-makers can use the presented information to develop high-quality, digital learning procedures.


Grey scale ultrasound appearances in hepatocellular carcinoma.
Thirty patients with histologically proven hepatocellular carcinoma were examined ultrasonically. All except two of these cases were reported ultrasonically as having a solid mass. Forty-three per cent of these lesions appeared multiple and 90% had irregular walls or boundaries. Stretching or distortion of the inferior margin of the liver is considered significant and 53% of cases demonstrated this feature. Just over two-thirds (67%) of the lesions were echogenic and under one-third (27%) were mixed lesions with echogenic and transonic areas. These transonic areas are considered to be due to the necrosis within the tumour. Most patients presented late and died within three months. Ninety per cent had clinical hepatomegaly or an epigastric mass. So far the main benefits of ultrasonography have been the recognition or exclusion of treatable disease such as liver abscess, cysts and congestive conditions of the liver, which may also present with unexplained hepatomegaly or epigastric masses. The possibility of a recognisable echo pattern for hepatocellular carcinoma emerged from this study. By conducting selective ultrasonic surveys in endemic areas and by employing the ultrasonic criteria described early diagnosis may be possible. Aspects of management and research may be assisted.


[Criteria for differentiating self- or other-inflicted injuries of alleged or real victims].
A synoptic study of six cases of self-inflicted sharp force injuries is presented, where young, mostly female people had simulated assaults to gain sympathy or other personal advantage. The morphological distinctives of simulated assault wounds from such of real assault are worked out and the common situative and motivative background is cleared up.


The Impact of Low Skeletal Muscle Mass on Short- and Long-Term Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal metastases from colorectal cancer (CRC) or pseudomyxoma peritonei (PMP). Because of the considerable morbidity of this treatment, optimal patient selection is key. This study aimed to assess the impact of low skeletal muscle mass (SMM) on outcomes after CRS-HIPEC. Patients who underwent CRS-HIPEC between 2014 and 2020 at a tertiary center were included. SMM was measured on computed tomography by means of the L3 muscle index. Postoperative complications and survival outcomes were compared between groups by use of logistic regression and Kaplan-Meier survival analyses. Of 284 included patients, 149 had low SMM. Occurrence of severe postoperative complications did not differ between groups (28.9% for patients with low vs. 34.1% for patients with normal SMM). Low SMM was not associated with postoperative complications (p = 0.344). For CRC patients, no significant differences were observed in disease-free (DFS) or overall survival (OS) between patients with low (median DFS 7 months [IQR 4-14], median OS 33 months [IQR 14-NR]) and patients with normal SMM (median DFS 8 months [IQR 5-20], median OS 35 months [IQR 18-NR]). Regarding PMP, survival outcomes did not significantly differ between groups (3-year DFS 47.3% for patients with low SMM vs. 54.5% for patients with normal SMM, p = 0.676; 3-year OS 70.8% vs. 90.9% respectively, p = 0.172). Low SMM could not be identified as a predictor of severe complications or survival outcomes after CRS-HIPEC.


An experimentally observed trimetallofullerene Sm3@I(h)-C80: encapsulation of three metal atoms in a cage without a nonmetallic mediator.
We report the synthesis, isolation, and characterizations of the novel trimetallofullerene Sm3@I(h)-C80. Importantly, the experimental X-ray structure of Sm3@I(h)-C80 verified for the first time that three metal atoms can be stabilized in a fullerene cage without a nonmetal mediator. Furthermore, computational studies demonstrated the electronic features of Sm3@I(h)-C80, which are similar to that of theoretically studied Y3@I(h)-C80. Electrochemical studies of Sm3@I(h)-C80 showed a major difference from those of the well-studied isoelectronic species Sc3N@I(h)-C80 and La2@I(h)-C80.


Leukocyte adherence inhibition (LAI) for detecting specific tumor immunity in colorectal cancer.
Immunity to colorectal cancer antigen was tested by the tube leukocyte adherence inhibition (LAI) assay, using spent medium of human carcinoma cell lines as a source of antigen. The assay was positive in 18 out of 43 patients (41%) with colorectal tumor in comparison to only 2 out of 34 (5.8%) of colorectal cancer patients clinically free of disease, and to 4 out of 150 (2.6%) healthy subjects. The frequency of positive results correlated negatively with the tumor burden, 16 out of 29 (55.1%) patients with Dukes' A, B and C being positive compared to only 2 out of 14 (14.2%) patients with Dukes' stage D disease. Addition of PGE2 enhanced the sensitivity of the assay without affecting its specificity. The number of positive assays increased from 18 to 32 (41.8% to 74.4%) in the whole group of 43 colorectal cancer patients without altering significantly the frequency of positive results in the control group. The results with all groups of patients were influenced similarly by the addition of prostaglandins, the frequency of positive assays increasing from 55.1% to 82.7% and from 14.1% to 57.1% in early and advanced disease, respectively. These results lend further support to the value of the LAI assay in diagnosis and monitoring of the immune response in human colorectal cancer.


Photodynamic therapy of cancer. Basic principles and applications.
Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved for clinical treatment of several types of cancer and non-oncological disorders. In PDT, a compound with photosensitising properties (photosensitiser, PS) is selectively accumulated in malignant tissues. The subsequent activation of the PS by visible light, preferentially in the red region of the visible spectrum (lambda>or=600 nm), where tissues are more permeable to light, generates reactive oxygen species, mainly singlet oxygen ((1)O(2)), responsible for cytotoxicity of neoplastic cells and tumour regression. There are three main mechanisms described by which (1)O(2) contributes to the destruction of tumours by PDT: direct cellular damage, vascular shutdown and activation of immune response against tumour cells. The advantages of PDT over other conventional cancer treatments are its low systemic toxicity and its ability to selectively destroy tumours accessible to light. Therefore, PDT is being used for the treatment of endoscopically accessible tumours such as lung, bladder, gastrointestinal and gynaecological neoplasms, and also in dermatology for the treatment of non-melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic keratosis). Photofrin, ALA and its ester derivatives are the main compounds used in clinical trials, though newer and more efficient PSs are being evaluated nowadays.


Implementing an Urban Public Health Observatory for (Near) Real-Time Surveillance for the COVID-19 Pandemic.
The COVID-19 pandemic is broadly undercutting global health and economies, while disproportionally impacting socially disadvantaged populations. An impactful pandemic surveillance solution must draw from multi-dimensional integration of social determinants of health (SDoH) to contextually inform traditional epidemiological factors. In this article, we describe an Urban Public Health Observatory (UPHO) model which we have put into action in a mid-sized U.S. metropolitan region to provide near real-time analysis and dashboarding of ongoing COVID-19 conditions. Our goal is to illuminate associations between SDoH factors and downstream pandemic health outcomes to inform specific policy decisions and public health planning.


Comparative proteomic analysis of human whole saliva of children with protein-energy undernutrition.
The aim of the present study was to investigate the protein profile of children with different levels of protein-energy undernutrition (PEU) through a proteomic approach of human whole saliva. Initially, saliva samples of children with mild, moderate, and severe PEU were collected and lyophilized. Saliva samples of healthy children were used as controls. Samples were analyzed for total protein using the Bradford method. Saliva samples were analyzed by two-dimensional electrophoresis according to their isoelectric point (pI) and their molecular weights (MWs). Comparisons of protein bands among the healthy and mildly, moderately, and severely undernourished children showed significant differences in the MWs (P = 0.001) and pI values (P = 0.03). In total 159 spots were identified in the healthy children; 156, 168, and 221 spots were observed in mildly, moderately, and severely undernourished children, respectively. Mildly undernourished children presented with the spot with the highest MW of 293 kDa (pI = 7.77) and the lowest MW of 5 kDa (pI = 4.83). Moderately undernourished children were the only ones who did not present with a protein band with an MW of 30 kDa. The presence of a protein band with an MW of 123 kDa (pI = 516), possibly a cyclin-dependent protein kinase, was also observed only in this group. The protein profile in saliva varies according to the presence or absence of PEU, and these variations are specifically expressed in different grades of undernutrition. Thus, saliva may be an important diagnostic tool for the assessment of PEU.


Complete mineralization of phenolic compounds in visible-light-driven photocatalytic ozonation with single-crystal WO3 nanosheets: Performance and mechanism investigation.
Complete mineralization of phenolic compounds into CO2 and H2O is desirable for removing them in wastewater, but it is challenging due to the generated recalcitrant intermediates, which requires highly effective advanced oxidation process with proper catalysts. Herein, we found that single-crystal WO3 nanosheets (NSs)-based photocatalytic ozonation (PCO) can realize complete mineralization of phenols (phenol and 2-chlorophenol) under visible light irradiation. Almost 100% mineralization ratio of phenols was achieved through WO3 NSs-based PCO system within short time. By comparing their performances with those of polycrystalline WO3 nanoparticles, detecting and analyzing the intermediates, identifying the dominant radicals and conducting some electrochemical characterizations, the origin of superior catalytic activity of WO3 NSs was uncovered, the mineralization pathways and the overall mechanism were proposed. The excellent PCO performance of WO3 NSs was contributed to their nanosheet morphology with single-crystal microstructure and good dispersion, which can provide continuous interior channels for the photogenerated charge transport from the bulk to surface of WO3 NSs and enough active sites for the surface reactions triggered by these charges. This work puts forwards new ideas to design highly active photocatalysts for PCO and helps deepen understanding of the catalytic mechanism of PCO.


