Lead induced oxidative stress and its recovery following co-administration of melatonin or N-acetylcysteine during chelation with succimer in male rats.
Lead is a ubiquitous element in the environment causing oxidative burst in the exposed individuals leading to tissue damage. Antioxidants have long been known to reduce the free radical-mediated oxidative stress while, thiol chelators have been used to treat arsenic toxicity. The therapeutic efficacy of melatonin or N-acetylcysteine (NAC) was studied in the present study, both individually and in combination with a potent thiol-chelating agent, meso 2,3-dimercaptosuccinic acid (DMSA), in reducing lead concentration in blood and other soft tissues. Their ability to restore altered haematopoietic, hepatic and other biochemical variables indicative of tissue oxidative stress in male rats was also investigated. Administration of melatonin and NAC individually, provided significant protection to lead induced disturbed antioxidant defense that may significantly compromise normal cellular function. Administration of melatonin and NAC also provided a significant protection to thiobarbituric acid reactive substances (TBARS) levels, reduced glutathione (GSH) and oxidized glutathione (GSSG) contents in tissues, suggesting their ability to act as a free radical scavenger and in protecting cells against toxic insult. NAC, a thiol containing antioxidant, has been used under several clinical conditions with few adverse side effects. It has a high toxicity threshold and its wide therapeutic window enhances its utility. The antioxidant action of NAC is due to its ability to interact with reactive oxygen species (ROS) or its ability to stimulate endogenous glutathione (GSH) synthesis. DMSA, on the other hand when given alone, provided significant recovery in restoring the altered lead sensitive biochemical indices like blood delta-aminolevulinic acid dehydratase (ALAD), urinary delta-aminolevulinic acid (ALA), beside increasing urinary lead excretion and decreasing lead concentration in blood and soft tissues. Interestingly, combined treatment of DMSA and NAC provided more pronounced efficacy in restoring altered biochemical variables and in reducing body lead burden than monotherapy with DMSA. The results thus, suggest the involvement of ROS in lead toxicity and a pronounced beneficial role of NAC in therapeutic implications of lead poisoning when co-administered with a thiol chelator (DMSA) supporting the hypothesis that cellular redox status may be significantly reversed by utilizing a thiol containing antioxidant compound. It can be concluded that, combined therapy with an antioxidant moiety and a thiol-chelating agent may be a better choice for treating plumbism.


Low frequency of paleoviral infiltration across the avian phylogeny.
Mammalian genomes commonly harbor endogenous viral elements. Due to a lack of comparable genome-scale sequence data, far less is known about endogenous viral elements in avian species, even though their small genomes may enable important insights into the patterns and processes of endogenous viral element evolution. Through a systematic screening of the genomes of 48 species sampled across the avian phylogeny we reveal that birds harbor a limited number of endogenous viral elements compared to mammals, with only five viral families observed: Retroviridae, Hepadnaviridae, Bornaviridae, Circoviridae, and Parvoviridae. All nonretroviral endogenous viral elements are present at low copy numbers and in few species, with only endogenous hepadnaviruses widely distributed, although these have been purged in some cases. We also provide the first evidence for endogenous bornaviruses and circoviruses in avian genomes, although at very low copy numbers. A comparative analysis of vertebrate genomes revealed a simple linear relationship between endogenous viral element abundance and host genome size, such that the occurrence of endogenous viral elements in bird genomes is 6- to 13-fold less frequent than in mammals. These results reveal that avian genomes harbor relatively small numbers of endogenous viruses, particularly those derived from RNA viruses, and hence are either less susceptible to viral invasions or purge them more effectively.


miR-126-3p and miR-451a correlate with clinicopathological features of lung adenocarcinoma: The underlying molecular mechanisms.
Lung cancer is the most common malignancy worldwide. This study aimed to identify miRNA biomarkers of lung adenocarcinoma and to investigate their molecular mechanisms. miRNA expression profiling of tumor tissues and adjacent normal tissues from 10 patients were detected using microarray. Differentially expressed miRNAs (DEMs) were identified, and were verified using quantitative reverse transcription-PCR. Thereafter, correlations between DEM expression and clinicopathological features were determined in 49 patients. Furthermore, Targetscan was utilized to predict target genes, among which transcription factors (TFs) were identified. The interactions among miRNAs, TFs and target genes were used to construct an miRNA-TF-target network. Totally, 11 DEMs were identified, among which two downregulated miRNAs (miR-126-3p and miR-451a) were validated. Low levels of miR-126-3p and miR-451a were associated with poor pathological stage, large tumor diameter and lymph node metastasis (P<0.05). Receiver operating characteristic analysis showed that both miRNAs could predict pathological stage, tumor diameter and lymph node metastasis of lung adenocarcinoma (AUC >0.65, P<0.05). For miR-126-3p, 154 target genes were predicted (e.g., PLXNB2), which were enriched in 29 pathways mainly concerning apoptosis and cancer. For miR‑451a, 397 target genes were predicted, which were enriched in 5 pathways including 'PPAR signaling pathway'. Ten genes were co-regulated by miR-126-3p and miR-451a, e.g., TSC1. Furthermore, an miRNA-TF-target network was constructed, and a sub-network was identified, including 2 miRNAs, 15 targets, and 7 TFs. In conclusion, miR-126-3p and miR-451a predicted the severity of lung adenocarcinoma. However, the possible mechanisms explored by bioinformatics need to be further validated.


A unique funding opportunity for public health in Texas.
In addition to the Affordable Care Act, states are more frequently turning to Medicaid waivers to achieve the "Triple Aim" goals of improving the experience of care, improving population health, and reducing per capita costs. These demonstration waivers provide opportunities to test innovative ways to finance and deliver care. Texas is currently implementing a waiver known as the Transformation and Quality Improvement Program. Its inclusion of public health agencies is a unique approach to a system typically limited to traditional providers. San Antonio Metropolitan Health District is one public health agency taking advantage of this new funding opportunity to implement 6 new or expanded programs targeting health issues of highest priority in this south Texas region. This article discusses the use of Medicaid waivers and the advantages and challenges of public health agency participation.


Validation of the Surgical Apgar Score After Laparotomy at a Tertiary Referral Hospital in Rwanda.
The surgical Apgar score (SAS) has demonstrated utility in predicting postoperative outcomes in a variety of surgical disciplines. However, there has not been a study validating the utility of the SAS in surgical patients in low-income countries. We conducted a prospective, observational study of patients undergoing laparotomy at a tertiary referral hospital in Rwanda and determined the ability of SAS to predict inpatient major complications and mortality. All adult patients undergoing laparotomy in a tertiary referral hospital in Rwanda from October 2014 to January 2015 were included. Data were collected on patient and operative characteristics. SAS was calculated and patients were divided into four SAS categories. Primary outcomes were in-hospital mortality and major complications. Rates and odds of in-hospital mortality and major complications were examined across the four SAS categories. Logistic regression modeling and calculation of c-statistics was used to determine the discriminative ability of SAS. 218 patients underwent laparotomy during the study period. One hundred and forty-three (65.6%) were male, and the median age was 34 years (IQR 27-51 years). The most common diagnosis was intestinal obstruction (97 [44.5%]). A high proportion of patients (170 [78%]) underwent emergency surgery. Thirty-nine (18.3%) patients died, and 61 (28.6%) patients had a major complication. In-hospital mortality occurred in 25 (50%) patients in the high-risk group, 12 (16%) in the moderate-risk group, 2 (3%) in the mild-risk group and there were no deaths in the low-risk group. Major complications occurred in 32 (64%) patients in the high-risk group, 22 (29%) in the moderate-risk group, 7 (11%) in the mild-risk group and there were no complications in the low-risk group. SAS was a good predictor of postoperative mortality (c-statistic 0.79) and major complications (c-statistic 0.75). SAS can be used to predict in-hospital mortality and major complications after laparotomy in a Rwandan tertiary referral hospital.


N-acetyltransferase 2 single-nucleotide polymorphisms and risk of gastric carcinoma.
To explore whether an association exists between the NAT2 genotype and the risk of developing gastric cancer.METHODS. Ninety-nine patients with gastric adenocarcinoma and 258 healthy subjects were analysed for single-nucleotide polymorphisms at the NAT2 gene locus, which give rise to gene variants known to be associated with slow-acetylation status. The functional NAT2*4 (wild-type) allele is over-represented among patients (40.4% of all allelic variants) compared with control subjects [25.8%, odds ratio (OR) 1.95, 95% confidence interval (CI) 1.36, 2.8]. According to the NAT2 genotype, 69 patients (69.9%) and 119 healthy subjects (46%) were classified as rapid acetylators (OR 2.69, 95% CI 1.6, 4.54). Our results, which need independent confirmation, suggest that individuals with NAT2 genotypes leading to high levels of NAT2 enzyme activity are at increased risk of developing gastric carcinoma.


Cladribine: an investigational immunomodulatory agent for multiple sclerosis.
To review the pharmacology, pharmacokinetics, efficacy, and safety of cladribine, a purine analog undergoing Phase III trials for approval of its use in the treatment of multiple sclerosis (MS). A MEDLINE search (1966-September 2006) was conducted using the key words cladribine and multiple sclerosis. No limits were placed on the search. Studies and review articles related to cladribine and MS were reviewed. The trials examining the role of cladribine in MS were analyzed. Cladribine is a purine analog that demonstrates lymphocytotoxic activity. Recent data suggest that cladribine may have a role in the treatment of relapsing-remitting and the progressive forms of MS. In these studies, cladribine has shown mixed results in decreasing neurologic disability, as measured by various rating scales, but has consistently shown positive results in reducing the number of enhancing lesions, which reflects a measure of disease activity. To date, there is one ongoing study examining the role of oral cladribine in the treatment of relapsing-remitting MS. The incidence of adverse effects with cladribine has been significantly greater than with placebo, with the most common being myelosuppression. While data do not support its use as a first-line MS treatment, cladribine may be a promising agent for refractory patients with secondary progressive MS. Further studies are warranted.


