LHX2 Is a Potential Biomarker and Associated with Immune Infiltration in Breast Cancer.
Worldwide, breast cancer is the most common malignancy. LHX2, a member of the LIM homeobox gene family and a transcription factor, plays a crucial role in numerous tumors, but the function of LHX2 in breast cancer progression remains unknown. In this study, we show that LHX2 is upregulated in breast cancer tissues and positively correlated with breast cancer progression. Meanwhile, the clinical characteristics of breast cancer and LHX2 expression showed a strong correlation. GSEA showed that a high LHX2 expression may activate the T-cell activation pathway, PI3K/AKT/mTOR signaling pathway, and apoptosis pathway. Moreover, ssGSEA showed that Th1 cells and Th2 cells had a positive correlation with LHX2 expression in breast cancer. Experiments showed that LHX2 promotes the proliferation, colony formation, migration, and invasion of breast cancer cells. Immunohistochemistry and immunofluorescence assays helped to analyze LHX2-associated immune infiltration in breast cancer. A Western blot assay proved that LHX2 activated the PI3K/AKT/mTOR pathway and the apoptosis pathway. A TUNEL assay confirmed that LHX2 inhibited apoptosis. Taken together, LHX2 plays a vital role in breast cancer's progression and prognosis and could be an immune infiltration biomarker for breast cancer, and LHX2 activates the PI3K/AKT/mTOR pathway and apoptosis pathway in breast cancer.


Multiple helical configuration and quantity threshold of graphene nanoribbons inside a single-walled carbon nanotube.
Molecular dynamics simulation has been carried out to explore the configuration and quantity threshold of multiple graphene nanoribbons (GNRs) in single-walled carbon nanotube (SWCNT). The simulation results showed that several GNRs tangled together to form a perfect spiral structure to maximize the π-π stacking area when filling inside SWCNT. The formation of multiple helical configuration is influenced by the combined effect of structure stability, initial arrangement and tube space, meanwhile its forming time is related to helical angle. The simulated threshold of GNRs in SWCNT decreases with GNR width but increases with SWCNT diameter, and two formulas have come up in this study to estimate the quantity threshold for GNRs. It has been found that multilayered graphite is hard to be stripped in SWCNT because the special helical configuration with incompletely separated GNRs is metastable. This work provides a possibility to control the configuration of GNR@SWCNT.


72-Week Safety and Tolerability of Dimethyl Fumarate in Japanese Patients with Relapsing-remitting Multiple Sclerosis: Analysis of the Randomised, Double Blind, Placebo-Controlled, Phase III APEX Study and its Open-Label Extension.
The long-term safety of dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (RRMS) has been studied in mainly Caucasian patients. The present interim analysis aimed to evaluate the 72-week safety of DMF in Japanese patients with RRMS. Safety data of Japanese subjects enrolled in the 24-week randomised, double-blind, placebo-controlled APEX study (Part I) and its following open-label extension (Part II) were analysed at 72 weeks from the beginning of Part I. In Part I, subjects were randomised to DMF treatment or matching placebo while all subjects received DMF treatment during Part II. Adverse events (AEs) reported throughout the study period were recorded. Overall, 109 Japanese subjects completed 72 weeks of treatment. The incidence of AEs and serious AEs was 95% and 19%, respectively, in the DMF group compared with 84% and 18%, respectively, in the placebo group at 24 weeks. Common AEs (at least 5%) reported with treatment included nasopharyngitis, flushing, hot flush, gastrointestinal events, pruritus, rash, headache, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). AEs led to discontinuation of DMF in 5% of patients and included MS relapse, flushing, abdominal pain, liver disorder and increased ALT/AST. After an initial decrease from baseline of 17% in the DMF group at week 24, the mean lymphocyte counts stabilised and were maintained until week 72. No opportunistic/serious infections nor malignancies were reported with DMF treatment. The incidences of AEs, serious AEs, and discontinuation due to AEs were similar between the DMF and the placebo groups. The 72-week safety profile of DMF in Japanese patients with RRMS was consistent with previous studies that enrolled mostly Caucasian patients, with a lower incidence of flushing and related symptoms and a lower reduction in the lymphocyte count compared with previous reports. ClinicalTrials.gov identifier NCT01838668. Biogen Japan Ltd.


Comparing naming, lexical decision, and eye fixation times: word frequency effects and individual differences.
Performance on three different tasks was compared: naming, lexical decision, and reading (with eye fixation times on a target word measured). We examined the word frequency effect for a common set of words for each task and each subject. Naming and reading (particularly gaze duration) yielded similar frequency effects for the target words. The frequency effect found in lexical decision was greater than that found in naming and in eye fixation times. In all tasks, there was a correlation between the frequency effect and average response time. In general, the results suggest that both the naming and the lexical decision tasks yield data about word recognition processes that are consistent with effects found in eye fixations during silent reading.


Tar ball pollution under the influence of ocean circulation in the Bohai Sea, China.
The deposition of tar balls of unknown sources on the coast poses a great threat to the fishery, tourism and coastal biodiversity in the Bohai Sea. This work aimed to identify the sources of tar balls by using oil fingerprint technique. Tar ball samples were collected from the seashore of two islands of the western Bohai Sea and divided into two groups (Group I and Group II). Principal component analysis showed that although Caofeidian oilfield was one of the closest oilfields to the sampling area it was not a source. Fingerprints of characteristic hopanes and steranes showed that samples of Group I were similar to the crude oils from the nearby Jidong oilfield, and samples of Group II were similar to the Penglai-19-3 crude oils. Combined with cross-plots of the samples and the reference oils, it indicated that Group I may come from Jidong and Group II may come from Penglai-19-3. The weathering characteristics of alkanes and polycyclic aromatic hydrocarbons showed that the samples were affected by natural weathering processes (e.g., evaporation, photooxidation and biodegradation). It revealed that oil pollution from the nearby oilfields can also affect other areas under the influence of ocean circulation. It is the first study on source identification of tar balls from the Bohai Sea and the effects of ocean circulation on the tar ball transport. This study can considerably help to further understand the evolution of tar balls and consequently determine their sources.


Clinical Benefits of Sodium-Glucose Cotransporter 2 Inhibitors and the Mechanisms Underlying Their Cardiovascular Effects.
In addition to showing antidiabetic effects, sodium-glucose cotransporter 2 (SGLT2) inhibitors also reduce cardiovascular events in patients with type 2 diabetes mellitus. In major trials of cardiovascular outcomes, SGLT2 inhibitors have been shown to improve cardiovascular and renal outcomes, including reduced rehospitalization in patients with heart failure, regardless of the presence of diabetes. A recent report showed that the benefits of SGLT2 inhibitors in terms of cardiovascular deaths/admissions caused by heart failure and reduced ejection fraction were greater in Asians than in Whites. In this review, the first part demonstrates the results of recent clinical trials and their clinical implications and outlines current trials and upcoming research areas. The second part provides a general overview of the current understanding of the mechanisms of the cardiovascular benefits of SGLT2 inhibitors.


Efficacy of cyanoacrylate in the prevention of delayed bleeding after endoscopic mucosal resection of large colorectal polyps: a pilot study.
Postoperative bleeding is a common complication after endoscopic polypectomy, particularly after endoscopic mucosal resection (EMR) of large non-pedunculated polyps, despite prophylactic clipping can reduce its occurrence. Cyanoacrylate glue has recently been proposed as a useful tool in reducing bleeding in surgery because of its adhesive and haemostatic properties. The aim of this study is to evaluate the usefulness of endoscopic application of a modified cyanoacrylate glue in the prevention of early or delayed post EMR bleeding. This is a pilot study. Inclusion criteria were patients between 18 and 75 years old affected by sessile or flat colonic polyps larger than 2 cm. Patients enrolled in the study were randomized in two groups: group A (EMR) and group B (EMR with the application of 0.3 ml of N-butyl-2-cyanoacrylate + methacryloxysulfolane-Glubran 2®). Fifteen patients in both group A and B were enrolled. There were no intraoperative complications but haemostatic clipping was necessary in 3 patients in each group because of active bleeding. Delayed (after 24 h) bleeding occurred in two patients (13.3%) in group A requiring hospital readmission and re-do endoscopy with apposition of haemostatic clips. No case of bleeding was recorded in group B (p = 0.48). The results of this pilot study suggest a potential role of local spray application of Glubran®2 in reducing post-procedural bleeding.


St John's wort versus placebo in obsessive-compulsive disorder: results from a double-blind study.
Although St John's wort (Hypericum perforatum) is one of the most widely used and studied herbal medicines for depression, less is known about its efficacy in anxiety disorders, in spite of the fact that patients with anxiety disorders are among the most likely to self-medicate using alternative treatments. Pharmacokinetic evidence for the serotonergic, domaminergic and GABAminergic activity of hypericum, and a recent successful open-label study, suggests that it may be effective for obsessive-compulsive disorder (OCD). Sixty subjects were randomized to 12 weeks of treatment with St John's wort (LI 160) or matching placebo. Subjects with Hamilton Depression Scale scores of 16 or above were excluded. A flexible-dose schedule was utilized (600-1800 mg/day). The mean change on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) with St John's wort (3.43) was not significantly different than the mean change found with placebo (3.60) (P=899). No significant differences were found on any of the Y-BOCS subscales. The percentage of patients rated as 'much' or 'very much' improved at endpoint was not significantly different between St John's wort (17.9%) and placebo (16.7%) (P=0.905). Only one patient from each group discontinued due to adverse events [sinus infection (St John's wort); confusion (placebo)]. The results fail to support the efficacy of St John's wort for OCD.


Inhibition of HIV-1 reverse transcriptase and HIV-1 replication by Calophyllum coumarins and xanthones.
As part of our continuing study on the Calophyllum species, a number of coumarins, xanthones and chromene acids from different Calophyllum species of Sri Lanka were tested for inhibitory activity against the HIV-1 and its virally-encoded reverse transcriptase (RT). These compounds were found to be inactive in both the HIV-1 RT and whole virus systems. In contrast, cordatolide A and B demonstrated IC(50) values of 19.3 and 11.7 microM, respectively, against HIV-1 replication in a novel green fluorescent protein (GFP)-based reporter cell assay (HOG.R5).


