Alleviation of the doxorubicin-induced nephrotoxicity by fasudil in vivo and in vitro.
Treatment with the chemotherapeutic agent, doxorubicin (DOX), is limited by side effects. We have previously demonstrated that fasudil, a Rho/ROCK inhibitor, has antioxidant, anti-inflammatory and anti-apoptotic effects in contrast-induced acute kidney injury model. The present study to investigated the possible protective effect of fasudil, on DOX-induced nephrotoxicity. In vivo: Forty male C57BL/6 male mice were randomly divided into 4 groups: Control group, DOX treatment group (DOX group), DOX + low dose fasudil (DOX + L group), DOX + high dose fasudil (DOX + H group). Mice in 2-4 groups received DOX (2.5 mg/kg, i.p.) once a week for 8 weeks. The 3 and 4 group were given 2 mg/kg/d or 10 mg/kg/d fasudil before DOX injection. respectively. Meanwhile, the control group received saline. At the end of week eight, blood samples were collected for biochemical testing. The kidneys were removed for histological, immunohistochemical, Western blot, quantitative real-time PCR (qRT-PCR), and molecular detection. In vitro: NRK-52E cells were treated with 40 uM fasudil for 12 h, then incubated with 1 uM DOX for 24 h. Cells then collected for qRT-PCR and Western blot. In vivo, fasudil treatment ameliorated DOX-induced immunofluorescence reaction of DNA damage-related factors (8-OHdG), decreased the expression of Bax, Caspase-3, p16, p21 and p53, and increased the expression of protein of Bcl-2, Bmi-1 and Sirt-1. In the mouse model, administration of fasudil significantly ameliorated DOX-induced kidney damage, suppressed cell apoptosis and senescence, ameliorated redox imbalance and DNA damage. At the same time, DOX produced obvious kidney damage revealed by kidney functions changes: increased serum creatinine (SCr) and blood urea nitrogen (BUN) concentrations. In addition, kidney tissue staining in the DOX group showed abnormal structure and fibroproliferative disorders. And DOX could promote the oxidation and senescence of kidney cells, leading to increased expression of 8-OHdG and senescence and apoptosis-related factors. On the contrary, fasudil treatment can effectively inhibit redox imbalance and DNA damage caused by DOX, and inhibit cell senescence and apoptosis. Fasudil can inhibit excessive activation of Rho/ROCK signaling pathway, thereby improving kidney tissue fibrosis and recovery kidney function. Fasudil has a protective effect on DOX-induced nephrotoxicity in mice and NRK-52E cells, which can inhibit oxidative stress and DNA damage, inhibit apoptosis, and delays cell senescence by inhibiting RhoA/Rho kinase (ROCK) signaling pathway.


Treatment compliance and challenges among tuberculosis patients across selected health facilities in Osun State Nigeria.
Tuberculosis (TB) is a major public health problem in the world and Africa has approximately one quarter of the world's cases. One of the greatest challenges facing most TB programmes is the non-compliance to TB treatment among TB patients. This study aimed at determining the challenges of management of tuberculosis (TB) across selected Osun State health facilities. The study employed a descriptive cross-sectional design. A semi-structured questionnaire was used to collect data from 102 TB patients in the health facilities. The instrument measured socio-demographic variables, patient related factors, socio-economic variables, health care system related factors to TB disease and treatment. Data were analysed and summarized using descriptive and inferential statistics. Statistical significance was placed at p < 0.05. TB patients who had no formal education (χ2 = 12.941, p < 0.05), who were smoking during treatment (χ2 = 13.194, p < 0.001), who consumed alcohol during TB treatment (χ2 = 6.371, p < 0.05) and those who were HIV positive (χ2 = 23.039, p < 0.001) significantly failed to comply with TB treatment. TB patients who waited for one hour or more at heath facilities (χ2 = 21.761, p < 0.001), who reported that TB treatment should be stopped before six month (χ2 = 9.804, p < 0.05) or when patient felt better (χ2 = 35.185, p < 0.001) and travelled for 10 km or more (χ2 = 13.610, p < 0.001) significantly failed to comply with TB treatment. This study concluded that non-compliance rate to tuberculosis treatment among TB patients in this study is high. Both health facility and patient-related factors were largely responsible.


Dental aspects of maxillofacial injuries.
The chief progress of maxillofacial surgery in recent years has been the preservation and the retention of functional tissue. The recent advances in microvascular and reimplantation surgery are examples. Similarly the preservation of the masticatory apparatus is best served by the retention of all viable components. Additional benefits derived from this approach include the facilitation with alignment of the bony fragments, proper occlusion of the teeth and maintenance of the vertical relationship between the upper and lower jaws; in addition to the restoration of appearance and the functions of mastication and speech. Although injuries of the teeth and their supporting stuctures at first glance may seem to be simple problems, frequently they turn out to be complicated. The most common injury is partial avulsion of the alveolar bone with loss of attached teeth, which may produce a severe defect in the jaw bone. During healing there is additional resorbtion of alveolar bone, which is quite a normal physiologic phenomenon. Therefore, the eventual defect is likely to be more severe yet. For this reason more concern should be shown for these lesser injuries.


Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015.
In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure.


Millennial climate oscillations controlled the structure and evolution of Termination II.
The controls that affect the structure and timing of terminations are still poorly understood. We studied a tufa deposit from the Iberian Peninsula that covers Termination II (T-II) and whose chronology was synchronized to speleothem records. We used the same chronology to synchronize ocean sediments from the North Atlantic to correlate major climate events in a common timescale. We identify two stages within T-II. The first stage started with the increase of boreal summer integrated solar insolation, and during this stage three millennial climate oscillations were recorded. These oscillations resulted from complex ocean-atmosphere interactions in the Nordic seas, caused by the progressive decay of Northern Hemisphere ice-sheets. The second stage commenced after a glacial outburst that caused the collapse of the Thermohaline Circulation, a massive Heinrich event, and the onset of the Bipolar Seesaw Mechanism (BSM) that eventually permitted the completion of T-II. The pace of the millennial oscillations during the first stage of T-II controlled the onset of the second stage, when the termination became a non-reversible and global phenomenon that accelerated the deglaciation. During the last the two terminations, the BSM was triggered by different detailed climate interactions, which suggests the occurrence of different modes of terminations.


Evolution of thymidine and thymidylate kinases: the possibility of independent capture of TK genes by different groups of viruses.
Phylogenetic analysis of viral and cellular thymidine and thymidylate kinases was performed using computer-assisted methods. Multiple alignments and tentative phylogenetic trees were generated for the two families of these enzymes, which include a) thymidine kinases (TK) of mammals, poxviruses, African swine fever virus, E. coli, and bacteriophage T4; and b) thymidylate kinases (ThyK) of yeast and poxviruses and distantly related herpesvirus proteins with both enzymatic activities. Analysis of the alignment of the TKs of the first family highlighted three strongly conserved segments. Two of these corresponded to the A and B motifs of the purine NTP-binding pattern. The third, C-terminal segment, showing the highest conservation, encompassed a modified Zn finger motif. It is speculated that this motif might be involved in TK oligomerization. Phylogenetic trees constructed by three different methods suggested that cellular TK genes could be captured independently by T4 bacteriophage, African swine fever virus, fowlpox virus, and the other poxviruses. The observed tree topologies appear to contradict the popular virus-host coevolution schemes and to imply that different subdivisions of poxviruses diverged at earlier stages of evolution than their hosts did. It was shown that deoxynucleoside monophosphate kinase of bacteriophage T4 is related to the ThyK family. Phylogenetic analysis suggested that ThyK genes probably have been acquired independently by phage T4, poxviruses, and herpes-viruses.


Recent insights into Entamoeba development: identification of transcriptional networks associated with stage conversion.
Entamoeba histolytica is an important human pathogen and a leading parasitic cause of death globally. The parasite life cycle alternates between the trophozoite form, which is motile and causes invasive disease and the cyst stage, which is environmentally resistant and transmits infection. Understanding the triggers that initiate stage conversion is an important yet understudied area of investigation. Recent progress in dissecting the transcriptional networks that regulate E. histolytica development is outlined in this paper.


Effect of pulse steroid therapy in a patient with Langerhans' cell histiocytosis.
Langerhans' cell histiocytosis (LCH) is a condition in which granulomas form in various tissues through the accumulation of abnormal histiocytes (Langerhans' cells), granulocytes and lymphocytes. An important distinction between LCH and primary pulmonary histiocytosis (PPH) is that smoking cessation is known to often lead to spontaneous improvement in PPH patients, while this has not been demonstrated in patients with multisystem LCH. In this case report, we describe the case of a 20-year-old man who presented with cough and palpably enlarged lymph nodes in his neck. An inguinal lymph node biopsy led to the diagnosis of multisystem LCH in the lungs, the cervical, intra-abdominal, and inguinal lymph nodes and the spleen. The patient was a smoker, and had averaged 30 cigarettes per day for 7 years. To address the multisystem involvement, intravenous pulse steroid therapy was administered (30-40 mg/kg daily) in two 3-day treatment periods separated by 3-4 weeks. The patient was also advised to stop smoking, and did so. Serial follow-up examinations confirmed an objective improvement with complete remission. The patient was still healthy at 18 months post-treatment, reflecting a dramatic and positive response to pulse steroid therapy. This encouraging result makes this case an important one to highlight.