Antithrombin III deficiency in ischaemic stroke.
AT III activity and concentration were measured in 36 patients (mean age 65.5 yrs, range 43-77 yrs) with ischaemic stroke within maximally 48 h of the acute event. In 12 patients (= 33%) AT III activity was reduced below 18.4 IU/ml: 50% of these patients showed normal and 50% reduced AT III concentration of less than 22 mg/dl. In 15 patients AT III activity and concentration were measured in the acute phase on admission to hospital and 12 months later. In the acute phase, AT III activity was reduced when compared with AT III concentration (y = 0.19 chi + 15.5) and did not correlate with the latter. 12 months later, however, AT III activity and concentration correlated significantly (r = 0.92; p less than 0.001) and the regression line was steeper (y = 0.8 chi). During the acute phase of ischaemic stroke, intravascular coagulation is evidently increased and inactive AT III-thrombin complexes are formed, whereby the concentration of active AT III decreases. A patient with progressive stroke and reduced AT III activity of 14.2 IU/ml was therefore substituted with AT III concentrate. The further neurological course was favourable.


Changes in cerebral activation in individuals with and without visual vertigo during optic flow: A functional near-infrared spectroscopy study.
Individuals with visual vertigo (VV) describe symptoms of dizziness, disorientation, and/or impaired balance in environments with conflicting visual and vestibular information or complex visual stimuli. Physical therapists often prescribe habituation exercises using optic flow to treat these symptoms, but it is not known how individuals with VV process the visual stimuli. The primary purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to determine if individuals with VV have different cerebral activation during optic flow compared with control subjects. Fifteen individuals (5 males and 10 females in each group) with VV seeking care for dizziness and 15 healthy controls (CON) stood in a virtual reality environment and viewed anterior-posterior optic flow. The support surface was either fixed or sway-referenced. Changes in cerebral activation were recorded using fNIRS during periods of optic flow relative to a stationary visual environment. Postural sway of the head and center of mass was recorded using an electromagnetic tracker. Compared with CON, the VV group displayed decreased activation in the bilateral middle frontal regions when viewing optic flow while standing on a fixed platform. Despite both groups having significantly increased activation in most regions while viewing optic flow on a sway-referenced surface, the VV group did not have as much of an increase in the right middle frontal region when viewing unpredictable optic flow in comparison with the CON group. Individuals with VV produced a pattern of reduced middle frontal cerebral activation when viewing optic flow compared with CON. Decreased activation in the middle frontal regions of the cerebral cortex may represent an alteration in control over the normal reciprocal inhibitory visual-vestibular interaction in visually dependent individuals. Although preliminary, these findings add to a growing body of literature using functional brain imaging to explore changes in cerebral activation in individuals with complaints of dizziness, disorientation, and unsteadiness. Future studies in larger samples should explore if this decreased activation is modified following a rehabilitation regimen consisting of visual habituation exercises.


The moderating effect of liquidity on the relationship between sustainability and firms' specifics: Empirical evidence from indian manufacturing sector.
The current study attempts to examine the moderating effect of liquidity on the relationship between firms' specific and sustainability expenses. The study is based on secondary data over a period from 2015 to 2021. The results are estimated using panel data with fixed-effect models. The results indicate that liquidity enhances and strengthens the ability of a company to spend more on environmental, social, and employee compensation sustainability expenses. In the same context, the results reveal that there is an insignificant moderation effect of liquidity with the financial performance of a company, indicating that the liquidity of companies with higher financial performance does not enhance and strength their ability to spend more on sustainability expenses. Further, the extent of liquidity in larger companies affects positively and significantly the level of employee compensation but not environmental and social spending. Finally, the findings show that greater leverage with less liquidity negatively affects the levels of sustainability spending. This study provides a unique contribution to the existing literature by introducing the moderating effect of liquidity on the relationship between firms' specific and sustainability expenditures. It highlights the direct effect of firms' specific determinants and the moderating effect of liquidity on three categories of sustainability expenses which are environmental expenses, social expenses, and employee compensations. Therefore, this research has valuable implications for company managers, financial analysts, policymakers, and other stakeholders.


Use of a Bipolar Device (LigaSure) to Seal the Appendiceal Stump in Pediatric Laparoscopic Appendectomy: 10-year Latin-American Experience.
Closure of the appendiceal stump is a critical step during an appendectomy. There is a lack of knowledge about the feasibility of using electrosurgical devices for the occlusion of the appendix. This study aims to determine the safety of this technique in pediatric patients. We performed a cross-sectional analytical study in patients less than 18 years of age treated at Hospital Militar Central Colombia between 2012 and 2021. Our institution's ethics committee approved the study. We analyzed the data using SPSS 22 statistical program. We present frequencies for qualitative variables and measures of central tendency or dispersion for quantitative variables depending on the distribution measured by the Kolmogorov-Smirnov test. In addition, we measured the association of nominal variables with the Chi-square test or Fisher's exact test. For numerical variables, the difference of means with the Student's t-test or the difference of medians with the Mann-Whitney U test. We treated 209 patients. One hundred sixteen (55.5%) were boys, and the mean age was 9.7 years (SD 3.2). The median intraoperative time was 60 min, and the hospital stay was 2.8 days on average. There were no cases of stump leakage, and only two patients (1%) had an organ-space surgical site infection, which was unrelated to the closure technique. We found no association between procedural complications and appendicular status (p = 0.450). Our research suggests that using a bipolar sealing device (Ligasure, Medtronic, USA) for appendiceal stump closure in pediatric patients undergoing laparoscopic appendectomy is feasible and should be further studied. Treatment study. Level III.


Nonimmune hydrops fetalis--a rational attitude of management.
A rational attitude of management of the nonimmune hydrops fetalis (NIHF) is stressed in order to achieve an optimal outcome of both the mother and the newborn. Of the two cases reported, both had an underlying cardiac condition. The first was due to rapid supraventricular tachyarrhythmia and responded favorably to intrauterine medication with digoxin and the subsequent delivery of a well baby. In the second case, cesarean section was performed unnecessarily for a fetal indication, since the hydropic infant died soon after birth from a severe cardiac malformation which was not unequivocally diagnosed prior to birth.


[Some properties of complexes formed by small heat shock proteins with denatured actin].
We applied different methods to analyze the effects of the recombinant wild-type small heat shock protein with an apparent molecular mass of 27 kD (Hsp27-wt) and its S15,78,82D mutant (Hsp27-3D), which mimics the naturally occurring phosphorylation of this protein, on the thermal denaturation and aggregation of F-actin. It has been shown that, at the weight ratio of Hsp27/actin equal to 1/4, both Hsp27-wt and Hsp27-3D do not affect the thermal unfolding of F-actin but effectively prevent the aggregation of F-actin by forming soluble complexes with denatured actin. The formation of these complexes occurs upon heating and accompanies the F-actin thermal denaturation. It is known that Hsp27-wt forms high-molecular-mass oligomers, whereas Hsp27-3D forms small dimers or tetramers. However, the complexes formed by Hsp27-wt and Hsp27-3D with denatured actin did not differ in their size, as measured by dynamic light scattering, and demonstrated the same hydrodynamic radius of 17-18 nm. On the other hand, the sedimentation coefficients of these complexes were distributed within the range 10-45 S in the case of Hsp27-3D and 18-60 S in the case of Hsp27-wt. Thus, the ability of Hsp27 to form soluble complexes with denatured actin does not significantly depend on the initial oligomeric state of Hsp27.


Extracellular vesicles influence the pulmonary arterial extracellular matrix in congenital diaphragmatic hernia.
Abnormal pulmonary vasculature directly affects the development and progression of congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension (PH). Though overarching structural and cellular changes in CDH-affected pulmonary arteries have been documented, the precise role of the extracellular matrix (ECM) in the pulmonary artery (PA) pathophysiology remains undefined. Here, we quantify the structural, compositional, and mechanical CDH-induced changes in the main and distal PA ECM and investigate the efficacy of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) as a therapy to ameliorate pathological vascular ECM changes. Pregnant Sprague-Dawley rodents were administered nitrofen to induce CDH-affected pulmonary vasculature in the offspring. A portion of CDH-affected pups was treated with intravenous infusion of MSC-EVs (1 × 1010 /mL) upon birth. A suite of histological, mechanical, and transmission electron microscopic analyses were utilized to characterize the PA ECM. The CDH model main PA presented significantly altered characteristics-including greater vessel thickness, greater lysyl oxidase (LOX) expression, and a relatively lower ultimate tensile strength of 13.6 MPa compared to control tissue (25.1 MPa), suggesting that CDH incurs ECM structural disorganization. MSC-EV treatment demonstrated the potential to reverse CDH-related changes, particularly through rapid inhibition of ECM remodeling enzymes (LOX and MMP-9). Additionally, MSC-EV treatment bolstered structural aspects of the PA ECM and mitigated pathological disorganization as exhibited by increased medial wall thickness and stiffness that, while not significantly altered, trends away from CDH-affected tissue. These data demonstrate notable ECM remodeling in the CDH pulmonary vasculature, along with the capacity of MSC-EVs to attenuate pathological ECM remodeling, identifying MSC-EVs as a potentially efficacious therapeutic for CDH-associated pulmonary hypertension.