Regulation of mitochondrial function and endoplasmic reticulum stress by nitric oxide in pluripotent stem cells.
Mitochondrial dysfunction and endoplasmic reticulum stress (ERS) are global processes that are interrelated and regulated by several stress factors. Nitric oxide (NO) is a multifunctional biomolecule with many varieties of physiological and pathological functions, such as the regulation of cytochrome c inhibition and activation of the immune response, ERS and DNA damage; these actions are dose-dependent. It has been reported that in embryonic stem cells, NO has a dual role, controlling differentiation, survival and pluripotency, but the molecular mechanisms by which it modulates these functions are not yet known. Low levels of NO maintain pluripotency and induce mitochondrial biogenesis. It is well established that NO disrupts the mitochondrial respiratory chain and causes changes in mitochondrial Ca2+ flux that induce ERS. Thus, at high concentrations, NO becomes a potential differentiation agent due to the relationship between ERS and the unfolded protein response in many differentiated cell lines. Nevertheless, many studies have demonstrated the need for physiological levels of NO for a proper ERS response. In this review, we stress the importance of the relationships between NO levels, ERS and mitochondrial dysfunction that control stem cell fate as a new approach to possible cell therapy strategies.


The Importance of Social Support, Optimism and Resilience on the Quality of Life of Cancer Patients.
The aim of the present study is to carry out a multidimensional analysis on the relation between satisfaction with social support received, resilience and optimism in cancer patients and their quality of life. Data were gathered through questionnaires fulfilled by 142 cancer patients. Data relate to sociodemographic, health, quality of life, social support, resilience and optimism. Satisfaction with the sources and types of support, resilience and optimism relates positively with quality of life. Predictive models show that informational support from friends is the variable that most increases patients' general health, while emotional support from the partner is the one that best improves how patients cope with the disease. In the same line, emotional support from the partner, together with informational support from family are the ones that most contribute to reduce patients' symptoms. Resilience improves general health and functioning, and reduces symptoms. Patients' optimism and resilience also reduce symptoms. Gender differences were found, with females showing lower quality of life than males, mainly in how they cope with cancer. Patients in the stage of treatment showed lower quality of life and higher symptoms. Such increase was observed in patients who received hormonotherapy or chemotherapy. Important practical implications can be drawn from results, which could help improve cancer patients' quality of life through intervention strategies aimed at increasing their resilience, optimism and the social support provided by their closer sources.


Uniform convergence of basic Fourier-Bessel series on a q-linear grid.
We study Fourier-Bessel series on a q-linear grid, defined as expansions in complete q-orthogonal systems constructed with the third Jackson q-Bessel function, and obtain sufficient conditions for uniform convergence. The convergence results are illustrated with specific examples of expansions in q-Fourier-Bessel series.


The Utility of Monitoring Potassium in Transgender, Gender Diverse, and Nonbinary Individuals on Spironolactone.
Current Endocrine Society guidelines recommend that transgender women taking spironolactone have their potassium levels checked every 3 months for the first year after initiating therapy and annually thereafter to monitor for hyperkalemia. The goal of this study was to assess the need for such frequent potassium monitoring and to investigate whether age plays a role in potassium abnormalities in transgender, gender diverse, and nonbinary (TGDNB) individuals taking spironolactone. Using EPIC-Clarity, a retrospective study of healthy, adult individuals with gender-identity disorder listed in their problem list and taking spironolactone was performed. We analyzed the incidence of hyperkalemia in this population. Data from June 2006 through November 2021 were obtained. Exclusion criteria included hypertension, renal failure, diabetes mellitus, heart failure, and medications that affect the renin-angiotensin-aldosterone system. 318 healthy TGDNB individuals met our inclusion criteria. We identified 8/318 (2.5%) individuals with hyperkalemia on spironolactone. There was a significant difference in incidence of hyperkalemia events in those >45 years old and those ≤45 years old (8.9% vs 1.5%, P = .016). Our data suggest the incidence of hyperkalemia in our TGDNB population is low, particularly in those ≤45 years old; however, this risk increases with age. These findings suggest practice guidelines may need to be adjusted to minimize unnecessary testing in the population ≤45 years old who are not plagued by comorbidities that affect potassium handling.


Association Between Low-Grade Systemic Inflammation and Type 2 Diabetes Mellitus Among Men and Women from the ATTICA Study.
To investigate the relationship between low-grade inflammation and several glycemic indices in a population-based sample of men and women. The ATTICA study is a population-based cohort that randomly enrolled 1514 men and 1528 women (aged >18 years old), stratified by age and gender, from the Greater Athens area, during 2001-2002. Among several characteristics, inflammation markers (high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, homocysteine and amyloid A) and glycemic control indices (fasting blood glucose, insulin, HOMA) were measured in the participants. The prevalence of diabetes was 7.8% in men and 6.0% in women. The prevalence of impaired fasting glucose (IFG) was 21% in men and 12% in women. Diabetic subjects had 57% higher mean levels of C-reactive protein (p < 0.001), 22% higher mean levels of interleukin-6 (p < 0.001) and 60% higher levels of tumor necrosis factor-alpha (p < 0.001) compared to non-diabetic subjects. Homocysteine and serum amyloid A levels did not show significant differences among groups. Our study supports a positive association between low-grade inflammation and diabetes in a population-based sample of men and women without any evidence of cardiovascular disease, which is independent of demographic, clinical and lifestyle characteristics, including physical activity and dietary factors.


[Electrophysiological effect of atorvastatin on isolated rat hearts injured by ischemia/reperfusion].
To investigate the myocardial electrophysiological effect and its underlying mechanisms of atorvastatin (Ator) on isolated rat hearts injured by ischemia/reperfusion (I/R). Isolated SD rat hearts were mounted on Langendorff system, and a local I/R was induced by ligation (30 min) and release (15 min) of the left anterior descending artery. During the reperfusion period, the effect of Ator on diastolic excitation threshold (DET), effective refractory period (ERP) and ventricular fibrillation threshold (VFT) on rat heart were measured. Compared with the control group, medium concentration of Ator prolonged the ERP in normal rat hearts; low, medium and high concentration of Ator significantly inhibited the decrease of DET, ERP and VFT induced by I/R. However, pretreatment with L-NAME cancelled these cardiac electrophysiological effects of Ator. Ator reduced electrophysiological alteration induced by I/R in isolated rat hearts, which may be mediated by activating nitric oxide pathway to enhance the myocardial electrophysiological stability.


TWEAK enhances E-selectin and ICAM-1 expression, and may contribute to the development of cutaneous vasculitis.
Our previous work indicated that TWEAK is associated with various types of cutaneous vasculitis (CV). Herein, we investigate the effects of TWEAK on vascular injury and adhesion molecule expression in CV mice. We showed that TWEAK priming in mice induced a local CV. Furthermore, TWEAK priming also increased the extravasation of FITC-BSA, myeloperoxidase activity and the expression of E-selectin and ICAM-1. Conversely, TWEAK blockade ameliorated the LPS-induced vascular damage, leukocyte infiltrates and adhesion molecules expression in LPS-induced CV. In addition, TWEAK treatment of HDMECs up-regulated E-selectin and ICAM-1 expression at both mRNA and protein levels. TWEAK also enhanced the adhesion of PMNs to HDMECs. Finally, western blot data revealed that TWEAK can induce phosphorylation of p38, JNK and ERK in HDMECs. These data suggest that TWEAK acted as an inducer of E-selectin and ICAM-1 expression in CV mice and HDMECs, may contribute to the development of CV.


Transcriptome profiles associated with resilience and susceptibility to single prolonged stress in the locus coeruleus and nucleus accumbens in male sprague-dawley rats.
Although most people are subjected to traumatic stress at least once in their lifetime, only a subset develop long-lasting, stress-triggered neuropsychiatric disorders, such as PTSD. Here we examined different transcriptome profiles within the locus coeruleus (LC) and nucleus accumbens (NAc) that may contribute to stress susceptibility. Sprague Dawley male rats were exposed to the single prolonged stress (SPS) model for PTSD. Two weeks later they were tested for their anxiety/avoidance behavior on the Elevated Plus Maze (EPM) and were divided into high and low anxiety-like subgroups. RNA (n = 5 per group) was subsequently isolated from LC and NAc and subjected to RNAseq. Transcriptome analysis was used to identify differentially-expressed genes (DEGs) which differed by at least 50 % with significance of 0.01. The LC had more than six times the number of DEGs than the NAc. Only one DEG was regulated similarly in both locations. Many of the DEGs in the LC were associated with morphological changes, including regulation of actin cytoskeleton, growth factor activity, regulation of cell size, brain development and memory, with KEGG pathway of regulation of actin cytoskeleton. The DEGs in the NAc were primarily related to DNA repair and synthesis, and differential regulation of cytokine production. The analysis identified MTPN (myotrophin) and NR3C1 (glucocorticoid receptor) as important upstream regulators of stress susceptibility in the LC. Overall the study provides new insight into molecular pathways in the LC and NAc that are associated with anxiety-like behavior triggered by stress susceptibility or resilience.


Psychosis management in patients with hiv: case report.
Human immunodeficiency virus (HIV) infection can cause neuropsychiatric disorders such as cognitive impairment, behavioural difficulties or psychiatric symptoms –for instance, mania and psychosis. HIV patients with psychiatric comorbidities need an appropriate treatment which tackles the HIV infection as much as the particular mental symptoms. Here we present the case of a patient suffering from delusions, which turned out to be caused by encephalitis secondary to a previously unknown HIV infection. A review of psychosis in HIV-infected patients is also presented. This review is focused on the epidemiology, etiopathogenesis and clinical presentation of HIV-induced psychosis, as well as the recommended pharmacological treatment (antiretroviral therapy and antipsychotic medication) and the expected treatment response. We also present wide information concerning pharmacological interactions between antiretroviral and antipsychotic medications that we hope will help the clinician to better manage this complex condition.


Housework share between partners: Experimental evidence on gender-specific preferences.
This paper uses a novel vignette-based experimental design to investigate the reasons underlying the gendered division of housework. We are particularly interested in the role of gender-specific preferences: are there differences in the utility that men and women derive from housework, and might these be responsible for the fact that women continue to do more housework than men? It is difficult to address these questions with conventional survey data, because of inherent problems with endogeneity and ex-post rationalization; our experimental design circumvents these problems. We find remarkably little evidence of any systematic gender differences in preferences, and a general inclination towards an equal distribution of housework; this suggests that the reasons for the gendered division of housework do not derive from gender differences in preferences, and must lie elsewhere.


