Application of Drug Repurposing Approach for Therapeutic Intervention of Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-non-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti-inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.


Bone conducted vibration activates the vestibulo-ocular reflex in the guinea pig.
The aim of the study was: (a) to test whether short duration (6 ms) 500 Hz bone-conducted vibration (BCV) of the skull in alert head free guinea pigs would elicit eye movements; (b) to test whether these eye movements were vestibular in origin; and (c) to determine whether they corresponded to human eye movements to such stimuli. In this way we sought to establish the guinea pig as an acceptable model for testing the mechanism of the effect BCV on the vestibulo-ocular reflex. Consistent short-latency stimulus-locked responses to BCV were observed. The magnitude of eye displacement was directly related to stimulus intensity as recorded by accelerometers cemented onto the animal's skull. The strongest and most consistent response component was intorsion of both eyes. In lateral-eyed animals intorsion is produced by the combined contraction of the inferior rectus and superior oblique muscles. In humans the same pair of muscles acts to cause depression of the eye. To test whether the movements were vestibular we selectively ablated the vestibular endorgans: 3 of the 8 animals underwent a bilateral intratympanic injection of gentamicin, an ototoxic aminoglycoside antibiotic, to ablate their vestibular receptors. After ablation there was an overall reduction in the magnitude of eye displacement, as well as a reduction in the effectiveness of the BCV stimulus to elicit eye movements. The animals' hearing, as measured by the threshold for auditory brainstem responses, remained unchanged after gentamicin, confirming that the cochlea was not affected. The reduced magnitude of responses after vestibular receptor ablation demonstrates that the eye-movement responses to BCV are probably caused by the stimulation of vestibular receptors, which in turn activate the vestibulo-ocular reflex.


Low 68Ga-PSMA PET/CT Uptake in Chronic Intramuscular Nodular Fasciitis.
Nodular fasciitis is an uncommon benign mass-forming myofibroblastic proliferation, most frequently found in the upper limbs, with only rare intramuscular cases. We describe herein a case of chronic nodular fasciitis of the left triceps muscle with a low Ga-labeled prostate-specific membrane antigen (PSMA) ligand uptake on PET/CT. Ga-PSMA ligands bind to PSMA-expressing prostate cancer cells, but uptake has also been demonstrated in other solid neoplasms and various benign lesions. Nodular fasciitis should be included in the differential diagnosis of soft tissue lesions with variable Ga-PSMA uptake.


The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies.
Human Epidermal Growth Factor Receptor 2-positive breast cancer (HER2+ BC) is defined by increased amplification of the ERBB2/neu oncogene and/or overexpression of its associated HER2 transmembrane receptor protein. HER2+ BC represents approximately 15-20% of breast cancer, and it is independently associated with a higher grade, more aggressive phenotype, and worse prognosis. With the advent of trastuzumab, the prognostic landscape for HER2+ BC patients has considerably improved. However, both de novo and acquired resistance to trastuzumab remain a significant obstacle for many patients, requiring novel therapies for further clinical benefit. Over the last two decades, there has been extraordinary progress in the development of HER2+ BC treatment regimens, with extensions into HER2-amplified gastroesophageal junction cancer via the NCI-MATCH precision medicine trial program (NCT02465060). Trastuzumab, pertuzumab, T-DM1, and lapatinib are commonly recommended as a single agent (along with chemotherapy) or in combinations of anti-HER2 agents in neoadjuvant, adjuvant and metastatic settings according to National Comprehensive Cancer Network (NCCN) guidelines. Currently, the combination of trastuzumab, pertuzumab, and taxane chemotherapy are first-line for HER2+/HR- metastatic breast cancer with potential breakthrough therapies such as trastuzumab-deruxtecan (DS-8201a), margetuximab and tucatinib (ONT-380) on the horizon. Furthermore, recent clinical trials have demonstrated the potential utility of hormone receptor status, PAM-50 luminal intrinsic subtype, PD-L1, and TIL as predictive biomarkers for response to HER2+ therapies. We briefly introduce the origin of HER2, the invention of trastuzumab, and the classification of HER2+ BC. Each HER2-targeted therapy is then presented by indication, mechanism of action, and relevant clinical trials with subsequent elaboration and contextualization within clinical settings with an epilogue of potential future biomarkers for clinical use in HER2+ BC. We summarize the most significant and updated research in clinical practice relevant to HER2+ BC management and highlight the clinical status of upcoming anti-HER2 agents as well as immunotherapy drugs in combination with anti-HER2 agents.


Mapping the virome in wild-caught Aedes aegypti from Cairns and Bangkok.
Medically important arboviruses such as dengue, Zika, and chikungunya viruses are primarily transmitted by the globally distributed mosquito Aedes aegypti. Increasing evidence suggests that transmission can be influenced by mosquito viromes. Herein RNA-Seq was used to characterize RNA metaviromes of wild-caught Ae. aegypti from Bangkok (Thailand) and from Cairns (Australia). The two mosquito populations showed a high degree of similarity in their viromes. BLAST searches of assembled contigs suggest up to 27 insect-specific viruses may infect Ae. aegypti, with up to 23 of these currently uncharacterized and up to 16 infecting mosquitoes from both Cairns and Bangkok. Three characterized viruses dominated, Phasi Charoen-like virus, Humaita-Tubiacanga virus and Cell fusing agent virus, and comparisons with other available RNA-Seq datasets suggested infection levels with these viruses may vary in laboratory-reared mosquitoes. As expected, mosquitoes from Bangkok showed higher mitochondrial diversity and carried alleles associated with knock-down resistance to pyrethroids. Blood meal reads primarily mapped to human genes, with a small number also showing homology with rat/mouse and dog genes. These results highlight the wide spectrum of data that can be obtained from such RNA-Seq analyses, and suggests differing viromes may need to be considered in arbovirus vector competence studies.


Glucagonoma-induced acute heart failure.
Neuroendocrine tumours (NETs) represent a broad spectrum of tumours, of which the serotonin-producing carcinoid is the most common and has been shown to cause right ventricular heart failure. However, an association between heart failure and NETs other than carcinoid has not been established so far. In this case report, we describe a 51-year-old patient with a glucagon-producing NET of the pancreas who developed acute heart failure and even cardiogenic shock despite therapy. Heart failure eventually regressed after initialising i.v. treatment with the somatostatin analogue octreotide. Chromogranin A as a tumour marker was shown to be significantly elevated, and it decreased with clinical improvement of the patient. The effects of long-time stimulation of glucagon on the myocardium have not been studied yet; however, sarcoplasmic reticulum calcium leak can be discussed as a possible mechanism for glucagon-induced heart failure. Glucagonoma can be a cause for heart failure.i.v. infusion of octreotide can be successfully used to treat glucagonoma-induced acute heart failure.We suggest that cardiac function should be monitored in all NET patients.


Effect of Modifiable Risk Factors on Preterm Birth: A Population Based-Cohort.
Objectives The purpose of this study is to evaluate the prevalence, impact, and interaction of short interpregnancy interval (IPI), pre-pregnancy body mass index (BMI) category, and pregnancy weight gain (PWG) on the rate of preterm birth. Methods This is a population-based retrospective cohort study using vital statistics birth records from 2006 to 2011 in OH, US, analyzing singleton live births to multiparous mothers with recorded IPI (n = 393,441). Preterm birth rate at <37 weeks gestational age was compared between the referent pregnancy (defined as normal pre-pregnancy maternal BMI, IPI of 12-24 months, and Institute of Medicine (IOM) recommended PWG) and those with short or long IPI, abnormal BMI (underweight, overweight, and obese), and high or low PWG (under or exceeding IOM recommendations). Results Only 6 % of the women in this study had a referent pregnancy, with a preterm birth rate of 7.6 % for this group. Short IPIs of <6 and 6-12 months were associated with increased rates of preterm birth rate to 12.9 and 10.4 %, respectively. Low PWG compared to IOM recommendations for pre-pregnancy BMI class was also associated with increased preterm birth rate of 13.2 % for all BMI classes combined. However, the highest rate of preterm birth of 25.2 % occurred in underweight women with short IPI and inadequate weight gain with adjOR 3.44 (95 % CI 2.80, 4.23). The fraction of preterm births observed in this cohort that can be attributed to short IPIs is 5.9 %, long IPIs is 8.3 %, inadequate PWG is 7.5 %, and low pre-pregnancy BMI is 2.2 %. Conclusions Our analysis indicates that a significant proportion of preterm births in Ohio are associated with potentially modifiable risk factors. These data suggest public health initiatives focused on preterm birth prevention could include counseling and interventions to optimize preconception health and prenatal nutrition.


Prussian blue type nanoparticles for biomedical applications.
Prussian blue type nanoparticles are exciting nano-objects that combine the advantages of molecule-based materials and nanochemistry. Here we provide a short overview focalizing on the recent advances of these nano-objects designed for biomedical applications and give an outlook on the future research orientations in this domain.


Posterior cricoarytenoid as a speech muscle.
It is well known that the posterior crioarytenoid muscle (PCA) is the only abductor of the vocal folds, but its role in speech has not fully been clarified. Our recent electromyographic (EMG) studies indicate active participation of PCA in the production of voiceless consonants and breathy phonation in different languages. In the experiments to be reported here, computer-averaged EMG data were obtained from PCA of native speakers of American English, Japanese, and Danish who uttered test words embedded in frame sentences. The results indicated that there was consistent increases in PCA activity for the voiceless portion of the test words. The EMG results were compared to the degree of glottal opening estimated by means of the fiberoptic technique. It was suggested that the degree and timing of PCA activity were directly responsible for determining the size and temporal course of the glottal opening for voiceless segments, although the suppression of the adductors might also have to be taken into consideration for a complete description of voiceless segment production.