School-based obesity policy, social capital, and gender differences in weight control behaviors.
We examined the associations among school-based obesity policies, social capital, and adolescents' self-reported weight control behaviors, focusing on how the collective roles of community and adopted policies affect gender groups differently. We estimated state-level ecologic models using 1-way random effects seemingly unrelated regressions derived from panel data for 43 states from 1991 to 2009, which we obtained from the Centers for Disease Control and Prevention's Youth Risk Behavior Surveillance System. We used multiplicative interaction terms to assess how social capital moderates the effects of school-based obesity policies. School-based obesity policies in active communities were mixed in improving weight control behaviors. They increased both healthy and unhealthy weight control behaviors among boys but did not increase healthy weight control behaviors among girls. Social capital is an important contextual factor that conditions policy effectiveness in large contexts. Heterogeneous behavioral responses are associated with both school-based obesity policies and social capital. Building social capital and developing policy programs to balance outcomes for both gender groups may be challenging in managing childhood obesity.


Real-world Data for High-risk Stage II Colorectal Cancer - The Role of Tumor Side in the Adjuvant Setting.
The impact of sidedness in the high-risk stage II colorectal cancer (CRC) setting is uncertain. Although controversial, available data suggest a possible modest benefit of adjuvant chemotherapy (CT) in the adjuvant scenario. The aim of this study is to analyze the overall survival (OS) and recurrence-free survival (RFS) according to the tumor side. In this single-center retrospective cohort, we analyzed patients treated between January 2011 and December 2018. We evaluated OS and RFS of high-risk patients according to the tumor side and considering adjuvant CT exposure and clinical and molecular features. A total of 1047 patients with stage II CRC were evaluated. Of these, 540 had high-risk criteria and microsatellite stability (MSS) or unknown status. One hundred fifty-seven (29%) patients had right-sided tumors, and 352 (65.2%) had left-sided tumors. Most patients received adjuvant CT, and the majority of them had T3 stage tumors, ≥ 12 lymph node resection, left tumor, MSS, and moderate differentiation. OS did not differ according to tumor side (5-year OS rates: 81.9% for right-sided tumors vs. 83% for left-sided tumors; hazard ratio, 0.91; 95% confidence interval, 0.55-1.53; P = .744). Adjuvant CT was associated with a superior RFS and OS, with 5-year OS rates of 87.7% versus 76.1% in the no-adjuvant group (hazard ratio, 0.46; 95% CI, 0.28-0.73; P = .001). The tumor side did not influence the outcomes in this study. Adjuvant CT was associated with improved RFS and OS in patients with high-risk stage II CRC, with a total gain of 11.6% in 5-year OS.


Leeuwenhoek and the structure of dentine.
This short paper includes extracts from the original translations of Leeuwenhoek's descriptions of the histology of teeth, investigates his findings and demonstrates that in addition to describing dentinal tubules, he may have identified the presence of calcospherites within that tissue.


Healthcare costs and outcomes associated with laboratory-confirmed Lyme disease in Ontario, Canada: A population-based cohort study.
The objective of this study was to estimate the economic burden attributable to laboratory-confirmed Lyme disease (LD) in Ontario, Canada and assess health outcomes associated with LD. We conducted a cohort study using laboratory-confirmed LD cases accrued between 2006 and 2018. The exposed cohort was matched 1:3 to the unexposed cohort using a combination of hard and propensity score matching. We used phase-of-care costing methods to calculate attributable costs for four phases of illness: pre-diagnosis, acute care, post-acute care, and continuing care in 2018 Canadian dollars. We used ICD-10-CA and OHIP billing codes to identify emergency department visits, physician billings and hospitalizations related to LD sequelae to assess health outcomes. A total of 2,808 cases were identified with a mean age of 46.5 (20.7) years and 44% female. Within 30-days, 404 (14.3%) cases required an ED visit and 63 (2.4%) cases required hospitalization. The mean (95% CI) total costs for LD cases in pre-diagnosis, acute, and post-acute care phases were $209 ($181, 238), $1,084 ($956, $1,212), and $1,714 ($1,499, $1,927), respectively. The highest mean attributable 10-day cost was $275 ($231, $319) during acute care. At 1-year post-infection, LD increased the relative risk of nerve palsies by 62 (20, 197), and polyneuropathy by 24 (3.0, 190). LD resulted in 16 Lyme meningitis events vs. 0 events in the unexposed. Individuals with laboratory-confirmed LD have increased healthcare resource use pre-diagnosis and up to six months post-diagnosis, and were more likely to seek healthcare services related to LD sequelae.


A new Asian genus of the tribe Elicini (Hemiptera: Fulgoromorpha: Tropiduchidae) with two new species from Vietnam.
A new genus Connelicita gen. nov. with 2 new species (C. backyensis sp. nov. and C. haiphongensis sp. nov.) of Tropiduchidae Elicini from Vietnam are described and illustrated. The Chinese species C. lungchowensis (Chou et Lu, 1977) comb. nov. is transferred into this new genus from the genus Sassula (Nogodinidae). A key to species of the new genus distributed in North Vietnam and China (Guangxi) is provided.


LA phonospirometry technique compared to pediatric respiratory assessment measure and peak expiratory flow measurement as a novel technique to assess the severity of an asthma exacerbation.
Objective: Asthma is a common chronic disease treated in emergency departments. The measurements of Peak Expiratory Flow (PEF) and Pediatric Respiratory Assessment Measure (PRAM) scores have been recommended as objective techniques in the assessment of acute asthma exacerbations, but have multiple barriers limiting their use. The Los Angeles phonospirometry technique is an easier, trans-cultural technique. The technique assesses dyspnea by measuring how many seconds a child is able to chant "LA LA LA" in a single breath. The objective of this study is to determine the correlation of this technique with PEF measurements and PRAM scores in children with acute asthma exacerbations, both before and after nebulized bronchodilator treatment. Methods: A convenient sample of children aged 5-17 years being treated for asthma in the ED was enrolled. Phonospirometry, PRAM, and PEF measurements were obtained through pre and post inhaled bronchodilator treatments. The highest values from each measurement were correlated using Spearman's correlation coefficient. Results: A total of 91 children were enrolled. The correlations at pre-treatment, after first, second, and third treatments between phonospirometry and PEF were 0.38 (p < 0.001), 0.60 (p < 0.001), 0.54 (p < 0.001), 0.52 (p < 0.01), respectively; between phonospirometry and PRAM were -0.37 (p < 0.001), -0.42 (p < 0.001), -0.26 (p < 0.05), and -0.06 (p > 0.05), respectively; and between PEF and PRAM were -0.6 (p < 0.01), -0.54 (p < 0.001), -0.38 (p < 0.01), and -0.36 (p - 0.05), respectively. Conclusions: This novel technique correlates mild to moderately with PEF, and shows promising aide in the assessment of children with acute asthma exacerbations.


Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine.
Compared with men, women show enhanced responses to drugs of abuse, and consequently are thought to be more vulnerable to addiction. The ovarian hormone estradiol has emerged as a key facilitator in the heightened development of addiction in females. These actions of estradiol appear mediated by estrogen receptor (ER) activation of metabotropic glutamate receptor type 5 (mGluR5). However, the downstream effectors of this ER/mGluR5 signaling pathway are unknown. Here we investigate whether cannabinoid 1 receptor (CB1R) activation is a part of the mechanism whereby estradiol influences behavioral and synaptic correlates of addiction. Following repeated cocaine administration, estradiol-treated ovariectomized rats exhibited both sensitized locomotor responses and decreases in the dendritic spine density of nucleus accumbens core medium-spiny neurons in comparison to oil-treated controls. Both effects of estradiol were blocked by AM251, a CB1R inverse agonist. These results indicate that part of the signaling mechanism through which estradiol impacts behavioral and synaptic correlates of addiction in female rats requires activation of CB1Rs.


L-Measure: a web-accessible tool for the analysis, comparison and search of digital reconstructions of neuronal morphologies.
L-Measure (LM) is a freely available software tool for the quantitative characterization of neuronal morphology. LM computes a large number of neuroanatomical parameters from 3D digital reconstruction files starting from and combining a set of core metrics. After more than six years of development and use in the neuroscience community, LM enables the execution of commonly adopted analyses as well as of more advanced functions. This report illustrates several LM protocols: (i) extraction of basic morphological parameters, (ii) computation of frequency distributions, (iii) measurements from user-specified subregions of the neuronal arbors, (iv) statistical comparison between two groups of cells and (v) filtered selections and searches from collections of neurons based on any Boolean combination of the available morphometric measures. These functionalities are easily accessed and deployed through a user-friendly graphical interface and typically execute within few minutes on a set of approximately 20 neurons. The tool is available at http://krasnow.gmu.edu/cn3 for either online use on any Java-enabled browser and platform or download for local execution under Windows and Linux.


Range of motion of the metacarpophalangeal joint in rheumatoid patients, with and without a flexible joint replacement prosthesis, compared with normal subjects.
The metacarpophalangeal is commonly affected by rheumatoid arthritis. This may lead to joint replacement with a flexible prosthesis. The aims of this study were to determine the effects of rheumatoid arthritis on joint motion and to determine whether joint replacement needs to restore the full range of motion. Three-dimensional motion analysis was used to measure the range of motion of the metacarpophalangeal joint in rheumatoid patients with and without a flexible silicone arthroplasty, when performing pinch and key grips, when making a fist and when spreading the fingers. The results were compared with those from younger and older normal subjects. There appeared to be a trend for a decrease in range of motion from younger normal to older normal to rheumatoid (no prosthesis) to rheumatoid (with prosthesis) subject groups. However, statistically different (p<0.05) results were only observed for some movements (mostly involved in making a fist), in some fingers and between some subject groups. The only exception to this apparent trend was in flexion/extension when spreading the fingers into abduction. Making a fist is the most sensitive simple measure of range of motion in the metacarpophalangeal joint. Successful replacement of the metacarpophalangeal joint in patients with rheumatoid arthritis need not restore the normal range of motion.