A Novel Cell Therapy Method for Recovering after Brain Stroke in Rats.
Nowadays, stroke leads to a significant part of the adult mortality and morbidity and also it could result in some neurological deficits in the patients' lives. Cell therapy has opened a new approach to treat the brain ischemia and reduce its terrible effects on the patients' lives. There are several articles which show that the cell therapy could be beneficial for treating brain stroke. In this study, we have planned to present a new cell therapy method for stroke by administration of Mesenchymal stem cells and differentiated neural stem cells without astrocytes. The Mesenchymal stem cells were isolated from tibia and femur of a 250~300 g rat and they were cultured in DMEM/F12, 10% fetal bovine serum, 1% Pen/Strep. Neural stem cells were isolated from 14 days rat embryo ganglion eminence and were cultured in NSA media containing Neurobasal, 2% B27, bFGF 10 ng/ml and EGF 20 ng/ml after 5 days they formed some neurospheres. The isolated neural stem cells were differentiated to neural lineages by adding 5% fetal bovine serum to their culture media. After 48 hours the astrocytes were depleted by using MACS kit. The group that received Mesenchymal stem cells systemically and differentiated neural stem cells without astrocytes had the best neurological outcomes and the least infarct volume and apoptosis. It could be understood that this cell therapy method might cause almost full recovery after brain stoke. Using combination cell therapy with Mesenchymal stem cells and differentiated neural stem cells with removed astrocyte could provide a novel method for curing brain stroke.


Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau.
We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.


Exploring the age of intracranial aneurysms using carbon birth dating: preliminary results.
There is a controversy about the time span over which cerebral aneurysms develop. In particular, it is unknown whether collagen in ruptured aneurysms undergoes more rapid turnover than in unruptured aneurysms.(14)C birth dating of collagen could be used to address this question. Aneurysmal domes from patients undergoing surgical treatment for ruptured or unruptured aneurysms were excised. Aneurysmal collagen was isolated and purified after pepsin digestion. Collagen from mouse tendons served as controls. F(14)C levels in collagen were analyzed by accelerator mass spectrometry and correlated with patient age and aneurysm size. Analysis of 10 aneurysms from 9 patients (6 ruptured, 3 unruptured) revealed an average aneurysm collagen age of <5 years, generally irrespective of patient age and aneurysm size or rupture status. Interestingly, F(14)C levels correlated with patient age as well as aneurysm size in ruptured aneurysm collagen samples. Our preliminary data suggest that collagen extracted from intracranial aneurysms generally has a high turnover, associated with aneurysm size and patient age. The correlation of patient age and aneurysm F(14)C levels could explain models of aneurysm development. Although preliminary, our findings may have implications for the biological and structural stability of ruptured and unruptured intracranial aneurysms.


Differences between 'congenital mirror movements' and 'associated movements' in normal children: a neurophysiological case study.
In this study we analysed how far physiological associated movements in normal children (which may be present up to the age of 10 years) share the same physiological mechanism with clinically apparent mirror movements. Transcranial magnetic stimulation (TMS) and kinematic movement analysis were applied in a 4-year-old child with congenital mirror movements (CMM). The results were compared with a normative data base of clinically normal children. In the child with CMM focal TMS of one motor cortex induced bilaterally symmetrical responses in distal and proximal upper extremities muscles with identical ipsi- and contralateral latencies. Also kinematic analysis showed a precise symmetrical onset of intended and unintended contralateral movements, whereas normal children with associated movements showed a variable movement onset delay between extremities. The data suggest a different physiological mechanism underlying these two varieties of elementary associated motor activity in childhood.


Short-term management of macroprolactinomas with a new injectable form of bromocriptine.
Three cases (2 men, 1 woman) of expansive macroprolactinoma treated with a single 50-mg intramuscular dose of a new form of injectable, long-acting bromocriptine are presented. Clinical manifestations included visual disturbances (2 cases), headache (1 case), and hypogonadism (3 cases). Laboratory tests demonstrated high basal serum prolactin (PRL) levels and evidence of involvement of other anterior pituitary hormones in all cases. Treatment was followed by marked improvement of symptoms paralleled by a sharp decrease of serum PRL levels, which normalized in 1 case. Some other anterior pituitary functions also improved. Computed tomography scan revealed shrinkage of the tumor in all cases. There were no local or serious systemic side effects. These initial findings suggest that long-acting injectable bromocriptine has a place in the initial treatment of macroprolactinomas, especially for those with neurological and/or visual manifestations. It can also be used to select patients for surgery, in the cases where clinical and radiological improvement could not be obtained. The effects of long-term use remain to be established by further studies.


3-(Methoxycarbonyl)-amino-beta-carboline reduces both the sedative and anticonvulsant effects of diazepam.
The intrinsic effects of the benzodiazepine receptor ligand beta-CMC (3-(methoxycarbonyl)-amino-beta-carboline) and its interaction with the anticonvulsant and sedative effects of diazepam were assessed. beta-CMC (100 mg/kg i.p.) significantly elevated seizure threshold to bicuculline. beta-CMC (10 mg/kg) failed to alter the anticonvulsant action of diazepam (5 mg/kg i.p.), but significantly attenuated diazepam's sedative effect. A higher dose of beta-CMC (40 mg/kg) did attenuate diazepam's anticonvulsant action. The data suggest that beta-CMC is a partial agonist at benzodiazepine receptors.


Effect of lipopolysaccharides on the morphology of erythrocyte membranes.
The effect of lipopolysaccharide (LPS) isolated from Gram-negative bacteria Salmonella typhi on erythrocyte membranes was investigated by electron microscopy. The LPS was found to be irregularly distributed on the surface of erythrocytes and their envelopes. It caused the formation of short bilayer rods associated at one end with the erythrocyte membrane of vesicular formations localized horizontally on or in the membrane, and of lamellar structures.


Appraising the Associations Between Systemic Iron Status and Epigenetic Clocks: A Genetic Correlation and Bidirectional Mendelian Randomization Study.
Genetic correlations (Rg) and bidirectional causal effects between systemic iron status and epigenetic clocks have not been fully investigated, although observational studies have suggested systemic iron status is associated with human aging. We explored the genetic correlations and bidirectional causal effects between systemic iron status and epigenetic clocks. Leveraging large-scale genome-wide association study summary-level statistics for 4 systemic iron status biomarkers (ferritin, serum iron, transferrin, and transferrin saturation) (N = 48,972) and 4 measures for epigenetic age (GrimAge, PhenoAge, intrinsic epigenetic age acceleration (IEAA), and HannumAge) (N = 34,710), genetic correlations, and bidirectional causal effects were estimated between them mainly by applying linkage disequilibrium score (LDSC) regression, Mendelian randomization (MR), and MR based on Bayesian model averaging. The main analyses were conducted employing multiplicative random-effects inverse-variance weighted MR. MR-Egger, weighted median, weighted mode, and MR-PRESSO were performed as sensitivity analyses to support the robustness of causal effects. The LDSC results illustrated Rg between serum iron and PhenoAge (Rg = 0.1971, P = 0.048) and between transferrin saturation and PhenoAge (Rg = 0.196, P = 0.0469). We found that increased ferritin and transferrin saturation significantly increased all 4 measures of epigenetic age acceleration (all P < 0.0125, β > 0). Each standard deviation genetically increases in serum iron only significantly associated with increased IEAA (β: 0.36; 95% CI: 0.16, 0.57; P = 6.01 × 10-4) and increased HannumAge acceleration (β: 0.32; 95% CI: 0.11, 0.52; P = 2.69 × 10-3). Evidence showed a suggestively significant causal effect of transferrin on epigenetic age acceleration (all 0.0125 <P < 0.05). Additionally, reverse MR study indicated no significant causal effect of epigenetic clocks on systemic iron status. All 4 iron status biomarkers had a significant or suggestively significant causal effect on epigenetic clocks, whereas reverse MR studies did not.