The impact of glutathione S-transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.
Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one-third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S-methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S-transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA-related ADRs in Chinese Han patients with IBD. We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P < 0.001). There was also a significant underrepresentation of GSTP1*-105V allele among patients developing ADRs (odds ratio [OR] = 0.125, 95% confidence interval [CI] = 0.022-0.709, P = 0.0012). The patients with higher GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST-P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA-related ADRs.


Penetrating keratoplasty with anterior or posterior chamber intraocular lens implantation.
To compare the outcome of anterior chamber (AC) intraocular lens (IOL) implantation with the outcome of posterior chamber (PC) IOL implantation at the time of penetrating keratoplasty in the absence of capsular support. Retrospective study of 122 eyes that underwent secondary IOL implantation without capsular support at the time of penetrating keratoplasty. Ninety eyes received an AC IOL and 32 received a PC IOL sutured to the iris or the ciliary sulcus. Survival analysis showed the probability of a clear graft to be 86% for eyes with an AC IOL and 90% for eyes with a PC IOL at 1 year. Intraocular pressure rose by 5 mm Hg or more in 30% of eyes with AC IOLs and 5% of eyes with PC IOLs. Visual acuity was better than 20/200 in 48% of eyes with AC IOLs and 68% of eyes with PC IOLs. This study demonstrated a trend for a better outcome with PC IOLs than AC IOLs for secondary implantation at time of penetrating keratoplasty in the absence of capsular support.


Oral prevalence and clearance of oncogenic human papilloma virus in a rehabilitation community for substance abusers in Italy: a case of behavioral correction?
Human papilloma virus oral infection can be related to several factors including HIV infection, cigarette smoking, marijuana consumption and number of sexual partners. We conducted a study on oral HPV prevalence and clearance among the hosts of the San Patrignano community, a population considered at "high-risk" for HPV due to their previous habits. From March 2007 to September 2010 all subjects were submitted to oropharyngeal brushing and saliva collection at baseline, after 6, 12 and 48 months (for subjects HPV positive at baseline). Samples were analyzed to detect HPV DNA and virus genotypes. The correlation between HPV prevalence and demographic, behavioral or immunological characteristics was assessed. Among 194 subjects, 30 (15%) were HPV positive with 25 (13%) high-risk (HR)-HPV at baseline brushing. At 12 months HPV infection was cleared in all cases. However at 48 months HPV was newly detected in 33% of subjects. A correlation between time spent in the community and increase in the ratio of "low-risk" (LR) HPV and HR-HPV was observed. HPV infection was not associated with age, gender, HIV status, HCV, alcohol and/or drug exposure, number of years spent in community, sex with drug-addicts and condom use. Only AIDS under antiretroviral treatment was inversely correlated with the risk of infection. At 1 year a complete HPV clearance was observed which could be related to adoption of healthier lifestyles of participants. New HPV infections were detected even in the absence of the recognized and declared risky behavioral factors, suggesting a re-expression from a latent infection.


Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients carrying TTN mutations.
Dilated cardiomyopathy (DCM) is a common heart disease that can lead to heart failure and sudden cardiac death. Mutations in the TTN gene are the most frequent cause of DCM. Here, we generated two human induced pluripotent stem cell (iPSC) lines from the peripheral blood mononuclear cells (PBMCs) of two DCM patients carrying c.94816C>T and c.104188A>G mutations in TTN, respectively. The two lines exhibited a normal morphology, full expression of pluripotency markers, a normal karyotype and the ability of trilineage differentiation. The two lines can serve as useful tools for drug screening and mechanism studies on DCM.


Depersonalization, vertigo and Ménière's disease.
Ménière's disease is generally accepted to be a consequence of distention of the endolymphatic sac of the inner ear. Although the exact etiology is unclear, there is a body of research suggesting that Ménière's disease is of psychosomatic origin. While we do not intend to review the literature exhaustively, we briefly review several frequently cited studies. Even though this literature is so severely flawed that no solid conclusions may be drawn from it, certain questions about the psychological aspect of this disorder continue to surface. Our limited access to patients with vertigo has not allowed us to undertake a carefully designed study. However, in clinical practice we have noted that many persons who complain of vertigo (whether due to Ménière's disease or other causes) also report symptoms of depersonalization and derealization. In this paper we present the cases of two women with Ménière's disease who also experienced concurrent feelings of unreality. It appears likely that feelings of unreality may occur regularly in association with syndromes causing vertigo, presumably as a consequence of vestibular dysfunction. We argue that emotional disturbances previously identified as predisposing causes of Ménière's disease are more likely effects of the disease. Although the discussion of two uncontrolled cases can do little to help solve nagging questions about a psychosomatic component to this disorder, we believe it may suggest a different perspective from which to investigate these complex phenomena.


Significance of nm23 mRNA expression in human hepatocellular carcinoma.
It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in the metastasis of human tumors. In order to investigate its role in the human hepatocellular carcinoma (HCC), 18 matched pairs of tumorous and adjacent nontumorous liver tissues of hepatectomy from patients with HCC were studied by quantitative reverse transcription-PCR. Further analyses of the nm23-H1 gene were also done. The results of these molecular studies were correlated with the clinicopathologic features of the patients. Nm23-H1 transcript was expressed in all neoplastic and adjacent nontumorous liver tissue. The level of expression, however, did not correlate well with the extension or metastatic potential of the tumors. Instead, in 15 (83.3%) of 18 HCC, nm23-H1 expression was higher in the tumorous tissues, compared with the adjacent nontumorous tissues; and significantly higher levels of nm23-H1 mRNA expression was detected in HCC with poor differentiation (Edmonson classification, III and IV) than those with moderate differentiation (I and II). Southern blot analysis of nm23-H1 gene revealed neither amplification nor loss of heterozygosity of all HCC tissues examined. Direct sequencing of the nm23-H1 gene in all HCC tissues detected no mutations. Our findings suggested that increased nm23-H1 mRNA expression is correlated with HCC tumor progression.


Enzymatic effects of Pleurotus ostreatus spent substrate on whole-plant corn silage and performance of lactating goats.
Pleurotus ostreatus (oyster mushroom) synthesizes enzymes that degrade lignin, cellulose, and hemicellulose. The objectives of this study were to evaluate the effect of Pleurotus ostreatus spent substrate (POSS) on whole-plant corn silage (WPCS) chemical composition, antioxidant capacity, lignin monomers, and in vitro digestibility, as well as the performance of lactating goats fed corn silage treated with different levels of POSS. In experiment 1, 4 levels of lignocellulolytic enzymes were tested in a complete randomized design: 0, 10, 20, and 30 mg of lignocellulosic enzymes per kilogram of fresh matter, 4 replicates per treatment (vacuum-sealed bags). The bags were opened 60 d after ensiling. In experiment 2, corn silage treated with 3 enzyme levels (0, 10, or 30 mg/kg of fresh matter) was fed to lactating goats as part of the total mixed ration. Nine lactating Saanen goats (62.68 ± 7.62 kg BW; 44 ± 8 d in milk; 2.91 ± 0.81 kg of milk/day, mean ± SD) were assigned to three 3 × 3 Latin squares. Data were analyzed using the GLIMMIX procedure of SAS (version 9.4, SAS Institute Inc.), and means were compared by linear and quadratic orthogonal contrast. In experiment 1, neutral detergent fiber (NDF), acid detergent fiber (ADF), lignin, and cellulose quadratically decreased in the WPCS treated with POSS. At the nadir point, POSS decreased NDF by 14.1%, ADF by 19.5%, lignin by 9.07%, and cellulose by 22.1% compared with the untreated silage. Therefore, POSS led to a quadratic increase in in vitro dry matter digestibility of WPCS (+8.88% at the vertex) compared with the untreated silage. In experiment 2, POSS quadratically increased the in vivo total-tract ADF digestibility. Also, the concentration of polyphenols in the milk of goats linearly increased with the addition of POSS, and no differences were observed among treatments for milk yield and composition. In summary, adding 10 mg of lignocellulolytic enzymes from POSS per kilogram of fresh matter of whole-plant corn at ensiling had a more evident reduction in lignin and cellulose concentration, leading to greater in vitro digestibility, as well as greater in vivo ADF digestibility; however, milk yield was not different among treatments.


Kikuchi's disease: an unusual presentation and a therapeutic challenge.
Kikuchi's disease, or necrotizing histiocytic lymphadenitis, is a rare disease that presents predominantly in young women in their 20s and 30s from the Far East. Our case depicts an African-American male, in his sixth decade of life, presenting with Kikuchi's disease, making our case unusual. The clinical presentation, together with laboratory and pathological tests described here, specifically the utilization of immunohistochemistry, aid in establishing a diagnosis. We advocate the use of steroids as symptomatic therapy and provide a novel and successful therapeutic regimen. We do not recommend antibiotic therapy until an infectious etiology is confirmed.