The association between toxic anterior segment syndrome and intraocular pressure.
To investigate the association between toxic anterior segment syndrome (TASS) and intraocular pressure (IOP). This is a retrospective, controlled, single-site study. Patients who developed TASS following a clear corneal incision cataract surgery in Rabin Medical Center (Petah Tikva, Israel), between the years 2010-2018, were enrolled. The primary outcome was IOP measured 1, 7 (± 2), and 30 (± 7) days after surgery. The need for ocular hypotensive treatment was the secondary outcome. The study and control groups included 374 and 127 eyes, respectively. The mean IOP in the study and the control groups were 16.3 ± 7.1 and 15.3 ± 3.0 (p = 0.02) at day 1, 13.2 ± 5.0 and 13.7 ± 2.9 (p = 0.18) at day 7, and 13.7 ± 4.1 and 13.5 ± 2.8 (p = 0.65) at day 30. Prevalence of high IOP (> 21 mmHg) was significantly higher in the study group solely on the first postoperative day (12.7% and 3.2%, p = 0.002). In the study group, 9%, 3.7%, and 1.6% of the patients required hypotensive medications at day 1, 7, and 30, respectively. Four patients (~ 1%) in the study group developed acute angle closure due to pupillary block, 1-3 weeks after surgery and required laser iridotomy and topical treatment. High IOP is considered a concerning characteristic of the late stages of TASS although such association lack supporting evidence. This study did not detect such an association. High IOP was found only in a small group of TASS patients in the early perioperative period.


Chaperone release and unfolding of substrates in type III secretion.
Type III protein secretion systems are essential virulence factors of many bacteria pathogenic to humans, animals and plants. These systems mediate the transfer of bacterial virulence proteins directly into the host cell cytoplasm. Proteins are thought to travel this pathway in a largely unfolded manner, and a family of customized cytoplasmic chaperones, which specifically bind cognate secreted proteins, are essential for secretion. Here we show that InvC, an ATPase associated with a Salmonella enterica type III secretion system, has a critical function in substrate recognition. Furthermore, InvC induces chaperone release from and unfolding of the cognate secreted protein in an ATP-dependent manner. Our results show a similarity between the mechanisms of substrate recognition by type III protein secretion systems and AAA + ATPase disassembly machines.


Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration.
The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. In several of the hereditary ataxias, the causative gene plays an important role in DNA repair: ataxia telangiectasia and ataxia telangiectasia-like disorder, and ataxia with oculomotor apraxia type I and II. Mitochondrial metabolism is impaired in another group of inherited ataxias including the emergent group of defects in coenzyme Q10 synthesis. Few of these disorders are amenable to effective treatment, the most important of these being vitamin E-responsive ataxia. The autosomal dominant spinocerebellar ataxias are rare in childhood. Some of them, especially SCA7 and SCA2, may begin in childhood or even infancy, family history being positive in these cases. Additional clinical clues such as presence or absence of neuropathy or oculomotor apraxia still help in making a definitive diagnosis albeit there are still many unsolved cases. In pontocerebellar hypoplasia, a neurodegenerative disease with prenatal onset, the genetic basis of the different subtypes has recently been elucidated and involves genes with different functions.


Social-psychological Determinants of the Implementation of Green Infrastructure for Residential Stormwater Management.
Climate change effects and increasing levels of imperviousness, cause many urban areas globally to experience larger rainfall runoff volumes that need to be managed to protect property and infrastructure, and avoid environmental pollution. Conventionally engineered, 'grey' stormwater infrastructure often is outdated and unable to control these increased runoff volumes. Green stormwater infrastructure (GSI) can complement grey infrastructure, but public land for its installation is limited. Consequently, municipalities often look to residential properties to install GSI at the lot-level. While many studies have been conducted in the engineering aspects of GSI, less is known about what determines residents' decisions to install GSI on their properties. To help close this knowledge gap, we conducted a survey of social-psychological determinants of residential GSI implementation using the Theory of Planned Behavior as theoretical framework, and analyzing our data with partial least squares path modeling. Results from three neighborhoods of our case study area suggest that residents' decisions to install GSI largely are determined by social norms and perceived control factors such as available finances and time. However, residents' beliefs and attitudes toward the effectiveness and attractiveness of GSI did not seem to play a significant role. Neighborhood characteristics including local flooding history did not seem to affect residents' decisions about GSI installation either. We recommend creation of effective municipal education and outreach programs regarding urban stormwater management that speak to residents' shared responsibility and options for addressing this issue, as well as creation of financial instruments that provide meaningful subsidies for residential GSI adoption.


Immobilization of recombinant lysostaphin on nanoparticle through biotin-streptavidin conjugation technology as a geometrical progressed confrontation against Staphylococcus aureus infection.
Antibiotic resistance and the colonization of resistant bacteria such as Staphylococcus aureus on surfaces, often in the form of biofilms, prolong hospitalization periods and increase mortality, thus is a significant concern for healthcare providers. To prevent biofilm formation, the inadequate concentration of using nanoparticles as antibacterial coating agents is one of the major obstacles. This study aimed to design a hypervalency TiO2 nanocomposite as a reserved base to carry a high amount of active antibacterial agents such as lysostaphin via a biotin-streptavidin-biotin bridge. The utilization of the streptavidin-biotin system could increase the abundance of lysostaphin. Lysostaphin was expressed in Escherichia coli and purified. Both recombinant lysostaphin and titanium oxide nanocomposite were conjugated with biotin and linked to a streptavidin bridge. The kinetics and activity of the enzyme were examined after each step utilizing N-acetylhexaglycine as a substrate. Physical characteristics of nanoparticles containing lysostaphin were determined using AFM, SEM, FTIR, and zeta potential. The results showed changes in size, charge, and morphology of the nanoparticles following the lysostaphin attachment. Also, the stability and kinetics of the active biological enzymes on nanoparticles were reexamined following 8 months of storage. Exploiting this approach, various biotinylated antibacterial agents could be prepared and rapidly immobilized on a nanoparticle as an active net against related infectious agents.


The pregnancy coexisting with experimentally induced nephrotic syndrome (NS) in rats--the histological assessment of kidneys in light microscopy.
The purpose of this study was histological evaluation in light microscopy of kidneys of pregnant female rats, which before pregnancy suffered from adriamycin-induced NS. The result show numerous changes in glomerules and renal convoluted tubules, which were the evidence of increased protein loss with urine.


Cationic amphipathic peptide analogs of cathelicidin LL-37 as a probe in the development of antimicrobial/anticancer agents.
Cathelicidin LL-37 belongs to the class of human defense peptides and is overexpressed in many cancers. Segments of LL-37 derived through biochemical processes have a wide range of activities. In this study, novel analogs of the 13-amino acid cathelicidin 17-29 amide segment F17 KRIV21 QR23 IK25 DF27 LR-NH2 were prepared and examined for their antimicrobial and hemolytic activities, as well as for their cytotoxicity on cancer bronchial epithelial cells. Selected substitutions were performed on residues R23 and K25 in the hydrophilic side, V21 and F27 in the hydrophobic side of the interphase, and F17 that interacts with cell membranes. Specific motifs IIKK and LLKKL with anticancer and antimicrobial activities isolated from animals were also inserted into the 17-29 fragment to investigate how they affect activity. Substitution of the amino-terminal positive charge by acetylation and replacement of lysine by the aliphatic leucine in the peptide analog Ac-FKRIVQRIL25 DFLR-NH2 resulted in significant cytotoxicity against A549 cancer cells with an IC50 value 3.90 μg/mL, with no cytotoxicity to human erythrocytes. The peptide Ac-FKRIVQI23 IKK26 FLR-NH2 , which incorporates the IIKK motif and the peptides FKRIVQL23 L24 KK26 L27 LR-NH2 and Ac-FKRIVQL23 L24 KK26 L27 LR-NH2 , which incorporate the LLKKL motif, displayed potent antimicrobial activity against gram-negative bacteria (MIC 3-7.5 μg/mL) and substantial cytotoxicity against bronchial epithelial cancer cells, (IC50 12.9-9.8 μg/mL), with no cytotoxic activity for human erythrocytes. The helical conformation of the synthetic peptides was confirmed by circular dichroism. Our study shows that appropriate substitutions, mainly in positions of the interphase, as well as the insertion of the motifs IIKK and LLKKL in the cathelicidin 17-29 segment, may lead to the preparation of effective biological compounds.


Differences between men and women regarding attitudes toward dental local anesthesia among junior students at a United Kingdom dental school.
The aim of this study was to assess the attitudes of junior dental students at a United Kingdom dental school regarding the administration and receipt of a local anesthetic injection. The effect of teaching on these attitudes was also evaluated. Data were collected by questionnaire. Previous experience with local anesthesia in a dental office did not affect students' attitudes toward administration and receipt of a local anesthetic injection from a classmate. Female students were more anxious about giving and receiving local anesthetic injections than male students. Didactic teaching decreased anxiety in relation to administration and receipt of a local anesthetic injection. The results showed that male and female students in a United Kingdom dental school differed in their attitudes toward local anesthesia.


Effects of ionic strength of immersion medium on the structure of peripheral nerve myelin.
A study of the effects of hypertonic solutions on the structure of peripheral nerve myelin reveals an expansion rather than a contraction of the layer spacing. This suggests the absence of "free" water between the myelin layers. Hypotonic solutions bring about a change in radial repeat period from 171 A to 250 to 270 A. These findings are of significance in relation to the structure of myelin.


BJN Award Runner Up: Oncology Nurse of the Year.
To contact Michelle about setting up an acute oncology service, send her an email: firstname.lastname@example.com.


Hypometric primary saccades and increased variability in visually-guided saccades in Huntington's disease.
Eye movement abnormalities can be distinctive and suggestive of a specific pathophysiology. To further investigate the deficits in the control of saccades in patients with Huntington's disease (HD), we investigated the ability of 11 HD patients and 11 matched controls to perform visually-guided saccades. We adopted reflexive saccade tasks involving predictable and unpredictable sequences, at different amplitudes of target step (10 degrees, 20 degrees, 30 degrees, 40 degrees ), as well as voluntary self-paced saccades. Prolongation of initiation was observed in the HD group as the target amplitude of predictable saccades increased. During the self-paced saccade task, the HD patients had increased intersaccadic intervals, performed fewer saccades in the allocated time and displayed an increased temporal variability in comparison to the controls. Furthermore, hypometric primary saccades, and an increased number of corrective saccades, were observed during both reflexive and voluntary saccades in the HD group. The delayed initiation of large saccades, deficits in voluntary, self-paced saccades, impaired saccadic accuracy and increased corrective saccades in HD, were interpreted in light of other ocular motor and limb studies, and appear to be due to damage to the fronto-striatal loop, including the supplementary eye fields, as well as possible brainstem and cerebellar involvement.