Estimating the potential impact of the Australian government's reformulation targets on household sugar purchases.
Countries around the world are putting in place sugar reformulation targets for packaged foods to reduce excess sugar consumption. The Australian government released its voluntary sugar reformulation targets for nine food categories in 2020. We estimated the potential impact of these targets on household sugar purchases and examined differences by income. For comparison, we also modelled the potential impact of the UK sugar reduction targets on per capita sugar purchases as the UK has one of the most comprehensive sugar reduction strategies in the world. Grocery purchase data from a nationally representative consumer panel (n=7,188) in Australia was linked with a large database (FoodSwitch) with product-specific sugar content information for packaged foods (n=25,261); both datasets were collected in 2018. Potential reductions in per capita sugar purchases were calculated overall and by food category. Differences in sugar reduction across income level were assessed by analysis of variance. In 2018, the total sugar acquired from packaged food and beverage purchases consumed at-home was 56.1 g/day per capita. Australia's voluntary reformulation targets for sugar covered 2,471/25,261 (9.8%) unique products in the FoodSwitch dataset. Under the scenario that all food companies adhered to the voluntary targets, sugar purchases were estimated to be reduced by 0.9 g/day per capita, which represents a 1.5% reduction in sugar purchased from packaged foods. However, if Australia adopted the UK targets, over twice as many products would be covered (n=4,667), and this would result in a more than four times greater reduction in sugar purchases (4.1 g/day per capita). It was also estimated that if all food companies complied with Australia's voluntary sugar targets, reductions to sugar would be slightly greater in low-income households compared with high-income households by 0.3 g/day (95%CI 0.2 - 0.4 g/day, p<0.001). Sugar-reduction policies have the potential to substantially reduce population sugar consumption and may help to reduce health inequalities related to excess sugar consumption. However, the current reformulation targets in Australia are estimated to achieve only a small reduction to sugar intakes, particularly in comparison to the UK's sugar reduction program.


Adenine compounds: cerebrovascular effects in vitro with reference to their possible involvement in migraine.
Adenosine and adenine compounds (AMP, cyclic AMP, ADP and ATP) markedly dilated feline and human pial arteries in vitro, the effect being more prominent with increasing tone of the vessel (active tonic contraction induced by prostaglandin F 2 alpha or serotonin). In contrast, the various adenine compounds were unable to produce any dilation of extracranial arteries tested (branches of lingual, external maxillary, and superficial temporal arteries). The degree of dilatation depended upon the perivascular potassium concentration, so that low potassium increased Emax and reduced ED50 values. Possible involvement of adenine compounds in the vasodilatory phase of the migraine attack is discussed.


Inhibitory effect of human serum albumin on Cu-induced Aβ(40) aggregation and toxicity.
It has been suggested that the aggregation and cytotoxicity of amyloid-β (Aβ) peptide with transition-metal ions in neuronal cells is involved in the development and progression of Alzheimer's disease (AD). As the most abundant protein in blood plasma and in cerebrospinal fluid, human serum albumin (HSA) can bind Aβ in vivo and subsequently inhibit Aβ fibril growth. However, the roles of albumin in Cu-induced Aβ aggregation and toxicity, and its potential biological relevance to AD therapy, were not stressed enough. Here, we showed that HSA was capable of binding Cu (I) with much higher affinity than Aβ, competitively inhibiting the interaction of Aβ and Cu ions. In the presence of biological reducing agent ascorbate, HSA inhibited Cu (II)/Cu (I)-mediated Aβ40 aggregation, reactive oxygen species production, and neurotoxicity. However, in the absence of Cu (II)/Cu (I), HSA could not effectively inhibit Aβ40 aggregation and neurotoxicity at 24 h (or less) incubation time, but decreased Aβ40 aggregation at much longer incubation (120 h). Our data suggested that through competitively decreasing Cu-Aβ interaction, HSA could effectively inhibit Cu (II)/Cu (I)-induced Aβ40 aggregation and neurotoxicity, and play important roles in regulating redox balance as well as metal homeostasis in AD prevention and therapy.


Intraperitoneal chromic phosphate P 32 as salvage therapy for persistent carcinoma of the ovary after surgical restaging.
From 1977 through 1984, 23 patients with persistent epithelial carcinomas of the ovary received intraperitoneal instillation with chromic phosphate P 32 suspension as salvage therapy after second- or third-look laparotomy. Patients received a median 10 cycles of chemotherapy before chromic phosphate P 32. Disease consisted of microscopic residual only in 10 patients (43%), macroscopic residual that was completely resected in eight (35%), and macroscopic residual disease in which the largest diameter was less than 0.5 cm in five patients (22%). Ten patients are free of disease at 13 to 94 months after chromic phosphate P 32 salvage therapy. Life table survival is 75% at 2 years and 57% at 4 years, with a disease-free survival rate of 54% at 2 years and 27% at 4 years. Patients with no gross residual disease had median disease-free survival of 27 months versus 9 months for patients with macroscopic residual disease (p greater than 0.1). Only three patients (13%) developed surgical bowel complications related to chromic phosphate P 32. Compared with previous studies, intraperitoneal chromic phosphate P 32 as salvage therapy for patients with minimal residual ovarian carcinoma defined at secondary surgical evaluation results in comparable survival and fewer complications than does salvage abdominopelvic irradiation and should be considered as an option to further chemotherapy in selected patients.


Molecular epidemiological study of vertical transmission of vaginal Lactobacillus species from mothers to newborn infants in Japanese, by arbitrarily primed polymerase chain reaction.
We investigated mother-to-newborn infant transmission of Lactobacillus species in Japanese by the typing of isolates from the vagina of pregnant women and stool specimens from their newborn infants. All infants were born by uncomplicated vaginal delivery and were basically fed breast milk. Lactobacillus strains were fingerprinted by arbitrarily primed polymerase chain reaction (AP-PCR), using ERIC1R and ERIC2 primers. Of 86 pregnant women tested, 71 (82.6%) were positive for vaginal lactobacilli. At 5 days after birth, 24 (33.8%) of the 71 infants whose mothers were lactobacilli-positive had fecal lactobacilli, while only 1 (6.7%) of the 15 infants delivered from the vaginal lactobacilli-negative mothers was lactobacilli-positive ( P < 0.01). Lactobacillus crispatus was the most prevalent species of vaginal lactobacilli in mothers and of fecal lactobacilli in infants at 5 days of age, whereas Lactobacillus gasseri was the most common in infants at 1 month of age. Identification to the species level, followed by AP-PCR typing, demonstrated that 23.3% of the 86 infants were likely to be colonized in the intestine by the vaginal lactobacilli of their mothers, and that only 2 of the infants retained the same vaginal lactobacilli until 1 month of age. These results suggest that approximately one-fourth of infants acquire vaginal lactobacilli from their mothers at birth, and that the acquired lactobacilli do not last in the intestine of the infant long-term, but rather, are replaced by ones from milk or unknown sources after birth. AP-PCR with primers ERIC1R and ERIC2 is indicated as a potential tool for the typing of Lactobacillus strains.


Biomarkers predict hemorrhagic transformation and stroke severity after acute ischemic stroke.
Hemorrhagic transformation (HT) is a complication occurring in patients with acute ischemic stroke (AIS) either spontaneously or post-thrombolysis leading to significant morbidity and mortality. We assessed circulating matrix metalloproteinase-9 (MMP-9), Claudin-5, and soluble serum stimulation-2 (sST2) in HT and stroke severity in AIS based on their temporal distribution. We prospectively enrolled 111 AIS patients within 12 h from onset. Patient demographic, clinical, and imaging details were documented. Follow-up imaging was conducted 24-48 h after admission. Blood samples were taken at three time-points from stroke onset. HT was classified according to the European Co-operative Acute Stroke Study-III(ECASS-III). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Multiple logistic regression and receiver operating characteristic curve were conducted to determine the discriminative capacity. Mean age was 62.3 ± 11.7 years and median baseline NIHSS was 12[IQR 8.0-18.0]. HT was detected in 30(27%) patients. Biomarker levels at 12 h were elevated with median MMP-9 concentration of 153.9 ng/mL[IQR 110.6-309 ng/mL] indicating a trend toward significant positive correlation with HT(P = 0.05). Claudin-5 levels at 12 h was elevated but was not statistically significant (43.1 pg/mL[IQR:26.7-72.6 pg/mL] vs 59.4 pg/mL[IQR:24.5-100.8 pg/mL];P = 0.4). Multiple logistic regression indicated Claudin-5 levels at 12 h (OR 9.46;95% CI:1.97-64.6;P = 0.010) and baseline low ASPECTS score(OR 20.3;95% CI:3.46-193; P = 0.003) independently predicted HT. MMP-9 at 12 h was significantly elevated in patients with moderate to severe strokes (P = 0.04). Claudin-5 and low ASPECTS independently predicted HT. MMP-9 was positively correlated with baseline stroke severity.


An investigation of client mood in the initial and final sessions of cognitive-behavioral therapy and psychodynamic-interpersonal therapy.
Our aim was to examine client mood in the initial and final sessions of cognitive-behavioral therapy (CBT) and psychodynamic-interpersonal therapy (PIT) and to determine how client mood is related to therapy outcomes. Hierarchical linear modeling was applied to data from a clinical trial comparing CBT with PIT. In this trial, client mood was assessed before and after sessions with the Session Evaluation Questionnaire-Positivity Subscale (SEQ-P). In the initial sessions, CBT clients had higher pre-session and post-session SEQ-P ratings and greater pre-to-post session mood change than did clients in PIT. In the final sessions, these pre, post, and change scores were generally equivalent across CBT and PIT. CBT outcome was predicted by pre- and post-session SEQ-P ratings from both the initial sessions and the final sessions of CBT. However, PIT outcome was predicted by pre- and post-session SEQ-P ratings from the final sessions only. Pre-to-post session mood change was unrelated to outcome in both treatments. These results suggest different change processes are at work in CBT and PIT.


A mini-rapid-scan-spectrophotometer.
The mini-rapid-scan-spectrophotometer (Mini-RSS) is a scanning single-beam spectrophotometer that has been patented. It is based on a minimum of reflections and involves exclusively mirrors as beam-deflecting components. This way stray light is minimized, which results in an excellent light-throughput, high dynamics, low cost, compactness and rigidity. The Mini-RSS has been designed as a multi-purpose instrument that allows absorption, transmission, reflection, fluorescence and luminescence measurements in a single-beam mode. Its spectral range extends from the UV and visible spectrum to the IR. This provides for the possibility to measure even optically unfavorable, highly turbid or scattering samples that would be otherwise inaccessible to investigations with commercial spectrophotometers. A miniaturized and very sensitive photomultiplier-module (PM) of high dynamics allows in the visible spectral range absorbance measurements that cover up to four OD units. The Mini-RSS is capable of scanning up to 100 spectra per second with a resolution of 12 bit and 500 points. The linear dispersion is currently 5 nm and the stray light level <0.01%.