A sonographic study of perinatal hip development: from 34 weeks of gestation to 6 weeks of age.
A sonographic study of perinatal hip development was performed by consecutive measurement of Graf's alpha and beta angles in fetal and newborn hips. The study group consisted of infants with sonographically normal hip findings at birth. Forty fetuses were examined by fetal hip sonography at 34, 36 and 38 weeks of gestation. Postnatally, hip sonography was performed in the first and sixth week of age. Maturation curves of the bony (alpha-angle) and cartilaginous (beta-angle) acetabular roof from 34 weeks of gestation to 6 weeks of age were established. Prenatally, the mean alpha-angles were above the level that corresponds to a mature hip joint. A significantly higher value of the mean alpha-angles was found after birth. The mean beta-angles of the fetuses did not differ from those of the newborns. Our results revealed that the fetal hip joint is sonographically mature at 34 weeks of gestation. Further progression of hip development occurs around term.


Reduced cohesin destabilizes high-level gene amplification by disrupting pre-replication complex bindings in human cancers with chromosomal instability.
Gene amplification is a hallmark of cancer with chromosomal instability although the underlying mechanism by which altered copy numbers are maintained is largely unclear. Cohesin, involved in sister chromatid cohesion, DNA repair, cell cycle progression and transcriptional regulation of key developmental genes, is frequently overexpressed in human cancer. Here we show that cohesin-dependent change in DNA replication controls the copy numbers of amplified genes in cancer cells with chromosomal instability. We found that the down-regulation of elevated cohesin leads to copy number-associated gene expression changes without disturbing chromosomal segregation. Highly amplified genes form typical long-range chromatin interactions, which are stabilized by enriched cohesin. The spatial proximities among cohesin binding sites within amplified genes are decreased by RAD21-knockdown, resulting in the rapid decline of amplified gene expression. After several passages, cohesin depletion inhibits DNA replication initiation by reducing the recruitment of pre-replication complexes such as minichromosome maintenance subunits 7 (MCM7), DNA polymerase α, and CDC45 at replication origins near the amplified regions, and as a result, decreases the DNA copy numbers of highly amplified genes. Collectively, our data demonstrate that cohesin-mediated chromatin organization and DNA replication are important for stabilizing gene amplification in cancer cells with chromosomal instability.


Acute relapsing pancreatitis in primary hyperparathyroidism with hypercalcemia aggravated after aspiration cytology: report of a case.
In 1957, Cope and his associates first noted 2 cases of pancreatitis associated with primary hyperparathyroidism. They emphasized the association of hyperparathyroidism and pancreatitis. Since then pancreatitis has become a diagnostic clue to primary hyperparathyroidism. We report herein a 39-year-old woman who had suffered from acute relapsing pancreatitis 3 times in the past 2 years. Hypercalcemia persisted throughout the course. A movable mass 3 x 3 cm in diameter was noted over the right thyroid area on physical examination. A hypoechogenic mass 3.5 x 2.7 x 1.4 cm was found between the right lobe of the thyroid and the carotid artery. Because of a persistently high serum level of Ca2+, normal saline and furosemide were infused; the serum Ca2+ decreased gradually. After aspiration of the suspected mass, the serum level of Ca2+ increased from 8.7 mg/dL to 18 mg/dL. Because of the impression of parathyroid adenoma, surgery was performed and a 3 x 2.5 x 1.5 cm well-encapsulated mass was excised without difficulty. Pathologic examination revealed a well-encapsulated parathyroid adenoma. This case reveals that primary hyperparathyroidism maybe one of the causes of pancreatitis, and aspiration cytology, although it may be helpful for the diagnosis, can aggravate the hypercalcemia.


Immunocytochemical demonstration of a neuropeptide in Ascaris suum (Nematoda) using an antiserum to FMRFamide.
A FMRFamide-like peptide has been detected in the nematode Ascaris suum, using the peroxidase-anti-peroxidase (PAP) immunocytochemical technique. Positive reactions were obtained in both the central nervous system and the peripheral nervous system of the worm, the strongest reactions being in the anterior nerve ring, the cephalic papillary ganglia, the lateral ganglia and the dorso-rectal ganglion. Immunoreactivity was observed along the length of the main nerve cords of the worm and, to a lesser extent, in the pharyngeal nerve cords. The possible role of this neuropeptide in the physiology of the nematode is discussed.


Spin-electron-phonon excitation in Re-based half-metallic double perovskites.
A remarkable hardening (~30 cm(-1)) of the normal mode of vibration associated with the symmetric stretching of the oxygen octahedra for the Ba(2)FeReO(6) and Sr(2)CrReO(6) double perovskites is observed below the corresponding magnetic ordering temperatures. The very large magnitude of this effect and its absence for the antisymmetric stretching mode provide evidence against a conventional spin-phonon coupling mechanism. Our observations are consistent with a collective excitation formed by the combination of the vibrational mode with oscillations of Fe or Cr 3d and Re 5d occupations and spin magnitudes.


Effect of ginger essential oil and 6-gingerol on a multispecies biofilm of Listeria monocytogenes, Salmonella Typhimurium, and Pseudomonas aeruginosa.
The objective of this study was to evaluate the potential antimicrobial and antibiofilm effect of ginger essential oil (GEO) and 6-gingerol on a multispecies biofilm formed by Listeria monocytogenes, Salmonella Typhimurium, and Pseudomonas aeruginosa on a polypropylene surface. The minimum inhibitory concentration concentrations obtained for GEO were 100 and 50 mg/mL and for 6-gingerol 1.25 mg/mL. Sessile cell counts ranged within 5.35-7.35 log CFU/cm2 in the control biofilm, with the highest sessile growth at 72 h. GEO treatments acted on the total population regardless of concentration at 1 and 48 h. L. monocytogenes behaved similarly to the total population, showing GEO action at 1 h and keeping the same pattern at 48, 72, and 96 h. Better action on S. Typhimurium was obtained at times of 1, 72, and 96 h. P. aeruginosa showed logarithmic reduction only when treated with GEO 50 mg at 24 h. As for 6-gingerol, in general, there was no significant action (p > 0.05) on the evaluated sessile cells. GEO showed antimicrobial activity against L. monocytogenes, S. Typhimurium, and P. aeruginosa, acting as an inhibitor of biofilm formation. As for 6-gingerol, it was considered a possible antimicrobial agent but without efficacy during biofilm formation.


Vetlife Financial Support grant.
Members of the veterinary community may be finding it tough to make ends meet as the social restrictions imposed to help combat Covid-19 affect their ability to earn a living. Vetlife Honorary Secretary Elaine Garvican explains that Vetlife Financial Support can provide assistance to veterinary surgeons experiencing financial hardship.


Self in Art/Self As Art: Museum Selfies As Identity Work.
Selfies, digital images characterized by the desire to frame the self in a picture taken to be shared with an online audience, are important reflections of the contemporary self. Much extant psychological research on selfies has taken a pathologizing view of the phenomenon, focusing on its relationship to narcissism. Our investigation seeks to contribute to a holistic, contextualized and cultural perspective. We focus on the context of museums, places where art, history, education, and culture merge into the selfie taking behaviors of patrons. First, we explore theory salient to our topic of selfie taking, finding selfies to be an important way to construct ongoing series of narratives about the self. We use concepts of identity work, dramaturgy, and impression management to understand it in this light. We relate embodiment within the museum to the selfie's performative acts and expand upon notions that emphasize and distinguish the aesthetic elements present in many aspects of everyday life. We also question the ability of the museum selfie to destabilize. We also explore the contextual effects of mimicry and social norms. After describing our ethnographic and netnographic method, we investigate the museum selfie phenomenon. We begin with some observations on the extent of selfie-taking in contemporary culture as well as its evolution. Then, we consider selfies as a type of dynamic art form. Our analysis identifies a range of different types of museum selfies: art interactions, blending into art, mirror selfies, silly/clever selfies, contemplative selfies, and iconic selfies. Considered and studied in context, the museum selfie phenomenon reveals far more than the narcissism of the sort explored by past psychological research. The museum provides a stage for identity work that offers an opportunity for the selfie to be used not only for superficial performances but also in the pursuit of more profound self-reflection and its communication. Our ethnographic exploration of the selfie sees it as more than a quest for attention but less than a genuinely destabilizing social force. Selfie taking is complex and multidimensional, a cultural and social act, a call for connection, an act of mimicry, and part of people's ever-incomplete identity projects.


Nonicteric liver damage with a gamma-glutamyl transpeptidase level of 5,609 units/l in a renal-transplant recipient receiving azathioprine.
A 26-year-old male with renal allograft, who received immunosuppressive treatment with azathioprine, presented marked elevations of serum biliary tract enzymes, such as gamma-glutamyl transpeptidase (5,609 units/l) and alkaline phosphatase (60.5 Bessey-Lowry units), 14 months after transplantation. Two months later the patient became icteric; he died of respiratory failure 19 months after the renal allograft. Postmortem examination revealed intrahepatic cholestasis with minimal inflammatory cell infiltration, indicating drug hepatotoxicity.


Distinct requirements for energy metabolism in mouse primordial germ cells and their reprogramming to embryonic germ cells.
Primordial germ cells (PGCs), undifferentiated embryonic germ cells, are the only cells that have the ability to become gametes and to reacquire totipotency upon fertilization. It is generally understood that the development of PGCs proceeds through the expression of germ cell-specific transcription factors and characteristic epigenomic changes. However, little is known about the properties of PGCs at the metabolite and protein levels, which are directly responsible for the control of cell function. Here, we report the distinct energy metabolism of PGCs compared with that of embryonic stem cells. Specifically, we observed remarkably enhanced oxidative phosphorylation (OXPHOS) and decreased glycolysis in embryonic day 13.5 (E13.5) PGCs, a pattern that was gradually established during PGC differentiation. We also demonstrate that glycolysis and OXPHOS are important for the control of PGC reprogramming and specification of pluripotent stem cells (PSCs) into PGCs in culture. Our findings about the unique metabolic property of PGCs provide insights into our understanding of the importance of distinct facets of energy metabolism for switching PGC and PSC status.