Premature atherosclerotic peripheral artery disease: An underrecognized and undertreated disorder with a rising global prevalence.
Premature atherosclerotic peripheral artery disease (PAD) of the lower extremities is characterized by disease diagnosis before the age of 50 years. The global prevalence of premature PAD has increased, and the disease is often underdiagnosed given heterogenous patient symptoms. Traditional cardiovascular risk factors like smoking, diabetes, hypertension, and hyperlipidemia as well as non-traditional risk factors like elevated lipoprotein(a), family history of PAD, hypercoagulability, and systemic inflammation are associated with premature PAD. Patients with premature PAD tend to have an aggressive vascular disease process, a high burden of cardiovascular risk factors, and other concomitant atherosclerotic vascular diseases like coronary artery disease. Prevention of cardiovascular events, improvement of symptoms and functional status, and prevention of adverse limb events are the main goals of patient management. In this review, we discuss the epidemiology, risk factors, clinical evaluation, and management of patients with premature PAD.


Bioequivalence study of two liquid formulations of benzydamine.
A bioequivalence study of two liquid formulations containing benzydamine hydrochloride was carried out to evaluate the influence of a change of the excipients and the addition of a flavouring agent, ICEBERG AR 84/05/15, on the absorption of benzydamine. No statistically significant differences were observed suggesting that the two formulations are bioequivalent.


A Novel Method of Somatic Cell Nuclear Transfer with Minimum Equipment.
Somatic cell nuclear transfer (SCNT) is an exceptional experimental biology technique with an arguably great contribution to our current understanding of developmental plasticity. Many students and young researchers are interested in taking advantage of SCNT virtues in their experiments but the cost of micromanipulation microscopes, intensive training programs, and also the sophisticated process of SCNT may dissuade them from entering this amazing field of science. Here, we describe the details of a streamlined manual method of SCNT that can be performed using very basic equipment found in every embryology laboratory: the Pasteur pipette and stereomicroscope. The overall method introduced is very simple and a person with no previous experience in cloning can learn and adopt the basic routines of this technique independently.


Early steps in neural crest specification.
The neural crest is a multipotent cell population that arise at the border of the neural plate and non-neural ectoderm. Studies conducted in a number of model organisms including chickens, frogs, zebrafish and mice have been instrumental in elucidating this molecular mechanisms underlying neural crest formation. Signaling molecules of the Wnt, BMP, and FGF families and their downstream effectors have been shown to mediate neural crest induction. Transcription factors including members of the Snail and SoxE gene families as well as FoxD3, c-Myc and others have been implicated in specification of the neural crest. These studies represent an important step in understanding the regulatory interactions involved in generating this complex and interesting cell type.


Regression-Derived Ileal Endogenous Amino Acid Losses in Broiler Chickens and Cannulated Pigs Fed Corn Fiber, Wheat Bran, and Pectin.
The objective of these studies was to determine the effect corn fiber (CF), wheat bran (WB) and pectin (PEC) on basal ileal endogenous amino acid (EAA) losses in broiler chickens (Exp. 1) and cannulated pigs (Exp. 2) using the regression method. Semi-purified diets containing 100 g/kg of CF, WB, or PEC (broiler chickens) and CF or PEC (pigs) were fed to replicate cages consisting of eight birds per cage of 21-d-old broiler chickens and six replicates of pigs consisting of one pig per pen. Ileal endogenous His, Glu, and Pro losses were higher (p < 0.05) for CF and WB compared with birds fed diets containing PEC. Contrasts between CF and WB showed higher (p < 0.05) ileal endogenous nitrogen, total amino acid, His, Ile, Met, Glu, Pro, and Tyr losses in birds fed the CF diets (Exp. 1). Contrasts of EAA losses between birds fed the WB and PEC diets showed higher (p < 0.05) losses for His, Glu, and Pro. In the cannulated pigs, CF resulted in higher (p < 0.05) ileal endogenous His, Leu, and Tyr losses. In summary, CF induced higher ileal EAA losses in broiler chickens and cannulated pigs.


Detection of stenoses in the internal carotid artery by waveform analysis of continuous wave ultrasound signals (I).
In this prospective study, the reliability of the morphologic analysis of the continuous Doppler signal was evaluated. Three parameters were considered: the maximum systolic frequency (max A), a resistance parameter (RP) and the degree of spectral broadening (SB). The apparatus used allowed us to construct a color arterial image. Seventy-four subjects were included in this study: 17 volunteers investigated by ultrasound only, and 57 patients investigated by ultrasound and arteriography. Anatomic correlation was obtained in 31 operated cases. The threshold values, as determined in the volunteers, were as follows: 3.5 kHz for max A, 0.86 for RP and 58% for SB. Sensitivity was 94% when max A, SB and cartography were combined to detect tight stenoses. The sensitivity for each of the parameters alone was much weaker (61% for max A and 33% for RP). For all carotid lesions, the sensitivity of detection when all parameters were combined was 68%. Specificity was 77%. The study of the carotid bifurcation by the continuous Doppler effect allowed us to identify tight stenosis with reliability. On the other hand, it was impossible to distinguish between normal arteries and moderate stenosis, or between tight stenosis and complete occlusion.


Efficacy and safety of bifidobacterium quadruple viable tablets in the treatment of Helicobacter pylori-infected peptic ulcer or gastritis patients: a systematic review and meta-analysis.
To better understand the efficacy and safety of Bifidobacterium quadruple viable tablets in the treatment of helicobacter pylori (H. pylori)-infected peptic ulcer or gastritis patients. A systematic review of the studies published to June 2022 was performed in English database PubMed, Embase, Chinese database CNKI, Wanfang. There were 17 studies were included in this systematic review and meta-analysis. The outcomes measured included H. pylori eradication rate, changes in clinical symptoms of epigastric pain scores, and the incidence of adverse reactions. The results of the fixed effect model showed that the eradication rate of H. pylori in the combination of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was greater than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (OR = 3.73, 95%CI (2.79,5.00), Z = 2.78, P < 0.001; I2 = 0.0%, P > 0.999). The results of random effects model showed that the epigastric pain score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.70, 95%CI (-1.06,-0.34), Z = 3.82, P < 0.001; I2 = 96.7%, P < 0.001). The results of random effects model showed that the acid reflux score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.98, 95%CI (-1.70,-0.26), Z = 2.66, P < 0.001; I2 = 99.7%, P < 0.001). The eradication rate of H. pylori by Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing quadruple therapy is better than that of bismuth-containing quadruple therapy. The improvement of clinical symptoms of patients is better than that of bismuth-containing quadruple therapy, and the incidence of adverse reactions is lower than that of bismuth-containing quadruple therapy. Bifidobacterium quadruple viable bacteria tablet combined with bismuth-containing quadruple therapy was effective and safe. It provides a new way to treat patients with H. pylori.


Treatment of pneumonia in patients at risk of infection with gram-negative bacilli.
Patients with a history of chronic debilitating disease due to a variety of causes are known to be at risk for infection with coliform gram-negative bacilli when they present with community-acquired pneumonia. Empiric treatment with broad-spectrum parenteral antibiotics is often begun in such patients pending the result of blood and other cultures. The optimal duration of broad-spectrum empiric therapy in such patients when cultures fail to reveal a specific pathogen is unknown. Review was made of the charts of 131 patients with community-acquired pneumonia admitted to the hospital and treated with broad-spectrum parenteral antibiotics in whom a specific pathogen was never isolated. Overall, 89 percent of these patients were cured without complication or relapse. Patients receiving broad-spectrum therapy for four days or less due to rapid clinical improvement had a successful outcome in 95 percent of cases. It is concluded that broad-spectrum parenteral antibiotic therapy can safely be abbreviated provided response to therapy is prompt.


Proteomic analysis to identification of hypoxia related markers in spinal tuberculosis: a study based on weighted gene co-expression network analysis and machine learning.
This article aims at exploring the role of hypoxia-related genes and immune cells in spinal tuberculosis and tuberculosis involving other organs. In this study, label-free quantitative proteomics analysis was performed on the intervertebral discs (fibrous cartilaginous tissues) obtained from five spinal tuberculosis (TB) patients. Key proteins associated with hypoxia were identified using molecular complex detection (MCODE), weighted gene co-expression network analysis(WGCNA), least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature Elimination (SVM-REF) methods, and their diagnostic and predictive values were assessed. Immune cell correlation analysis was then performed using the Single Sample Gene Set Enrichment Analysis (ssGSEA) method. In addition, a pharmaco-transcriptomic analysis was also performed to identify targets for treatment. The three genes, namely proteasome 20 S subunit beta 9 (PSMB9), signal transducer and activator of transcription 1 (STAT1), and transporter 1 (TAP1), were identified in the present study. The expression of these genes was found to be particularly high in patients with spinal TB and other extrapulmonary TB, as well as in TB and multidrug-resistant TB (p-value < 0.05). They revealed high diagnostic and predictive values and were closely related to the expression of multiple immune cells (p-value < 0.05). It was inferred that the expression of PSMB9, STAT 1, and TAP1 could be regulated by different medicinal chemicals. PSMB9, STAT1, and TAP1, might play a key role in the pathogenesis of TB, including spinal TB, and the protein product of the genes can be served as diagnostic markers and potential therapeutic target for TB.