Structural biology of CRISPR-Cas immunity and genome editing enzymes.
CRISPR-Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, we examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR-Cas immune systems and deployed for wide-ranging genome editing applications. We explore the adaptive and interference aspects of CRISPR-Cas function as well as open questions about the molecular mechanisms responsible for genome targeting. These structural insights reflect close evolutionary links between CRISPR-Cas systems and mobile genetic elements, including the origins and evolution of CRISPR-Cas systems from DNA transposons, retrotransposons and toxin-antitoxin modules. We discuss how the evolution and structural diversity of CRISPR-Cas systems explain their functional complexity and utility as genome editing tools.


Deficits in fronto-posterior interactions point to inefficient resource allocation in schizophrenia.
Fronto-posterior networks have been implicated in various cognitive processes that are impaired in schizophrenia. This is the first study on time and frequency resolved fronto-posterior coherence during cognitive control in schizophrenia. We examined 16 schizophrenic/schizoaffective patients and 20 age-matched controls performing a choice-reaction task. Fronto-posterior coherence was analyzed for event-related increases with respect to the inter-trial interval. Furthermore, we compared the two groups for event-related coherence during the task-related time intervals which showed a significant coherence increase with respect to the inter-trial interval, as well as for absolute coherence during the inter-trial interval. Event-related coherence was significantly reduced in patients during time intervals (0-250 ms poststimulus) when controls showed significant event-related coherence increases. However, patients showed significantly higher absolute coherence during the inter-trial interval. These results pointed to differential deficits in fronto-posterior connectivity during the inter-trial interval and task-related conditions in schizophrenia. Cognitive deficits in schizophrenia might be driven by abnormal fronto-posterior communication. Task-related hypo-connectivity and inter-trial interval hyper-connectivity point to resource allocation deficits. The timing of cortico-cortical interactions during crucial task-related intervals may be impaired, while frontal and posterior areas may exhibit increased interactions between the trials.


Discrepancy of cytogenetic analysis in Western and eastern Taiwan.
This study aimed at investigating the results of second-trimester amniocyte karyotyping in western and eastern Taiwan, and identifying any regional differences in the prevalence of fetal chromosomal anomalies. From 2004 to 2009, pregnant women who underwent amniocentesis in their second trimester at three hospitals in western Taiwan and at four hospitals in eastern Taiwan were included. All the cytogenetic analyses of cultured amniocytes were performed in the cytogenetics laboratory of the Genetic Counseling Center of Hualien Buddhist Tzu Chi General Hospital. We used the chi-square test, Student t test, and Mann-Whitney U test to evaluate the variants of clinical indications, amniocyte karyotyping results, and prevalence and types of chromosomal anomalies in western and eastern Taiwan. During the study period, 3573 samples, 1990 (55.7%) from western Taiwan and 1583 (44.3%) from eastern Taiwan, were collected and analyzed. The main indication for amniocyte karyotyping was advanced maternal age (69.0% in western Taiwan, 67.1% in eastern Taiwan). The detection rates of chromosomal anomalies by amniocyte karyotyping in eastern Taiwan (45/1582, 2.8%) did not differ significantly from that in western Taiwan (42/1989, 2.1%) (p = 1.58). Mothers who had abnormal ultrasound findings and histories of familial hereditary diseases or chromosomal anomalies had higher detection rates of chromosomal anomalies (9.3% and 7.2%, respectively). The detection rate of autosomal anomalies was higher in eastern Taiwan (93.3% vs. 78.6%, p = 0.046), but the detection rate of sex-linked chromosomal anomalies was higher in western Taiwan (21.4% vs. 6.7%, p = 0.046). We demonstrated regional differences in second-trimester amniocyte karyotyping results and established a database of common chromosomal anomalies that could be useful for genetic counseling, especially in eastern Taiwan.


DAPI staining and DNA content estimation of nuclei in uncultivable microbial eukaryotes (Arcellinida and Ciliates).
Though representing a major component of eukaryotic biodiversity, many microbial eukaryotes remain poorly studied, including the focus of the present work, testate amoebae of the order Arcellinida (Amoebozoa) and non-model lineages of ciliates (Alveolata). In particular, knowledge of genome structures and changes in genome content over the often-complex life cycles of these lineages remains enigmatic. However, the limited available knowledge suggests that microbial eukaryotes have the potential to challenge our textbook views on eukaryotic genomes and genome evolution. In this study, we developed protocols for DAPI (4',6-diamidino-2-phenylindole) staining of Arcellinida nuclei and adapted protocols for ciliates. In addition, image analysis software was used to estimate the DNA content in the nuclei of Arcellinida and ciliates, and the measurements of target organisms were compared to those of well-known model organisms.The results demonstrate that the methods we have developed for nuclear staining in these lineages are effective and can be applied to other microbial eukaryotic groups by adjusting certain stages in the protocols.


ED utilization of medical clearance testing for psychiatric admission: National Hospital Ambulatory Medical Care Survey analysis.
Routine medical clearance testing of emergency department (ED) patients with acute psychiatric illnesses in the absence of a medical indication has minimal proven utility. Little is known about the variations in clinical practice of ordering medical clearance tests. This study was an analysis of data from the annual United States National Hospital Ambulatory Medical Care Survey from 2010 to 2014. The study population was defined as ED visits by patients ≥18years old admitted to a psychiatric facility. We sought to determine the percentage of these ED visits in which at least one medical clearance test was ordered. Using a multivariate logistic regression model, we also evaluated whether patient visit factors or regional variation was associated with use of medical clearance tests. A medical clearance test was ordered in 80.4% of ED visits ending with a psychiatric admission. Multivariate logistic regression demonstrated a statistically significant increased odds ratio (OR) of medical clearance testing based on age (OR 1.02, 95%CI 1.01, 1.03), among visits involving an injury or poisoning (OR 2.38, 95%CI 1.54, 3.68), and in the Midwest region as compared to the Northeast region (OR 2.2, 95% confidence interval [CI] 1.09, 4.46), after adjusting for other predictors. Our study demonstrated that, on a national level, 4 out of 5 ED visits resulting in a psychiatric facility admission had a medical clearance test ordered. Future research is needed to investigate the reasons underlying the discrepancies in ordering patterns across the U.S., including the effect of local psychiatric admission policies.


Differential 5S RNA gene expression in vitro.
In extracts derived from activated eggs of Xenopus, oocyte 5S RNA gene transcription complexes are destabilized under conditions where somatic 5S RNA gene transcription complexes are stable. Trans-acting factors in destabilized complexes are in equilibrium with free factors in the extract, and thus transcription becomes dependent upon the concentration of the limiting factor in the extract. By reducing TFIIIA, a limiting factor in the egg extract, a cloned somatic 5S RNA gene is transcribed as much as 400-fold more efficiently than a cloned oocyte 5S RNA gene.


Evidence of charge susceptibility and multiplef-chybridization configurations with the La doping in CeGe: a DFT + DMFT study.
Kondo coupling has been extensively investigated in several Ce-based systems. However, the search for materials showing the interplay between the Kondo effect, spin-orbit interaction, and crystal-field effect along with the presence of local charge susceptibility; remains a challenge for the condensed matter community. Actually, in Ce-based systems, the strong coupling of the conduction electrons to the local magnetic moments usually hides these properties. Here, we present a detailed investigation of Ce0.6La0.4Ge through a combined density functional theory and dynamic mean-field theory study. Our investigations give evidence of the significant charge susceptibility and the multiple differentf-chybridization configurations. The weakening of the magnetization owing to the dilution of the Ce-site is the main cause for the appearance of such properties, which is believed to occur due to the presence of the relevant local moment andf-chybridization over the competition with the on-site Coulomb interaction.


[Endovascular treatment of stenosis of the renal artery in transplanted kidney].
The incidence of renal artery stenosis in the transplanted kidney (TRAS) varies between 2 and 23%, being the most frequent vascular complication following renal trasplantation. The delay in diagnosis and treatment can lead to functional graft loss. Percutaneous trasluminal angioplasty with stent (PTAS) is the treatment of choice to restore kidney perfusion. Retrospective review of renal transplant casuistic in our institution between September 2005 and August 2009. Were included patients with greater than 70% TRAS and impaired graft function, treated with PTAS. Follow-up at 3, 12 and 36 months was done with creatinine, glomerular filtration rate (GFR) and Doppler ultrasonography (DUS). Technical success was defined as correct stent placement associated with decreased flow, and clinical success as improve renal function during follow-up. Incidence of TRAS was 7.3% (22/298), 60% PTAS subsidiary. 100% technical success and 84.6% clinical success, 15.4% without changes in renal function. 84% decreases flow rate greater than 70% by DUS, and 26% up to 60%. Wave changes from type III to type II were recorded in 69% and to type I in 33%. The PTAS is a safe and effective procedure for the treatment of selected TRAS patients, as it preserves vascular permeability in short and medium term, ensuring the functionality of the graft. DUS is the method of choice for diagnosis and monitoring TRAS.


Acute titanium dioxide nanoparticles exposure impaired spatial cognitive performance through neurotoxic and oxidative mechanisms in Wistar rats.
Titanium dioxide nanoparticles (TiO2-NPs) are used in many commercial products. However, their effects on human and animal organism remained to be clarified. The present study aimed to investigate the effects of TiO2-NPs on the behavioural performance, monoamine neurotransmitters and oxidative stress in the rat brain. Rats were injected intravenously with a single dose of TiO2-NPs (20 mg/kg body weight) and were subjected to cognitive and emotional tests using Morris water maze and elevated plus maze. Cognitive capacity as well as the emotional reactivity were significantly disrupted, in TiO2-NPs-administered rats compared to control group. These behavioural effects were correlated with changes in brain neurotransmitter contents reflected by a significant increase in dopamine and a decrease in serotonin levels. TiO2-NPs also induced oxidative stress in the brain manifested by increased levels of H2O2 and malondialdehyde, associated with antioxidant enzymes activities disturbance, in particular, superoxide dismutase and catalase activities. Moreover, TiO2-NPs administration caused histological damages in the brain tissue with abundant lymphocytic clusters, capillary dilations, vascular congestion and oedema. Acute intravenous injection of TiO2-NPs impaired behaviour performances through brain biochemical and structural changes and precautions should be taken to their usage in food additive and medical applications.