Diphenyleneiodonium and dimethylsulfoxide for treatment of reperfusion injury in cerebral ischemia of the rat.
Diphenyleneiodonium (DPI) is an inhibitor of the free radical producing NAD(P)H-oxidase. We tested whether DPI shows neuroprotective properties after focal cerebral ischemia and we used dimethylsulfoxide (DMSO), a nonspecific free radical scavenger, as a solvent. In male Wistar rats middle cerebral artery occlusion (1.5 h) and subsequent reperfusion (48 h) (MCAO/R) was induced with the filament model. Immediately after reperfusion the animals received either 0.25 ml normal saline, DMSO, or a combination of DMSO and DPI; each group consisted of 10 animals. MRI was performed at different times after reperfusion. Gelatine zymography of brain tissue for MMP-2 and MMP-9 was performed. The infarct sizes and BBB damage showed a significant difference between controls and the DPI/DMSO group for almost all points in time in all sequences. The activity of MMP-2 and MMP-9 was significantly reduced by DPI/DMSO but not by DMSO alone. DMSO treatment alone resulted in a protective effect with reduced lesion sizes measured by MRI at selected points of time, consistent with its known free radical scavenger effect. The combination of DMSO with DPI partly augmented this effect, presumably due to the additional inhibition of MMP-2 and MMP-9 by DPI. Moreover, the neurological outcome in both therapeutic groups was improved compared to controls with a significant difference between the therapeutic groups in favour of DPI and DMSO. The combination of DPI and DMSO reduced the activity of MMP-2 and MMP-9, attenuated the postischemic blood-brain barrier damage and improved neurological outcome. This was most likely due to reduced oxidative stress.


[Production of cinchona in the French empire: A. Yersin and E. Perrot].
In the wake of the war of 1914-1918, Professor E. Perrot and Dr A. Yersin were concerned with providing various territories of the French empire with sufficient cinchona resources to fight off malaria. This aim was particularly important in case of a conflict which could impede the supply of quinine due to the quasi-monopoly held by the Netherlands with their overseas possessions in Indonesia. Beginning with documents, in particular the correspondence held by the Museum of Materia Medica at the Faculty of Pharmacy in Paris, an attempt is made to illustrate the policy carried out with difficulty by Perrot and Yersin.


Shear bond strength of metal brackets to ceramic surfaces using a universal bonding resin.
Assure Plus is a recently introduced universal adhesive with the ability to bond to various restorations. This study compared the shear bond strength of brackets bonded to two types of ceramics using conventional bonding agent and Assure Plus. Surface damage caused by debonding was also evaluated. In this in vitro study, 40 feldspathic and lithium disilicate ceramic discs were sandblasted, etched with 9.6% hydrofluoric acid and divided into two groups. In group 1, silane was applied and air-dried followed by application of Transbond XT primer, which was light-cured. In group 2, Assure Plus was applied and air-dried. In both groups, maxillary central incisor brackets were bonded. After incubation in distilled water at 37°C for 24 hours and 2000 thermal cycles, bond strength was measured using a universal testing machine, and the adhesive remnant index (ARI) and failure modes were determined. ANOVA and LSD tests were used to compare bond strength values; chi-squared test was used to compare ARI scores. Bracket bond to lithium disilicate by Assure Plus was significantly stronger than that to Feldspathic porcelain (P=0.041). Only in the Assure Plus/lithium disilicate group did some adhesive remain on the surface following debonding (40% of samples, P<0.05). Cohesive porcelain fracture had the lowest frequency in the lithium disilicate/Assure Plus group. Assure Plus provided high bond strength between ceramic and brackets and minimized damage to lithium disilicate ceramic during debonding. Assure Plus is recommended for use in orthodontic treatment of adults with ceramic restorations. Key words:Adhesives, ceramics, dental bonding, shear bond strength.


[Chemotherapy of advanced pancreatic cancer with 5-fluorouracil, doxorubicin and high-dose methotrexate].
The aim of the present phase II clinical trial was to investigate the therapeutic efficacy and tolerance of a combination chemotherapeutic protocol consisting of 4-weekly intervals of 5-fluorouracil, doxorubicin and high-dose methotrexate (FAMeth-regimen) in patients with advanced measurable pancreatic cancer. After a median treatment duration of 4 (2-12) months, one complete and one partial response were achieved in the 13 evaluable patients. Two additional patients had evidence of objective tumour regression, although response was less than 50% of pretreatment tumor measurements. Stable disease was noted in 3 patients, and the tumour progressed in 6. The median survival of all evaluable patients from start of therapy is 7 (2-17) months. Side-effects associated with FAMeth-chemotherapy were generally mild and reversible and primarily included gastrointestinal symptoms (38%) and leukopenia (62%). There was 1 treatment related death due to pancytopenia and sepsis. Our preliminary data suggest some antitumour activity of the regimen against pancreatic cancer, although final assessment of therapeutic results must await accrural of additional patients.


Mass transport and reaction kinetic parameters determined electrochemically for immobilized glucose oxidase.
Mass-transfer resistances often have pronounced effects on the overall reaction rates of enzymes immobilized at interfaces or in polymeric matrices. In the present work glucose oxidase was immobilized on the surface of a platinum disk electrode by one of three attachment techniques: silane-glutaraldehyde, allylamine-glutaraldehyde, and albumin-glutaraldehyde. In one group of studies the electrodes were rotated, and methods were employed to determine the diffusion and shielding coefficients for transport of a model electroactive compound, i.e., potassium ferrocyanide, through the enzyme matrix. A model electrochemically active compound was used because glucose exhibits a very slow rate of electron transfer at a platinum surface. The diffusion coefficient for ferrocyanide was reduced 7% by the silane-enzyme and 25% by the allylamine-enzyme matrices. In a second group of studies the electrodes were held stationary. Marked internal diffusional resistance was noted for the albumin-glutaraldehyde-enzyme matrix. The calculated flux of ferrocyanide was decreased by a factor of 2000-8500 for transport through albumin-enzyme matrices 0.21-0.063 cm thick, as compared to transport through free solution. In a third group of studies the rotating enzyme-matrix electrode was utilized in determining apparent values of the Michaelis constant for glucose. The velocity of the reaction was determined by amperometric measurement of the concentration of hydrogen peroxide reaching the ring electrode. The results, determined from Eadie-Hofstee type plots of reaction current and substrate concentration, gave values between 12 and 36 mM for the three methods of immobilization.(ABSTRACT TRUNCATED AT 250 WORDS)


[Non-hemorrhagic stroke, of possible aortoembolic origin, in the course of acute myocardial infarct treated with thrombolysis].
We describe the case of a middle-aged man with nonhemorrhagic stroke occurred during thrombolysis for acute myocardial infarction. The ischemic etiology of stroke was demonstrated by cerebral computed tomography scan. Transthoracic echocardiogram excluded left ventricular thrombosis. Transesophageal echocardiogram displayed complicated atheromas of the aortic arch. The reported case emphasizes that aortic atheromas may be the source of emboli during thrombolytic therapy.


[Antibiotic therapy in bacterial infections in gynaecology].
A brief review of the special aspects concerning the use and selection of chemotherapeutic agents and antibiotics in bacterial infections occurring in gynaecology both specifically and generally. In case of severe bacterial infections such as sepsis it is recommended to combine two antibodies (e.g. beta-lactam antibiotics with aminoglycosides or several beta-lactam antibiotics together). Special attention is given to the particularly effective broad-spectrum penicillins and cephalosporins as well as to the aminoglycoside antibiotics etc. Individual well-tried antibiotics are briefly characterised in respect of their anti-bacterial efficacy (sensitivity and resistance), their field of application, and their dosage. In particular, the possibilities of the therapy of infections by anaerobic microorganisms and fungi are pointed out. In addition, a brief description is given of antibacterial chemotherapy of pneumonias of urinary tract infections and specifically gynaecological infections (such as adnexitis, endometritis, parametritis, pelveoperitonitis) under the aspects of rational antibiotic treatment. The article includes by pointing out the possibilities of prophylactic administration of antibiotics especially in surgical procedures in the sense of a perioperative short-term prophylaxis.


High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations.
Cystathionine beta-synthase (CBS) is a crucial regulator of plasma levels of the thrombogenic amino acid homocysteine (Hcy). Homocystinuria due to CBS deficiency confers a dramatically increased risk of thrombosis. Early diagnosis usually occurs after the observation of ectopia lentis, mental retardation, or characteristic skeletal abnormalities. Homocystinurics with this phenotype typically carry mutations in the catalytic region of the protein that abolish CBS activity. We describe a novel class of missense mutations consisting of I435T, P422L, and S466L that are located in the non-catalytic C-terminal region of CBS that yield enzymes that are catalytically active but deficient in their response to S-adenosylmethionine (AdoMet). The P422L and S466L mutations were found in patients suffering premature thrombosis and homocystinuric levels of Hcy but lacking any of the connective tissue disorders typical of homocystinuria due to CBS deficiency. The P422L and S466L mutants demonstrated a level of CBS activity comparable to that of the AdoMet stimulated wild-type CBS but could not be further induced by the addition of AdoMet. In terms of temperature stability, oligomeric organization, and heme saturation the I435T, P422L, and S466L mutants are indistinguishable from wild-type CBS. Our findings illustrate the importance of AdoMet for the regulation of Hcy metabolism and are consistent with the possibility that the characteristic connective tissue disturbances observed in homocystinuria due to CBS deficiency may not be due to elevated Hcy.