Respiratory syncytial virus: the virus, the disease and the immune response.
RSV is the primary cause of hospitalisation in the first year of life for children in most parts of the world, and nearly 100% of children in the USA are infected with the virus by 2 to 3 years of age. The agent is an enveloped RNA virus with a non-segmented single-stranded negative-sense genome. The viral genome encodes 8 structural and 2 non-structural proteins. Important structural proteins include the fusion (F) protein and the attachment (G) protein which are essential for viral penetration and attachment to the host cells. Both proteins are important in development of immune responses. The virus is estimated to cause 3000 to 4000 deaths annually. Primary infections are as a rule symptomatic. The spectrum of clinical manifestations ranges from mild upper tract illness, infection in middle ear which progresses to acute otitis media, croup, to apnoea in premature infants, pneumonia and bronchiolitis. Premature babies born at 30-35 weeks of gestation, infants with cyanotic congenital heart disease, HIV-infected subjects, and patients on intensive immunosuppressive therapy especially after bone marrow transplant are considered to be at risk for increased mortality and morbidity during RSV infection. The virus does not normally replicate outside of the bronchopulmonary tree and the infection is exquisitely restricted to the respiratory mucosa. However, development of extrapulmonary disease has been observed in certain T and B cell immunodeficiency states. The association of RSV with asthma and reversible reactive airway disease in early childhood has attracted significant attention. Recurrent wheezing for up to 5 to 7 years of age and established airway disease has been observed in a significant number of children with a strong family history of allergy, after primary infection or reinfection with RSV. Immune response to primary infection is relatively small but on reinfection, a significant booster effect with sustained immunologic reactivity is observed in serum and respiratory mucosa. Both CD(4)- and CD(8)-specific as well as Th(1)- and Th(2)-cell specific immune responses have been observed during human infection. In addition, proinflammatory as well as immunoregulatory cytokines and chemokines are induced in the respiratory tract after natural and induced (in vitro) infection. Significant progress has been made in understanding the role of Th(1) vs. Th(2), IgE, viral induced cytokines and chemokines in the mechanisms of pathogenesis of the disease, development of wheezing and in the prevention and treatment of the infection and its sequelae. Respiratory syncytial virus (RSV) is one of the commonest human viral infections, and virtually every child is infected by the third birthday. Because of its restricted mucosal immunopathology, and frequent association with bronchial hyperreactivity and development of wheezing, RSV has served as an important model to investigate mechanisms of mucosal immune responses and development of mucosal disease following infection. The importance of RSV in bronchopulmonary disease and development of bronchial hyperreactivity has been the focus of several recent symposia [Kimpen JL, Simoes EAF. Am J Respir Crit Care Med 2001; 163:S1-S6]. This brief report will only summarise, based on selected references, the historical landmarks of its discovery and current understanding of the mechanisms of immunity, and their possible role in the pathogenesis of bronchopulmonary disease.


Different dexamethasone doses in the perioperative period improve short-term outcomes of total hip arthroplasty: a randomized controlled trial.
This study aimed to evaluate the efficacy of different dexamethasone doses in the perioperative period of total hip arthroplasty (THA). We randomly divided 180 patients into three groups: three perioperative saline injections (Group A, placebo); two perioperative doses of 15 mg dexamethasone plus a postoperative saline injection at 48 h (Group B); and three perioperative doses of dexamethasone (10 mg) (Group C). Primary outcomes were postoperative pain at rest and while walking. We also recorded consumption of analgesics and antiemetics, incidence of postoperative nausea and vomiting (PONV), C-reactive protein (CRP) and interleukin-6 (IL-6) levels, postoperative length of stay (p-LOS), range of motion (ROM), nausea, Identity-Consequence-Fatigue-Scale (ICFS), and severe complications (e.g., incidence of surgical site infection, SSI and gastrointestinal bleeding, GIB). Group B and C had significantly lower pain scores at rest than Group A on postoperative day 1. Group B and C also had significantly lower dynamic pain score, CRP, and IL-6 than Group A on postoperative day 1, 2, and 3. Patients in Group B and C had lower PONV incidence, reduced use of analgesics and antiemetics, improved ROM, shorter p-LOS, lower VAS nausea score, and lower ICFS than Group A patients. On postoperative day 3, patients in Group C had significantly lower dynamic pain and ICFS scores, IL-6, and CRP than Group B patients, as well as higher ROM. None of the groups exhibited SSI or GIB. Dexamethasone provides short-term advantages in reducing pain, PONV, inflammation, and ICFS, and increasing ROM in the early postoperative period after THA. Dexamethasone efficacy in reducing post-THA pain, inflammation, and PONV at 10 mg and 15 mg is similar during the first 48 h. Dexamethasone (30 mg) divided into three 10 mg doses was superior to two doses (15 mg) in reducing pain, inflammation, and ICFS, as well as in increasing ROM on postoperative day 3.


Factors Associated With Implantable Pulse Generator Site Pain: A Multicenter Cross-Sectional Study.
Implantable pulse generator (IPG) site pain following neuromodulation procedures is a recognized complication. The site of the IPG placement varies depending on the neuromodulation type and physician preference. The incidence of IPG site pain as a function of the site of IPG implantation has not been studied systematically. We performed a multicenter cross-sectional survey of the incidence, severity, and quality of IPG site pain, location of the IPG, the pain management needs, functional impairment, and cosmetic appearance related to the IPG placement. Contingency table analysis was conducted for categorical variables, and logistic regression analysis and linear regression model was used. The survey response rate was 60.5% (n = 510). Overall, 31.0% of patients reported pain at the IPG site in the last 72 hours with 31.4% reporting moderate to severe pain and 7.6% reporting severe pain. Older age was inversely associated with IPG-related pain (OR = 0.97, 95% CI = 0.96-0.99, p = 0.001). IPG implantation site did not have a statistically significant interaction with IPG site pain (p > 0.05). The most important factor for IPG site-associated pain was having a spinal cord stimulator implanted as compared to a deep brain stimulator, or sacral nerve stimulator. Most subjects reported no functional impairment related to IPG site pain (91%), found the IPG site pain as expected (80%), and found IPG site cosmetic appearance as expected (96%). The incidence of IPG site pain is an important complication of invasive neuromodulation. The anatomic location of the IPG placement does not appear to affect the incidence or severity of IPG site pain. However, the presence of a pre-implant chronic pain disorder does appear to affect the frequency and severity of IPG site pain.


Use of olanzapine for elderly patients with psychotic disorders: a review.
The number of elderly persons with psychosis will increase with the increasing geriatric population. Olanzapine is one of the newer atypical antipsychotics with efficacy for positive and negative symptoms and safer side effect profile compared to conventional antipsychotics. The manuscript describes the pharmacology, efficacy and tolerability studies, adverse effects and dosing considerations in the elderly. Further studies are needed to fully assess the efficacy and safety of olanzapine in the elderly. Current research supports a role for olanzapine in treating elderly patients with schizophrenia, schizoaffective disorder and behavioral and psychological symptoms of dementia.


A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human.
Ethylene (ET) is the largest volume organic chemical. Mammals metabolize the olefin to ethylene oxide (EO), another important industrial chemical. The epoxide alkylates macromolecules and has mutagenic and carcinogenic properties. In order to estimate the EO burden in mice, rats, and humans resulting from inhalation exposure to gaseous ET or EO, a physiological toxicokinetic model was developed. It consists of the compartments lung, richly perfused tissues, kidneys, muscle, fat, arterial blood, venous blood, and liver containing the sub-compartment endoplasmic reticulum. Modeled ET metabolism is mediated by hepatic cytochrome P450 2E1, EO metabolism by hepatic microsomal epoxide hydrolase or cytosolic glutathione S-transferase in various tissues. EO is also spontaneously hydrolyzed or conjugated with glutathione. The model was validated on experimental data collected in mice, rats, and humans. Modeled were uptake by inhalation, wash-in-wash-out effect in the upper respiratory airways, distribution into tissues and organs, elimination via exhalation and metabolism, and formation of 2-hydroxyethyl adducts with hemoglobin and DNA. Simulated concentration-time courses of ET or EO in inhaled (gas uptake studies) or exhaled air, and of EO in blood during exposures to ET or EO agreed excellently with measured data. Predicted levels of adducts with DNA and hemoglobin, induced by ET or EO, agreed with reported levels. Exposures to 10000 ppm ET were predicted to induce the same adduct levels as EO exposures to 3.95 (mice), 5.67 (rats), or 0.313 ppm (humans). The model is concluded to be applicable for assessing health risks from inhalation exposure to ET or EO.


(-)-Arctigenin as a lead compound for anticancer agent.
(-)-Arctigenin, an important active constituent of the traditional Chinese herb Fructus Arctii, was found to exhibit various bioactivities, so it can be used as a good lead compound for further structure modification in order to find a safer and more potent medicine. (-)-Arctigenin derivatives 1-5 of (-)-arctingen were obtained by modifying with ammonolysis at the lactone ring and sulphonylation at C (6') and C (6″) and O-demethylation at CH3O-C (3'), CH3O-C (3″) and CH3O-C (4″), and their anticancer bioactivities were examined.


Glycation of lysine-containing dipeptides.
Protein glycation through Maillard reaction (MR) is a fundamental reaction both in foods and in the human body. The first step of the reaction is the formation of Amadori product (AP) that is converted into intermediate and advanced MR products during reaction development. Although the MR is not an enzymatic reaction, a certain degree of specificity in the glycation site has been observed. In the present study, we have monitored the glycation of different lysine-containing dipeptides to evaluate the influence on the NH(2) reactivity of the neighboring amino acid.Lysine dipeptides were reacted with glucose, galactose, lactose and maltose. The formation and identification of glycated compounds were monitored by mass spectrometry (MALDI-TOF and ESI-MS/MS) and by HPLC of their Fmoc derivatives. MS/MS analysis showed that the glucose APs formed on dipeptides have a characteristic fragmentation pattern: the fragment at [M - 84](+) due to the formation of pyrylium and furylium ion is mainly present in the monoglucosylated form, while the [M - 162](+) and the [M - 324](+) are more evident in the fragmentation pattern of the diglucosylated forms. The nature of the vicinal amino acids strongly affects lysine reactivity towards the different carbohydrates: the presence of hydrophobic residues such as Ile, Leu, Phe strongly increases lysine reactivity. Contrasting results were obtained with basic residues. The Lys-Arg dipeptide was among the most reactive while the Lys-Lys was not.


[Medicine and humanism: clinical ethics and the community dimension of geriatrics].
Clinical ethics is generally related to the clinical bedside activity. Clinical ethics constitutes one aspect of bioethics. In particular, its aim consists in facilitating the solving of conflicts of values in practical care. By encouraging effective communication and discussion within the interdisciplinary team, geriatricians will be able to make adequate diagnostic and therapeutic interventions, in accordance with the fundamental desire of the patient and her or his family.