Perioperative immunonutrition in normo-nourished patients undergoing laparoscopic colorectal resection.
To determine whether the joint implementation of immunonutrition and a laparoscopic approach improves morbidity, mortality, and length of stay (LOS) compared with dietary advice. Despite progress in recent years in the surgical management of patients with colorectal cancer, postoperative complications are frequent. Nutritional supplements enriched with immunonutrients have recently been introduced into clinical practice. However, the immunonutrition benefits in patients undergoing colorectal laparoscopic surgery are unknown. This study was a prospective, randomized trial with two parallel treatment groups receiving an immune-enhancing dietary supplement for 7 days before colorectal resection and 5 days postoperatively or dietary advice. A total of 128 patients were randomized. At baseline, both groups were comparable with respect to age, sex, surgical risk, comorbidities, and analytical and nutritional parameters. The median postoperative LOS was 5 days and was not significantly different between the groups. Wound infection differed significantly between the groups (11.50 vs. 0.00 %, p = 0.006). No other differences between the groups were identified. The joint use of laparoscopy and supplementation with immunonutrients reduces surgical wound infection in patients undergoing colorectal surgery. This study is registered with ClinicalTrial.gov : NCT0239396.


Application of conventional and FPG staining for the analysis of chromosome aberrations induced by low levels of dose in human lymphocytes.
Human peripheral lymphocytes were irradiated with 0.05-0.5 Gy of 220 keV X-rays. After application of either a conventional or the fluorescence plus Giemsa (FPG) staining technique, the dose response for dicentrics and acentrics was studied. The analysis of exclusively first-division cells (M1), carried out by the FPG method, revealed significantly higher aberration yields as compared with the results of the conventional method. The data from M1 cells support the assumption of a linear dose response for both dicentrics and acentrics. The results are discussed with regard to the application of chromosome analyses for a cytogenetic dosimetry after exposure to low levels of ionizing radiation.


The Role of Aspirin After High-Risk Percutaneous Coronary Intervention: The Ticagrelor with Aspirin or Alone in High-Risk Patients After Coronary Intervention Clinical Trial Experience.
Traditionally, aspirin has played a significant role in both primary and secondary prevention of cardiovascular disease. However, emerging antithrombotic regimens with better efficacy and safety have challenged the foundation of aspirin. Aspirin-free strategies consisting of P2Y12 inhibitor monotherapy following percutaneous coronary intervention (PCI) have now been tested in several large randomized controlled trials. In this article, we provide a contemporary overview of these data and suggest an algorithm to inform clinical decision with respect to antiplatelet pharmacotherapy after PCI.


Gaze-contingent display technology can help to reduce the ipsilesional attention bias in hemispatial neglect following stroke.
Hemispatial neglect results from unilateral brain damage and represents a disabling unawareness for objects in the hemispace opposite the brain lesion (contralesional). The patients' attentional bias for ipsilesional hemispace represents a hallmark of neglect, which results from an imbalanced attentional priority map in the brain. The aim of this study was to investigate whether gaze-contingent display (GCD) technology, reducing the visual salience of objects in ipsilesional hemispace, is able to rebalance this map and increase awareness and exploration of objects in the neglected contralesional hemispace. Using remote eye-tracking, we recorded gaze positions in 19 patients with left hemispatial neglect following right-hemisphere stroke and 22 healthy control subjects, while they were watching static naturalistic scenes. There were two task conditions, free viewing (FV) or goal-directed visual search (VS), and four modification conditions including the unmodified original picture, a purely static modification and two differently strong modifications with an additional gaze-contingent mask (GC-LOW, GC-HIGH), that continuously reduced color saturation and contrast of objects in the right hemispace. The patients' median gaze position (Center of Fixation) in the original pictures was markedly deviated to the right in both tasks (FV: 6.8° ± 0.8; VS: 5.5° ± 0.7), reflecting the neglect-typical ipsilesional attention bias. GC modification significantly reduced this bias in FV (GC-HIGH: d = - 3.2 ± 0.4°; p < 0.001). Furthermore, in FV and VS, GC modification increased the likelihood to start visual exploration in the (neglected) left hemifield by about 20%. This alleviation of the ipsilesional fixation bias was not associated with an improvement in detecting left-side targets, in contrast, the GC mask even decreased and slowed the detection of right-side targets. Subjectively, patients found the intervention pleasant and most of the patients did not notice any modification. GCD technology can be used to positively influence visual exploration patterns in patients with hemispatial neglect. Despite an alleviation of the neglect-related ipsilesional fixation bias, a concomitant functional benefit (improved detection of contralesional targets) was not achieved. Future studies may investigate individualized GCD-based modifications as augmented reality applications during the activities of daily living.


Clinical and Ultrasonographic Characterization of Hidradenitis Suppurativa in Female Patients: Impact of Early Recognition of the Disease.
Hidradenitis suppurativa (HS) is considered a post-pubertal disease; however, earlier onset is not infrequent. The burden of HS on the female population is very relevant, and early identification might reduce the quality of life impairment and improve the therapeutic approach. In this study, we investigated clinical biomarkers of HS that could impact the management of patients affected by HS. Female patients affected by stable HS were prospectively included in this study. Anamnestic data, clinical and ultrasonographic features were collected and analyzed. Overall, 53 patients were included in this study. The median age of onset was 19 (IQR: 14-25). Early onset was reported by 22/53 patients (median age of onset: 14; IQR: 11-16). Four patients had pre-menstruation occurrence. Early-onset patients had an earlier first-menstrual-cycle age and more frequent genital localization of HS, and were more often treated with biologics. Patients with early-onset-HS and genital localization had more severe disease with a higher number of areas affected, Hurley, and IHS4 scores. Genital involvement might be prevalent in patients with early-onset HS, leading to a worse impact on the global severity of the disease and tailored treatment protocols, including multidisciplinary approaches, in order to improve the early recognition of hidden lesions.


Effect of coronary dominance on 2-year outcomes after percutaneous coronary intervention in patients with acute coronary syndrome.
This retrospective, single-center, observational analysis from prospectively collected database evaluated whether left dominance affected the long-term outcomes of acute coronary syndrome patients undergoing percutaneous coronary intervention, and whether the effect was independent of SYNTAX score. Left dominance is believed to be associated with worse prognoses. The anatomical SYNTAX score is a scoring system based on the complexity and severity of coronary lesions and is thought to be a prognostic tool to predict short- and long-term outcomes. There are few studies about whether the effect of left dominance is independent of SYNTAX score. Between January 2013 and December 2013, 6255 consecutive acute coronary syndrome patients who were admitted to Fuwai hospital and underwent percutaneous coronary intervention (PCI) were enrolled in this study. Based on coronary dominance and the calculation methods of the SYNTAX score, patients were divided into a left-dominant group (LD group; 390 patients) and a right-dominant or co-dominant group (RD + Co group, 5865 patients). The 2-year mortality rate was significantly higher in the LD group than in the RD + Co group (2.58% vs. 1.23%, P = 0.024). In multivariate Cox analysis, the independent predictors of mortality were coronary dominance, IABP support, age, baseline SYNTAX score, and ejection fraction. LD was an independent predictor of long-term mortality in ACS patients undergoing PCI. The effect of LD still existed after adjustment for several important variables and was independent of SYNTAX score. © 2017 Wiley Periodicals, Inc.


First evidences of interaction between pyranoanthocyanins and salivary proline-rich proteins.
The contribution of other classes of polyphenol compounds besides tannins to the overall perception of astringency is still poorly understood. So, this work aimed to study the interaction between a family of salivary proline-rich proteins (aPRPs) and representative pyranoanthocyanins in red wines [pyranomalvidin-3-glucoside (vitisin B), pyranomalvidin-3-glucoside-catechol, and pyranomalvidin-3-glucoside-epicatechin] using saturation transfer difference-NMR and MALDI-TOF. For vitisin B KD was of 1.74mM; for pyranomalvidin-3-glucoside-catechol was 1.17mM and for pyranomalvidin-3-glucoside-epicatechin it was 0.87mM. The presence of the flavanol structural unit in the pyranoanthocyanins led to an increase in their interaction with aPRPs. Further, it is also interesting that the values obtained were in the range of KD obtained previously reported for the interaction between the human saliva proline-rich peptides (IB714 and IB937) and procyanidins. Overall, the results obtained suggest that, along with tannins, other polyphenols present in red wine, namely pyranoanthocyanins, could actively contribute to red wine global astringency.


Relationship between long working hours and depression in two working populations: a structural equation model approach.
To test the hypothesis that relationship reported between long working hours and depression was inconsistent in previous studies because job demand was treated as a confounder. Structural equation modeling was used to construct five models, using work-related factors and depressive mood scale obtained from 218 clerical workers, to test for goodness of fit and was externally validated with data obtained from 1160 sales workers. Multiple logistic regression analysis was also performed. The model that showed that long working hours increased depression risk when job demand was regarded as an intermediate variable was the best fitted model (goodness-of-fit index/root-mean-square error of approximation: 0.981 to 0.996/0.042 to 0.044). The odds ratio for depression risk with work that was high demand and 60 hours or more per week was estimated at 2 to 4 versus work that was low demand and less than 60 hours per week. Long working hours increased depression risk, with job demand being an intermediate variable.


Effects of stent structure on stent flexibility measurements.
Adequate delivery and placement of intracoronary artery stents is dependent on various properties of the stent itself, including flexibility and high-radial strength. Although these properties can be assessed via determination of the bending stiffness and radial stiffness of a stent, the mesh structure of the stent does not lend easily to such measurements. The goal of the present study was to determine an optimal method for determining stent bending stiffness. The four-points bending test was used to evaluate stent flexibility, and the finite element method (FEM) was employed to assess the effect of stent structure on flexibility in stents with differing link structures. The four-points bending test yielded the following bending stiffness values: 85.28 N mm2 for the stent with an S-shaped link; 41.67 N mm2 for the stent with an N-shaped link; 78.79 N mm2 for the stent with a modified W-shaped link; and 188.67 N mm2 for the stent with a W-shaped link. The stent with the point symmetric link configuration (S-, N- and modified W-shaped link) had high flexibility. FEM analysis revealed that low flexibility resulted from interference between the struts at the compressive side. Further, the flexibility predicted from FEM analysis correlated with bending stiffness of the stents. We conclude that use of the four-points bending test yields information that is critical for the design of flexible stents.