Hospice emergency kit for veterans: a pilot study.
Although the provision of hospice emergency kits (HEKs) by home hospice agencies is thought to be widespread, little is known about their use, safety, and impact. This study evaluated HEK medication utilization, safety, diversion, and perceived impact. Evaluation consisted of a retrospective patient chart abstraction and an anonymous questionnaire for home hospice nurses. Chart abstraction examined the computerized records of deceased veterans discharged to home hospice in 2009 (N=76). The questionnaire was completed by 78 home hospice nurses from 16 agencies. Chart abstraction examined HEK medication utilization, symptoms addressed, and safety/diversion concerns. The hospice nurse questionnaire assessed their perceptions of HEK utilization, safety, and impact, including efficacy for preventing emergency department (ED) visits and hospitalizations. Of patients who received an HEK, its use was documented in 50% of cases. The most used items were morphine concentrate and antibiotics. Nurses estimated that the HEK was utilized in 66.3% of cases, with the most frequently used medications being morphine, lorazepam, promethazine, and haloperidol. Fifty-nine percent of nurses felt HEKs were helpful 100% of the time (mean=84.2%; median=100% of the time) and 93% felt that an emergency department (ED) visit or hospitalization was avoided by having the kit in the home. Eighteen percent believed that medications in the kit are used by someone other than the patient. HEKs have value as a means to alleviate many symptoms that emerge predictably in home hospice patients and may avoid unwanted hospitalizations and ED visits.


Cortical and subcortical white matter damage without Wernicke's encephalopathy after recovery from thiamine deficiency in the rat.
The relative etiologic roles of ethanol and thiamine deficiency in the cortical atrophy and loss of cerebral white matter in chronic alcoholics are uncertain. The present study examined the distribution of degenerating axons within cortical and subcortical tracts 1 week after recovery from early to late symptomatic stages of thiamine deficiency in the absence of ethanol in Sprague-Dawley rats. The brains of rats exposed to an early symptomatic stage of pyrithiamine-induced thiamine deficiency, 12-13 days of treatment, contained degenerating axons in corpus callosum, anterior commissure, external and internal capsules, optic and olfactory tracts, and fornix and mammillothalamic tracts. A dense pattern of degenerating axons was evident in layers III-IV of frontal and parietal cortex. Less intense and more evenly distributed degenerating axons were present in layers IV-VI of frontal, parietal, cingulate, temporal, retrosplenial, occipital, and granular insular cortex. Neuronal counts in mammillary body nuclei and areal measurements of the mammillary body were unchanged from controls and the thalamus was relatively undamaged. In animals reversed at later and more advanced symptomatic stages of thiamine deficiency, 14-15 days of treatment, degenerating axons were found in other cortical regions and hippocampus and there was extensive neuronal loss and gliosis within mammillary body and medial thalamus. These results demonstrate that a single episode of thiamine deficiency can selectively damage cortical white matter tracts while sparing the thalamus and mammillary body and may be a critical factor responsible for the pathological and behavioral changes observed in alcoholics without Wernicke's encephalopathy.


Anova Health Institute's harm reduction initiatives for people who use drugs.
Chemsex is the colloquial term used for a specific pattern of drug use that is increasingly common among men who have sex with men (MSM) globally. The recreational substances employed are used specifically in a sexualized context. The reasons for chemsex among MSM are complex. The Anova Health Institute (Anova) provided harm-reduction services in Cape Town, South Africa in 2013 and 2014. This project, known as Tikking the Boxes had two objectives: first to provide direct harm-reduction services to drug-using MSM in Cape Town, South Africa, and second, to reduce HIV and hepatitis B and C transmission among this population. This was done by identifying drug-using behaviour among MSM and linking them to harm-reduction services. Employing people who were currently using drugs was a novel aspect of this program, and successfully facilitated access to MSM drug-using networks. At the launch of the project, the concept of harm reduction was easily misunderstood by MSM. Another challenge was that the harm-reduction service, encompassing needle exchange, excluded opioid substitution therapy. People who use drugs were employed as outreach workers, requiring the project to be very flexible and adaptable to sometimes complex lives and difficult-to-reach peers. JAB SMART is Anova's new harm-reduction initiative and started in May 2017, with support from the City of Johannesburg Health Department, and is the first project of its kind in the city to provide harm-reduction services to people who inject drugs (PWID) and their sexual partners.


Molecular regulation of the HKalpha2 subunit of the H+,K(+)-ATPases.
H+, K(+)-Adenosine triphosphatases (H+, K(+)-ATPase) located in the mammalian kidney participate in maintaining ion and acid/base balance. The molecular mechanisms by which physiological conditions lead to an upregulation of H+, K(+)-ATPase activity are poorly understood. However, studies in recent years have provided tangible progress towards understanding the role of the renal H+, K(+)-ATPases. The cloning of cDNAs from the kidneys of several mammalian species has provided evidence for the presence of several H+, K(+)-ATPase isoforms. The different H+, K(+)-ATPases may make distinct contributions to ion and acid/base balance. Studies of mRNA, protein and H+, K(+)ATPase activity levels in the kidney under a variety of physiological conditions have revealed that the HKalpha2 (colonic) subunit of the H+, K(+)ATPase is highly regulated. The pump is responsive to potassium, sodium and probably hormones. Recent developments have focused on defining the HKa2 gene promoter. Analysis of the 5' end of the HKalpha2 gene from human, rat and rabbit has identified conserved elements that may serve as core promoter and regulatory elements. This review will summarize recent data related to the molecular regulation of the HKalpha2 subunit of the H+, K(+)-ATPase.


Ectopic expression of DNA encoding IFN-alpha 1 in the cornea protects mice from herpes simplex virus type 1-induced encephalitis.
A novel approach to combat acute herpes simplex virus type 1 (HSV-1) infection has recently been developed by administration with a plasmid DNA construct encoding cytokine genes. Cytokines, especially type I IFNs (IFN-alpha and IFN-beta) play an important role in controlling acute HSV-1 infection. The purpose of the present study was to investigate the potential efficacy of ectopically expressed IFN-alpha 1 against ocular HSV-1 infection following in situ transfection of mouse cornea with a naked IFN-alpha 1-containing plasmid DNA. Topical administration of the IFN-alpha 1 plasmid DNA exerted protection against ocular HSV-1 challenge in a time- and dose-dependent manner and antagonized HSV-1 reactivation. In addition, IFN-alpha 1-transfected eyes expressed a fivefold increase in MHC class I mRNA over vector-treated controls. The protective efficacy of the IFN-alpha 1 transgene antagonized viral replication, as evidenced by the reduction of the viral gene transcripts (infected cell polypeptide 27, thymidine kinase, and viral protein 16) and viral load in eyes and trigeminal ganglia during acute infection. The administration of neutralizing Ab to IFN-alpha beta antagonized the protective effect of the IFN-alpha 1 transgene in mice. Collectively, these findings demonstrate the potential of using naked plasmid DNA transfection in the eye to achieve ectopic gene expression of therapeutically active agents.


Biocompatibility--the interaction of biomaterials and host response.
Future developments for better biocompatibility of dental implants are possible and are discussed here. On each level of local host response, which is subdivided into four phases, improvements of knowledge in basic mechanisms concerning the interaction of biomaterial and host are necessary. For the development of new biomaterials, the limits for load with foreign ions and particles acting on cellular and extracellular matrix should be determined. An example is given for ZrO2-containing glass ceramics. Biochemistry of soft and hard tissue bonding to biomaterials should be investigated. Biomechanical properties of implants could be adapted to individual needs of patients. New composite materials are candidates for the design of long-term functioning implants.


[Development of Micro-Spectrometer with a Function of Timely Temperature Compensation].
Temperature drift will be brought to Micro-Spectrometer used for demodulating the Varied Line-Space(VLS) grating position sensor on aircraft due to high-low temperature shock. We successfully made a Micro-Spectrometer, for the VLS grating position sensor on aircraft, which still have stable output under temperature shock enviro nment. In order to present a real time temperature compensation scheme, the effects temperature change has on Micro-Spectrometer are analyzed and the traditional cross Czerny-Turner (C-T)optical structure is optimized. Both optical structures are analyzed by optics design software ZEMAX and proved that comparedwithtraditional cross C-T optical structure, the newone can accomplish not only smaller spectrum drift but also spectrum drift with better linearity. Based on the new optical structure. The scheme of using reference wavelength to accomplish real time temperature compensation was proposed and a Micro-fiber Spectrometer was successfully manufactured, whith is with Volume of 80 mm X 70 mmX 70 mm, integration time of 8 ~1 000 ms and FullWidthHalfMaximum(FWHM) of 2 nm. Experiments show that the new spectrometer meets the design requirement. Under high temperature in the range of nearly 60 °C, the standard error of wavelength of this new spectrometer is smaller than 0. 1 nm, and the maximum error of wavelength is 0. 14 nm, which is much smaller than required 0. 3 nm. Innovations of this paper are the schemeof real time temperature compensation, the new cross C-T optical structure and a Micro-fiber Spectrometer based on it.


Lead(II) Binding in Metallothioneins.
Heavy metal exposure has long been associated with metallothionein (MT) regulation and its functions. MT is a ubiquitous, cysteine-rich protein that is involved in homeostatic metal response for the essential metals zinc and copper, as well as detoxification of heavy metals; the most commonly proposed being cadmium. MT binds in vivo to a number of metals in addition to zinc, cadmium and copper, such as bismuth. In vitro, metallation with a wide range of metals (especially mercury, arsenic, and lead) has been reported using a variety of analytical methods. To fully understand MT and its role with lead metabolism, we will describe how MT interacts with a wide variety of metals that bind in vitro. In general, affinity to the metal-binding cysteine residues of MT follows that of metal binding to thiols: Zn(II) < Pb(II) < Cd (II) < Cu(I) < Ag(I) < Hg(II) < Bi(III). To introduce the metal binding properties that we feel directly relate to the metallation of metallothionein by Pb(II), we will explore MT's interactions with metals long known as toxic, particularly, Cd(II), Hg(II), and As(III), along with xenobiotic metals, and how these metal-binding studies complement those of lead binding. Lead's effects on an organism's physiological functions are not fully understood, but it is known that chronic exposure inflicts amongst other factors pernicious anemia and developmental issues in the brain, especially in children who are more vulnerable to its toxic effects. Understanding the interaction of lead with metallothioneins throughout the biosphere, from bacteria, to algae, to fish, to humans, is important in determining pathways for lead to enter and damage physiologically significant protein function, and thereby its toxicity.