Insulin-like growth factor-I serum levels and their biological effects on Leishmania isolates from different clinical forms of American tegumentary leishmaniasis.
American tegumentary leishmaniasis (ATL) in Brazil is mostly caused by Leishmania (Viannia) braziliensis, with known forms of the disease being cutaneous (CL), mucosal (ML) and disseminated (DL) leishmaniasis. The development of the lesion in ATL is related both to the persistence of the Leishmania in the skin and to the parasite-triggered immune and inflammatory responses that ensue lesions. In this context one factor with expected role in the pathogenesis is insulin-like growth factor (IGF)-I with known effects on parasite growth and healing and inflammatory processes. In the present study, we addressed the effect of IGF-I on intracellular amastigote isolates from CL, ML and DL patients within human macrophage and we evaluated the IGF-I and IGF-binding protein-3 (IGFBP3) serum levels in patients presenting different clinical forms and controls from the endemic area. We evaluated biological variability in the responses of intracellular amastigotes of Leishmania isolates derived from CL, ML, and DL patients from an area for ATL in response to IGF-I. Intracellular amastigote growth was evaluated using the human macrophage cell line THP-1. Arginase activity in infected cells was evaluated quantifying the generated urea concentration. Serum samples from patients and controls were assayed using chemiluminescent immunometric assay to determine IGF-I and IGFBP3 levels. We observed an increase in intracellular parasitism upon IGF-I stimulus in 62.5 % of isolates from CL, in 85.7 % from ML and only 42.8 % from DL cases. In DL, the basal arginase activity was lower than that of CL. We then evaluated the IGF-I and IGFBP3 serum levels in patients, and we observed significantly lower levels in ML and DL than in CL and control samples. The data suggest that IGF-I is modulated distinctly in different clinical forms of tegumentary leishmaniasis. IGF-I seemingly exerts effect on parasite growth likely contributing to its persistence in the skin in earlier phase. In addition the decreased IGF-I serum levels may affect the modulation of inflammation and lesion healing in chronic phase. In view of potential role of IGF-I in the pathogenesis of ATL we can speculate on therapeutic procedures taking into account the local IGF-I level.


Oral Administration of Coronavirus Spike Protein Provides Protection to Newborn Pigs When Challenged with PEDV.
To investigate whether oral administration of maize-produced S antigen can provide passive immunity to piglets against porcine epidemic diarrhea virus (PEDV), 16 pregnant sows were randomly assigned to one of four treatments: (1) injection of PEDV vaccine (INJ), (2) maize grain without S protein (CON), (3) maize grain containing low dose of S antigen (LOV) and (4) maize grain containing a high dose of S antigen (HOV). Vaccines were administered on days 57, 85 and 110 of gestation. Sows' serum and colostrum were collected at farrowing and milk on day 6 post-challenge to quantify neutralizing antibodies (NABs) and cytokines. Piglets were challenged with PEDV 3-5 d after farrowing, and severity of disease and mortality assessed on day 11 post-challenge. Disease severity was lower in LOV and INJ compared with HOV and CON, whereas the survival rate increased in piglets from LOV sows compared with HOV and CON (p ≤ 0.001). Higher titers of NABs and lower levels of cytokine granulocyte-macrophage colony-stimulating factor in sows' milk were positively correlated with piglet survivability (p ≤ 0.05). These data suggest that feeding S protein in corn to pregnant sows protects nursing piglets against PEDV.


Cumulative concussion exposure in rugby players: neurocognitive and symptomatic outcomes.
A total of 111 rugby players underwent comprehensive testing to determine the impact of self-reported concussion exposure. Reliable estimates of concussion exposure were associated with an increase in postconcussion symptoms (PCS), but not diminished neurocognitive functioning. Importantly, the effects of concussion exposure on PCS varied as a function of player status. More specifically, extent of concussion exposure was associated with increased memory complaints and overall PCS endorsements in a dose-dependent manner for retired and older recreational players, but not for those who were younger and playing at more competitive levels. Future work should systematically evaluate the constituent participant factors that may influence differential concussion outcomes.


Ionic liquid-assisted cellulose coating of chitosan hydrogel beads and their application as drug carriers.
The present study proposes a simple yet effective method of cellulose coating onto chitosan (CS) hydrogel beads and application thereof as drug carriers. The beads were coated with cellulose dissolved in 1-ethyl-3-methylimidazolium acetate, an ionic liquid (IL) via a one-pot one-step process. Water molecules present in the CS beads diffused outward upon contact with the cellulose-IL mixture and acted as an anti-solvent. This allowed the surface of the beads to be coated with the regenerated cellulose. The regenerated cellulose was characterized by FE-SEM, FT-IR, and XRD analyses. To test potential application of the cellulose-coated CS hydrogel beads as a drug carrier, verapamil hydrochloride (VRP), used as a model drug, was impregnated into the beads. When the VRP-impregnated beads were immersed in the simulated gastric fluid (pH 1.2), the VRP was released in an almost ideal linear pattern. This easily fabricated cellulose-coated CS beads showed the possibility for application as carriers for drug release control.


Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles.
Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis.


High cryptic species diversity is revealed by genome-wide polymorphisms in a wild relative of banana, Musa itinerans, and implications for its conservation in subtropical China.
Species delimitation is a challenging but essential task in conservation biology. Morphologically similar species are sometimes difficult to recognize even after examination by experienced taxonomists. With the advent of molecular approaches in species delimitation, this hidden diversity has received much recent attention. In addition to DNA barcoding approaches, analytical tools based on the multi-species coalescence model (MSC) have been developed for species delimitation. Musa itinerans is widely distributed in subtropical Asia, and at least six varieties have been documented. However, the number of evolutionarily distinct lineages remains unknown. Using genome resequencing data of five populations (making up four varieties), we examined genome-wide variation and found four varieties that were evolutionary significant units. A Bayesian Phylogenetics and Phylogeography (BP&P) analysis using 123 single copy nuclear genes support three speciation events of M. itinerans varieties with robust posterior speciation probabilities; However, a Bayes factor delimitation of species with genomic data (BFD*) analysis using 1201 unlinked single nucleotide polymorphisms gave decisive support for a five-lineage model. When reconciling divergence time estimates with a speciation time scale, a modified three-lineage model was consistent with that of BP&P, in which the speciation time of two varieties (M. itinerans var. itinerans and M. itinerans var. lechangensis) were dated to 26.2 kya and 10.7 kya, respectively. In contrast, other two varieties (M. itinerans var. chinensis and M. itinerans var. guangdongensis) diverged only 3.8 kya in the Anthropocene; this may be a consequence of genetic drift rather than a speciation event. Our results showed that the M. itinerans species complex harbours high cryptic species diversity. We recommend that M. itinerans var. itinerans and M. itinerans var. lechangensis be elevated to subspecies status, and the extremely rare latter subspecies be given priority for conservation. We also recommend that the very recently diverged M. itinerans var. chinensis and M. itinerans var. guangdongensis should be merged under the subspecies M. itinerans var. chinensis. Finally, we speculate that species delimitation of recently diverged lineages may be more effective using genome-wide bi-allelic SNP markers with BFD* than by using unlinked loci and BP&P.


The effect of excess antigen on the enzyme-linked immunosorbent assay of onco-placental proteins.
The time course of the antigen-antibody reaction between human chorionic gonadotrophin, pregnancy specific beta 1 glycoprotein and pregnancy associated plasma protein A and their respective immobilised antibodies has been investigated. All 3 antigens showed enhanced binding with increasing length of incubation up to a maximum value, followed by a decrease. It is suggested that the diminution in binding at high antigen concentration is caused by the solubilisation of the immobilised antigen-antibody complex and that this is promoted by the high concentration of antigen.


[Successful cardiopulmonary resuscitation in prone position].
In certain surgical positions standard cardiopulmonary resuscitation (CPR) cannot be carried out. It is sometimes impossible or time-consuming to establish a supine position without increasing the no-flow-time and therefore creating a negative outcome of the patient. The case of CPR in a prone position during an emergency evacuation of a cerebellar hematoma is reported. The resuscitation was initiated in the prone position to decrease the no-flow-time. This was very effective because the return of spontaneous circulation (ROSC) started before turning the patient to the supine position. Resuscitation in the prone position in this case was equally as effective as in the traditional supine position.


Pituitary enlargement with target organ deficiency: hypothyroidism and hypogonadism.
Three women with pituitary enlargements associated with preexisting target organ failures are reported. Two pituitary enlargements owing to primary hypothyroidism and one to primary hypogonadism were shown to be regressed on computed tomography after the replacement therapy. Clinically and pathologically, the differentiation of a pituitary hyperplasia from a pituitary adenoma is often very difficult. Moreover, the treatments for these conditions are quite different. Adequate medication can diminish a pituitary enlargement because of the feedback mechanism. Existence of the target organ deficiency should always be checked before the management of pituitary tumor.