Occurrence and spatial distribution of microplastics in the intertidal sediments along the Oman Sea.
Microplastics (MPs) have been found in marine systems more frequently. We aim to analyze the MPs abundances, distribution, and characteristics in the intertidal sediments along the Oman Sea. Samples were collected from 7 locations with three replicates. Density separation was used to extract MPs, which were then visually counted and categorized based on their size, shape, and color. MPs abundance ranged between 219.6 ± 38.3 particles.kg-1dw and 617.3 ± 99.9 particles.kg-1dw with a mean abundance of 315.4 ± 24.4 particles.kg-1 dw. Fragments and fibers were the dominant shapes. Red and blue colors were observed in 61.6 % of the collected MPs. In addition, 100-500 μm size range of MPs were more abundant. Micro-Raman spectroscopy analysis revealed polypropylene was the major polymer constituent. The present study revealed the widespread occurrence of MPs as anthropogenic pollutants throughout the Oman Sea and highlighted the urgent need for regulations and policies to reduce the entry of this material into marine environments.


Phenylalanine hydroxylase (PAH) plays a positive role during WSSV and Vibrio parahaemolyticus infection in Litopenaeus vannamei.
Phenylalanine hydroxylase (PAH) is involved in immune defence reactions by providing the starting material, tyrosine, to synthesise catecholamines and melanin. PAH is an important metabolic enzyme of aromatic amino acids and the rate-limiting enzyme in the hydroxylation of amino acid phenylalanine to tyrosine. In the present study, a PAH gene, LvPAH, was cloned and identified from Litopenaeus vannamei. The open reading frame (ORF) of LvPAH was 1383 bp, encoding a protein of 460 amino acids comprised of an ACT domain and a Biopterin_H domain. LvPAH was constitutively expressed in healthy L. vannamei, with the highest expression levels in the eyestalk and the lowest in the hepatopancreas. Both white spot syndrome virus (WSSV) and Vibrio parahaemolyticus infection upregulated LvPAH expression in hemocytes, hepatopancreas and gills of L. vannamei. Inhibition of LvPAH resulted in a significantly lower survival rate of L. vannamei after WSSV infection than the control group, consistent with the observation that WSSV viral load was significantly higher in LvPAH-silenced L. vannamei. After a V. parahaemolyticus challenge, there was no significant difference between the survival rate of LvPAH-silenced and the control L. vannamei. However, the load of V. parahaemolyticus in LvPAH-silenced L. vannamei was significantly higher than the control population for L. vannamei. The effect of LvPAH on L. vannamei from a neuroendocrinological perspective was assessed by measuring l-DOPA, dopamine (DA) and noradrenaline (NE) levels in the hemocytes after the knockdown of LvPAH. The results showed that phenoloxidase (PO), l-DOPA and DA levels in the hemolymph of LvPAH-silenced L. vannamei were significantly decreased starting from 24hpi. In contrast, the NE levels in the hemolymph of shrimp decreased significantly at first and then increased. The results suggest that LvPAH may play an important role in antiviral and bacterial immunity in L. vannamei.


Genetic testing in domestic cats.
Varieties of genetic tests are currently available for the domestic cat that support veterinary health care, breed management, species identification, and forensic investigations. Approximately thirty-five genes contain over fifty mutations that cause feline health problems or alterations in the cat's appearance. Specific genes, such as sweet and drug receptors, have been knocked-out of Felidae during evolution and can be used along with mtDNA markers for species identification. Both STR and SNP panels differentiate cat race, breed, and individual identity, as well as gender-specific markers to determine sex of an individual. Cat genetic tests are common offerings for commercial laboratories, allowing both the veterinary clinician and the private owner to obtain DNA test results. This article will review the genetic tests for the domestic cat, and their various applications in different fields of science. Highlighted are genetic tests specific to the individual cat, which are a part of the cat's genome.


Rapid prenatal diagnosis of aneuploidies and zygosity in multiple pregnancies by amniocentesis with single insertion of the needle and quantitative fluorescent PCR.
To investigate amniotic fluid (AF) samples retrieved in multiple pregnancies by single insertion of the needle, for rapid assessment of chromosome copy number, zygosity, and cross-contamination between fetuses, using Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR) amplification of highly polymorphic microsatellite markers. Fifty-two multiple pregnancies were selected (47 twins, 5 triplets) and 108 samples of amniotic fluid were sampled between 12 to 20 weeks of gestation (mean 15.5) using the single-needle technique. Aneuploidy screening by QF-PCR amplification of short tandem repeats (STRs) on chromosomes X, Y, 21, 13, and 18 was carried out within 24 h of collection. Owing to the sampling procedure, the eventual presence of contamination between fetuses was also evaluated in every case. Normal and aneuploid fetuses were readily identified by QF-PCR. Fetal reduction was made available, for trisomic fetuses, without further waiting for completion of fetal karyotyping. In twin gestations, the ultrasound examination of chorionicity was always in agreement with the molecular assessment of zygosity. Contamination between fetuses due to the sampling procedure with a single puncture was never observed. Rapid prenatal diagnosis of aneuploidies by QF-PCR is a sensitive, efficient, and reliable assay. When applied in multiple pregnancies, it has the added value of allowing the assessment of zygosity in all cases, independently of chorionicity and fetal sex.


Synthesis and antibacterial activity of littorachalcone and related diphenyl ethers.
Littorachalcone (1) and diacid 10 were synthesized by direct routes. The antibacterial activity of 1, 10 and synthetic precursors were evaluated. Dialdehyde 3a showed potent antibacterial activity.


Design and synthesis of photoactivatable aryl diketo acid-containing HIV-1 integrase inhibitors as potential affinity probes.
Aryl diketo acids (ADKs) represent an important new class of HIV-1 integrase (IN) inhibitors. In order to facilitate examination of the structural basis underlying IN?ADK interaction, biphenyl ketone and phenyl azide photophores were incorporated into ADK structures. Of particular note is the novel dual utilization of azide and phenyketone moieties for both enzyme recognition and for crosslinking. The resulting analogues maintained low micromolar inhibitory potency against IN in recombinant in vitro assays. These potential HIV-1 integrase photoaffinity labels may provide useful tools for studying enzyme interactions of the ADK inhibitor class.


Long-term effects of pioglitazone and metformin on insulin sensitivity in patients with Type 2 diabetes mellitus.
Despite their comparable glycaemic effects in patients with Type 2 diabetes mellitus (T2DM), pioglitazone and metformin may have different effects on insulin sensitivity because they have different mechanisms of action. We studied the changes in insulin sensitivity, as assessed by the Quantitative Insulin Sensitivity Check Index (QUICKI), in patients with T2DM who used metformin or pioglitazone as monotherapy or in combination therapy with sulphonylurea. Data in this report are from two multicentre, randomized, double-blind, double-dummy studies conducted in Europe (monotherapy) or in Europe and Canada (combination therapy study). Patients were randomized to 52 weeks of treatment consisting of a 12-week forced titration period and a 40-week maintenance period. HbA(1c), fasting plasma glucose (FPG) and fasting serum insulin (FSI) were quantified from a single blood sample at weeks 0, 8, 16, 24, 32, 42 and 52. Insulin sensitivity was assessed with QUICKI, which is calculated from FSI and fasting blood glucose (FBG) concentrations using the formula 1/(log(10) FSI + log(10) FBG). Time course effects of the treatments were compared by repeated measures analysis of covariance. As monotherapy, pioglitazone and metformin increased QUICKI compared with baseline (baseline vs. end point [mean +/- sem]; pioglitazone [0.303 +/- 0.001 vs. 0.321 +/- 0.001; P < 0.001] and metformin [0.304 +/- 0.001 vs. 0.315 +/- 0.001; P < 0.001]). Pioglitazone increased insulin sensitivity more than metformin from week 4 through week 52. There were significant increases in QUICKI from baseline in both combination therapy groups (baseline vs. end point; pioglitazone + sulphonylurea [0.305 +/- 0.001 vs. 0.319 +/- 0.001; P < 0.001] and metformin + sulphonylurea [0.306 +/- 0.001 vs. 0.317 +/- 0.001; P < 0.001]). Overall, pioglitazone + sulphonylurea significantly increased insulin sensitivity more than metformin + sulphonylurea. Pioglitazone differed from metformin in its effects on insulin sensitivity despite both drugs having comparable glycaemic effects.


Prefabrication and free transfer of a tissue engineered composite flap - An experimental model in the rat.
The technique of flap-prefabrication has been successfully established in tissue engineering: missing intrinsic vascularisation of engineered tissue can be generated in vivo by microsurgical vesselloop construction. It is possible to move engineered tissue into a defect with microsurgery. In the literature, the combination of engineered tissue covered with skin is not widely reported. Aim of this study was to establish a model to investigate scaffold prefabrication with full thickness skin graft coverage with subsequent free tissue transfer. 8 Wistar rats were operated in 2 separate steps: 1) after creating an arteriovenous loop with the femoral vessels, a porous scaffold was placed on the loop and covered with an inguinally based skin flap. A control was implanted without loop into the contralateral groin. 2) 6 weeks later the prefabricated composite flaps were microsurgically transferred to the cervical region. Skin-island monitoring was performed with Laser Doppler-scanner after the transfer. Continuous loss of the skin islands was observed within 72 hours. Complications included wound-dehiscence, thrombosis and death from anaesthesia; in spite of consistent loop viability. Evaluation showed that modifications are necessary to maintain the skin-island cove.