Cardiac arrest after methylprednisolone pulse therapy rescued using extracorporeal membrane oxygenation in patients with acute cardiac rejection: two case reports.
Patients receive methylprednisolone pulse therapy (MPT) when acute cardiac rejection occurs. Although the regimen is generally safe and effective, severe complications occasionally develop. From 1997 to 2007, there were 210 cardiac transplantation procedures performed at our hospital. Among these patients, there were 23 episodes of acute rejection treated with MPT, 10 mg/kg/d. Two patients in our series had cardiac arrest within 36 hours after initiating the therapy. Endomyocardial biopsy specimens showed International Society for Heart Transplantation grade 1B allograft rejection in both cases. Emergent intubation and cardiopulmonary resuscitation were performed. Venoarterial extracorporeal membrane oxygenation (ECMO) was used to rescue the patients. The cardiac function in both patients recovered gradually. Left ventricular ejection fraction increased from 16.2% to 47% in one patient and from 27% to 30% in the other patient. One patient was successfully weaned from ECMO after 2 days of support. The other patient was discharged against medical advice because of hypoxia-related brain death after 3 days. Both patients had a history of tachyarrhythmias before initiation of MPT. Although the relationship between mechanisms of cardiac arrest and MPT is uncertain, the risk of cardiac arrest cannot be overlooked when initiating MPT, especially in patients with a history of tachyarrhythmia. Meanwhile, ECMO can serve as a rescue method if cardiac arrest occurs.


Kinetics of ADP, ATP transport in mitochondria as studied by the quench-flow method.
The kinetics in the millisecond range of ADP, ATP counterexchange in rat liver mitochondria were investigated using a quench-flow apparatus. The exchange was stopped with atractylate and the mitochondria were separated by centrifugation. 1. After correcting for leakage due to flow stress, apparent biphasic exchange kinetics were observed, with a more rapid phase within 100--200 ms, which extends to 10% of the total exchange. In general, the extent of the rapid phase increased when the translocation rate was changed under various conditions, in agreement with the model of the quench mechanism by atractylate. 2. The nature of the "rapid" phase was analyzed in the "steady" and "transient" state of the translocation and was shown to be caused by a delayed binding of atractylate due to competition with ADP. This quench delay results in a residual exchange which could explain the rapid part of the kinetics. 3. Deenergization of mitochondria by valinomycin or by uncoupler largely abolishes the rapid kinetic phase. This is explained by an increased availability of carrier sites at the outer face of the membrane to atractylate in the deenergized state, resulting in a more rapid quench. 4. The interpretation of the rapid exchange phase as a function of carrier sites accessible to atractylate quenching at the outer membrane face was simulated by a computer program based on the reorientating carrier model. With a set of rate constants, an approximate fit for the extent of quench delay with the experimental data is obtained.


Immediate postoperative regression of retroodontoid pannus after lateral mass reconstruction in a patient with rheumatoid disease of the craniovertebral junction. Case report.
The authors report the case of a 35-year-old man who had polyarthritic affliction with rheumatoid disease. He presented with complaints of quadriparesis that had progressed over the course of 2 years. Investigations revealed telltale evidence of rheumatoid disease of the craniovertebral junction with retroodontoid pannus, basilar invagination, and "fixed" atlantoaxial dislocation. The patient underwent lateral mass reconstruction with distraction of the facets and impaction of a spiked metal spacer and bone graft within the joint. Investigations done in the immediate postoperative phase showed complete disappearance of retroodontoid pannus in addition to reduction of basilar invagination and atlantoaxial dislocation. He had remarkable and sustained relief from symptoms. The authors also review the pathogenesis and treatment of retroodontoid pannus.


Association of maternal and paternal IQ with offspring conduct, emotional, and attention problem scores. Transgenerational evidence from the 1958 British Birth Cohort Study.
Individuals with lower IQ scores have an increased risk of psychological disorders, mental health problems, and suicide; similarly, children with low IQ scores are more likely to have behavioral, emotional, and anxiety disorders. However, little is known about the effect of parental IQ on the mental health outcomes of their children. To determine whether maternal and paternal IQ scores are associated with offspring conduct, emotional, and attention scores. Cohort study. General population. Members of the 1958 National Child Development Study and their offspring were studied. Of 2984 parent-offspring pairs with nonadopted children 4 years or older, 2202 pairs had complete data regarding all variables of interest and were included in the analyses. Offspring conduct, emotional, and attention scores based on the Behavioral Problems Index for children aged 4 to 6 years or the Rutter A scale for children and adolescents 7 years and older. Little evidence was observed of any association of parental IQ with conduct or emotional problems in children aged 4 to 6 years. However, among children and adolescents 7 years or older, strong evidence was observed from age- and sex-adjusted models to support a decrease in conduct, emotional, and attention problems in those whose parents had higher IQ scores. These associations were linear across the full IQ range. Individual adjustments for socioeconomic status and the child's own IQ had limited effect. However, adjustments for Home Observation for Measurement of the Environment scores and parental malaise attenuated associations with the mother's IQ but had little effect on associations with the father's IQ (scores were available for only 1 parent for each child or adolescent). Strong associations were no longer evident in models that simultaneously adjusted for all 4 potential mediating variables. Children whose parents score poorly on IQ tests may have an increased risk of conduct, emotional, and attention problems. The home environment, parental malaise, and the child's own IQ may have a role in explaining these associations.


Simplified oscillation method for assessing nasal obstruction non-invasively and under spontaneous ventilation: a pilot study.
The clinical application of the current methods of measuring nasal obstruction has been limited by complicated, invasive and stressful procedures that require the full co-operation of the patient. A pilot study is described where a simple way of evaluating nasal obstruction, based on oscillation methods, was investigated. The technique did not disturb spontaneous breathing and required little co-operation and comprehension. Significant differences were obtained when clinically classified normal (5.2 +/- 1.8 cmH2O l(-1) s) and patient (10.6 +/- 5.9 cmH2O l(-1) s) groups were evaluated (p<0.01). A significant reduction (p<0.02) was also observed in impedance results before (8.5 +/- 1.1 cmH2O l(-1) s) and after (5.2 +/- 1.7 cmH2O l(-1) s) clinically successful nasal surgery, closely reflecting the clinical conditions of the subjects. This simple forced oscillation technique showed good potential for future clinical applications in the pre-screening of nasal patients and the evaluation of therapeutic surgery.


Genetic engineering for enhanced biological nitrogen fixation in cereal crops.
Enhancing biological nitrogen (N) fixation in cereal crops has been a long-sought objective. Recently, Yan et al. identified plant compounds that induce biofilm production of diazotrophic bacteria and then performed genetic engineering in order to improve nitrogen fixation in rice plants. These findings hold promise for sustainable agriculture.


Spatiotemporal variations of surface ozone and its influencing factors across Tibet: A Geodetector-based study.
Reasons regarding surface ozone formation and distribution in remote regions is limited. Tibet is an important remote area on Earth, with various climates and extremely high elevation (average ~ 4000 m), which makes it a good place to study the spatiotemporal distribution of surface ozone and explore the causes. Based on ground monitoring data from 18 stations on Tibet between 2015 and 2019, the annual, seasonal, monthly, and diurnal variations of surface ozone were analyzed. The annual mean values (60.7-72.5 μg/m3) presented an increasing trend during the past five years, with seasonal concentrations of surface ozone higher in spring than in winter. Spatially, both the ground observations and high-resolution remote sensing data indicated that the surface ozone was relatively high in the southwest regions of Tibet, and low in the southeast and northeast areas. Geodetector analysis found that relative humidity (RH), normalized difference vegetation index (NDVI), and solar radiation (SR) were the top three individual factors affecting surface ozone distribution, while NO2, PM10, and PM2.5 showed less influence. All influencing factors showed an improvement through the two-factor interaction. The associations of RH∩PM10 (q = 0.77), RH∩NDVI (q = 0.72), and NDVI∩SR (q = 0.73) exhibited a strong impact on surface ozone distribution, suggesting that places with sparse vegetation cover, dry climate and strong SR would usually cause high atmospheric ozone burden. This could also explain why concentrations of surface ozone continue to increase in some remote areas worldwide with ecological deterioration and desertification.


Prophylactic lymphaticovenous anastomoses for resection of soft tissue tumors of the thigh to prevent secondary lymphedema-a retrospective comparative cohort analysis.
Patients with soft tissue tumors of extremities are at risk to develop secondary lymphedema after tumor resection caused by disruption of lymphatic vessels and sclerosis. Subsequently, this study aimed to evaluate the beneficial effects of lymphaticovenous anastomoses (LVAs) after soft tissue tumor resection of the thigh in a prophylactic approach. In a retrospective cohort study, we compared eight patients with a median age of 68.5 years (49-80) who received LVAs in combination with tumor resection for treatment of soft tissue tumors of the thigh region with a prior cohort of 20 patients with a median age of 63.0 years (23-84) who received soft tissue sarcoma resection of the thigh region. All patients of LVA cohort received 1-2 LVAs (mean 1.25 ± 0.49) at the dorsum of the foot and three patients at the SEKI-point (mean 0.375 ± 0.51). Mean maximum tumor diameter of LVA group was 19.5 ± 5.2 cm and 12.3 ± 6.6 cm of control group. All patients receiving LVA were assessed for development of lymphedema via bilateral measurements of circumference and assessment of lymphedema quality of life index (LyQLI). One of the eight patients who received LVAs showed moderate impairment in the LyQLI at a follow-up of 12 months while 45% of the control cohort complained about symptoms of secondary lymphedema at a median follow-up of 22 months (p-values LyQLI: p = .018 [physical domain]; p = .018 [psychosocial domain]; p = .020 [practical domain]). LVAs performed in combination with tumor resection of thigh soft tissue tumors reduce negative consequences of lymph stasis and prevent development of secondary lymphedema.