Selective labelling of 5-HT7 receptor recognition sites in rat brain using [3H]5-carboxamidotryptamine.
The aim of the present study was to establish a radioligand binding assay to selectively label the native 5-HT7 receptor expressed in rat brain. In rat whole brain (minus cerebellum and striatum) homogenate, (+/-)-pindolol (10 microM)-insensitive [3H]5-CT ([3H]5-carboxamidotryptamine; 0.5 nM) specific binding (defined by 5-HT, 10 microM) displayed a pharmacological profile similar to the recombinant 5-HT7 receptor, although the Hill coefficients for competition curves generated by methiothepin, ritanserin, sumatriptan, clozapine and pimozide were significantly less than unity. In homogenates of rat hypothalamus, (+/-)-pindolol (10 microM)-insensitive [3H]5-CT recognition sites also resembled, pharmacologically, the 5-HT7 receptor, although pimozide still generated Hill coefficients significantly less than unity. Subsequent studies were performed in the additional presence of WAY100635 (100 nM) to prevent [3H]5-CT binding to residual, possibly, 5-HT1A sites. Competition for this [3H]5-CT binding indicated the labelling in whole rat brain homogenate of a homogenous population of sites with the pharmacological profile of the 5-HT7 receptor. Saturation studies also indicated that (+/-)-pindolol (10 microM)/WAY 100635 (100 nM)-insensitive [3H]5-CT binding to homogenates of whole rat brain was saturable and to an apparently homogenous population of sites which were labelled with nanomolar affinity (Bmax=33.2+/-0.7 fmol mg(-1) protein, pKd=8.78+/-0.05, mean+/-S.E.M., n=3). The development of this 5-HT7 receptor binding assay will aid investigation of the rat native 5-HT7 receptor.


Regulation of adipose tissue energy availability through blood flow control in the metabolic syndrome.
Maintenance of blood flow rate is a critical factor for tissue oxygen and substrate supply. The potentially large mass of adipose tissue deeply influences the body distribution of blood flow. This is due to increased peripheral resistance in obesity and the role of this tissue as the ultimate destination of unused excess of dietary energy. However, adipose tissue cannot grow indefinitely, and the tissue must defend itself against the avalanche of nutrients provoking inordinate growth and inflammation. In the obese, large adipose tissue masses show lower blood flow, limiting the access of excess circulating substrates. Blood flow restriction is achieved by vasoconstriction, despite increased production of nitric oxide, the vasodilatation effects of which are overridden by catecholamines (and probably also by angiotensin II and endothelin). Decreased blood flow reduces the availability of oxygen, provoking massive glycolysis (hyperglycemic conditions), which results in the production of lactate, exported to the liver for processing. However, this produces local acidosis, which elicits the rapid dissociation of oxyhemoglobin, freeing bursts of oxygen in localized zones of the tissue. The excess of oxygen (and of nitric oxide) induces the production of reactive oxygen species, which deeply affect the endothelial, blood, and adipose cells, inducing oxidative and nitrosative damage and eliciting an increased immune response, which translates into inflammation. The result of the defense mechanism for adipose tissue, localized vasoconstriction, may thus help develop a more generalized pathologic response within the metabolic syndrome parameters, extending its effects to the whole body.


Presence of organophosphate flame retardants (OPEs) in different functional areas in residential homes in Beijing, China.
The production and application of organophosphate esters (OPEs) have dramatically increased in recent years due to their use as a replacement for brominated flame retardants. In this study, 13 OPEs (Σ13OPEs) were analyzed in indoor air samples from kitchens and living rooms in 14 residential homes in Beijing, China. The concentrations of Σ13OPEs in kitchen air samples (mean: 13 ng/m3) were significantly (p < 0.05) higher than in living room air samples (5.0 ng/m3). In addition, paired window surface organic film samples were collected and analyzed to investigate film-air partitioning, exhibiting a mean concentration of Σ13OPEs of 4100 ng/m2. The congener profiles showed that tris(2-chloroisopropyl) phosphate (TCPP) was the predominant compound in both window film samples (48%) and the corresponding indoor air sample (56%). The estimated daily intakes (EDI) of OPEs via indoor air inhalation were 2.8 and 1.4 ng/kg/day for infants and adults, respectively, both of which are below the reference dose values (RfDs). Overall, these findings indicate that OPEs in the indoor air environment of residential homes in Beijing are not likely to pose a health risk to the general population.


Vitamin C status and other nutritional indices in patients with stroke and other acute illnesses: a case-control study.
Sixty-three patients with acute thrombotic stroke were compared with 47 age and sex-matched patients admitted concurrently with acute ischaemic cardiac pain and a further 44 with acute noncardiovascular illnesses. Overall the stroke patients scored highest on a questionnaire designed to estimate mean daily intake of vitamin C before hospital admission. There were problems with this retrospective dietary assessment, however, and the diet scores of the 27 stroke patients able to answer the questionnaire themselves fell between those of the other two groups. There were no significant differences between the three patient groups in plasma ascorbic acid or uric acid levels, but plasma magnesium and albumin levels were higher in the stroke patients. These findings were similar for patients aged over and under 70 but intergroup differences in magnesium and albumin levels were more marked in the elderly. These results do not support the postulated inverse relationship between vitamin C status and the risk of stroke.


The lesser saphenous vein: autogenous tissue for lower extremity revascularization.
From December 1980 to December 1985, 54 patients underwent 56 lower extremity arterial procedures with the use of lesser saphenous vein (LSV) as graft material. LSV was used in all cases because a satisfactory greater saphenous vein (GSV) was unavailable to accomplish the proposed revascularization. Indications for operation were rest pain, ulceration, and gangrene (74%), and 26% had claudication alone. Fifty of the 56 procedures were femorotibial and femoroperoneal bypasses. Three graft combinations were used: LSV alone (29), lesser saphenous vein and other autogenous vein composites (LSV/AUTO) (14), and lesser saphenous vein with synthetic composite grafts (LSV/SYN) (13). Graft patency rates were determined by life-table analysis. The 3-year patency rate for LSV was 60% and for LSV/AUTO was 38%. LSV/SYN graft composites had a graft patency rate at 18 months of 21%. These data suggest that the LSV may function as an autogenous venous graft for lower extremity revascularization when sufficient GSV is not available.


[First results of an investigation on trichinosis in wildlife in France (1976--1977) (author's transl)].
201 red foxes, 18 brown rats, 1 muskrat, 1 red squirrel, 1 wood mouse, 8 hares, 3 rabbits, 2 wild boars, 4 roe deers, 1 chamois, 3 reindeers (for farming) were examined by peptic digestion to detect trichinosis. Eight Foxes captured in the east and south-east of France were found infested by this parasite.


Mast Cell-Intervertebral disc cell interactions regulate inflammation, catabolism and angiogenesis in Discogenic Back Pain.
Low back pain (LBP) is a widespread debilitating disorder of significant socio-economic importance and intervertebral disc (IVD) degeneration has been implicated in its pathogenesis. Despite its high prevalence the underlying causes of LBP and IVD degeneration are not well understood. Recent work in musculoskeletal degenerative diseases such as osteoarthritis have revealed a critical role for immune cells, specifically mast cells in their pathophysiology, eluding to a potential role for these cells in the pathogenesis of IVD degeneration. This study sought to characterize the presence and role of mast cells within the IVD, specifically, mast cell-IVD cell interactions using immunohistochemistry and 3D in-vitro cell culture methods. Mast cells were upregulated in painful human IVD tissue and induced an inflammatory, catabolic and pro-angiogenic phenotype in bovine nucleus pulposus and cartilage endplate cells at the gene level. Healthy bovine annulus fibrosus cells, however, demonstrated a protective role against key inflammatory (IL-1β and TNFα) and pro-angiogenic (VEGFA) genes expressed by mast cells, and mitigated neo-angiogenesis formation in vitro. In conclusion, mast cells can infiltrate and elicit a degenerate phenotype in IVD cells, enhancing key disease processes that characterize the degenerate IVD, making them a potential therapeutic target for LBP.


The use of a national transplant registry to benchmark transplant outcome for patients undergoing autologous and allogeneic stem cell transplantation in the United Kingdom and Ireland.
As part of its clinical governance programme the British Society for Blood and Marrow Transplantation (BSBMT) undertook an analysis of transplant outcome for adults undergoing human leucocyte antigen - identical sibling allogeneic transplantation for chronic myeloid leukaemia (CML) in first chronic phase (CP1) or autologous transplantation for Hodgkin's disease (HD). The study aimed to compare transplant-related mortality (TRM) and survival for patients reported to the BSBMT with patients transplanted in the rest of Europe, reported to the European Group for Blood and Marrow Transplantation (EBMT). The outcomes for 104 allogeneic transplants for CML in 24 UK/Irish centres were compared with 775 allografts in 145 other European centres. For HD, 241 autografts from 38 UK/Irish centres were compared with 1145 transplants in 239 other European centres. For both diseases, the cohorts were broadly matched with the exception of CML, where 85% of patients were transplanted <1 year from diagnosis in the UK/Ireland compared with 68% in the EBMT (P = 0.001). Cox regression analysis was undertaken using known delineated variables affecting transplant outcome in addition to the registry of origin. The adjusted survival curves for CML showed no significant differences between the two groups, with 3-year survival probabilities of 70.2% and 67.1% for the EBMT and BSBMT cohorts respectively. Likewise, the analysis for HD showed overlapping survival curves, with 3-year survival probabilities of 71.8% (EBMT) and 70.8% (BSBMT). TRM was not statistically different in either disease. This study demonstrates the potential for using national registries to benchmark transplant outcome against the EBMT registry.