The use of low-energy laser (LEL) for the prevention of chemotherapy- and/or radiotherapy-induced oral mucositis in cancer patients: results from two prospective studies.
Low-energy laser (LEL) treatment has been suggested as an effective and safe method to prevent and/or treat oral mucositis induced by chemotherapy and/or radiotherapy; however, it has not gained wide acceptance so far. We conducted two clinical trials testing the LEL technique: firstly, as a secondary prevention in patients with various solid tumors treated with chemotherapy who all developed severe mucositis after a previous identical chemotherapy and, secondly, as therapeutic intervention (compared to sham illumination in a randomized way) in patients with hematological tumors receiving intensive chemotherapy and having developed low-grade oral mucositis. We entered 26 eligible patients in the first study and 36 were randomized in the second study. The success rate was 81% (95%CI = 61-93%) when LEL was given as a preventive treatment. In the second study, in patients with existing lesions, the therapeutic success rate was 83% (95%CI = 59-96%), which was significantly different from the success rate reached in the sham-treated patients (11%; 95%CI = 1-35%); the time to development of grade 3 mucositis was also significantly shorter in the sham-treated patients (p < 0.001). Our results strongly support the already available literature, suggesting that LEL is an effective and safe approach to prevent or treat oral mucositis resulting from cancer chemotherapy.


Mechanosensitive brain tumor cells construct blood-tumor barrier to mask chemosensitivity.
Major obstacles in brain cancer treatment include the blood-tumor barrier (BTB), which limits the access of most therapeutic agents, and quiescent tumor cells, which resist conventional chemotherapy. Here, we show that Sox2+ tumor cells project cellular processes to ensheathe capillaries in mouse medulloblastoma (MB), a process that depends on the mechanosensitive ion channel Piezo2. MB develops a tissue stiffness gradient as a function of distance to capillaries. Sox2+ tumor cells perceive substrate stiffness to sustain local intracellular calcium, actomyosin tension, and adhesion to promote cellular process growth and cell surface sequestration of β-catenin. Piezo2 knockout reverses WNT/β-catenin signaling states between Sox2+ tumor cells and endothelial cells, compromises the BTB, reduces the quiescence of Sox2+ tumor cells, and markedly enhances the MB response to chemotherapy. Our study reveals that mechanosensitive tumor cells construct the BTB to mask tumor chemosensitivity. Targeting Piezo2 addresses the BTB and tumor quiescence properties that underlie treatment failures in brain cancer.


Expression of tenascin-C in intraductal carcinoma of human breast: relationship to invasion.
Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that appears in areas of epithelial-mesenchymal interaction during fetal development and in neoplasia. The immunohistochemical expression of Tn-C and its relationship to histology, nuclear grade, microinvasion, oestrogen (ER) and progesterone receptors (PR), and to cell proliferation measured by Ki-67 expression were studied in 89 intraductal breast carcinomas (DCIS). Periductal Tn-C was noted in 87% and stromal Tn-C in 25% of the tumours. Stromal expression was associated with moderate to strong periductal expression and microinvasion. Periductal expression was associated with comedo-type, nuclear grade, microinvasion, Ki-67 expression, and lack of PR. The distribution of Tn-C was compared in DCIS and in the intraductal component from another series of small axillary node-negative invasive breast carcinomas (n = 44). Tn-C was present in the stroma of pure DCIS in 25% and in the intraductal component of the other series in 82%. Thus, stromal or moderate to strong periductal Tn-C expression in DCIS may relate to early invasion. DCIS with weak periductal or missing Tn-C expression may be a subgroup with benign behaviour.


Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing.
BCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this. The present study aims to present an in-depth analysis of resistant mechanisms and to explore potential novel therapeutic targets for relapse of BCMA CAR-T treatment via single-cell RNA sequencing (scRNA-seq) of BM plasma cells and immune cells. This study used 10X Genomic scRNA-seq to identify cell populations in R/R-MM CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. Cell Ranger pipeline and CellChat were used to perform detailed analysis. We compared the heterogeneity of CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We found that the proportion of monocytes/macrophages increased, while the percentage of T cells decreased at relapse after BCMA CAR-T treatment. We then reclustered and analyzed the alterations in plasma cells, T cells, NK cells, DCs, neutrophils, and monocytes/macrophages in the BM microenvironment before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We show here that the percentage of BCMA positive plasma cells increased at relapse after BCMA CAR-T cell therapy. Other targets such as CD38, CD24, SLAMF7, CD138, and GPRC5D were also found to be expressed in plasma cells of the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Furthermore, exhausted T cells, TIGIT+NK cells, interferon-responsive DCs, and interferon-responsive neutrophils, increased in the R/R-MM patient at relapse after BCMA CAR-T cell treatment. Significantly, the proportion of IL1βhi Mφ, S100A9hi Mφ, interferon-responsive Mφ, CD16hi Mφ, MARCO hi Mφ, and S100A11hi Mφ significantly increased in the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Cell-cell communication analysis indicated that monocytes/macrophages, especially the MIF and APRIL signaling pathway are key players in R/R-MM patient at relapse after BCMA CAR-T cell therapy. Taken together, our data extend the understanding of intrinsic and extrinsic relapse of BCMA CAR-T treatment in R/R-MM patient and the potential mechanisms involved in the alterations of antigens and the induced immunosuppressive microenvironment, which may provide a basis for the optimization of BCMA CAR-T strategies. Further studies should be performed to confirm these findings.


Computed tomography of acoustic neuromas with emphasis on small tumor detectability.
The results of CT analysis of 41 acoustic neuromas are presented. Large and medium-sized tumors are easily detected: our results are comparable to the reported findings of other authors. The detectability of small acoustic neuromas is considerably improved by the application of newer-generation CT apparatus and the use of specific scanning parameters, including extremely thin overlapping slices, low scan speed, high gantry tilt, short time between contrast agent application and tumor scanning, and computer-assisted magnification of the posterior fossa.


CL4-modified exosomes deliver lncRNA DARS-AS1 siRNA to suppress triple-negative breast cancer progression and attenuate doxorubicin resistance by inhibiting autophagy.
Triple-negative breast cancer (TNBC) is a fatal disease. Drug resistance and the lack of effective drugs are the leading causes of death in patients with TNBC. Recently, long non-coding RNAs have been proven to be effective drug design targets owing to their high tissue specificity; however, an effective drug delivery system is necessary for their clinical application. In this study, we constructed a novel nanodrug delivery system based on the epidermal growth factor receptor (EGFR)-targeted aptamer CL4-modified exosomes (EXOs-CL4) for the targeted delivery of aspartyl-tRNA synthetase-antisense RNA 1 (DARS-AS1) small interfering RNA (siRNA) and doxorubicin (DOX) to TNBC cells in vitro and in vivo. This delivery system exerted potent anti-proliferation, anti-migration, and pro-apoptotic effects on TNBC cells. Silencing DARS-AS1 increased the sensitivity of TNBC cells to DOX by suppressing the transforming growth factor-β (TGF-β)/Smad3 signaling pathway-induced autophagy, thereby enhancing the synergetic antitumor effects. Collectively, our findings revealed that EXOs-CL4-mediated delivery of DARS-AS1 siRNA can be used as a new treatment strategy for DOX-resistant TNBC. Moreover, EXOs-CL4 can be used as effective drug delivery systems for targeted TNBC therapy.


[Spargelstangenuntersuchungen zur Haupterntezeit auf Infektionen mitFusarium spp. und Kontaminationen mit Fumonisin B1 Investigation on asparagus spears during the main harvest byFusarium spp.- infections and contamination by Fumonisin B1].
Asparagus spears collected from a total of six commercial plantings in Austria during the main harvest periods in May and June of 2003 and 2004 were examined for endophytic colonization byFusarium spp., particularlyF. proliferatum. Potentially toxigenic fungi such asF. proliferatum were isolated and identified by morphological characteristics using light microscopy. Fumonisin B1 inF. proliferatum-infected asparagus spears was detected with IAS-HPLC-FLD or HPLC-MS/MS. The identity of endophytic fungi colonizing of a total of 816 individual spears was determined. The incidence of infection byF. proliferatum and otherFusarium spp. was highly dependent on location and sampling date. The dominantFusarium species among the endophytic microflora wasF. oxysporum. Other frequently isolated species includedF. proliferatum, F. sambucinum, F. culmorum, F. avenaceum andF. equiseti. The incidence ofF. proliferatum-infected asparagus spears was less than 10% at four of the six sampling locations. At the two remaining locations, 20-47% of the spears examined were infected withF. proliferatum. Further exploration of FB1 generation in asparagus is required because the low levels of FB1 (10-50 (μg/kg) detected in harvested spears in 2003 and 2004 cannot be explained by the results of this study.


Proteolysis-mediated protection of gold nanoparticles for sensitive activity assay of peptidases.
Rapid, sensitive and quantitative assays for peptide hydrolysis enzymes are of paramount importance for drug development and in the diagnosis of disease. Here, we proposed a novel biosensor for sensitive and selective active screening of peptidases. This strategy relies on the proteolysis-mediated protection of gold nanoparticles (AuNPs) that were decorated with biotin-labeled substrate peptides and can be aggregated by streptavidin. Enzyme-mediated protection of AuNPs offers this strategy high specificity, and the use of AuNPs additionally allows a visual and homogeneous assay format, thus permitting improved simplicity and throughput of the assays. As a model case, desirable selectivity and sensitivity in peptidase assay were achieved in the active assays of pancreatic elastase with a wide linear response range from 0.005 to 0.10 U/mL and a detection limit of 0.003 U/mL. The results indicated that this strategy can offer a simple, robust and convenient platform for visualized peptidase activity analysis and related biochemical studies with high sensitivity and selectivity.