Factors associated with risk of death by suicide after psychiatric hospitalization by the Unified Health System in Brazil (2002-2015).
To investigate overall and sex-related characteristics associated with the risk of death by suicide within 365 days of discharge in patients admitted to psychiatric hospitals in the Brazilian Unified Health System (SUS). A non-concurrent prospective cohort of adult patients admitted to psychiatric hospitals in the SUS, from 2002 to 2015. Patients were stratified according to sociodemographic and clinical variables. Adjusted hazard ratios (aHRs) of suicide within 365 days of discharge were estimated using Cox proportional hazard regression models. This sample comprised 1,228,784 adult patients admitted to psychiatric hospitals. Of these, 3201 died by suicide within 365 days of discharge. The risk of suicide was positively associated with male sex, age between 18 and 29 years, living in the South region, and living in rural or intermediate municipalities. The highest risk of suicide was among patients with depressive disorders (aHR, 3.87; 95%CI, 3.41-4.38) follow by opioid-related disorders (aHR, 2.71; 95%CI, 2.00-3.67), particularly among female patients. Patients with a psychiatric hospital admission should have access to mental health care services immediately after discharge and in the long term. Findings of this study may support suicide prevention policies and have implications for clinical decisions related to patient discharge and follow-up.


Preoperative successful thrombectomy and thrombolysis of acute extensive splanchnic venous system and TIPSS thrombosis in a child with Budd-Chiari syndrome-Creating a window to enable living donor liver transplantation.
Preoperative extensive PV thrombosis can pose a technical challenge during liver transplantation surgery. Several strategies adopted to mitigate this problem include creation of a superior mesenteric vein-PV jump graft, use of a polytetrafluoroethylene graft, renoportal anastomosis, or cavoportal hemitransposition. Extensive and diffuse thrombosis of the splanchnic venous system may even necessitate multivisceral transplantation. We describe the case of a pediatric patient with Budd-Chiari syndrome and decompensated cirrhosis, who developed extensive thrombosis of the porto-spleno-mesenteric venous system prior to liver transplantation. We used a combination technique of thrombus aspiration by a novel trans-TIPPS approach followed by thrombolysis. Complete preoperative resolution of the extensive thrombosis was achieved. This allowed the creation of a brief window to enable planned LDLT. In prudently selected patients, performing an early mechanical and chemical thrombolysis of an extensive acute splanchnic venous thrombosis can thus help expedite a planned LDLT.


Intravitreal aflibercept (Eylea) injection for cystoid macular edema secondary to retinitis pigmentosa - a first case report and short review of the literature.
Cystoid macular edema (CME) in retinitis pigmentosa (RP) has been managed in several ways as documented in the literature, with little success, though. The aim of our study was to report for the first time in literature the use of aflibercept in a patient with RP and CME. A 52-year-old man presented for blurred vision in his right eye. Best-corrected visual acuity (BCVA) was 3/10 in his right eye and 7/10 in his left eye. Physical examination and appropriate laboratory tests lead to the diagnosis of bilateral RP with CME in the right eye. Retinal thickness in the foveal area of the right eye was 631 μm. The patient was treated with a single intravitreal injection of 0.05 ml/0.5 mg aflibercept. One month later, BCVA of the right eye increased to 4/10, while BCVA of the left eye was unchanged. RT in the right eye decreased to 129 μm. Multifocal electroretinogram response did not improve, yet peaks were better-shaped and no areas of eccentral vision were present. Three and six months after injection, these improvements were maintained. This first-reported case indicates that intravitreal aflibercept injection for addressing CME in RP seems to be an effective treatment.


[Electron microscopic study of the liver in chronic viral hepatitis C complicated by alcoholic liver disease].
Combination of HCV-infection and alcoholic liver disease is associated with enhancement of hepatocellular damage (lipid and hydropic degeneration become diffuse), a decrease of hepatocyte necrotic foci and lymphomacrophagal infiltration, an increase of hepatocyte apoptosis and liver fibrosis, absence of lymphoid follicles. An important role in the genesis of these liver alterations is attributed to the combination of viral and alcoholic factors with persistence of hepatitis C virus and liver reticulo-endothelial system depression.


Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice.
Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical 'proof of concept' stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40-60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4+ and CD8+ T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM.


Thermoregulatory and locomotor effects of DSIP: paradoxical interaction with d-amphetamine.
A low dose (0.1 mg/kg) of peripherally administered delta sleep-inducing peptide (DSIP) caused hypothermia in rats maintained at 4 degrees C but larger doses (1.0 or 3.0 mg/kg) did not. At 22 degrees C all 3 doses of DSIP caused hyperthermia. The interaction of d-amphetamine with DSIP was dependent on ambient temperature; at 4 degrees C DSIP had no effect on d-amphetamine-induced hypothermia, but at 22 degrees C DSIP reversed the usual d-amphetamine-induced effect of hyperthermia to hypothermia. At 4 degrees C, DSIP also potentiated the hypermotility effects of d-amphetamine but blocked it at 22 degrees C. Many rats receiving DSIP (0.1 mg/kg) and d-amphetamine (15.0 mg/kg) at 22 degrees C paradoxically exhibited what appeared to be sleep. This sleep-like effect was not found after several other doses of DSIP and d-amphetamine, chlorpromazine, or at a cold ambient temperature. Sodium methohexital caused apparent sleep in animals treated with DSIP alone or with DSIP and d-amphetamine, but was unable to induce this effect in rats receiving d-amphetamine alone. The results suggest that the effects of peripherally injected DSIP on body temperature are independent from its effects on locomotion and that both effects are dependent upon ambient temperature.


Infiltration of Lynch colorectal cancers by activated immune cells associates with early staging of the primary tumor and absence of lymph node metastases.
Lynch syndrome colorectal cancers often lose human leukocyte antigen (HLA) class I expression. The outgrowth of clones with immune evasive phenotypes is thought to be positively selected by the action of cytotoxic T cells that target HLA class I-positive cancer cells. To investigate this hypothesis, we related the type and density of tumor lymphocytic infiltrate in Lynch colorectal cancers with their HLA class I phenotype and clinicopathologic stage. HLA class I expression was assessed by means of immunohistochemistry. Characterization of tumor-infiltrating lymphocytes was carried out by using a triple immunofluorescence procedure that allowed the simultaneous detection of CD3-, CD8-, and granzyme B (GZMB)-positive cells. Additional markers were also used for further characterization of an elusive CD3(-)/CD8(-)/GZMB(+) cell population. We discovered that high tumor infiltration by activated CD8(+) T cells correlated with aberrant HLA class I expression and associated with early tumor stages (P < 0.05). CD8(+) T cells were most abundant in HLA class I heterogeneous tumors (P = 0.02) and frequent in HLA class I-negative cases (P = 0.04) when compared with HLA class I-positive carcinomas. An elusive immune cell population (CD45(+)/CD8(-)/CD56(-)/GZMB(+)) was characteristic for HLA class I-negative tumors lacking lymph node metastases (P < 0.01). The immune system assumes an important role in counteracting the progression of Lynch colorectal cancers and in selecting abnormal HLA class I phenotypes. Our findings support the development of clinical strategies that explore the natural antitumor immune responses occurring in Lynch syndrome carriers.


Reference signal less Fourier analysis based motion artifact removal algorithm for wearable photoplethysmography devices to estimate heart rate during physical exercises.
Accurate and reliable heart rate (HR) estimation using photoplethysmographic (PPG)-enabled wearable devices in real-time during daily life activities is challenging. A PPG signal recorded using a wearable PPG device is corrupted by motion artifacts. Therefore, the main challenge of monitoring HR in real time is the accurate reconstruction of a clean PPG signal by suppressing motion artifacts. The proposed algorithm employs the Fourier theory-based Fourier decomposition method (FDM) to suppress motion artifacts and a fast Fourier transform (FFT)-based method to estimate the HR. In this paper, a computationally efficient algorithm that does not require a reference accelerometer signal to suppress motion artifacts to estimate HR in real time during physical activities is proposed. The noisy PPG signal is decomposed into a desired set of orthogonal Fourier intrinsic band functions (FIBFs). A clean PPG signal is obtained by discarding the FIBFs corrupted with noise and superpositioning the clean FIBFs. Clean FIBFs were further used to estimate the HR. The proposed method is evaluated by computing the mean absolute error (MAE) and percentage absolute error (PAE) on two publicly available datasets, IEEE SPC (training and test) and BAMI (BAMI-I and BAMI-II). The MAE and PAE values computed with the proposed method using the IEEE SPC dataset were (1.87, 1.71). The MAE and PAE values computed using the proposed method on the BAMI-I and BAMI-II datasets were (1.33, 1.13) and (1.45, 1.17), respectively. The computed MAE and PAE values were more accurate than those of state-of-the-art techniques presented in the literature. Owing to the improved accuracy and speed, the proposed HR estimation algorithm can be implemented in wearable health monitoring devices for continuous and reliable HR estimation in real time. The proposed algorithm can be applied to denoise PPG signals with different sampling rates.


Polychemotherapy in squamous cell carcinoma of the buccal mucosa.
Thirty-nine patients with previously untreated squamous cell carcinoma of the buccal mucosa were treated by two polychemotherapeutic regimens. The first regimen consisted of bleomycin and methotrexate (BLM-MTX): bleomycin 30 mg was given intravenously twice weekly, and methotrexate 25 mg intravenously twice weekly for 2 1/2 and two weeks, respectively. The second program consisted of Cytoxan (cyclophosphamide), methotrexate and 5-FU (CMF): methotrexate 25 mg twice weekly for two weeks, Cytoxan 100 mg/day for two weeks, and 5-FU 500 mg twice weekly for 1 1/2 weeks. All of the patients were evaluated one week after completion of their chemotherapy regimen. Although the patients were not randomly allocated to either treatment, they matched in age and extent of disease. High response rates (88.9%) were noted with the BLM-MTX combination, which is comparable to the best responses reported previously using cis-platinum, Oncovin (vincristine), and methotrexate. This may suggest that buccal cancers are highly sensitive to an initial treatment by BLM-MTX, and therefore the authors highly recommend its use as preoperative adjuvant therapy in patients who present with Stage III and IV (Mo) disease.


Periodate oxidation analysis of carbohydrates. XIII. Simultaneous gas chromatographic determination of the aldehydes in the periodate oxidation products of non-dialyzable urinary carbohydrate materials as diethyl dithioacetals.
The aldehydes in the periodate oxidation products of non-dialyzable urinary carbohydrate materials were determined simultaneously by gas chromatography of their diethyl dithioacetal derivatives. The yields of aldehydes for normal male urine varied considerably among subjects, but their molar ratios were almost constant. The average values for glyceraldehyde/glyoxal and lactaldehyde/glyoxal molar ratios were 0.41 and 0.27, respectively. The average amount of L-fucose at the non-reducing terminals of carbohydrate chains, as estimated from the yield of lactaldehyde, was about 5 mg/day.