A case of incarcerated lesser sac hernia protruding simultaneously through both the gastrocolic and gastrohepatic omenta.
Small bowel obstruction due to lesser sac herniation through both the gastrocolic and gastrohepatic omenta is extremely rare, and only a few reported cases have been concerned with imaging diagnosis. CT images showed distended bowel loops at the level of the cephalad part of the stomach, collapsed triangular loops and attached mesentery were depicted just behind the caudal part of the stomach. These findings provided clues to the diagnosis of this type of lesser sac hernia.


Frequency correlated photon generation at telecom band using silicon nitride ring cavities.
Frequency entangled photon sources are in high demand in a variety of optical quantum technologies, including quantum key distribution, cluster state quantum computation and quantum metrology. In the recent decade, chip-scale entangled photon sources have been developed using silicon platforms, offering robustness, large scalability and CMOS technology compatibility. Here, we report the generation of frequency correlated photon pairs using a 150-GHz silicon nitride ring cavity. First, the device is characterized for studying the phase matching condition during spontaneous four-wave mixing. Next, we evaluate the joint spectrum intensity of the generated photons and confirm the photon pair generation in a total of 42 correlated frequency mode pairs, corresponding to a bandwidth of 51.25 nm. Finally, the experimental results are analyzed and the joint spectral intensity is quantified in terms of the phase matching condition.


Generation of momentum transport in weakly turbulent β-plane magnetohydrodynamics.
Magnetohydrodynamic turbulence on a β plane with an in-plane mean field, a system which serves as a simple model for the solar tachocline, is investigated analytically and computationally. We first derive two useful analytic constraints: We express the mean turbulent cross-helicity in terms of the mean turbulent magnetic energy, and then show that (for weak turbulence) the time-averaged momentum transport in the system can be expressed in terms of the cross-helicity spectrum. We then complete a closure of the system using weak turbulence theory, appropriately extended to a system with multiple interacting eigenmodes. We use this closure to perturbatively solve for the spectra at lowest order in the Rossby parameter β and thereby show that the momentum transport in the system is O(β^{2}), thus quantifying the transition away from Alfvénized turbulence. Finally, we verify our theoretical results by performing direct numerical simulations of the system over a broad range of β.


Efficacy of Cognitive Behavioural Therapy for Bipolar Disorder: a Systematic Review.
Bipolar disorder (BD) is a serious mental illness with a chronic course and significant morbidity and mortality. BD has a lifetime prevalence rate of 1% to 1.5% and is characterised by recurrent episodes of mania and depression, or a mixture of both phases. Although it has harmacological and psychotherapeutic treatment, cognitive behavioural therapy (CBT) has shown beneficial effects, but there is not enough clinical information in the current literature. The main aim was to determine the efficacy of CBT alone or as an adjunct to pharmacological treatment for BD. A systematic review of 17 articles was carried out. The inclusion criteria were: quantitative or qualitative research aimed at examining the efficacy of CBT in BD patients with/without medication; publications in English language; and) being 18-65 years of age. The exclusion criteria were: review and meta-analysis articles; articles that included patients with other diagnoses in addition to BD and that did not separate the results based on such diagnoses; and studies with patients who did not meet the DSM or ICD criteria for BD. The PubMed, PsycINFO and Web of Science databases were searched up to 5 January 2020. The search strategy was: "Bipolar Disorder" AND "Cognitive Behavioral Therapy". A total of 1,531 patients both sexes were included. The weighted mean age was 40.703 years. The number of sessions ranged from 8-30, with a total duration of 45-120minutes. All the studies show variable results in improving the level of depression and the severity of mania, improving functionality, reducing relapses and recurrences, and reducing anxiety levels and the severity of insomnia. The use of CBT alone or adjunctive therapy in BD patients is considered to show promising results after treatment and during follow-up. Benefits include reduced levels of depression and mania, fewer relapses and recurrences, and higher levels of psychosocial functioning. More studies are needed.


Normal range of BMD in proximal tibia as a different skeletal site at women.
Osteoporosis is progressive metabolic bone disease that decreases bone density and features deterioration of bone structure. Dual-energy X-ray absorptiometry (DXA) is commonly used and reliable method to measure bone mineral density (BMD). Aim of this study was to determine normal ranges of BMD in left proximal tibia. Fifty-five females were included in this study. BMD was measured at the lumbar spine and the left proximal tibia using DXA. BMD value of subregions in the left proximal tibia was significantly correlated with BMD value of the total lumbar spine (r=0.111-0.766). New average BMD values of the left proximal tibia were calculated according to age using linear regression formula, leading to average BMD value for the total lumbar spine (L1-L4) in normal population. New simulated T-scores for proximal subregions of the tibia were then calculated. T-scores for proximal subregions were not different from T-scores of total lumbar spine (p>0.05). It was concluded that proximal tibia is an ideal region for measurement of BMD in osteoporosis.


Replication of human immunodeficiency virus in two T-cell lines and their application as antigens for immunofluorescence.
Two T-cell lines, TALL-1 and CCRF-CEM, were infected with human immunodeficiency virus (HIV), strain LAV, to explore the time course of the appearance of various virus specific antigens, and to establish an antibody assay system by indirect immunofluorescence (IF). These cells were infected with LAV at two different input multiplicity of infection (MOI). Antigens were tested by Western blot analysis (WB) and IF. Antigens for WB were extracted from the infected cells at various times after infection, but pooled sera of American HIV carriers could not recognize gp41 or gp160. Antigen expression was highest in CCRF-CEM, but, as the antigen for IF, TALL-1 infected at the MOI of 8.0 was the most suitable 7 days after infection, because it includes a fairly large number of uninfected cells, which served as the internal control.


A review of the razorfishes (Perciformes: Labridae) of the eastern Pacific Ocean.
Several new species of the razorfish genus Xyrichtys have been discovered recently in the tropical eastern Pacific region. The taxonomy of this group of fishes is not clear, since juveniles, females, and males often have different color patterns and morphologies, and some species descriptions are incomplete. We review the members of this genus in this region based on our recent collections and describe the juvenile, initial, and terminal phase color patterns of the Cape razorfish, Xyrichtys mundiceps. We question the validity of Xyrichtys perlas, which appears to represent the initial phase of X. mundiceps. We conclude that six species of Xyrichtys are present in the tropical eastern Pacific, including one undescribed species we have collected from the Galapagos Islands and one uncollected new species from the Revillagigedos Islands. Xyrichtys mundiceps is found in Baja California and in Panama Xyrichtys pavo is a large species found throughout the Indo-Pacific and eastern Pacific. Xyrichtys victori is a colorful species native to the Galapagos and Cocos Islands, and Xyrichtys wellingtoni is apparently endemic to Clipperton Atoll. The undescribed species is known only from the Galapagos Islands and has a dark-colored juvenile with extended first dorsal fin rays that are not separated from the remainder of the fin. The terminal phase of this species is unknown. We present keys to the known juvenile and initial phase stages of five species. In addition, we document the allometric growth of the head of razorfishes and show that the head shape of small individuals of Xyrichtys razorfishes is no different from that of the razorfish genus Novaculichthys, and therefore we suggest caution in using this character to distinguish these genera.


Stereospecific synthesis of 3 beta-hydroxylated bile alcohols.
This paper describes the synthesis of 5 beta-cholestane-3 beta, 7 alpha,25-triol and 5 beta-cholestane-3 beta, 7 alpha, 12 alpha, 25-tetrol from their corresponding 3 alpha-analogs. The method consists of refluxing a mixture of a steroid alcohol, triphenylphosphine, and diethyl azodicarboxylate in benzene solution with an acid such as formic acid. The sterically pure ester (3 beta-formate) so formed after saponification then allows an easy access to the epimer of the starting alcohol. Differentiation of these 3 beta-hydroxy bile alcohols from their corresponding 3 alpha-epimeric analogs was made possible on the basis of proton, 13C-NMR, and mass spectra as well as chromatographic mobility. Steric requirements of sterols and nucleophilicity of attacking acidic components played an important role for the success of this synthesis. Only equatorial hydroxyl groups in these bile alcohols reacted under mild conditions and epimerization, as well as protection of the alcoholic group, was achieved in one step. Formic acid was the acid of choice since the axial formate ester formed is sufficiently reactive to be hydrolyzed (KHCO3/aq X MeOH) under mild conditions.


Calcium-activated potassium channels of large unitary conductance.
The large unitary conductance Ca2+-activated K+ channel is a widely distributed channel in cellular membranes of diverse tissues. This type of channel may serve as a link between membrane excitability and cell metabolism. In this review we discuss some aspects of the gating mechanism, calcium activation and function and modulation of BK channels.