Beliefs and expectations of patients with fibromyalgia about telerehabilitation during Covid-19 pandemic: A qualitative study.
Telerehabilitation as an alternative to physiotherapeutic care has been increasingly implemented in diverse populations. However, this mode of service can evoke beliefs and expectations in patients with fibromyalgia, depending on sociocultural and clinical context, that can cause poor adaptation and dropout from treatment. To explore beliefs and expectations of individuals with fibromyalgia about physical exercises delivered through telerehabilitation. Thirty individual semi-structured interviews were conducted via videoconference with women with fibromyalgia recruited during COVID-19 pandemic through intentional sampling. These interviews were guided by four questions addressing the beliefs and expectations about telerehabilitation. The interviews were recorded after consent and transcribed using the MAXQDA® software. The inductive approach was performed in which raw data were coded into categories and subcategories. Participants expect to benefit from telerehabilitation due to flexible hours, no need of travel, socialization, and lower risk of contamination. However, they believe they have difficulties related to the physical absence of the therapist, complexity of the exercises, internet connection problems, adaptation to the domestic routine and availability of schedules. Women with fibromyalgia showed positive expectations about telerehabilitation, relating better socialization with other individuals diagnosed with fibromyalgia, home care with flexible schedule and, to provide needed service to underserved. However, they listed barriers such as the physical absence of the therapist and instability of the internet connection and, the FM symptoms themselves.


Elastin and collagen enhances electrospun aligned polyurethane as scaffolds for vascular graft.
Mismatch in mechanical properties between synthetic vascular graft and arteries contribute to graft failure. The viscoelastic properties of arteries are conferred by elastin and collagen. In this study, the mechanical properties and cellular interactions of aligned nanofibrous polyurethane (PU) scaffolds blended with elastin, collagen or a mixture of both proteins were examined. Elastin softened PU to a peak stress and strain of 7.86 MPa and 112.28 % respectively, which are similar to those observed in blood vessels. Collagen-blended PU increased in peak stress to 28.14 MPa. The growth of smooth muscle cells (SMCs) on both collagen-blended and elastin/collagen-blended scaffold increased by 283 and 224 % respectively when compared to PU. Smooth muscle myosin staining indicated that the cells are contractile SMCs which are favored in vascular tissue engineering. Elastin and collagen are beneficial for creating compliant synthetic vascular grafts as elastin provided the necessary viscoelastic properties while collagen enhanced the cellular interactions.


In situ growth of carbon nanotubes on Ni/MgO: a facile preparation of efficient catalysts for the production of synthetic natural gas from syngas.
Ni/MgO-CNTs catalysts are prepared by in situ chemical vapor deposition growth of CNTs on Ni/MgO. These catalysts exhibit an improved performance for the production of synthetic natural gas from syngas, which is attributed to the formation of highly catalytic active interfaces among Ni, CNTs and MgO.


Comparison of computed tomography and conventional transverse axial tomography in radiotherapy treatment planning.
Treatment plans can differ widely depending on whether they were developed from anatomical information generated by computed tomography or conventional transverse axial tomography. In the present study, deviations between tumor doses calculated using the two methods were as great as 10%, increasing to 20% for the spinal cord.


Epidemiology of aging and associated cognitive disorders: Prevalence and incidence of Alzheimer's disease and other dementias.
The study of the incidence and prevalence of dementia is important to understand the distribution of dementing illness among age and sex groups, and for the detection of possible causes of these disorders. A variation in the incidence or prevalence of dementia, especially Alzheimer's disease (AD) by region or specific populations can be because of greater or lesser exposure to the causal agents of dementia. For example, in the past the striking differences in the incidence of coronary heart disease (CHD) led to the understanding of the relationship between dietary factors, such as saturated fat and dietary cholesterol, and the incidence of CHD. However, there is a high prevalence of dementia in elderly individuals around the world, and multiple studies conducted in industrialized and nonindustrialized countries have shown an age-standardized prevalence of dementia ranging from 5% to 7% in most countries. Dementia is not a specific disease but rather a constellation of cognitive changes and disability due to several "causes," i.e., AD, Lewy bodies, vascular disease, drugs, and alcohol. Whether there is a trend for reduced incidence of dementia has to be further evaluated. It is possible that the improvement in the treatments of risk factors, especially vascular disease, has resulted in decreased incidence. However, this could result in an increase in prevalence, since the improved therapies for risk factors will lead to increased longevity in patients with dementia.


Atrial natriuretic peptide attenuates kidney-lung crosstalk in kidney injury.
Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury after cardiovascular surgery, which in turn deteriorates oxygenation. Atrial natriuretic peptide (ANP) has natriuretic, diuretic, and anti-inflammatory effects. To elucidate whether renal IRI induces inflammation in the kidney and lung and ANP attenuates kidney-lung crosstalk. The rats were anesthetized, tracheostomized, mechanically ventilated, and randomized to four groups: saline + IRI (n = 12), ANP + IRI (n = 12), ANP + sham (n = 6), and saline + sham (n = 6). Saline (6 mL/kg/h) or ANP (0.2 μg/kg/min) at the rate of 6 mL/kg/h was started 5 min before clamping, respectively. Renal IRI was induced by clamping the left renal pedicle for 30 min. The hemodynamics, arterial blood gases, and plasma concentrations of creatinine and lactate were measured at baseline and 1, 2, and 3 h after declamping. Lung wet-to-dry ratio was measured. The mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL) 1β, and IL-6 and histologic localization of TNF-α in the kidney and lung were measured. Renal IRI induced metabolic acidosis, pulmonary edema, increases in plasma concentrations of creatinine and lactate, and augmentation of the cytokine mRNA expression and histologic localization of TNF-α in the kidney and Renal IRI induced lung. ANP prevented IRI-induced metabolic acidosis, pulmonary edema, increases in creatinine, lactate, and the cytokine mRNA expression, attenuated histologic localization of TNF-α in the kidney and lung, and increased oxygenation. ANP has renoprotective and anti-inflammatory effects on the kidney and lung in a rat model of renal IRI, suggesting that ANP attenuates kidney-lung crosstalk.


Auditory brainstem responses of children with developmental language disorders.
Brainstem auditory evoked potentials (BAEPs) were recorded from 48 children with language disorders (aged four to nine years old, IQs normal to borderline, normal audiometric thresholds and attending special school) and 20 healthy children (four to eight years old, with normal IQs, audiometry and school-level). The language-disabled group showed significantly lower absolute latency values of the BAEPs than controls. There were no significant differences in the central conduction time of the auditory pathway (I-V interval). Therefore, the only significant difference corresponded to a minor value for the first wave (auditory nerve discharge) of the BAEP. A reduction in the control mechanisms of the sensory inputs at the peripheral level, or a disturbance in the inhibitory mechanisms of cortico-subcortical modulation, might explain these findings.


The treatment of bilateral ulcerated lymph node metastases from carcinoma of the penis. A case report.
A 44-year-old patient with histologically proven bilateral ulcerated lymph node metastases from a carcinoma of the penis was treated by sequenced combined chemotherapy and radical irradiation. Methotrexate and bleomycin were administered at weekly intervals for 5 weeks, followed by radiation with a split-course coning-down technique. The patient remains well and clinically disease-free 63 months after commencing therapy.


Amphibian micronucleus test in vivo: evaluation of the genotoxicity of some major polycyclic aromatic hydrocarbons found in a crude oil.
The micronucleus test using erythrocytes of Pleurodeles waltl larvae (Amphibia, Salamandridae) was used to detect the possible genotoxicity of four polycyclic aromatic hydrocarbons (naphthalene, anthracene, phenanthrene and benzo[a]pyrene), which represent a major fraction of crude oil. Larvae were reared in water containing the test compound and the levels of micronucleated red blood cells were compared with those found in larvae reared in control water. The results are compared with published data from other tests used to evaluate the clastogenic or mutagenic properties of compounds. The results obtained confirm that benzo[a]pyrene has a strong genotoxic potential, whereas the genotoxicity of naphthalene is weak; in contrast, anthracene and phenanthrene gave a negative response.


Skin cancer: an overview of epidemiology and risk factors.
To provide a general overview of malignant melanoma and non-melanoma skin cancer, with an emphasis on epidemiology, clinical presentation, and the multiple and varied risk factors associated with skin cancer. Peer-reviewed journal articles, government health reports, book chapters, and Web-based resources. Skin cancer is the most common carcinoma, affecting millions worldwide. Incidence is increasing yearly, making it a pre-eminent public health threat. Myriad factors increase the risk of skin cancer and may serve as important prognostic indicators for the disease. To provide nurses with a clearer understanding of the causative mechanisms of skin cancer and an improved awareness of the risk factors associated with the disease.


IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer.
The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKKβ in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKKβ is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKKβ-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-κB signaling and reduced expression of important NF-κB target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKKβ in driving inflammation and enabling carcinogenesis in the intestine.


Alpha 1-adrenergic effects on intracellular pH and calcium and on myofilaments in single rat cardiac cells.
1. The cellular effects of alpha 1-adrenoceptor stimulation by phenylephrine were studied in the presence of propranolol in single cells isolated from the ventricles of rat hearts. 2. Phenylephrine (10-100 microM) induced a biphasic pattern of inotropism in these cells: a transient negative followed by a sustained positive inotropic effect as usually observed in cardiac tissues. 3. In Snarf-1-loaded cells, phenylephrine induced an alkalinization. This effect was reversible on wash-out and inhibited by prazosin, an alpha 1-adrenoceptor antagonist. 4. The alpha 1-adrenoceptor-mediated increase in intracellular pH (pHi) was 0.1 pH unit in HEPES buffer containing 4.4 mM-NaHCO3 and in Krebs buffer containing 25 mM-NaHCO3. 5. The alkalinization was blocked by the Na(+)-H+ antiport blocker, ethylisopropylamiloride (EIPA). 6. The recovery from an acidosis induced by a NH4Cl pre-pulse was accelerated by phenylephrine. The phenylephrine-induced alkalinization was attributed to activation of the Na(+)-H+ antiport. 7. Despite its ability to increase pHi, phenylephrine did not alter Ca2+ current amplitude and kinetics. 8. Ca2+ transients recorded in Indo-1-loaded cells were not augmented by phenylephrine. Diastolic calcium level was decreased. 9. In single skinned cells, the Ca2+ sensitivity of the contractile proteins was increased by a pre-treatment with phenylephrine even when the alpha 1-adrenoceptor-mediated alkalinizing effect had been prevented by EIPA. 10. These results lead us to propose that the alpha 1-adrenergic-induced positive inotropic response of heart muscle could result from an increased sensitivity of the myofilaments to Ca2+ ions. This alpha 1-adrenoceptor-mediated Ca2+ sensitization could result both from an intracellular alkalinization and from a direct effect on contractile proteins.