Manually controlled total intravenous anesthesia augmented by electrophysiologic monitoring for complex stereotactic neurosurgical procedures.
Stereotactically guided procedures are performed for an ever extending range of conditions. They present a unique anesthetic challenge. In our institution, a standardized anesthetic protocol for total intravenous anesthesia (TIVA) augmented by electrophysiologic monitoring with BIS or AEP monitors was introduced. We conducted a retrospective study of 21 patients (ASA status 2-3) presenting for stereotactically guided procedures who were anesthetized according to the protocol. Median duration of anesthesia was 260 minutes (222 to 325 min); on average 3.0 (1.0 to 4.2) adjustments to the TIVA-protocol were made per patient. Highest and lowest mean arterial blood pressures in relation to baselines were 100% (87.5% to 109.8%) and 68.7% (64.0% to 72.6%), respectively. Likewise highest and lowest heart rates recorded were 106.7% (98.5% to 119.0%) and 75.0% (68.2% to 83.3%). After discontinuation of TIVA, spontaneous breathing returned after 5.0 minutes (4.0 to 8.0 min), extubation was possible after 6.0 minutes (5.0 to 10.0 min) and patients were ready for discharge to the ward after 15.0 minutes (12.0 to 18.0 min). There were no cases of postoperative nausea or vomiting. We found that manually controlled TIVA, augmented by electrophysiologic monitoring, facilitated maintenance of an appropriate depth of anesthesia with stable hemodynamics and excellent recovery times.


Function of proteoglycans in the extracellular matrix.
Proteoglycans are glycosylated proteins which have covalently attached highly anionic glycosaminoglycans. Many forms of proteoglycans are present in virtually all extracellular matrices of connective tissues. The major biological function of proteoglycans derives from the physicochemical characteristics of the glycosaminoglycan component of the molecule, which provides hydration and swelling pressure to the tissue enabling it to withstand compressional forces. This function is best illustrated by the most abundant proteoglycan in cartilage tissues, aggrecan. During the past decade, diverse species of proteoglycans have been identified in many connective tissues, on cell surfaces and in intracellular compartments. These proteoglycans have distinct biological functions apart from their hydrodynamic functions, and their involvement in many aspects of cell and tissue activities has been demonstrated. For example, decorin, which is widely distributed in many connective tissues, may have functions in regulating collagen fibril formation and in modifying the activity of transforming growth factor-beta; perlecan, the major heparan sulfate proteoglycan in the glomerular basement membrane, may play an important role as the major anionic site responsible for the charge selectivity in glomerular filtration. Specific interactions between proteoglycans (through both their glycosaminoglycan and core protein components) and macromolecules in the extracellular matrix are the key factors in the functions of proteoglycans. Exciting biological functions of proteoglycans are now gradually emerging.


[The Weil osteotomy in metatarsalgia].
The purpose of the prospective study is to evaluate the results of Weil osteotomy in painful overloaded central forefoot with dislocation of the MTP joint. 19 left and 16 right feet underwent the Weil osteotomy. In 10 patients the procedure was performed on both feet. In 15 cases only one metatarsal was corrected (the 2 (nd) in 12 and the 3 (rd) in 3 cases), in 17 cases both the 2 (nd) and the 3 (rd) metatarsals and in 4 cases also with the 4 (th) one together. The simultaneous correction of hallux valgus was performed in 19 forefeet. The mean follow-up was 31 months (range, 19 to 41 months). All patients were satisfied with the result of the operation. The results were excellent in 29 cases (83 %) and good in 6 cases (17 %). The plantar callus disappeared in 27 feet (77 %) and decreased in 8 feet (23 %). In one patient the new callus formed under the head of the neighbouring metatarsal bone. The sufficient MTP joint reduction was found in 31 cases (89 %). It is possible with the Weil osteotomy to correct the metatarsal length accurately according to the preoperative planning. This results in the prevention of new callus formation under the neighbouring metatarsal head. Stable internal fixation allows the early mobilisation of the MTP joint.


Substance P release from rat hypothalamus and spinal cord.
A specific and sensitive radioimmunoassay for substance P has been developed to study the release of immunoreactive substance P from incubated rat hypothalamus and rat spinal cord in vitro. Release was significantly increased in the presence of two depolarizing stimuli (56 mM KCl and 75 microM veratrine) and was calcium-dependent. The released immunoreactive material diluted in parallel with synthetic substance P and showed close identity on Sephadex chromatography. A neuromodulator role for the peptide in the central nervous system is suggested.


Nasal cytologies--impact of sampling method, repeated sampling and interobserver variability.
The influence of sampling technique, repeated sampling and the interobserver variability on quantitative analysis of nasal cytologies were explored. Nasal cytologies from 12 healthy and 4 allergic volunteers were repeatedly collected with a total of three different sampling techniques. Cells were demonstrated by May-Grünwald-Giemsa staining and by immunostaining for CD45 and eosinophil peroxidase (EPO). To determine the interobserver variability specimens were evaluated by three observers with various levels of nasal cytology experience. When adjusted for the variability due to sampling method and repeated sampling, the staining index for CD45+ cells was 53.4 +/- 11% (interindividual coefficient of variation: 0.21) with an average intraindividual coefficient of variation of 0.14. For CD45, staining indices differed significantly between the washing techniques and the nasal swabs (p<0.01). Repeated sampling did significantly influence the staining indices of specimens collected with nasal swabs (p<0.05). Subjects with nasal allergy had less CD45+ cells in their nasal cytologies than the non-allergic subjects (p=0.02). A high level of compliance for the quantitative analysis of nasal cytologies between three observers was found (kappa(w) range 0.95-0.98). For studies that require repeated sampling, the lavage will be recommended as best suitable to obtain nasal cytologies.


Druggability of Voltage-Gated Sodium Channels-Exploring Old and New Drug Receptor Sites.
Voltage-gated ion channels are important drug targets because they play crucial physiological roles in both excitable and non-excitable cells. About 15% of clinical drugs used for treating human diseases target ion channels. However, most of these drugs do not provide sufficient specificity to a single subtype of the channels and their off-target side effects can be serious and sometimes fatal. Recent advancements in imaging techniques have enabled us for the first time to visualize unique and hidden parts of voltage-gated sodium channels in different structural conformations, and to develop drugs that further target a selected functional state in each channel subtype with the potential for high precision and low toxicity. In this review we describe the druggability of voltage-gated sodium channels in distinct functional states, which could potentially be used to selectively target the channels. We review classical drug receptors in the channels that have recently been structurally characterized by cryo-electron microscopy with natural neurotoxins and clinical drugs. We further examine recent drug discoveries for voltage-gated sodium channels and discuss opportunities to use distinct, state-dependent receptor sites in the voltage sensors as unique drug targets. Finally, we explore potential new receptor sites that are currently unknown for sodium channels but may be valuable for future drug discovery. The advancement presented here will help pave the way for drug development that selectively targets voltage-gated sodium channels.


[A repetition or a new start? About the reinstalling of psychoanalysis in West Germany after the War].
The concessions which the psychoanalysts made to the Nazi regime wounded them in their psychoanalytical identity. Parallels are established here between the officialization of psychotherapy in National Socialist Germany and the attempts at officialization by the Schultz-Hencke neo-analytical circle. The behavior seems comparable, irrespective of political regimes. On the other hand, Müller-Braunschweig's effort to revive classical psychoanalysis is presented as specifically characterised by the reproduction of "places of disturbance" ("Störstellen") and is interpreted as an attempt to restore, through these repetitions, his damaged psychoanalytical identity. Thus appears the ambivalence of the officialization of psychoanalysis in a social system as an element within the psychoanalytical identity which constantly seeks to elude self-analysis.


Effects of chlorthalidone plus amiloride compared with amlodipine on short-term blood pressure variability in individuals with hypertension and obstructive sleep apnea: a randomized controlled trial.
To compare the effects of chlortalidone plus amiloride and amlodipine on blood pressure (BP) variability in patients with hypertension and obstructive sleep apnea syndrome (OSA). A randomized, controlled, double-blind trial enrolled men and women aged 40 years or older with a diagnosis of OSA (apnea-hypopnea index 10-40 apneas/h of sleep) confirmed by overnight laboratory polysomnography and systolic BP 140-159 mmHg or diastolic BP 90-99 mmHg. Participants were randomized to receive chlortalidone 25 mg plus amiloride 5 mg daily or amlodipine 10 mg daily for 8 weeks. BP variability was calculated from 24-hour ambulatory BP monitoring at baseline and follow-up using the following indices: SD, coefficient of variation, average real variability (ARV), time-rate index, and variability independent of the mean (VIM). The study included 65 patients, with 33 assigned to the chlortalidone plus amiloride group and 32 to the amlodipine group. Participants in both groups had similar baseline characteristics. Short-term BP variability decreased within groups for SD and ARV indexes for 24-hour systolic BP and daytime systolic BP, but statistically significant time*group interactions were found for sleep systolic SD and VIM, with greater reduction in patients treated with amlodipine. In brief, our study has shown that the use of chlorthalidone in combination with amiloride and amlodipine produces comparable effects on short-term BP variability in patients with hypertension and OSA. Therefore, our findings suggest that BP variability may not be a significant factor when choosing between these medications for the treatment of hypertension and OSA.


Nurses, industrial action and ethics: considerations from the 2010 South African public-sector strike.
Several important ethical dilemmas emerge when nurses join a public-sector strike. Such industrial action is commonplace in South Africa and was most notably illustrated by a national wage negotiation in 2010. Media coverage of the proceedings suggested unethical behaviour on the part of nurses, and further exploration is merited. Laws, policies and provisional codes are meant to guide nurses' behaviour during industrial action, while ethical theories can be used to further illuminate the role of nurses in industrial action. There are, however, important aspects to consider before judging whether nurses act unethically when striking. Following Loewy's suggestion that the nature of the work, the proceeding commitment of the nurse to the patient, the prevailing situation when the strike is planned and the person(s) who stand(s) to benefit from the strike be considered, coupled with a consideration of the South African historical socio-political context, important aspects of the ethics of nurses' behaviour in industrial action transpire.