Hafnia, an enterobacterial genus naturally resistant to colistin revealed by three susceptibility testing methods.
To determine the susceptibility to colistin of Hafnia alvei and Hafnia paralvei, and to compare methods for colistin resistance detection in the Hafnia genus. A collection of 25 Hafnia isolates was studied. Species were identified by using 16S rRNA gene sequencing with subsequent phylogeny analysis. Susceptibility to colistin was determined using the broth microdilution (BMD) reference method, the Phoenix automated system, the Rapid Polymyxin NP test, the Etest system and the disc diffusion method. The collection consisted of 15 H. alvei and 10 H. paralvei isolates. Based on the 16S rRNA analysis, a close relationship of the Hafnia genus with naturally colistin-resistant enterobacterial genera (Proteus, Morganella, Providencia and Serratia) was identified. Susceptibility testing performed using the BMD method, the Phoenix automated system and the Rapid Polymyxin NP test revealed a high rate of colistin resistance (96%). Underestimation of colistin resistance using Etest strips (72%) and the disc diffusion method (0%) was observed. The high rate of colistin resistance observed within the Hafnia genus and its close phylogenetic relationship with naturally colistin-resistant genera suggest that Hafnia is a naturally colistin-resistant enterobacterial genus.


Major life events and risk of alcohol use disorders: a prospective cohort study.
To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD). Prospective cohort study with baseline examination in 1991-93 and linkage to national registers to identify AUD at follow-up. Copenhagen, Denmark. Individuals (aged 21-93 years) who participated in the Copenhagen City Heart Study in 1991-93 (n = 8758). The primary outcome was first registration with AUD during follow-up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity. Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD. Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.


Lateral Antebrachial Cutaneous Nerve as Autologous Graft for Mini-Invasive Corneal Neurotization (MICORNE).
We describe the first case of a novel surgical technique of mini-invasive corneal neurotization (MICORNE) using the lateral antebrachial cutaneous nerve as a graft nerve and the contralateral supraorbital nerve as a donor nerve in a herpetic patient with a neurotrophic keratopathy (NK). A MICORNE procedure was performed in a 32-year-old man with a 5-year history of herpes simplex virus (HSV)-related NK in the right eye (RE). Visual acuity and corneal sensation were assessed over 9 months of follow-up. HSV-1 and HSV-2 genomes were screened preoperatively and postoperatively in the patient's tears using the quantitative polymerase chain reaction technique. A high does of the oral antiviral prophylaxis was prescribed during the follow-up. Preoperative best-corrected visual acuity was 20/200 in the RE. A Cochet-Bonnet esthesiometer revealed complete corneal anesthesia (<5 mm ie, >15.9 g/mm) in all quadrants in a scarred and neovascularized cornea. Twelve months after the procedure, the visual acuity of the RE was 20/80 and corneal sensitivity had increased to 40 mm, that is, 0.8 g/mm (superior quadrant), 35 mm, that is, 1 g/mm (inferior quadrant), 40 mm (temporal quadrant), 35 mm, that is, 1 g/mm (nasal quadrant), and 40 mm (centrally). We observed no clinical recurrence of herpes, and HSV was not detected in tears during the follow-up period. We report the first case of MICORNE, a novel surgical technique of corneal neurotization in a herpetic patient with NK. Despite the potential risk of viral recurrence, our patient showed dramatic improvement in corneal sensation and visual acuity.


Alpha Lipoic Acid Plus Omega-3 Fatty Acids for Vestibulodynia Associated With Painful Bladder Syndrome.
This study assessed the effectiveness of alpha lipoic acid (ALA) plus omega-3 polyunsaturated fatty acids (n-3 PUFAs) in combination with amitriptyline therapy in patients with vestibulodynia/painful bladder syndrome (VBD/PBS). Women with VBD/PBS were randomly assigned to receive amitriptyline or amitriptyline plus a commercially available preparation (ALAnerv Age; Alfa Wassermann, Bologna, Italy) containing, in 2 capsules, ALA 600 mg plus docosahexaenoic acid 250 mg and eicosapentaenoic acid 16.67 mg. Symptoms of burning and pain were assessed using a 10-cm visual analog scale and the short form of the McGill-Melzack Pain Questionnaire. Among 84 women who were randomized, the mean ± standard deviation dose of amitriptyline was 21.7 ± 6.6 mg/day, without statistical difference between the two groups. Pain, as assessed using both the pain rating index of the visual analog scale and the short-form McGill Pain Questionnaire, decreased significantly in both trial groups, with a greater effect seen with the addition of ALA and n-3 PUFAs. The addition of ALA/n-3 PUFAs to amitriptyline treatment was also associated with improvements in dyspareunia and pelvic floor muscle tone. The overall incidence of adverse events was low, and none led to treatment discontinuation. The addition of ALA/n-3 PUFAs to amitriptyline treatment in patients with VBD/PBS appears to improve outcomes and may allow for a lower dosage of amitriptyline, which may lead to fewer adverse effects.


Alternating Sequence Controlled Copolymer Synthesis of α-Hydroxy Acids via Syndioselective Ring-Opening Polymerization of O-Carboxyanhydrides Using Zirconium/Hafnium Alkoxide Initiators.
The ring-opening polymerization (ROP) of O-carboxyanhydrides (OCAs) can give diverse poly(α-hydroxy acid)s (PAHAs) with different functional groups because of easy modification of the side group of OCAs, which can extend applications of PAHAs widely. The stereoselective polymerization of O-carboxyanhydrides and further sequence controlled alternating copolymerization of OCAs were still big challenges until now for lack of suitable catalysts/initiators. In this work, a highly syndioselective ROP of OCAs system as the first stereoselective example in this area is reported using zirconium/hafnium alkoxides as initiators with the highest Pr value up to 0.95. Furthermore, these initiators were successfully applied in the precisely alternating sequence controlled copolymerization of PheOCA and Tyr(Bn)OCA, and alternating copolymerization of LacOCA and PheOCA was also achieved.


Effects of pH and temperature on the wild-type and a mutant form of Neurospora glutamate dehydrogenase.
1. We confirm the observation of Bürk (1965) that Neurospora crassa NADP-linked glutamate dehydrogenase normally exists in an inactive form below pH7.0 and in a fully active form above pH8.0 in either tris or orthophosphate buffer. At pH7.4 the enzyme is about half activated at 25 degrees . 2. The variety of the enzyme produced by the mutant am(2l) shows a similar behaviour except that the transition is shifted about one pH unit in the alkaline direction. 3. The am(2l) enzyme has previously been reported to be activated by brief warming to 30 degrees in phosphate buffer at pH8.0. The wild-type enzyme shows a similar effect at pH7.0. In tris buffer this effect is much less pronounced. 4. The am(2l) enzyme is extremely unstable at 47 degrees at pH7.0; its stability is somewhat greater at lower pH, and is markedly increased by increasing the pH in the range 7.0-8.7. The wild-type enzyme also shows an indication of a stability minimum at pH7.0, but a temperature of 60 degrees is needed for a measurable rate of inactivation. 5. The inactive form of the enzyme is much more subject to thermal irreversible denaturation than is the active form.


Phrenic nerve stimulation, a rare complication of pacemaker: A case report.
The phrenic nerve stimulation (PNS) is a rare complication after pacemaker setting. We report a case report that describes this complication and how it can be resolved. An 88-year-old man presented himself to the emergency geriatric unit with intermittent painless abdominal contraction due to phrenic nerve stimulation. He has a history of transcatheter aortic valve implantation with cardiac resynchronization therapy pacemaker due to persistent left bundle branch block. All the usual causes for abdominal spasms were eliminated and the possibility of a link with the pacemaker was considered. The phrenic nerve stimulation is a rare complication of a pacemaker implantation. It can be clinically nonrelevant but challenging to diagnose for those not familiar with cardiac devices technology. Initial setting was an axis of stimulation between distal left ventricular (LV) and right ventricular. It was changed to LV and D1-M2. This noninvasive procedure managed to eradicate the involuntary abdominal spasms. PNS could be challenging to diagnose for those not familiar with cardiac devices technology but easy to manage with noninvasive methods.


Quality of life among breast cancer patients undergoing treatment in national cancer centers in Nepal.
To study the quality of life and to identify associated factors among breast cancer patients undergoing treatment in national cancer centers in Nepal. One hundred breast cancer patients were selected and interviewed using a structured questionnaire. European Organization of Research and Treatment of Cancer EORTC-QLQ-C30 and EORTC-QLQ-BR23 were used to assess quality of life and modified Medical Outcome Study -Social Support survey(mMOS-SS) was used to assess social support. Only multi-item scales of EORTC C30 and BR23 were analyzed for relationships. Independent sample T-tests and ANOVA were applied to analyze differences in mean scores. The score of global health status/quality of life (GHS/GQoL) was marginally above average (mean=52.8). The worst performed scales in C-30 were emotional and social function while best performed scales were physical and role function. In BR-23, most of the patients fell into the problematic group regarding sexual function and enjoyment. Almost 90% had financial difficulties. Symptom scales did not demonstrate many problems. Older individuals, patients with stage I breast cancer and thosewith good social support were found to have good GHS/GQoL. Of all the influencing factors, social support was established to have strong statistical associations with most of the functional scales: GHS/GQoL (0.003), emotional function (<0.001), cognitive function (0.020), social function (<0.001) and body image function (0.011). Body image was significantly associated with most of the influencing factors: monthly family income (0.003), type of treatment (<0.001), type of surgery (<0.001), stage of cancer (0.017) and social support (0.011). Strategies to improve social support of the patients undergoing treatment should be given priority and financial difficulties faced by breast cancer patients should be well addressed from a policy making level by initiating health financing system.


Logistic regression with image covariates via the combination of L1 and Sobolev regularizations.
The use of image covariates to build a classification model has lots of impact in various fields, such as computer science, medicine, and so on. The aim of this paper is to develop an estimation method for logistic regression model with image covariates. We propose a novel regularized estimation approach, where the regularization is a combination of L1 regularization and Sobolev norm regularization. The L1 penalty can perform variable selection, while the Sobolev norm penalty can capture the shape edges information of image data. We develop an efficient algorithm for the optimization problem. We also establish a nonasymptotic error bound on parameter estimation. Simulated studies and a real data application demonstrate that our proposed method performs very well.