Sympathectomy alters acetylcholinesterase expression in adult rat heart.
The aim of the study was to determine the significance of adrenergic nerve associated acetylcholinesterase for the pool of total acetylcholinesterase molecules. Acetylcholinesterase was analysed after destruction of adrenergic nerves by 6-hydroxydopamine or bilateral stellate sympathectomy. Effectiveness of treatment was verified by determining noradrenaline concentrations in right ventricle. Acetylcholinesterase activity was assayed in homogenates of atria and portions of left ventricular free wall. Adult male Sprague-Dawley rats were used, weight 225-260 g, n = 5 per experimental group. Sympathectomy caused a small decrease in acetylcholinesterase activity, due to a decrease in the activity of the tetrameric globular form of the enzyme. Choline acetylcholinesterase activity was not altered by sympathectomy, which is an indication that cholinergic nerves were not affected. The contribution of adrenergic neurones to the cardiac pool of acetylcholinesterase is measurable and consists primarily of the tetrameric globular form of the enzyme.


Bioaugmentation of a polychlorobiphenyl contaminated soil with two aerobic bacterial strains.
The consortium of aerobic bacterial strains Rhodococcus ruber P25 and Microbacterium sp. B51 was bioaugmented in natural and industrial soils, contaminated by commercial mixture of polychlorinated biphenyls (PCBs) Sovol. The results showed that the bioaugmentation of bacterial strains led to PCBs degradation in soil. Sovol at the initial concentration of about 100 mg kg(-1) was removed by 72.2% in the bioaugmented system with natural soil within 90 days, while the system with industrial soil removed 96.4% of this compound within the same period. The biodegradation kinetics of PCBs in the bioaugmented soil systems was not dependent on the presence of indigenous microflora. It was found that the growth dynamics of the strains R. ruber P25 and Microbacterium sp. B51 correlated with the specific degradation of Sovol. The strains R. ruber P25 and Microbacterium sp. B51 displayed high degradative activity to all congeners (ortho-, meta- and para-substituent) contained in Sovol. Removal percentage for each congeners amounted to 59-100% in the bioaugmented systems. This study suggests that augmentation of PCB-contaminated soils with strain R. ruber P25 and Microbacterium sp. B51 is promising in PCB bioremediation.


Achieving Synergy: Linking an Internet-Based Inflammatory Bowel Disease Cohort to a Community-Based Inception Cohort and Multicentered Cohort in Inflammatory Bowel Disease.
Traditional cohort studies are important contributors to our understanding of inflammatory bowel diseases, but they are labor intensive and often do not focus on patient-reported outcomes. Internet-based studies provide new opportunities to study patient-reported outcomes and can be efficiently implemented and scaled. If a traditional cohort study was linked to an Internet-based study, both studies could benefit from added synergy. Existing cohort studies provide an opportunity to develop and test processes for cohort linkage. The Crohn's and Colitis Foundation of America's (CCFA) Partners study is an Internet-based cohort of more than 14,000 participants. The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is an inception cohort. The Sinai-Helmsley Alliance for Research Excellence (SHARE) is a multicentered cohort of inflammatory bowel disease patients. Both the later cohorts include medical record abstraction, patient surveys, and biospecimen collection. Given the complementary nature of these existing cohorts, we sought to corecruit and link data. Eligible OSCCAR and SHARE participants were invited to join the CCFA Partners study and provide consent for data sharing between the 2 cohorts. After informed consent, participants were directed to the CCFA Partners website to complete enrollment and a baseline Web-based survey. Participants were linked across the 2 cohorts by the matching of an email address. We compared demographic and clinical characteristics between OSCCAR and SHARE participants who did and did not enroll in CCFA Partners and the data linkage. Of 408 participants in the OSCCAR cohort, 320 were eligible for participation in the CCFA Partners cohort. Of these participants, 243 consented to participation; however, only 44 enrolled in CCFA Partners and completed the linkage. OSCCAR participants who enrolled in CCFA Partners were better educated (17% with doctoral degrees) than those who did not (3% with doctoral degrees, P=.01). In the SHARE cohort, 436 participants enrolled and linked to the Partners cohort. More women (60% vs 50%) linked and those who linked were predominantly white (96%; P<.01). Crohn's disease patients who linked had lower mean scores on the Harvey-Bradshaw Index (3.6 vs 4.4, P<.01). Ulcerative colitis patients who linked had less extensive disease than those who did not link (45% vs 60%, P<.01). Linkage of CCFA Partners with cohorts such as OSCCAR and SHARE may be a cost-effective way to expand the infrastructure for clinical outcomes and translational research. Although linkage is feasible from a technical, legal, and regulatory perspective, participant willingness appears to be a limiting factor. Overcoming this barrier will be needed to generate meaningful sample sizes to conduct studies of biomarkers, natural history, and clinical effectiveness using linked data.


Effects of the beta-adrenoceptor antagonists acebutolol and metoprolol on sleep pattern in normal subjects.
The effects of acute introduction and withdrawal of 2 new beta-adrenergic blockers, acebutolol and metoprolol, on sleep in normal subjects were investigated. Both the subjective effects of the drug and EEG sleep variables were determined during a baseline period with placebo and in relation to the drug. The results showed that neither drug had a significant effect on sleep pattern in normal subjects. However, a transient effect on certain sleep parameters was seen on the first night of drug administration, with complete return to baseline, on the following night without any evidence of rebound. Possible mechanisms to explain the central actions of beta-adrenergic blockers are briefly discussed.


S gene mutations of HBV in children with HBV-associated glomerulonephritis.
Hepatitis B virus-associated glomerulonephritis (HBV-GN) is a kind of immune complex-induced glomerulonephritis. The present study was designed to determine whether mutation of Hepatitis B virus (HBV) S gene is associated with glomerulonephritis in Chinese children. Total 53 subjects, including 30 HBV-GN, 5 nephrosis with HBV carriers (control group 1), and 18 HBV carriers (control group 2) were included in this study. Polymerase chain reaction (PCR) was used to detect the HBV-GN S gene mutation. (1) The serotype of HBV was adw in the majority (52/53) of subjects, and was adr in only 1 subject in the control group 2; (2) the genotype of HBV was the type B in 51 subjects, the type E in 1 HBV-GN child, and the type C in 1 HBV carrier; (3) Seventeen point mutations in the S gene of HBV were identified in 21 of 30 (70%) HBV-GN patients. Among them, 16 of 21 (76.2%) mutations may cause amino acid substitutions of the HBV proteins, which occur predominantly (11/16 mutations) at threonine, serine or tyrosine phosphorylation sites of mitogen-activated protein kinase (MAPK) or protein tyrosine kinase (PTK). (4) In addition, single nucleotide mutations without amino acid substitutions (same sense mutation) were found in 2 subjects in each control group and 5 subjects in HBV-GN group. HBV S gene mutations and the subsequent amino acid substitutions in HBV proteins were found in most children with HBV-GN, suggesting that these mutations may play an important role in the pathogenesis of HBV-GN.


Activities of malate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and fructose-1,6-diphosphatase with regard to metabolic subpopulations of fast- and slow-twitch fibres in rabbit muscles.
Activities of malate dehydrogenase (MDH), 3-hydroxyacyl-CoA dehydrogenase (HAD) and fructose-1,6-diphosphatase (FDPase) were determined in single fibres dissected from freeze-dried rabbit psoas and soleus muscles. Slow-twitch fibres as determined by qualitative ATPase reaction represent a rather uniform population with regard to HAD and MDH activities. In these fibres the two enzymes are in constant proportions. FDPase is found at extremely low activities in slow-twitch fibres and because of its relatively high activity in fast-twitch fibres of soleus and psoas muscle it might be used as a marker enzyme. Fast-twitch fibres in psoas muscle represent a heterogeneous population with regard to activities of MDH as well as of HAD. The two enzyme activities are not proportional in fast-twitch psoas fibres. These findings suggest the existence of metabolic subpopulations of fast-twitch fibres having a wide range of aerobic oxidative capacities and having differences in their capacity to oxidizing fatty acids.


Treatment outcome comparisons of first-line targeted therapy in patients with KRAS wild-type metastatic colorectal cancer: A nationwide database study.
The first-line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first-line treatment for inoperable KRAS wild-type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti-EGFR mAb needs to be addressed. We established a cohort of patients with KRAS wild-type mCRC who were treated with first-line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation. A total of 6482 patients were included; bevacizumab and anti-EGFR mAb were the first-line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti-EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left-sided primary tumors, the OS and TTF benefits of anti-EGFR mAb remained. Among right-sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first-line anti-EGFR mAb therapy remained an independent predictor of longer OS and TTF for left-sided primary tumors. Patients who received anti-EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab. For patients who received first-line doublet chemotherapy for KRAS wild-type mCRC, adding anti-EGFR mAb was associated with significantly longer OS and TTF, especially for left-sided primary tumors.