Plasma beta-thromboglobulin levels in chronic renal failure patients.
Impaired platelet function is commonly recognized in uremia. It is partially improved by dialysis. However, in regular hemodialysis patients (RD), platelet function is not fully evaluated. This study investigated platelet activity in chronic renal failure (CRF) using beta-thromboglobulin (BTG) as a marker. BTG in RD were significantly higher than those in non-dialyzed CRF patients (P less than 0.05), and BTG in non-dialyzed CRF were higher than in normal controls (P less than 0.01). In non-dialyzed CRF, BTG were correlated to serum creatinine value (P less than 0.01). Arteriovenous fistula did not affect BTG. Hemodialysis and direct hemoperfusion with charcoal beads increased BTG but neither peritoneal dialysis nor hemofiltration altered BTG. RD treated over one year showed higher BTG than those treated for less than one year (P less than 0.01). In RD who showed elevated BTG, platelet aggregation and retention rates were depressed and bleeding times were prolonged. These results indicate that BTG can be used as the marker of impaired platelet function in CRF and of the blood compatibility of artificial kidneys.


Following the Footsteps of Chlamydial Gene Regulation.
Regulation of gene expression ensures an organism responds to stimuli and undergoes proper development. Although the regulatory networks in bacteria have been investigated in model microorganisms, nearly nothing is known about the evolution and plasticity of these networks in obligate, intracellular bacteria. The phylum Chlamydiae contains a vast array of host-associated microbes, including several human pathogens. The Chlamydiae are unique among obligate, intracellular bacteria as they undergo a complex biphasic developmental cycle in which large swaths of genes are temporally regulated. Coupled with the low number of transcription factors, these organisms offer a model to study the evolution of regulatory networks in intracellular organisms. We provide the first comprehensive analysis exploring the diversity and evolution of regulatory networks across the phylum. We utilized a comparative genomics approach to construct predicted coregulatory networks, which unveiled genus- and family-specific regulatory motifs and architectures, most notably those of virulence-associated genes. Surprisingly, our analysis suggests that few regulatory components are conserved across the phylum, and those that are conserved are involved in the exploitation of the intracellular niche. Our study thus lends insight into a component of chlamydial evolution that has otherwise remained largely unexplored.


[Endoscopic wedge-shaped lung biopsy--initial experience].
The authors publish their initial experience with wedge-shaped pulmonary biopsy by the endoscopic route. The group is formed by 18 patients who were indicated for the operation on account of a disseminated pulmonary process in order to assess the micromorphological appearance of the affected lung tissue. Two patients developed a complication during operation which therefore was completed by minor thoracotomy. In who patients the authors observed after operation slow expansion of the pulmonary parenchyma. No death after the operation was recorded. The authors assume, based on their initial experience, that this operation will soon be included among common diagnostic operations and will help to facilitate the diagnosis and selection of treatment in patients with disseminated lung disease.


Molecular characterization of the men1 tumor suppressor gene in sporadic pituitary tumors.
Anterior pituitary tumors arise sporadically, and also as part of the inherited multiple endocrine neoplasia type 1 (MEN 1) syndrome. To investigate the role of the recently isolated men1 gene in sporadic pituitary tumorigenesis, the complete coding sequence was screened for mutations in 45 sporadic anterior pituitary tumors, including 14 hormone-secreting tumors and 31 nonsecreting tumors, by dideoxy fingerprinting and sequence analysis. No pathogenic sequence changes were found in the men1 coding region. The men1 gene was expressed in 43 of these tumors with sufficient RNA, including one tumor with loss of heterozygosity (LOH) for several polymorphic markers on chromosomal region 11q13. Furthermore, both alleles were expressed in 19 tumors in which the constitutional DNA was heterozygous for intragenic polymorphisms. Thus, inactivation of the men1 tumor suppressor gene, by mutation or by imprinting, does not appear to play a prominent role in sporadic pituitary adenoma pathogenesis.


Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues.
PROTACs represent an emerging field in medicinal chemistry, which has already led to the development of compounds that reached clinical studies. Posttranslational modifications contribute to the complexity of proteomes, with 2846 disease-associated sites. PROTAC field is very advanced in targeting kinases, while its use for enzymes mediating posttranslational modifications of the basic amino acid residues, started to be developed recently. Therefore, we bring together this less popular class of PROTACs, targeting lysine acetyltransferases/deacetylases, lysine and arginine methyltransferases, ADP-ribosyltransferases, E3 ligases, and ubiquitin-specific proteases. We put special emphasis on structural aspects of PROTAC elements to facilitate the lengthy experimental endeavours directed towards developing PROTACs. We will cover the period from the inception of the field, 2017, to April 2023.


Soluble egg antigens from Schistosoma mansoni induce angiogenesis-related processes by up-regulating vascular endothelial growth factor in human endothelial cells.
Schistosomiasis mansoni is characterized by hepatic granuloma formation. Endothelial cell activation within these granulomas may contribute to their development and to increased vascularization in the granuloma periphery. The earliest event in granuloma formation is the lodging of schistosome eggs within presinusoidal capillaries. The eggs secrete factors that may activate endothelial cells. This study investigated the effects of Schistosoma mansoni soluble egg antigen (SEA) on angiogenic processes: proliferation, tube formation, and apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs require serum and growth factors to proliferate in vitro. Proliferation occurred when SEA or live eggs were substituted for growth factors, but not for serum. SEA increased HUVEC tube formation and decreased HUVEC apoptosis after serum and growth factor deprivation. Messenger RNA for vascular endothelial growth factor (VEGF) increased 2-fold in SEA-treated HUVECs. These findings suggest that products secreted by schistosome eggs may promote angiogenesis within hepatic granulomas by up-regulating endothelial cell VEGF.


Mechanisms of immunological tolerance in central nervous system inflammatory demyelination.
Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include induction of regulatory T cell populations, anergy and the induction of tolerogenic antigen-presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance by promoting the generation of regulatory T cells and inducing apoptosis of pathogenic T cells. Safe and effective methods of inducing long-lasting immune tolerance are essential for the treatment of multiple sclerosis. By exploring tolerogenic mechanisms, new strategies can be devised to strengthen the regulatory, anti-inflammatory cell populations thereby weakening the pathogenic, pro-inflammatory cell populations.


Leptin resistance in children with in utero exposure to maternal obesity and gestational diabetes.
Leptin resistance occurs with obesity, but it is unknown if individuals at risk for obesity develop leptin resistance prior to obesity. Investigate whether leptin resistance is independent of weight status in children at risk for obesity due to intrauterine exposure to maternal obesity or gestational diabetes mellitus (GDM). Mother-child dyads (N = 179) were grouped by maternal pregnancy weight and GDM status: (1) normal weight, no GDM; (2) overweight/obesity, no GDM; (3) overweight/obesity with GDM. Children (4-10 years) were further stratified by current body mass index (BMI) <85th or ≥85th percentile. Leptin resistance of children and mothers was calculated as fasting leptin/fat mass index. Two-way ANOVA was used to assess whether leptin concentrations and leptin resistance differed by current weight status or in utero exposure group, after adjusting for race, sex and Tanner stage. Children with a BMI ≥85th percentile had more leptin resistance than those with a BMI <85th percentile (p < 0.001), but leptin resistance did not differ by in utero exposure. Similarly, leptin resistance in women was associated with weight status and not prior GDM. Results suggest that leptin concentrations are associated with obesity but not risk for obesity based on in utero exposure to maternal obesity or GDM.


Mitigation of the effect of variability in digital PCR assays through use of duplexed reference assays for normalization.
Digital PCR has been promoted as a technique for obtaining absolute measures of the amount of nucleic acid target sequence in a sample, but still lacks standardization in data reporting. The initial method of representing data as copies per microliter produced inconsistent results and made inter-assay comparisons difficult. Normalizing copies to amount of nucleic acid gives more uniform results, but factors influencing the effective concentration of nucleic acid in the final digital PCR assay must be considered. Using droplet digital PCR and previously validated reference genes duplexed with target genes, a method of normalization was developed to estimate the amount of input nucleic acid in individual assays, subsequently reporting the number of copies of target gene relative to this amount. Correcting for the actual amount of amplifiable nucleic acid present demonstrated a higher correlation between various dilutions of sample mRNA and allowed more accurate comparisons of digital PCR results.


Four members of the HSP101 gene family are differently regulated in Triticum durum Desf.
Heat shock proteins play an essential role in preventing deleterious effects of high temperatures. In many plants, HSP101 has a central role in heat stress survival. We report the isolation and characterization of four cDNAs corresponding to different members of the durum wheat HSP101 gene family. Expression analysis revealed differences in their induction. Accordingly, durum wheat HSP101 genes are differently regulated, therefore having distinct roles in stress response and thermotolerance acquisition. These findings are important for further dissection of the molecular mechanisms underlying the stress response and for understanding the functions of the HSP101 family members. This information could be important for the exploitation of specific alleles in marker assisted selection for abiotic stress resistance.


Chromosome abnormalities in sperm from infertile men with asthenoteratozoospermia.
Research over the past few years has clearly demonstrated that infertile men have an increased frequency of chromosome abnormalities in their sperm. These studies have been further corroborated by an increased frequency of chromosome abnormalities in newborns and fetuses from pregnancies established by intracytoplasmic sperm injection. Most studies have considered men with any type of infertility. However, it is possible that some types of infertility have an increased risk of sperm chromosome abnormalities, whereas others do not. We studied 10 men with a specific type of infertility, asthenozoospermia (poor motility), by multicolor fluorescence in situ hybridization analysis to determine whether they had an increased frequency of disomy for chromosomes 13, 21, XX, YY, and XY, as well as diploidy. The patients ranged in age from 28 to 42 yr (mean 34.1 yr); they were compared with 18 normal control donors whose ages ranged from 23 to 58 yr (mean 35.6 yr). A total of 201 416 sperm were analyzed in the men with asthenozoospermia, with a minimum of 10 000 sperm analyzed per chromosome probe per donor. There was a significant increase in the frequency of disomy in men with asthenozoospermia compared with controls for chromosomes 13 and XX. Thus, this study indicates that infertile men with poorly motile sperm but normal concentration have a significantly increased frequency of sperm chromosome abnormalities.