The ethics and logistics of field-based genetic paternity studies.
The rapidly decreasing costs of generating genetic data sequencing and the ease of new DNA collection technologies have opened up new opportunities for anthropologists to conduct field-based genetic studies. An exciting aspect of this work comes from linking genetic data with the kinds of individual-level traits evolutionary anthropologists often rely on, such as those collected in long-term demographic and ethnographic studies. However, combining these two types of data raises a host of ethical questions related to the collection, analysis and reporting of such data. Here we address this conundrum by examining one particular case, the collection and analysis of paternity data. We are particularly interested in the logistics and ethics involved in genetic paternity testing in the localized settings where anthropologists often work. We discuss the particular issues related to paternity testing in these settings, including consent and disclosure, consideration of local identity and beliefs and developing a process of continued community engagement. We then present a case study of our own research in Namibia, where we developed a multi-tiered strategy for consent and community engagement, built around a double-blind procedure for data collection, analysis and reporting.


Postoperative self-efficacy and psychological morbidity in radical prostatectomy.
evaluate the general and perceived self-efficacy, psychological morbidity, and knowledge about postoperative care of patients submitted to radical prostatectomy. Identify the relationships between the variables and know the predictors of self-efficacy. descriptive, cross-sectional study, conducted with 76 hospitalized men. The scales used were the General and Perceived Self-efficacy Scale and the Hospital Anxiety and Depression Scale, in addition to sociodemographic, clinical and knowledge questionnaires. a negative relationship was found for self-efficacy in relation to anxiety and depression. Psychological morbidity was a significant predictor variable for self-efficacy. An active professional situation and the waiting time for surgery also proved to be relevant variables for anxiety and knowledge, respectively. participants had a good level of general and perceived self-efficacy and small percentage of depression. With these findings, it is possible to produce the profile of patients about their psychological needs after radical prostatectomy and, thus, allow the nursing professionals to act holistically, considering not only the need for care of physical nature, but also of psychosocial nature.


Seropositivity rates of HBsAg, anti-HCV, anti-HIV and VDRL in blood donors in Eastern Turkey.
Infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency viruses (HIV) remain the leading most important health problems worldwide. Screening tests such as HBsAg, anti-HCV, anti-HIV and VDRL are mandatory tests to look at before transfusion of blood or blood components. In this study, donors who applied to our Blood Center in a nine-year period were retrospectively evaluated with respect to HBsAg, anti-HCV, anti-HIV and syphilis seroprevalence. HBsAg, anti-HCV and anti-HIV were examined by microparticle ELISA system, and syphilis antibodies were screened by a syphilis test device. Of the total 39,002 individuals, 16,601 (42%) were females and 22,401 (58%) were males. HBsAg positivity was found in 2.55%, anti-HCV in 0.17%, anti-HIV in 0.036%, and VDRL in 0.057% of overall donors. As a result, HBsAg, anti-HCV, anti-HIV and VDRL seropositivity rates in donors living in our region were found lower than those in many regions of Turkey. Nevertheless, because there is no screening method to reduce the risk resulting from transfusion to zero, it appears that it is essential to adopt strict criteria in the selection of donors and to avoid unnecessary transfusion.


Tin(IV) halide complexes of AsPh3) The structures of trans-SnCl4(AsPh3)2 and SnBr4(AsPh3).AsPh3.
The structures of two 1 : 2 adducts between tin(IV) halides and AsPh(3) have been determined. SnCl(4)(AsPh(3))(2) adopts a six-coordinate geometry at tin in which the two organoarsine donors are mutually trans. In contrast, SnBr(4)(AsPh(3))(2) is five-coordinate at tin and only one arsine is directly bonded to the metal, in an axial site of the trigonal bipyramid. The second AsPh(3) group has a close contact with the axially bound bromine [As...Br: 3.567(3) angstroms], which is a unique structural variation that depicts an intermediate in a halogen-transfer reaction between Group 14 and Group 15 elements. AACVD using SnCl(4)(AsPh(3))(2) generates a film containing SnO(2) and a second crystalline material which is possibly SnCl(2), but which contains no arsenic.


Canine pemphigus foliaceus with concurrent immune-mediated thrombocytopenia.
A 3 yr old wirehaired fox terrier was presented to his primary care veterinarian with fever, thrombocytopenia, and generalized crusting dermatitis. The skin lesion had progressed for at least 18 days, and thrombocytopenia had developed 3 days before presentation. Histopathology and direct immunofluorescence studies of the skin were consistent with pemphigus foliaceus (PF). Immunofluorescence revealed immunoglobulin G deposition around the keratinocytes in the stratum spinosum. A diagnosis of immune-mediated thrombocytopenia (IMT) was confirmed by the presence of platelet surface-associated immunoglobulin using flow cytometry. Systemic immunosuppressive therapy with cyclosporine and azathioprine was effective, and the dog survived for >2 years from the initial presentation. IMT is rarely associated with PF. This appears to be the first detailed report of a definitive diagnosis of concurrent PF and IMT in a dog. The authors' findings indicate that canine PF could be complicated by hematologic immune-mediated diseases such as IMT.


Solamargine induces apoptosis of human renal carcinoma cells via downregulating phosphorylated STAT3 expression.
Solamargine (SM), an active compound derived from Solanum nigrum, triggers apoptosis and inhibits the metastatic and oxidative activities of various types of tumor cells. However, the effect of SM on human renal carcinoma cells remains unknown. In the present study, the molecular mechanisms underlying the antitumor effects of SM on ACHN and 786-O cells were elucidated. Specifically, MTT and colony formation assays were conducted to evaluate the impact of SM treatment on the proliferation of ACHN and 786-O cells, and flow cytometry was conducted to determine the influence of SM on the apoptosis rates of these cells. In addition, the expression of target proteins was determined by western blotting. The results revealed that SM not only inhibited cell viability but also promoted the apoptosis of ACHN and 786-O cells in a time- and dose-dependent manner. Moreover, treatment of ACHN and 786-O cells with SM significantly enhanced the caspase-3, caspase-8 and caspase-9 activities. Furthermore, SM downregulated the expression of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and Bcl-2 but increased the expression of cleaved caspase-3, -8, -9 and Bax. BAY2353, a p-STAT3 inhibitor, inhibited the viability of ACHN and 786-O cells, increased the expression of cleaved caspase-9 and Bax and decreased the expression of p-STAT3 and Bcl-2. Further experiments demonstrated that SM inhibited tumor growth in xenograft nude mice without causing specific toxicity to the major organs. Collectively, these findings indicated that SM not only inhibited the viability but also promoted the apoptosis of ACHN and 786-O cells, through a mechanism involving downregulation of p-STAT3 expression.


Cloning, sequencing and partial characterisation of sorbitol transporter (srlT) gene encoding phosphotransferase system, glucitol/sorbitol-specific IIBC components of Erwinia herbicola ATCC 21998.
A DNA fragment of approximately 1500 bp, harbouring the sorbitol transport gene (srlT), was amplified from the chromosomal DNA of Erwinia herbicola ATCC 21998 by PCR and cloned in Escherichia coli JM109. Degenerate oligonucleotide primers used were designed based on the conserved regions in the gene sequences within the gut operon of E. coli (Gene Bank accession no. J02708) and the srl operon of Erwinia amylovora (Gene Bank accession no. Y14603). The cloned DNA fragment was sequenced and found to contain an open reading frame of 1473 nucleotides coding for a protein of 491 amino acids, corresponding to a mass of 52410 Da. The nucleotide sequence of this ORF was highly homologous to that of the gutA gene of Escherichia coli gut operon, the srlE gene of Shigella flexrni and the sorbitol transporter gene sequence of Escherichia coli K12 (Gene Bank accession nos. J02708, AE016987 and D90892 respectively). The protein sequence showed significant homology to that of the phosphotransferase system i.e. the glucitol/sorbitol-specific IIBC components of Escherichia coli and Erwinia amylovora (P56580, O32522). The cloned DNA fragment was introduced into a pRA90 vector and the recombinant was used for developing srlT mutants of Erwinia herbicola, by homologous recombination. Mutants obtained were unable to grow on minimal medium with sorbitol. The insertion of the pRA90 vector inside the srlT gene sequence of the mutants was confirmed by DNA-DNA hybridisation.


Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate.
As it is suggested that the androgen receptor mechanism is required for prostatic development, we attempted to determine the appearance, expression and distribution of the androgen receptor in embryonic, infantile and pubertal human prostate. Using mono- and polyclonal antibodies and a digoxigenin-labeled 713 bp riboprobe, the androgen receptor expression in paraffin sections of fetal, infantile, and pubertal prostates was studied at the protein and RNA level. Under highly standardized conditions, application of the polyclonal antibodies resulted in a weak cytoplasmic and nuclear labeling of the epithelium of fetal glands. No immunoreaction was obtained with monoclonal antibodies. Applying the polyclonal antibody to pubertal and adult specimens, immunoreactivity of the androgen receptor was positive in nuclei of adluminal and basal epithelial cells, in interstitial and vascular smooth muscle cells and vascular endothelium, whereas ganglionic cells and enteroendocrine cells were negative. In situ hybridization with the digoxigenin-labeled riboprobe gave clear positive results already in epithelium of very young fetal specimens. A semiquantitative visual evaluation of in situ hybridizations showed that intermediate intensity of expression was increased in pubertal and adult specimens, whereas strong expression was reduced in prostatic epithelium. The essential findings are: (1) an early expression of androgen receptor mRNA in the fetal prostate; (2) no immunoreaction of monoclonal antibodies against the androgen receptor in the same specimens, (3) a decrease of androgen receptor mRNA expression, but increase in immunoreactivity of the androgen receptor protein with the onset of glandular maturation during puberty.