Acute respiratory distress syndrome due to COVID-19. Clinical and prognostic features from a medical Critical Care Unit in Valencia, Spain.
Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. 36-bed MCCU in referral tertiary hospital. SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. None MAIN VARIABLES OF INTEREST: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.


Pediatric nephrology workforce in Latin America.
Pediatric nephrology workforce issues were examined in a Latin American survey involving 14 countries. The number of children under 15 years per pediatric nephrologist varied widely among countries: Argentina, Cuba, Venezuela, and Uruguay had an unusually high number of pediatric nephrologists. Guatemala represents the opposite end of the spectrum of values (1,582.6 thousand children under 15 years per pediatric nephrologist). A significant inverse correlation was found between children under 15 years per pediatric nephrologist and national gross domestic product per capita (r=-0.52, P<0.05) and a significant correlation between children per pediatric nephrologist and infant mortality (r=0.82, P<0.005, Spearman's rank correlation coefficient). The same correlations were observed for total population per pediatric nephrologist. However, the pediatric nephrology workforce does not merely reflect national economic status. Official health care policies, market forces, and social regulations also have an influence. A study of the number of pediatric nephrologists necessary for adequate planning of care of children with renal disease in Latin America is urgently needed.


Mathematical analysis of multi-antibiotic resistance.
Multi-antibiotic resistance in bacterial infections is a growing threat to public health. Some experiments were carried out to study the multi-antibiotic resistance. The changes of the multi-antibiotic resistance with time were achieved by numerical simulations and the mathematical models, with the calculated temperature field, velocity field, and the antibiotic concentration field. The computed results and experimental results are compared. Both numerical simulations and the analytic models suggest that minor low concentrations of antibiotics could induce antibiotic resistance in bacteria.


Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria.
The increasing occurrence of multi-antibiotic resistant microbes has led to the search for alternative methods of killing pathogens and treating infections. Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill mammalian and microbial cells. Although the photodynamic inactivation of bacteria has been known for over a hundred years, its use to treat infections has not been much developed. This may be partly due to the difficulty of monitoring the effectiveness of PDT in animal models of infection. In order to facilitate this monitoring process, we have developed a procedure that uses bioluminescent genetically engineered bacteria and a light sensitive imaging system to allow real-time visualization of infections. When these bacteria are treated with PDT in vitro, the loss of luminescence parallels the loss of colony-forming ability. We have developed several models of infections in wounds and soft-tissue abscesses in mice that can be followed by bioluminescence imaging. The size and intensity of the infection can be sequentially monitored in a non-invasive fashion in individual mice in real-time. When photosensitizers are introduced into the infected tissue followed by illumination with red light, a light-dose dependent loss of luminescence is seen. If the bacterium is invasive, the loss of luminescence correlates with increased survival of the mice, whilst animals in control groups die of sepsis within five days. Healing of the PDT treated wounds is not impaired and may actually be improved. This approach can allow many animal models of localized infections to be accurately monitored for efficacy of treatment by PDT.


Fabrication strategies and biomedical applications of three-dimensional bacterial cellulose-based scaffolds: A review.
Bacterial cellulose (BC), an extracellular polysaccharide, is a versatile biopolymer due to its intrinsic physicochemical properties, broad-spectrum applications, and remarkable achievements in different fields, especially in the biomedical field. Presently, the focus of BC-related research is on the development of scaffolds containing other materials for in-vitro and in-vivo biomedical applications. To this end, prime research objectives concern the biocompatibility of BC and the development of three-dimensional (3D) BC-based scaffolds. This review summarizes the techniques used to develop 3D BC scaffolds and discusses their potential merits and limitations. In addition, we discuss the various biomedical applications of BC-based scaffolds for which the 3D BC matrix confers desired structural and conformational features. Overall, this review provides comprehensive coverage of the idea, requirements, synthetic strategies, and current and prospective applications of 3D BC scaffolds, and thus, should be useful for researchers working with polysaccharides, biopolymers, or composite materials.


[Results of treatment in a 6-month movement and sports therapy rehabilitation program of children with cerebral palsy].
The dynamic gait patterns in 9 children with cerebral palsy aged from 8 to 13 years was evaluated with a force plate before and after 6 months of movement- and sportstherapy. After the therapy clear modifications were found in timeparameters. The outstanding parameter was the vertical ground reaction force, which showed a positive increment in all important characteristics.


Neonatal transection of the corpus callosum affects paw preference lateralization of adult Swiss mice.
In the present work, the hypothesis that the ontogenetic development of the corpus callosum (CC) affects the establishment of behavioral lateralization was tested by studying paw preference performance in adult Swiss mice that were subjected to mid-sagittal transection of the CC on the first postnatal day. Magnitude and direction of laterality were evaluated independently. No significant differences between groups were found for the magnitude of paw preference. On the other hand, the transected group presented a significant populational bias favoring the left paw that was not present in the control groups. These results lend support to the hypothesis that the development of the CC plays a role in the establishment of the normal pattern of behavioral lateralization.


Differential expression of class II MHC antigens on cells derived from human tissue.
Human lymphomedullary tissue cells, separated on the basis of density, Fc and E receptors, show characteristic and consistent differences in their expression of class II MHC antigens. A low density, FcR-ve cell type displays high expression of HLA-DR and acts as the most efficient accessory cell in the induction of a Con A driven proliferative response. Exposure of cells to Con A inhibits subsequent binding of anti-HLA-DR antibodies. Addition of -methyl-D-mannoside reverses both the proliferative response to Con A and returns binding of anti-class II MHC antibodies to normal levels. This experimental system can be used to study: the nature of the association between cell bound molecules and class II MHC products, both spatially and functionally; and the relative functional importance of these products in antigen presentation.


Patients' preferences for headache acute and preventive treatment.
We aimed to explore patients' preferences for headache treatments with a self-administered questionnaire including the Q-No questionnaire for nocebo. Questionnaires from 514 outpatients naïve to neurostimulation and monoclonal antibodies were collected. Patients assessed that the efficacy of a treatment is more important than safety or route of administration. They preferred to use an external neurostimulation device for both acute (67.1%) and preventive treatment (62.8%). Most patients preferred to take a pill (86%) than any other drug given parenterally for symptomatic pharmaceutical treatment. For preventive pharmaceutical treatment, most patients preferred to take a pill once per day (52%) compared to an injection either subcutaneously or intravenously each month (9% and 4%), or three months (15% and 11%). 56.6% of all participants scored more than 15 in Q-No questionnaire indicating potential nocebo behaviors that contributed significantly in their choices. These patient preferences along with efficacy and safety data may help physicians better choose the right treatment for the right person.


Chemotherapy with estrogenic recruitment and surgery in locally advanced breast cancer: clinical and cytokinetic results.
Thirty-nine patients with locally advanced breast cancer (T3b-4, N1-3 or inflammatory carcinoma) received 3 cycles of induction chemotherapy with estrogenic recruitment before surgery. The therapeutic regimen consisted of diethylstilbestrol (DES) orally on days 1-3, 5-Fluorouracil + Doxorubicin + Cyclophosphamide on day 4 q 21 days (DES-FAC). After surgery 6 additional cycles of chemotherapy (3 DES-FAC alternating with 3 DES-CMF with Methotrexate + F and C as in FAC) were administered. The objective response rate was 71.8% with 15.4% CR, and 56.4% PR; after surgery 36/39 (92.3%) patients were rendered disease-free. So far, 13 of 26 patients in stage IIIb have relapsed (9 of 13 with inflammatory carcinomas). Three-year survival and progression-free survival are 60% and 53.5%, respectively. Twenty-three of the 39 patients were subjected to serial tumor biopsies during the first DES-FAC regimen to allow for tumor-cell kinetic studies during DES and chemotherapy. A significant estrogenic recruitment occurred in 16 patients (69.6%), irrespective of estrogen-receptor status. At surgery, 3-4 weeks after induction chemotherapy, tumor proliferative activity was significantly depressed in comparison to basal values. These results indicate that breast cancer cells can be recruited in vivo with DES and that chemotherapy following estrogenic stimulation is effective and feasible with acceptable toxicity.


Acutely administered antipsychotic drugs are highly selective for dopamine D2 over D3 receptors.
We showed previously, using [(3)H]-(+)-4-propyl-9-hydroxynaphthoxazine ([(3)H]-(+)-PHNO) autoradiography, that several antipsychotic drugs do not occupy dopamine D3 receptors at clinically-relevant doses in rat. This is an unexpected finding considering the near-equivalent in vitro affinity of these drugs for D2 and D3 receptors. The purpose of the current study was to address two possible methodological limitations of our previous report, namely that (1) [(3)H]-(+)-PHNO may have been administered at non-tracer dose, potentially causing underestimate of D3 receptor occupancy, and (2) antipsychotic drugs were administered chronically, potentially causing increased D3 receptor expression not accounted for in the vehicle-treated control group. We found that decreasing [(3)H]-(+)-PHNO dose from 5.6nmol/kg (our previous dose) to 0.6nmol/kg caused a >60% increase in [(3)H]-(+)-PHNO binding to D3 receptors in cerebellar lobes 9 and 10, indicating that our previous study was indeed conducted under non-tracer dose conditions. However, neither reducing [(3)H]-(+)-PHNO dose further to 0.3nmol/kg (a tracer dose), nor administering antipsychotics acutely affected antipsychotic receptor occupancy. At clinically-relevant levels of D2 occupancy (57-82% inhibition of striatal binding), neither olanzapine nor haloperidol occupied D3 receptors, while clozapine occupied D3 receptors at levels similar to our previous report (33%). Risperidone moderately occupied D3 receptors (40%), but at a dose occupying >90% of D2 receptors and therefore of questionable clinical relevance. These findings demonstrate that the lack of antipsychotic occupancy of D3 receptors is not attributable to limitations of our previous study. These results suggest that D3 receptor blockade is not necessary for the therapeutic effects of the antipsychotic drugs examined.