Sensor domain of histidine kinase ComD confers competence pherotype specificity in Streptoccoccus pneumoniae.
Competence for genetic transformation in Streptococcus pneumoniae is regulated by a quorum-sensing mechanism involving the pheromone competence stimulating peptide (CSP) encoded by comC and a two-component signal transduction system, ComD-ComE (TCS12). In the presence of CSP, the transmembrane histidine kinase ComD receptor activates the response regulator ComE. The comC, comD and comE genes are part of an operon denoted as comCDE. In this work, the comCDE locus of 17 S. pneumoniae strains was characterized by DNA sequencing. Two major allelic combinations, comC1-comD1 and comC2-comD2 were present. Two further allelic combinations, comC1-comD3 and comC1-comD4, were also present. Comparison of the deduced amino acid sequences of the four ComD allelic variants showed that all variations are localized in the N-terminal sensor domain. In order to have the four comD alleles in the same genetic background, we constructed four different isogenic strains in which comC was deleted and the DNA encoding the sensor domain of ComD was exchanged. To formally demonstrate that the sensor domain of ComD is responsible for competence pherotype specificity, CSP-1 and CSP-2 peptides were used to induce competence in the isogenic strains: (i) strains expressing the ComD1, ComD3 and ComD4 variants were induced to competence by CSP1; (ii) the strain expressing ComD2 was induced by CSP2. Moreover, cross-induction of competence by both CSPs was observed in the ComD2 and ComD3-carrying strains in the presence of high CSP doses. This is the first formal confirmation that the ComD sensor domain is responsible for competence pherotype specificity in S. pneumoniae.


Neurophysiological maturation deficit in behaviour disorder of children--an electrographic study.
1. The investigations in biological factors of childrens' behaviour disorder are becoming increasingly important as their significance in clinical management is being recognized with more precision and clarity. 2. One of such electroencephalographic investigations is finding of some delay or defect in chronological maturation of brain wave pattern. Presence of "slow posterior waves" are indicative of immature brain waves and thus behaviour disorder with this finding should be interpreted in terms of delayed or defective maturity of brain wave pattern. 3. Interestingly these children present no clinical neurological sign but unfavourable home, school and social environment do precipitate the aggressive behaviour mainly by the way of loss of temper. 4. Though behaviour disorder due to maturation deficit diminishes as age increases, however presenting symptoms if not controlled at the earlier onset, the suffering to child, family members and not to forget the academic progress will be negatively affected. 5. Thus the clinical management of behaviour disorder should be immediately started by the combined regime of behaviour modification and pharmacotherapy. 6. In this paper one such combined regime of carbamazepine and behaviour modification has shown superiority over behaviour modification alone.


Increasing the Number of Unloading/Reambulation Cycles does not Adversely Impact Body Composition and Lumbar Bone Mineral Density but Reduces Tissue Sensitivity.
A single exposure to hindlimb unloading leads to changes in body mass, body composition and bone, but the consequences of multiple exposures are not yet understood. Within a 18wk period, adult C57BL/6 male mice were exposed to one (1x-HLU), two (2x-HLU) or three (3x-HLU) cycles of 2 wk of hindlimb unloading (HLU) followed by 4 wk of reambulation (RA), or served as ambulatory age-matched controls. In vivo µCT longitudinally tracked changes in abdominal adipose and lean tissues, lumbar vertebral apparent volumetric bone mineral density (vBMD) and upper hindlimb muscle cross-sectional area before and after the final HLU and RA cycle. Significant decreases in total adipose tissue and vertebral vBMD were observed such that all unloaded animals reached similar values after the final unloading cycle. However, the magnitude of these losses diminished in mice undergoing their 2nd or 3rd HLU cycle. Irrespective of the number of HLU/RA cycles, total adipose tissue and vertebral vBMD recovered and were no different from age-matched controls after the final RA period. In contrast, upper hindlimb muscle cross-sectional area was significantly lower than controls in all unloaded groups after the final RA period. These results suggest that tissues in the abdominal region are more resilient to multiple bouts of unloading and more amenable to recovery during reambulation than the peripheral musculoskeletal system.


Management of skeletal class II malocclusion using bimaxillary skeletal anchorage supported fixed functional appliances : A novel technique.
To evaluate the treatment effects in growing skeletal class II patients subjected to a novel treatment technique, i.e., bimaxillary miniplates supported fixed functional appliance. The null hypothesis was that there is no statistically significant difference in skeletal changes of patients with class II malocclusion treated with bimaxillary skeletal anchorage supported fixed functional appliance and those who were not provided any intervention. The sample comprised 32 skeletal class II subjects (17 males and 15 females) with a Cervical Vertebrae Maturity Index (CVMI) demonstrating peak of pubertal growth spurt. Sixteen patients (12.37 ±1.09 years of age) were treated with bimaxillary skeletal anchorage supported fixed function appliance, while 16 well-matched subjects (12.06 ± 1.34 years of age) were included as controls. For both groups, cephalograms (T1, T2) were taken with a matched observational interval of about 7.5 months; 17 linear and 10 angular measurements were recorded. The intraclass correlation coefficient (ICC) was used to determine reliability of measurements recorded. Student t test was carried out to determine the changes produced by the treatment relative to control. When compared with the control group, the treatment group demonstrated significant maxillary retrusion. No significant changes were seen in mandibular growth pattern, whereas mandibular length increased significantly more than in the control group (B-VP: 3.05 mm; Co-Gn: 2.65 mm). Treatment mechanics had minimal effects on maxillary dentition. Mandibular incisors proclined by an average of 3.06°. Maxilla-mandibular relation improved significantly (ANB: -4.29°; NA-Pog: -3.76°). The new bimaxillary skeletal anchorage supported fixed functional appliance technique was found to be highly effective in the treatment of class II malocclusion with significant skeletal changes.


3T MR imaging of postoperative recurrent middle ear cholesteatomas: value of periodically rotated overlapping parallel lines with enhanced reconstruction diffusion-weighted MR imaging.
MR diagnostic of postoperative recurrent cholesteatomas is difficult. Our purpose was to compare multishot fast spin-echo periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) diffusion-weighted MR imaging (DWI) with array spatial sensitivity encoding technique (ASSET) single-shot echo-planar DWI and late postgadolinium T1-weighted MR imaging for the detection of postoperative recurrent middle ear cholesteatomas with a 3T imaging unit. Thirty-five patients with suggested postoperative recurrent middle ear cholesteatoma underwent 3T MR imaging with PROPELLER DWI, ASSET echo-planar DWI, and late postgadolinium T1-weighted MR imaging. Three radiologists (2 seniors, 1 fellow) analyzed unlabeled images for visualization of recurrence. Interobserver and intraobserver agreement was assessed by using the Cohen kappa statistic test. Sensitivity, specificity, and predictive value were assessed for the 3 observers. Nineteen recurrent cholesteatomas were diagnosed. PROPELLER interobserver agreement was very good (1, 0.89, 0.89) among the 3 observers. Intraobserver agreement between PROPELLER and T1-weighted imaging was very good to moderate (0.88, 0.57, 0.58). PROPELLER DWI provided less interobserver variability than other sequences, and the best sensitivity, specificity, and predictive value. On a 3T imaging unit, multishot fast spin-echo PROPELLER DWI allows an easier detection of postoperative recurrent middle ear cholesteatoma than T1-weighted imaging by reducing artifacts and by its better contrast. DWI with PROPELLER is diagnostically robust and accurate.


The Paired-box protein PAX-3 regulates the choice between lateral and ventral epidermal cell fates in C. elegans.
The development of the single cell layer skin or hypodermis of Caenorhabditis elegans is an excellent model for understanding cell fate specification and differentiation. Early in C. elegans embryogenesis, six rows of hypodermal cells adopt dorsal, lateral or ventral fates that go on to display distinct behaviors during larval life. Several transcription factors are known that function in specifying these major hypodermal cell fates, but our knowledge of the specification of these cell types is sparse, particularly in the case of the ventral hypodermal cells, which become Vulval Precursor Cells and form the vulval opening in response to extracellular signals. Previously, the gene pvl-4 was identified in a screen for mutants with defects in vulval development. We found by whole genome sequencing that pvl-4 is the Paired-box gene pax-3, which encodes the sole PAX-3 transcription factor homolog in C. elegans. pax-3 mutants show embryonic and larval lethality, and body morphology abnormalities indicative of hypodermal cell defects. We report that pax-3 is expressed in ventral P cells and their descendants during embryogenesis and early larval stages, and that in pax-3 reduction-of-function animals the ventral P cells undergo a cell fate transformation and express several markers of the lateral seam cell fate. Furthermore, forced expression of pax-3 in the lateral hypodermal cells causes them to lose expression of seam cell markers. We propose that pax-3 functions in the ventral hypodermal cells to prevent these cells from adopting the lateral seam cell fate. pax-3 represents the first gene required for specification solely of the ventral hypodermal fate in C. elegans providing insights into cell type diversification.