Stochasticity induced mixed-mode oscillations and distribution of recurrent outbreaks in an ecosystem.
The effect of stochasticity, in the form of Gaussian white noise, in a predator-prey model with two distinct time-scales is presented. A supercritical singular Hopf bifurcation yields a Type II excitability in the deterministic model. We explore the effect of stochasticity in the excitable regime, leading to dynamics that are not anticipated by its deterministic counterpart. The stochastic model admits several kinds of noise-driven mixed-mode oscillations which capture the intermediate dynamics between two cycles of population outbreaks. Depending on the strength of noise, the prey population exhibits intermediate to high-amplitude fluctuations (related to moderate or severe outbreaks respectively). We classify these fluctuations as isolated or intermittent or as clusters depending on their recurrences. We study the distribution of the random variable N, representing the number of small oscillations between successive spikes, as a function of the noise intensity and the distance to the Hopf bifurcation. The distribution of N is "asymptotically geometric" with the corresponding parameter related to the principal eigenvalue of a substochastic Markov chain. Finally, the stochastic model is transformed into its "normal form" which is used to obtain an estimate of the probability of repeated outbreaks.


Factors related to poor asthma control in Latvian asthma patients between 2013 and 2015.
To investigate whether beliefs about asthma medication, cognitive and emotional factors are related to poor asthma control in a sample of Latvian asthma patients in 2015. Cross-sectional, self-administered survey. Three hundred and fifty two asthma patients (mean age 57.5 years) attending outpatient pulmonologist consultations in Riga, Latvia during September 2013 to December 2015. The sample size was calculated to detect a prevalence of poor asthma control of 50% with a margin of error of 5% and a power of 95%. The validated Beliefs about Medication Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Good asthma control was assessed using the asthma control test (ACT), a validated five-item scale that reliably assesses asthma control over a recall period of four weeks. Logistic regression models were used to predict poor asthma control. Patients who had a good control of asthma medication (OR 0.70; 95% CI 0.61-0.79) or were confident that their asthma medication improves illness (OR 0.84; 95% CI 0.74-0.95) had a reduced risk of poor asthma control. The more symptoms (OR 1.63; 95% CI 1.44-1.84) the asthma patients perceived or the more their illness affects their life, the higher the probability of poor asthma control (OR 1.47; 95% CI 1.31-1.65). Some beliefs of necessity and concerns of asthma medication were also statistically significantly related to poor asthma control. Beliefs of necessity of asthma medication, cognitive and emotional illness perception factors correlate well with poor asthma control in Latvian patients.


Production of toxic-shock-associated protein(s) in Staphylococcus aureus strains isolated from 1956 through 1982.
A total of 281 Staphylococcus aureus strains selected from those submitted to the Centers for Disease Control for phage typing between 1956 and 1982 were tested for the production of toxic-shock-associated protein (TSAP) by isoelectric focusing (IEF) and solid-phase radioimmunoassay. The results suggest that the observed temporal trends in the incidence of toxic-shock syndrome were not primarily due to changes in the distribution of TSAP-positive strains of S. aureus. Overall, 39 (14%) were TSAP positive by both methods. The earliest positive strain was an isolate submitted in 1957. TSAP-positive strains were most prevalent in the group of isolates submitted in 1976 for which 29% reacted, but the percent positive subsequently declined for isolates submitted in later years. TSAP production was more frequent among strains of phage types 29, 29/52, and 52 than among other strains. The use of IEF to identify TSAP detected false-positive proteins. Seven strains were positive by IEF and negative by solid-phase radioimmunoassay, whereas only one was positive by solid-phase radioimmunoassay and negative by IEF.


Intervention for burnout among English education undergraduates: implications for curriculum innovation.
The present study investigated the effect of Rational Emotive Behavior Therapy (REBT) intervention on burnout among English education undergraduates in southeastern Nigeria. The study adopted a randomized controlled trial design. A total of 96 English education undergraduates with high burnout symptoms in the participating universities took part in the study. These were randomly assigned to groups - intervention group (n = 48) and control group (n = 48). The Oldenburg Burnout Inventory for students (OLBI-S) was used for data collection. The collected data were analyzed using 2-way mixed repeated measure ANOVA at .05 probability level. Results showed that the REBT program significantly reduced the burnout level among English education undergraduates in the intervention group compared to the students in the no-intervention control group as measured by the OLBI-S subscales. Also, the students who benefited from the REBT program maintained reduced burnout levels when the researchers conducted a follow-up. Given the present finding, the REBT program is an effective intervention for preventing and managing burnout among students. The present study has important curriculum innovation implications as far as English education is concerned especially in the Nigerian context. This intervention program can be included in the students' curriculum activities so as to equip the students with necessary therapeutic skills to manage burnout symptoms presently and in the future.


Super-resolution imaging method assisted by a left-handed medium slab based on a neural network.
In this study, a super-resolution imaging method is proposed that combines the physical properties of a left-handed medium (LHM) slab and the mathematical methods of a neural network. Firstly, for the problem of super-resolution information loss in the received scattering field in general scenes, the LHM slab is used to construct a perfect lens to recover the evanescent wave component that carries super-resolution information. Secondly, the compressed sensing (CS) method is applied to image the sparse targets under the LHM environment. However, the perfect focus only occurs in spot or line positions. Therefore, the imaging width of conventional methods is limited and a more powerful mathematical method is needed. Finally, the neural network method is introduced to relax the limitations of target imaging width due to its strong non-linear fitting capability. The simulation results demonstrate that the imaging resolution can reach λ/10 with the assistance of LHM, while the CS method can realize super-resolution imaging of λ/20 based on prior information of spatially sparse targets. In addition, the neural network method proposed in this paper relaxes the limitation of targets, realizing super-resolution imaging of λ/20 for general targets.


[Residues and Spatial Distribution Characteristics of Organochlorine Pesticides DDTs in Soil of Linyi City, Shandong Province].
Surface soil samples were collected every 36 km2 from Linyi City to study the residues, composition and origin, influencing factors, spatial distribution and environment quality characteristics of soil DDTs. Measurements were taken for DDTs, OrgC, N, etc. for all samples. The results indicated that the detectable rate of DDTs was 71. 75%, and the mean content of DDTs was 0. 035 µg.g-1. p,p'-DDT and p,p'-DDE were the predominant contaminant compounds, with mean concentrations of 0.033 µg.g-1 and 0.010 µg.g-1, and accounted for 60. 99% and 34. 62% of the detectable samples, respectively. The degradation rate of DDTs suggested that 58% surface soils were recently inputted, these newly inputted locations were especially distributed in the middle to south of the study area, meanwhile, p,p'-DDD/p,p'-DDE revealed that the degradation of DDTs was mainly under oxidizing condition, and o,p'-DDT/p,p'-DDT illustrated that 71. 37% DDTs in soils of the study area were concerned with technical DDTs sources. Besides, the correlation, analysis showed that the external factors affecting the distribution of DDTs included OrgC, N, C and pH etc. and the higher the p, p'-DDT proportion of DDTs, the greater the effect. The distribution of DDTs had an obvious point source characteristic, and significant concentration centers were located nearby the cities and counties, typically, the DDTs concentrations of middle to southern area were much higher. However, DDTs environmental quality assessment suggested that the pollution level was relatively low, and the soil was mainly classified into grade I or II, which accounted for 78. 95% and 21. 05% of the whole study area, respectively.


Infectious DNA of the human spumaretrovirus.
An infectious molecular clone (pHSRV) of the human Spumaretrovirus (HSRV) was constructed using viral DNA and cDNA clones. The infectivity of pHSRV was proven by transfection of cell cultures and subsequent infection of susceptible cultures with cell free transfection derived virus. pHSRV derived virus produced foamy virus typical cytopathic effects in susceptible cultures. Infected cells could be stained specifically with foamy virus antisera by means of indirect immunofluorescence. Radioimmunoprecipitation revealed the presence of characteristic HSRV structural proteins in pHSRV infected cultures. By cotransfection of pHSRV and an indicator plasmid it was found that pHSRV is able to transactivate the viral LTR. Viral transcripts were found to be approximately 200 bases longer in pHSRV infected cultures compared to wildtype infected cultures. This difference is most likely due to an insertion of DNA of non-viral origin in the U3 region of the 3'LTR of the infectious clone.


Creatine-kinase isoenzyme pattern in colonic infarction consequent to acute aortic dissection. A case report.
Bowel infarction can complicate acute aortic dissection (AAD); in that case early diagnosis, which decreases the high mortality, is often difficult. We report the case of one patient who underwent surgery for AAD and developed a colonic infarction, which was clinically manifest on the 4th postoperative day. However, bowel ischemia was suspected already 48 hours after surgery, on the basis of the suggestive CK pattern and the absence of myoglobin in plasma. Total CK activity reached the highest level only 48 hours after surgery (92,800 U/l); the peak was coincident with LDH, which increased proportionally less; CK-MM constituted 100% of total CK activity. The absence of myoglobin in plasma excluded the presence of rhabdomyolysis. We conclude that such laboratory findings suggest the occurrence of severe bowel ischemia.