What encourages and discourages children to smoke? Knowledge about health hazards and recommendations for health education.
A confidential smoking questionnaire was answered by 102 fourth formers and 89 sixth formers at a Dunedin High School. Thirty-nine percent of the sample were smoking (more than half infrequently), 42 percent had tried and given up and 19 percent had never tried a cigarette. Pupils' smoking habits were related to the smoking habits of their friends but not their parents. Most children associated cancer with smoking but only 37 percent associated it with cardiovascular disease and 18 percent gave an incorrect answer or answers. The main reason why children tried their first cigarette was curiosity (57 percent) but the main reason why "some children" take up smoking was to be tough and impress others (71 percent). Boys experimented earlier than girls (mean age boys, 10 years, two months, girls, 11 years, seven months). Children were most discouraged from smoking by the health risk (52 percent), and they thought that the best way to discourage others was to show them the harmful effects (32 percent) and increase health education (27 percent). Since 1961 smoking appears to have declined among European fourth form boys and increased among girls. More Maori or part-Maori pupils smoke than Europeans. The discussion includes suggestions for improving health education.


Competency-based psychiatric education.
The focus of training in a competency-based residency program is on ensuring that all residents attain prespecified levels of competence for particular objectives in each training activity. The authors examine the components of a competency-based program and describe the phases of development that their department went through in creating such a program. They conclude that the competency-based training model directly faces the issue of certifying competence by holding itself accountable in a demonstrable way for ensuring that its residents have mastered specific areas of knowledge, skills, and attitudes.


Strengthening health disaster risk management in Africa: multi-sectoral and people-centred approaches are required in the post-Hyogo Framework of Action era.
In November 2012, the 62nd session of the Regional Committee for Africa adopted a comprehensive 10-year regional strategy for health disaster risk management (DRM). This was intended to operationalize the World Health Organization's core commitments to health DRM and the Hyogo Framework for Action 2005-2015 in the health sectors of the 47 African member states. This study reported the formative evaluation of the strategy, including evaluation of the progress in achieving nine targets (expected to be achieved incrementally by 2014, 2017, and 2022). We proposed recommendations for accelerating the strategy's implementation within the Sendai Framework for Disaster Risk Reduction. This study used a mixed methods design. A cross-sectional quantitative survey was conducted along with a review of available reports and information on the implementation of the strategy. A review meeting to discuss and finalize the study findings was also conducted. In total, 58 % of the countries assessed had established DRM coordination units within their Ministry of Health (MOH). Most had dedicated MOH DRM staff (88 %) and national-level DRM committees (71 %). Only 14 (58 %) of the countries had health DRM subcommittees using a multi-sectoral disaster risk reduction platform. Less than 40 % had conducted surveys such as disaster risk analysis, hospital safety index, and mapping of health resources availability. Key challenges in implementing the strategy were inadequate political will and commitment resulting in poor funding for health DRM, weak health systems, and a dearth of scientific evidence on mainstreaming DRM and disaster risk reduction in longer-term health system development programs. Implementation of the strategy was behind anticipated targets despite some positive outcomes, such as an increase in the number of countries with health DRM incorporated in their national health legislation, MOH DRM units, and functional health sub-committees within national DRM committees. Health system-based, multi-sectoral, and people-centred approaches are proposed to accelerate implementation of the strategy in the post-Hyogo Framework of Action era.


ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice.
Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose-response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction.


An Empirical Analysis of Social Interaction in Online Teaching in Open Universities Based on Flipped Classroom.
As a teaching model, flipped classroom can stimulate students' learning interests and promote students' positive social interactions. As an adult university relying on information technology to carry out online teaching, open universities need to pay attention to the online learning quality of adult students. This study attempts to apply the concept of flipped classroom to online teaching in open universities. While exploring the feasibility of the online flipped classroom teaching model, it adopts an equal group experiment method, content analysis method, and social network analysis method to compare the social interaction level difference between online teaching based on flipped classroom and conventional online teaching. The results show that online flipped classroom has a positive and significant impact on student's cognitive processing level and knowledge construction level and can promote groups to form complex knowledge network forms. This shows that network teaching based on flipped classroom can exercise students' high-order thinking ability, enhance students' cooperative consciousness and behavior, and stimulate students' subjectivity in learning. The purpose of this study is to provide references for promoting interactive behavior and quality in online teaching.


Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the Neointimal Proliferation After Stent Implantation in a Diabetic/Hypercholesterolemic Swine Model.
The aim of the present study was to investigate the effects of glucose fluctuation on neointimal proliferation after stent implantation by optical coherence tomography (OCT) in a diabetic/hypercholesterolemic (DM/HC) swine model.A total of 24 everolimus-eluting stents (EES) were implanted in the right coronary artery (RCA) of the animals using a 20% overstretch ratio. The 24 swines were divided into a DM-high glucose fluctuation (HGF) group (n = 8), DMlow glucose fluctuation (LGF) group (n = 8), and a control group (n = 8). Percent diameter stenosis (%DS), late loss (LL), percent area stenosis (%AS), and neointimal thickness (NIT) were analyzed. The differences in neointimal characteristics and circulating oxidative stress and inflammation biomarkers were assessed and measured.At 28 days, the highest values of %DS, LL, %AS, and NIT were achieved in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). The highest frequency of the heterogeneous pattern was in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). This was also the case for the oxidative stress and inflammation biomarkers.DM might have a deleterious impact on neointimal proliferation after EES implantation in this DM/HC swine model. The extent of glucose fluctuation may be related to the degree of neointimal proliferation and this needs to be further confirmed by long-term follow-up and histology.


Sex- and Dose-Dependent Differences in the Development of an Addiction-Like Phenotype Following Extended-Access Fentanyl Self-Administration.
Opioid use disorder (OUD) is a major epidemic in the United States, and fentanyl is a major culprit. The National Institute on Drug Abuse has highlighted an urgent need for research on the risks and outcomes of OUD with fentanyl; a better understanding of sex/gender differences is also critically needed given that the opioid epidemic has been particularly impactful on women. In response to this need, we developed a rat model of OUD with fentanyl and showed that sex impacts relapse vulnerability following extended-access self-administration under a low fentanyl dose. Here, our goal was to determine sex differences across a broad dose range, including high doses expected to maximize the expression of addiction-like features (e.g., vulnerability to relapse and physical dependence). Male and female rats were assigned to self-administer one of four fentanyl doses (0.25, 0.75, 1.5, and 3.0 µg/kg/infusion), and once they acquired, they were given extended (24-h/day), intermittent access (2, 5 min trials/h, fixed-ratio 1) to fentanyl for 10 days. Physical dependence (spontaneous weight loss) was assessed during early withdrawal, and relapse vulnerability was assessed on withdrawal day 15 using an extinction/cue-induced reinstatement procedure. Despite markedly higher intake in the high- versus low-dose groups, each group responded similarly during relapse testing (extinction and cue-induced reinstatement). However, number of infusions, or frequency of use, during extended access was predictive of later vulnerability to relapse, whereas total intake impacted physical dependence given that weight loss only occurred following the discontinuation of fentanyl self-administration at the three highest doses. Females self-administered more fentanyl each day and within each binge (active trial), and had longer lasting weight loss during withdrawal than males. Relapse vulnerability was also higher in females than males and highest in females tested during estrus. These findings indicate that sex is an important risk factor for patterns and levels of fentanyl intake, relapse, and physical dependence, and while fentanyl intake predicts physical dependence, frequency of use predicts relapse.


'Candidatus Dichloromethanomonas elyunquensis' gen. nov., sp. nov., a dichloromethane-degrading anaerobe of the Peptococcaceae family.
Taxonomic assignments of anaerobic dichloromethane (DCM)-degrading bacteria remain poorly constrained but are important for understanding the microbial diversity of organisms contributing to DCM turnover in environmental systems. We describe the taxonomic classification of a novel DCM degrader in consortium RM obtained from pristine Rio Mameyes sediment. Phylogenetic analysis of full-length 16S rRNA gene sequences demonstrated that the DCM degrader was most closely related to members of the genera Dehalobacter and Syntrophobotulus, but sequence similarities did not exceed 94% and 93%, respectively. Genome-aggregate average amino acid identities against Peptococcaceae members did not exceed 66%, suggesting that the DCM degrader does not affiliate with any described genus. Phylogenetic analysis of conserved single-copy functional genes supported that the DCM degrader represents a novel clade. Growth strictly depended on the presence of DCM, which was consumed at a rate of 160±3μmolL-1 d-1. The DCM degrader attained 5.25×107±1.0×107 cells per μmol DCM consumed. Fluorescence in situ hybridization revealed rod-shaped cells 4±0.8μm long and 0.4±0.1μm wide. Based on the unique phylogenetic, genomic, and physiological characteristics, we propose that the DCM degrader represents a new genus and species, 'Candidatus Dichloromethanomonas elyunquensis'.


Does farming have an effect on health status? A comparison study in west Greece.
Investigating the health status of agricultural workers is a challenging goal. Contradictory outcomes concerning farmers' health are reported in the literature. In this cross-sectional study, certain clinical and neurobehavioral health outcomes were compared between farmers and non-farmers living in the same rural area. Farmers (328) and non-farmers (347), matched per age and sex, were selected randomly in an agricultural area in West Greece. Both groups underwent haematological and biochemical examinations and were administered two neurobehavioral tests, namely the Mini-Mental State Examination (MMSE) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Sociodemographic, personal medical, nutritional and lifestyle data were recorded. According to personal statements, farmers suffered from hypertension, cardiovascular, orthopaedic and ENT problems in higher frequency. Haematocrit, haemoglobin and serum cholinesterase's activity were found to be lower among farmers. Lower prevalence of hypertension and better performances on MMSE and MADRS tests were recorded in young farmers in relation to young non-farmers, while these findings were reversed in older ages. Odds Ratios were calculated through multivariate logistic regression models. Factors affecting these impairments remain to be clarified.


[Psychiatric disorders and cognitive deterioration in Friedreich ataxia].
The present study was designed with the aim of examining the presence of psychiatric diagnosis and intellectual impairment in a sample of patients with Friedreich's ataxia. A consecutive sample of 21 patients presenting with Friedreich's Ataxia were evaluated by means of a neuropsychiatric interview. Only one patient was diagnosed as mentally retarded. Out of the 15 patients of the sample who were evaluated with be WAIS, all of them fell within a normal intellectual range. The idea that Friedreich's Ataxia produces cognitive impairment and serious psychiatric symptoms came from the earliest descriptions of the disease at the beginning of this century, which probably included many patients in their samples who had other diseases.