Evaluation of the genotoxic potential of reactive black 5 solutions subjected to decolorizing treatments by three fungal strains.
The genotoxic potential of solutions of the textile dye "Reactive Black 5" that were subjected to decolorizing treatments with the fungal strains Coriolopsis polyzona MUCL33483, Penicillium sp. MUBA001 and Pycnoporus sp. MUBA002 was tested. The genotoxicity of the solutions was determined by evaluation of micronuclei formation in Vicia faba root cells and calculation of a damage index (MN(ID)). Non-treated Reactive Black 5 solutions (50-1000 ppm) caused a statistically significant increase in micronuclei formation and, by then, in damage index. Solutions of dye treated with C. polyzona MUCL33483 and Pycnoporus sp. MUBA002 showed color loss, probably due to enzymatic breakdown of the colorant, but maintenance or even an increase in genotoxicity. On the other hand, the Penicillium sp. strain MUBA001 caused decolorization of the dye, apparently by adsorption on mycelia, and, for solutions that initially contained 50 ppm of colorant, an elimination of the genotoxicity was observed after three weeks of treatment.


Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice.
We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) against refractory depression in adrenocorticotropic hormone (ACTH)-treated mice as a model of tricyclic antidepressant (TCA)-resistant depression. Chronic ACTH treatment (0.45 mg/kg, s.c., 14 days) weakened the antidepressant-like effects of imipramine (20 mg/kg, i.p., 6 days) in the forced-swim test (FST). Conversely, GLP-2 (3 μg/mice, i.c.v., 6 days) induced antidepressant-like effects in the ACTH-treated mice in the FST. ACTH-treatment increased basal serum corticosterone levels, with an additional increase induced by the FST. Imipramine or GLP-2 had no effect on the basal corticosterone level, but GLP-2 attenuated the additional increase caused by the FST. Moreover, GLP-2 increased 5-HT levels, but not 5-HIAA. These results suggest that GLP-2 induced antidepressant-like effects under imipramine-resistant conditions through increase in 5-HT levels.


Architecture of RNA-RNA interactions.
RNA molecules tend to form intricate tertiary structures via intramolecular RNA-RNA interactions (RRIs) to regulate transcription, RNA processing, and translation processes. In these biological processes, RNAs, especially noncoding RNAs, usually achieve their regulatory specificity through intermolecular RNA-RNA base pairing and execute their regulatory outcomes via associated RNA-binding proteins. Decoding intramolecular and intermolecular RRIs is a prerequisite for understanding the architecture of various RNA molecules and their regulatory roles in development, differentiation, and disease. Many sequencing-based methods have recently been invented and have revealed extraordinarily complicated RRIs in mammalian cells. Here, we discuss the technical advances and limitations of various methodologies developed for studying cellular RRIs, with a focus on the emerging architectural roles of RRIs in gene regulation.


Activation of peripheral opioid receptors has no effect on heart rate variability.
Opioid receptors involved in regulating the motility of the gastrointestinal tract have been localized in both contractile and neuronal tissues. Trimebutine, a peripheral opioid receptor agonist, modulates gastrointestinal motor activity in both directions and also may act on cardiac tissue. This study investigated the effects of trimebutine in clinical doses on cardiac autonomic functions with heart rate variability. The effect of trimebutine on cardiac autonomic outflows was evaluated in 11 healthy subjects. Trimebutine (200 mg) or placebo was administered orally at random in a double-blind, cross-over manner. Continuous electrocardiography recordings were obtained before and after drug administration during three states: rest, controlled breathing, and a hand grip exercise. Heart rate variability analysis showed that there was no significant difference between subjects administered with placebo or trimebutine throughout rest, controlled breathing, or the hand grip exercise. We concluded that trimebutine, in clinical doses, has no significant effect on cardiac autonomic functions.


Virtual screening and in vitro assays of novel hits as promising DPP-4 inhibitors.
Diabetes is a metabolic disorder that presents hyperglycemia and vascular complications due to the non-production of insulin or its inappropriate use by the body. One of the strategies to treat diabetes is the inhibition of dipeptidyl peptidase-4 (DPP-4) and it is interesting to conduct virtual screening studies to search for new inhibitors of the DPP-4 enzyme. This study involves a virtual screening using the crystallographic structure of DPP-4 and a compound subset from the ZINC database. To filter this compound subset, we used some physicochemical properties, positioning at the three DPP-4 binding sites, molecular interactions, and ADME-Tox properties. The conformations of ligands obtained from AutoDock Vina were analyzed using a consensus with other algorithms (AutoDock and GOLD). The compounds selected from virtual screening were submitted to biological assays using the "DPPIV-Glo™ protease assay". Cytotoxicity tests were also performed. One promising compound (ZINC1572309) established interactions with important residues at the binding site. The results of the ADME-Tox prediction for ZINC1572309 were compared with a reference drug (sitagliptin). The cytotoxicity of sitagliptin and ZINC1572309 were evaluated using the XTT short-term cytotoxic assay, including normal and tumor cell lines to observe the cellular response to inhibitor treatment at different genetic bases. Both compounds (ZINC1572309 and the reference drug - sitagliptin) also inhibited DPP-4 activity, suggesting interesting biological effects of the selected compound at non-cytotoxic concentrations. Therefore, from in silico and in vitro studies, a potential hit as DPP-4 inhibitor was discovered and it can be structurally optimized to achieve suitable activity and pharmacokinetic profiles.


Transcriptional regulation of mitochondrial HMG-CoA synthase in the control of ketogenesis.
Mitochondrial and cytosolic HMG-CoA synthases are encoded by two different genes. Control of ketogenesis is exerted by transcriptional regulation of mitochondrial HMG-CoA synthase. Fasting, cAMP, and fatty acids increase its transcriptional rate, while refeeding and insulin repress it. Fatty acids increase transcription through peroxisomal proliferator regulatory element (PPRE), to which peroxisome proliferator activated receptor (PPAR) can bind. Other transcription factors such as chicken ovalbumin upstream promoter transcription factor (COUP-TF) and hepatocyte nuclear factor 4 (HNF-4) compete for the PPRE site, modulating the response of PPAR.


Hermetia illucens (Diptera: Stratiomydae) larvae and prepupae: Biomass production, fatty acid profile and expression of key genes involved in lipid metabolism.
The Black Soldier Fly (BSF) Hermetia illucens provides a promising strategy in the waste valorisation process and a sustainable alternative source of valuable nutrients, including lipids for food and feed. In the present study, the differences in growth performances and nutritional values of BSF V instar larvae and prepupae reared on vegetable waste were analyzed and compared focusing on fat content. V instar larvae showed higher capacity to bioconvert the substrate into biomass than prepupae. The nutritional composition and the fatty acid profiles were dependent on the developmental stage. The expression levels of acetyl-CoA carboxylase (acc), fatty acid synthase (fas), lipase (lip) and acyl-CoA dehydrogenase (acd) genes involved in the lipid metabolism pathway and herein characterized for the first time, were evaluated in order to understand the molecular basis underlying the observed differences in fatty acid profiles. Our results suggest that the different fatty acid profiles of BSF V instar larvae and prepupae may be related to the modulation of the lipid metabolism-related genes expression during larval development. Our study highlights substantial differences between H. illucens V instar larvae and prepupae giving important features regarding the opportunity to modulate the preferable fatty acid profile to meet the industrial requirements.


Apomorphine-induced alterations in cortical EEG activity of rats. Involvement of D-1 and D-2 dopamine receptors.
EEG activity after activation of dopamine receptors of D-1 and/or D-2 type was studied by using telemetric recordings in rats. Apomorphine, a preferential D-2 agonist, produced a characteristic increase in the power of alpha-1 band (7.00-9.50 Hz) when given in doses mediating stereotypies (0.2 or 0.5 mg/kg s.c.). Low doses produced a general increase in the power of all of the bands except beta-2. In particular, delta activity was enhanced which seems to be in correspondence with the sedation observed after these doses (0.02 and 0.05 mg/kg). Haloperidol in a dose which is assumed to block both D-1 and D-2 receptors (0.1 mg/kg i.p.) completely antagonized the alpha-1 activation produced by apomorphine (0.5 mg/kg). A similar, although not complete inhibition of alpha-1 activation was found after administration of a large dose of the selective D-1 antagonist SCH 23390 (0.2 mg/kg i.p.). The selective agonist at D-2 receptors quinpirole (1.0 mg/kg s.c.) produced a less pronounced activation of the power in the alpha-1 band than apomorphine. In general, there was found to be a good correlation between the activation of the alpha-1 activity and stereotyped behaviour. The results suggest that for the full expression of alpha-1 activation, a pronounced activation of D-2 receptors and at least a minimal activation of D-1 receptors, for instance by the endogenous dopamine, is necessary.