Effect of ibopamine on the failing heart at rest and during isometric exercise: a noninvasive study.
Eleven patients suffering from heart failure were treated with oral ibopamine, a di-isobutyric ester of N-methyldopamine, 100 mg three times a day for 1 week and 200 mg three times a day for 3 weeks. Therapy was discontinued by one patient because of tachycardia. Left ventricular performance was evaluated with echocardiography and systolic time intervals at rest and after 3 minutes of isometric exercise using a handgrip. Six of 10 patients completing the study were in New York Heart Association (NYHA) functional class III, 2 in class IV, and 2 in class II. All patients, except one who remained stable in class II, improved their subjective condition by one functional class during 4 weeks of therapy (p less than 0.01). There were no changes in heart rate, blood pressure, rate-pressure product, cardiac index, or total peripheral vascular resistance. The left ventricular end-systolic diameter decreased after four weeks from 71.2 +/- 12.7 (SD) to 65.9 +/- 13.0 mm (p less than 0.001); the left ventricular end-diastolic diameter did not change. The ejection fraction increased from 26 +/- 8 to 32 +/- 9% (p less than 0.01). Afterload, that is, left ventricular circumferential systolic wall stress, declined as a result of decreased systolic diameter. Systolic time intervals did not vary. There were no changes due to ibopamine during isometric exercise probably owing to increased beta-adrenergic stimulation induced by the handgrip. Neither urine volume nor body weight changed. Side effects were mild except for tachycardia of one patient.(ABSTRACT TRUNCATED AT 250 WORDS)


Serological evidence for a defect in RT1.B (I-A) expression by the BDIX rat strain.
Astrocytes, astrocytic cell lines and endothelium from BDIX rats were stimulated with recombinant interferon-gamma (IFN-gamma) and the expression of MHC molecules quantified using an enzyme immunoassay (EIA). Using the two mouse anti-RT1.B monoclonal antibodies MRC OX4 and OX6, previously described as recognizing a monomorphic determinant on RT1.B, as well as polyvalent rabbit anti-rat class II antisera, we were unable to demonstrate any induction of RT1.B molecules on these cells under conditions that induced RT1.B expression in all other strains tested. In contrast, RT1.D locus class II molecules, detectable by the antibody MRC OX17, are more strongly expressed in BDIX than in other strains. In experiments using BDIX lymphocytes, this serologically detected defect in RT.1B expression was confirmed using four additional mouse anti-mouse I-Ak monoclonal antibodies, which cross-reacted on all rat strains tested except BDIX. It appears likely that BDIX rats lack either a structural or controlling gene required for RT1.B expression.


Passipassalus brevicornis n. sp.: a New Passalidae (Coleoptera) from Brazilian Amazonian, with a Key to the Species of Passipassalus Reyes-Castillo & Fonseca.
Passipassalus brevicornis n. sp. is described from two specimens from Tefé and Coari, Amazonas, Brazil. This species represents the fifth species recognized of Passipassalus and differs from the other species of the genus mainly by having an apex of central tubercle of median frontal structure not free, frontal fossae with some scarce setae, metasternal fossae with scarce setae, humeri fully pubescent, and marginal groove over anterior ventral edge of femur I marked and complete. Additionally, a key to the species of Passipassalus is given.


Comorbid depression, but not comorbid anxiety disorders, predicts poor outcome in anxiety disorders.
Influence of type of comorbidity was studied over the course of 1 year in a sample of 141 outpatients with panic disorder with or without agoraphobia and generalized anxiety disorder, who were receiving different forms of cognitive behavior therapy. Influence of type of comorbidity was determined on the basis of change scores (linear regression analysis) and remission data (Kaplan-Meier survival analysis). Three categories, as assessed at baseline, were compared: no comorbidity, comorbidity among anxiety disorders, and comorbidity with mood disorders. Primary outcome variable: State-Trait Anxiety Inventory State subscale measured at four assessments (0, 12, 24, and 52 weeks). Analyses of change and remission indicated that comorbidity with mood disorders led to (i) less improvement and (ii) a lower remission rate than comorbidity among anxiety disorders and no comorbidity. Because comorbidity has a critical influence on prognosis, it seems to be important to make a reliable diagnosis of the disorders present.


Pulmonary valve perforation with multiple cardiac anomalies: a case report.
Large pulmonary valve perforation, which is rarely seen with infective endocarditis, general atrophy, or congenital fenestration, often leads to potentially fatal outcomes, including heart failure. Transthoracic and transesophageal echocardiographic evaluation of a 69-year-old woman revealed a severely eccentric pulmonary regurgitation with concomitant pulmonary valve stenosis, patent ductus arteriosus, patent foramen ovale, and pulmonary artery aneurysm. In the operation, a large perforation was found in the pulmonary valve leaflet. She underwent complicated surgery that involved closure of the congenital heart defects and replacement of a pulmonary valve with successful results. But the cause of her pulmonary valve perforation remained undetermined. This case highlights two important points: the need for timely management of congenital heart disease and being aware of the possibility of pulmonary valve perforation, which in this case was indicated by an eccentric pulmonary regurgitant jet seen on echocardiography.


Myoglobin concentration in single type I and type II muscle fibres in man.
Histochemical visualization of myoglobin in a benzidine peroxidase reaction suggests that human skeletal muscle fibres are differentiated into fibres having either high or a low myoglobin content. In the present study myoglobin was quantified in single human muscle fibres after being classified as either type I ("slow-twitch") or type II ("fast twitch"). Samples were obtained from m. quadriceps femoris in 4 healthy untrained male subjects using the needle biopsy technique. After freeze-drying, individual fibres were dissected out and classified as either type I or type II by a myofibrillar ATPase stain. Myoglobin analyses were performed on these single fibres by a radioimmunoassay. The myoglobin concentrations were found to be significantly higher in type I than in type II muscle fibres in all 4 subjects and were, on the average, of the same magnitude as found in larger (mixed muscle) samples. The myoglobin concentration ratio between type I and type II fibres ranged from 1.4 to 1.7.


Dipyridamole-induced increase in production of rat dopaminergic neurons from mesencephalic precursors.
Dipyridamole (DIP) was tested for its ability to induce dopaminergic (DA) phenotype in cultures from epidermal growth factor-derived mesencephalic precursor cells. When these cells were incubated in media containing serum, the DA phenotype was rarely expressed. The addition of DIP increased (about 350%) the number of DA cells per neurosphere. Treatment with interleukin-1 alpha also induced a significant increase (about 300%) in the number of tyrosine hydroxylase-positive cells. However, the mixture of the most effective doses of these compounds did not induce a further increase in the number of DA cells. The results suggest that DIP may contribute to more efficient production of DA neurons for transplantation therapies in neurodegenerative diseases, and that this may be related to an enhancement of generation and/or survival of DA cells.


Polymorphous ventricular tachycardia associated with a marked prolongation of the Q-T interval induced by amiodarone.
We report the case of a patient who developed a life-threatening polymorphous ventricular tachycardia ( PVT ) after six weeks of treatment with amiodarone. The Q-T interval was markedly prolonged at 0.86 second. The drug induction of PVT was strongly suggested by the fact that PVT resolved four days after withdrawal of amiodarone when the Q-T interval had shortened to 0.60 second; the arrhythmia has not recurred in the nine months of follow-up since then. Amiodarone, though a very effective antiarrhythmic agent, may induce serious PVT .


A novel interstitial deletion of 10q24.2q24.32 in a patient with renal coloboma syndrome.
Renal coloboma syndrome (RCS) is considered to be a rare autosomal dominant inherited disorder characterized by renal malformations and optic disc coloboma. Ocular anomalies range from asymptomatic abnormalities in retinal blood vessel patterning to large excavations of the optic nerve associated with reduced visual acuity. Commonly observed manifestations of the kidney are renal hypoplasia and vesicoureteric reflux leading to end-stage renal disease. Mutations in the PAX2 gene on chromosome 10 have been identified in patients with RCS. Up to date, nucleotide substitutions, insertions, small deletions, one de novo translocation, and one 240 kb deletion of the coding region of the PAX2 gene have been described to be responsible for RCS. We report here a new case of a patient with RCS due to a deletion of 3.8 Mb on chromosome 10q. Deletions on the long arm of chromosome 10 harboring the PAX2 gene seem to be a rare cause for RCS. Nevertheless, array-CGH testing should represent an important and valuable addition to PAX2 gene sequencing in diagnostic of RCS.


Beneficial effects of UDCA and norUDCA in a rodent model of steatosis are linked to modulation of GPBAR1/FXR signaling.
Non-alcoholic steatosis (NAFLD) and steatohepatitis (NASH) are two highly prevalent human disorders for which therapy remains suboptimal. Bile acids play an essential role in regulating liver metabolism, and several bile acids-based therapy are currently investigated for their potential therapeutic efficacy in NAFLD/NASH. Bile acids exert their functions, at least in part, by modulating two main receptors the Farnesoid-x-receptor (FXR) and the G protein-coupled receptor, GPBAR1. In the present study we have compared the pharmacological effects of two bile acids, the ursodeoxycholic acid (UDCA) and its derivative norUDCA, in a model of NAFLD/NASH induced by feeding mice with a Western diet for 12 weeks. The results of these studies demonstrated that both UDCA and norUDCA protected against development of steatosis and fibrosis, but did not reduce the hepatocytes ballooning nor the development of a pro-atherogenic lipid profile. Both agents reduced liver lipogenesis and ameliorated insulin sensitivity and adipocytes signaling as shown by increased expression of adiponectin. Mechanistically, UDCA acts as weak GPBAR1 agonist, while norUDCA exerted no effect on both GPBAR1 and FXR. In vivo administration of UDCA resets bile acid synthesis and promotes a shift toward bile acids species that are GPBAR1 agonists, UDCA, TUDCA and hyodeoxycholic acid, and increases GLP1 expression in the ileum. In contrast norUDCA is poorly metabolized exerting a minimal impact on GPBAR1 signaling. Together, these data, highlight the potential role of UDCA and norUDCA in treating of NAFLD, though these beneficial effects are supported by different mechanisms.