Transcatheter aortic valve implantation in decompensated aortic stenosis within the same hospital admission: early clinical experience.
Severe decompensated aortic valve stenosis is associated with noticeable reduction in survival. Until recently the options for such patients were either high-risk surgery or percutaneous balloon valvuloplasty and medical therapy which does not add any survival benefits and associated with high rate of complications. We present our experience in the use of transcatheter aortic valve implantation (TAVI) in patients with decompensated severe aortic stenosis requiring urgent intervention in the same hospital admission. In this observational study, all patients who were admitted with decompensated severe aortic stenosis were enrolled. Elective patients were excluded from the study. Perioperative records were analysed and clinical, echocardiographic and survival data were presented. 76 patients with a mean age of 81±6 years were enrolled. All patients presented with New York Heart Association (NYHA) IV status. Femoral approach was performed in 86.8%. Median postoperative hospital stay was 6 days and intensive care unit admission rate was 15%. At follow-up, 61.8% of patients were in NYHA status I/II. Moderate or more paravalvular leak occurred in 5.2% of patients. Permanent pacemaker was required in 14.4% of patients. The incidence of in-hospital death was 2.6%. Kaplan-Meier analysis indicated a survival rate of 81% at 1 year. Urgent in-hospital TAVI is feasible as the first-line treatment in decompensated severe aortic stenosis. In our cohort, it showed to be safe and achieved satisfactory survival rates and symptom control.


Haloperidol versus Second-generation Antipsychotics on the cognitive performance of individuals with schizophrenia and related disorders: pairwise meta-analysis of randomized controlled trials.
Despite previous literature, the superiority of Second-generation Antipsychotics (SGAs) relative to First-generation Antipsychotics- especially haloperidol - on cognitive management in schizophrenia is still controversial. Thus, we aimed to compare the effects of haloperidol versus SGAs on the cognitive performance of individuals with schizophrenia or related disorders. We conducted an updated systematic review and nine pairwise meta-analyses of double-blinded randomized controlled trials published up to October 30th, 2022, using Medline, Web of Science, and Embase. Twenty-eight trials were included, enrolling 1,932 individuals. Compared to SGAs, haloperidol performed worse on cognitive composite (MD -0.13; 95% CI: -0.33 to -0.03; MD = mean difference, CI = confidence interval), processing speed (MD -0.17; 95% CI: -0.28 to -0.07), attention (MD -0.14; 95% CI: -0.26 to -0.02), motor performance (MD -0.17; 95% CI: -0.31 to -0.03), memory and verbal learning (MD -0.21; 95% CI: -0.35 to -0.08), and executive function (MD -0.27; 95% CI: -0.43 to -0.11). In contrast, there were no significant differences between SGAs and haloperidol on working memory (MD 0.10; 95% CI: -0.08 to 0.27), visual learning (MD 0.08; 95% CI: -0.05 to 0.21), social cognition (MD 0.29; 95% CI: -0.30 to 0.88), and visuoconstruction (MD 0.17; 95% CI: -0.04 to 0.39). Haloperidol had poorer performance in global cognition and in some cognitive domains, but with small effect sizes. Therefore, it was not possible to conclude that haloperidol is certainly worse than SGAs in the long-term cognitive management of schizophrenia.


Hyaluronan in radiation-induced lung disease in the rat.
We have used a previously described model of bilateral radiation-induced lung disease in the rat (Ward et al., Radiat. Res., 136, 15-21, 1993) to study the role of hyaluronan in this process. Hyaluronan was measured in the bronchoalveolar lavage fluid, serum and lung tissue of rats after gamma irradiation or sham irradiation. Four weeks after irradiation, during peak alveolitis (12-fold increase in protein in the lavage, 7-fold increase in lavaged cells) hyaluronan was elevated 5.5-fold in serum and 1.5-fold in the bronchoalveolar lavage fluid. Histochemical staining demonstrated hyaluronan was in the intra-alveolar edema fluid but was not increased in the alveolar walls; hyaluronan, measured by high-performance liquid chromatography, also was not elevated in lavaged lung tissue. Hyaluronan was not increased in bron-choalveolar lavage fluid, serum or lung tissue during pulmonary edema (2 weeks) or fibrosis (6 to 20 weeks). The administration of methylprednisolone significantly decreased the alveolitis, including the increase in hyaluronan in the alveolar space and serum, but did not suppress fibrosis. It appears that hyaluronan is a marker of inflammation and cannot be used as a serum marker to predict the onset of radiation pneumonitis. Furthermore, an increase in interstitial hyaluronan does not appear to be a necessary precursor in the evolution of radiation fibrosis.


Poststroke fatigue: an emerging, critical issue in stroke medicine.
Poststroke fatigue is a common and disabling condition. However, few studies on or therapeutic trials addressing poststroke fatigue have appeared in the literature. We aimed to review the prevalence, natural course, potential predisposing factors (physiological, psychocognitive, and organic), and pharmacological and nonpharmacological treatments of poststroke fatigue. Using PubMed CINAHL and PsycINFO, we reviewed all the available literature on poststroke fatigue and related issues. The prevalence of poststroke fatigue ranges from 23% to 75%, depending on the definition of fatigue and the characteristics of the patients included. Poststroke fatigue seems to be of complex etiology. Predisposing factors were physiological ones including functional disability, prestroke fatigue, medical comorbidities, medication, sleep disturbances, and nutritional problems; psychocognitive ones including depression and cognitive dysfunction; and organic ones including damage to particular brain areas with consequent neurochemical alterations, perfusion deficit, and neuroinflammation. Poststroke fatigue is a persistent and debilitating symptom in some patients, and can have adverse affects on patient's neurological recovery, quality of life, and mortality. Few therapeutic trials have been reported, and the therapy was rarely successful, possibly because of the complex nature of poststroke fatigue. Poststroke fatigue is a common and frequently disabling problem of complex etiology. Further studies are urgently needed to improve our understanding of the pathophysiology of poststroke fatigue and to develop better treatments for this condition.


Application of poly ethylene glycol hydrogel to overcome latex urinary catheter related problems.
Urinary catheterization is a routine procedure in an intensive care unit (ICU) for monitoring the urine output of critically ill patients. The catheters which are most often used to help with urinary incontinence and retention also face problems like blockage, leakage and infection. These problems are due to proteins that adhere to the catheter surface and quickly build up on each other forming a protein layer. As the layers build up they can crystallize, providing the major source of blockage and leakage. Current strategies to avoid these problems include coating a catheter with silver alloy to reduce bacteria on the catheter surface. However, silver alloy coatings can lead to increased silver resistance for bacteria. Since silver is already used as an antibacterial agent in many places in a hospital, it is even more possible that resistance can develop. An alternative solution is presented involving coating latex, a common urinary catheter material with a micro layer (5-100 microns) of polyethylene glycol. This hydrogel is applied using an interfacial photopolymerization process with ethyl eosin as the photoinitiator. A 25 ppm concentration of ethyl eosin provided the strongest gel to surface adhesion and significantly lowered protein adhesion when compared to an uncoated latex substrate.


[Tapia's syndrome : Rare complication of securing airways].
Nerve injuries are a rare complication of airway management. Two cases of Tapia's syndrome following orotracheal intubation are reported. Case 1: a 23-year-old male patient underwent an otorhinolaryngology (ENT) surgical procedure with orotracheal intubation. A left-sided Tapia's syndrome was verified 3 days later. Case 2: a 67-year-old patient developed a right-sided Tapia's syndrome following an arthroscopic intervention of the left shoulder in the beach-chair position. In both cases there was permanent damage of both nerves. On the basis of a comprehensive literature survey the reasons for an intubation-induced Tapia's syndrome are discussed. In order to avoid a glottis or immediate subglottic position it is recommended to check and to document the position of the cuff (depth of intubation) and the measured cuff pressure immediately after intubation. It also seems to be advisable to document an overstretched head position if required for the operation.


Elevated Circular RNA PVT1 Promotes Eutopic Endometrial Cell Proliferation and Invasion of Adenomyosis via miR-145/Talin1 Axis.
Several theories on the origin of adenomyosis (ADS) have been proposed, of which the most widely accepted is the fundamental pathogenic role of uterine eutopic endometrium. Emerging evidence suggests that circular RNAs participate in the multiple tumorgenesis. The vital importance of circular RNA PVT1 (circPVT1) in the pathological progress like malignancies has been well documented. Nevertheless, its underlying correlation with ADS remains elusive yet. The purpose of this study was to investigate the expression pattern, regulatory effect, and internal mechanism of circPVT1 in ADS. qRT-PCR was performed to detect the relative mRNA expression of circPVT1, miR-145, and Talin1 in ADS endometrial tissue and cells. The protein level of Talin1 was measured by Western blot and immunochemistry. Immunofluorescence was used to identify the primary endometrial epithelial and stromal cells. circPVT1 knockdown in vitro was achieved by transfecting with specific lentivirus vector CCK-8, and colony formation assays were utilized to assess cell proliferation; meanwhile, the transwell assay was employed for evaluating cell invasion ability. By conducting bioinformatics, dual-luciferase reporter assay, or RNA immunoprecipitation (RIP) experiment, the interaction between miR-145 and circPVT1 or Talin1 was verified. Rescue experiments further determined the regulatory effect of circPVT1/miR-145/Talin1 axis. We found both circPVT1 and Talin1 were markedly upregulated in ADS endometrial tissue and cells, whereas miR-145 was decreased. Elevated expression of circPVT1 was closely related to the severity of dysmenorrhea, menorrhagia, and uterine enlargement of patients with ADS. Knockdown of circPVT1 inhibited adenomyotic epithelial and stromal cell proliferation and invasion. Further mechanistic experiments revealed that circPVT1 negatively regulated miR-145 through serving as a molecular sponge. And the facilitating effect of circPVT1 was partially reversed by miR-145. Talin1 was demonstrated to be a down target of miR-145 and indirectly affected by circPVT1. Our findings unveiled that enhanced circPVT1 may be involved in the pathogenesis of ADS via stimulating endometrial cell proliferation and invasion. The establishment of circPVT1/miR-145/Talin1 pathway might present a novel therapeutic insight for ADS.