Revisional Surgery After Adjustable Gastric Banding: Sleeve Gastrectomy or Gastric Bypass?
Adjustable gastric banding was the most common type of bariatric surgery performed in Korea prior to 2019. Many patients that have undergone this procedure require revisional bariatric surgery while removing the gastric band, and it is important to select an appropriate revisional procedure. If reoperation is performed owing to insufficient weight loss or weight regain, a 1-step procedure can be considered. However, a 2-step procedure is preferred when complications such as band erosion or stomach perforation have occurred. Previous studies from Western countries have shown that revisional Roux-en-Y gastric bypass (RYGB) can achieve more effective postoperative weight loss than revisional sleeve gastrectomy, although this procedure may also carry a higher risk of morbidity, reoperation, and readmission to hospital. In Korea, the short-term outcomes of the 2 procedures may be similar. However, the potential risk of gastric cancer in the remnant stomach after RYGB must also be considered. The type of revisional surgery should be selected following discussions with the patient regarding the advantages and disadvantages associated with each procedure.


Measuring injury severity: time for a change?
The Injury Severity Score (ISS) does not take into account multiple injuries in the same body region, whereas a New ISS (NISS) may provide a more accurate measure of trauma severity by considering the patient's three greatest injuries regardless of body region. The purpose of this study was to evaluate the ISS and NISS in patients with blunt trauma. Consecutive individuals treated from January of 1992 to September of 1996 at one institution were included if they had sustained blunt trauma and satisfied triage standards (n = 2,328). For each patient, we computed the ISS and the NISS to determine how often the two scores were identical or discrepant. Discrepant cases were then further analyzed using receiver operating characteristic curves to determine which score better predicted short-term mortality. The mean ISS was 25 +/- 13, and the mean NISS was 33 +/- 18. The two predictive scores were identical in 32% of patients and discrepant in 68% of patients. Patients with identical scores had a lower mortality rate than patients with discrepant scores (10% vs. 13%; p < 0.02). In patients with discrepant scores, the area under the receiver operating characteristic curves was greater for the NISS than the ISS (0.852 vs. 0.799; p < 0.001), and greater amounts of discrepancy were associated with increasing rates of mortality (p < 0.001). The NISS often increases the apparent severity of injury and provides a more accurate prediction of short-term mortality. The benefit associated with using the NISS rather than the ISS must be weighed against the disadvantages of changing a scoring system and the potential for still greater improvements.


Using mouse models to explore genotype-phenotype relationship in Down syndrome.
Down Syndrome (DS) caused by trisomy 21 is characterized by a variety of phenotypes and involves multiple organs. Sequencing of human chromosome 21 (HSA21) and subsequently of its orthologues on mouse chromosome 16 have created an unprecedented opportunity to explore the complex relationship between various DS phenotypes and the extra copy of approximately 300 genes on HSA21. Advances in genetics together with the ability to generate genetically well-defined mouse models have been instrumental in understanding the relationships between genotype and phenotype in DS. Indeed, elucidation of these relationships will play an important role in understanding the pathophysiological basis of this disorder and helping to develop therapeutic interventions. A successful example of using such a strategy is our recent studies exploring the relationship between failed nerve growth factor (NGF) transport and amyloid precursor protein (App) overexpression. We found that increased dosage of the gene for App is linked to failed NGF signaling and cholinergic neurodegeneration in a mouse model of DS. Herein, we discuss several mouse models of DS and explore the emergence of exciting new insights into genotype-phenotype relationships, particularly those related to nervous system abnormalities. An important conclusion is that uncovering these relationships is enhanced by working from carefully defined phenotypes to the genes responsible.


Nitrosative stress predicts the presence and severity of nonalcoholic fatty liver at different stages of the development of insulin resistance and metabolic syndrome: possible role of vitamin A intake.
Although nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome, the mechanisms responsible for the development of NAFLD at different stages of the development of insulin resistance are unknown. Diet, adipokines, and nitrosative stress have been linked to both NAFLD and insulin resistance. We aimed to identify the factors that are specifically associated with NAFLD at different stages in the development of insulin resistance and the metabolic syndrome. Circulating concentrations of adipokines (ie, tumor necrosis factor-alpha, adiponectin, resistin, leptin, and interleukin-6), markers of nitrosative stress (nitrotyrosine), dietary habits, and MTP -493G/T polymorphism were cross-sectionally related to the presence and severity of insulin resistance (homeostasis model assessment index for insulin resistance: >or=2), the metabolic syndrome, and fatty liver in 64 nonobese nondiabetic patients with NAFLD (33 insulin-sensitive and 31 insulin-resistant subjects) and 74 control subjects without liver disease who were matched for sex, BMI, homeostasis model assessment index for insulin resistance status, and the various features of the metabolic syndrome. Persons with NAFLD had greater systemic nitrosative stress and a lower intake of vitamins A and E than did control subjects, but the 2 groups did not differ significantly in any other features. Nitrotyrosine and adiponectin concentrations and vitamin A intakes independently predicted alanine aminotransferase concentrations in NAFLD patients and liver histology in a subgroup of 29 subjects with biopsy-proven nonalcoholic steatohepatitis. Oxidative stress is operating in NAFLD and nonalcoholic steatohepatitis, even in the absence of insulin resistance, the metabolic syndrome, and hypoadiponectinemia, which aggravate liver histology at more severe stages of metabolic disease. The possible pathogenetic role of reduced vitamin A intake in NAFLD warrants further investigation.


Emergency/Adjunct services and attrition prevention for randomized clinical trials in children: the MTA manual-based solution.
Treatment studies in child and adolescent psychiatry are increasingly characterized by long-term, multisite, randomized clinical trials (RCTs). During the course of these RCTs it is common for clinical exigencies to emerge that require rapid, direct intervention. The challenge is to provide clinically appropriate responses that do not contaminate the delivery, distinctness, and interpretation of the treatments under investigation. In multisite studies, the problem is compounded by the need to minimize cross-site differences in the delivery of adjunct treatments. Such minimization requires fully operationalized and manual-based procedures for clinically mandated intervention. The NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (ADHD)--"the MTA"--is a long-term multisite collaborative study in which children with ADHD were randomly assigned to either medication management, behavioral treatment, the combination, or community-comparison assessment and referral. In designing its study, the MTA developed a manual-based set of procedures (the MTA Adjunct Services and Attrition Prevention [ASAP] Manual) for situations not covered by the protocol treatments. The majority of cases requiring adjunct services fell into two major categories: (1) crisis/emergent situations and (2) imminent risk of attrition. This report describes the ASAP guidelines for dealing with cases that required adjunct services that the MTA Steering Committee adopted before initiating the trial. Although the manual-based guidelines are especially applicable to multisite RCTs, many of the procedures in the ASAP Manual can apply to any treatment study in children.


Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation.
The UV-damaged DNA binding protein complex (UV-DDB) is implicated in global genomic nucleotide excision repair (NER) in mammalian cells. The complex consists of a heterodimer of p127 and p48. UV-DDB is defective in one complementation group (XP-E) of the heritable, skin cancer-prone disorder xeroderma pigmentosum. Upon UV irradiation of primate cells, UV-DDB associates tightly with chromatin, concomitant with the loss of extractable binding activity. We report here that an early event after UV, but not ionizing, radiation is the transient dose-dependent degradation of the small subunit, p48. Treatment of human cells with the proteasomal inhibitor NIP-L3VS blocks this UV-induced degradation of p48. In XP-E cell lines with impaired UV-DDB binding, p48 is resistant to degradation. UV-mediated degradation of p48 occurs independently of the expression of p53 and the cell's proficiency for NER, but recovery of p48 levels at later times (12 h and thereafter) is dependent upon the capacity of the cell to repair non-transcribed DNA. In addition, we find that the p127 subunit of UV-DDB binds in vivo to p300, a histone acetyltransferase. The data support a functional connection between UV-DDB binding activity, proteasomal degradation of p48 and chromatin remodeling during early steps of NER.


Omega-3 Polyunsaturated Fatty Acids in Critical Illness: Anti-Inflammatory, Proresolving, or Both?
Prognosis and outcomes of critically ill patients are strictly related with inflammatory status. Inflammation involves a multitude of interactions between different cell types and chemical mediators. Omega-3 polyunsaturated fatty acids (PUFAs), mainly represented by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are able to inhibit different pathways including leukocyte chemotaxis, adhesion molecule expression and interactions, and production of inflammatory cytokines, through the action of specialized proresolving mediators (SPMs). SPMs from omega-6 fatty acids, such as lipoxins, and from omega-3 fatty acids such as resolvins, protectins, and maresins, act in reducing/resolving the inflammatory process in critical diseases, stimulating the phases of resolution of inflammation. In this light, the resolution of inflammation is nowadays considered as an active process, instead of a passive process. In critical illness, SPMs regulate the excessive posttrauma inflammatory response, protecting organs from damage. This review focuses on the role of omega-3 PUFAs as pharma nutrition agents in acute inflammatory conditions, highlighting their effects as anti-inflammatory or proresolving agents.


Plant-produced Crimean-Congo haemorrhagic fever virus nucleoprotein for use in indirect ELISA.
Crimean-Congo haemorrhagic fever (CCHF) is a disease of serious public concern caused by the CCHF virus (CCHFV). Anti-CCHFV IgG in humans can be detected using ELISA with native antigen prepared from cell cultures which have been infected with virus or from brain tissue of suckling mice which have been inoculated with virus. However, the preparation of these reagents requires high biosafety levels and is expensive. A safer, more cost-effective recombinantly-produced NP reagent is desirable. Recently, plants have been shown to be a cost-effective and safe system for expression of recombinant proteins. This work describes cloning of the CCHFV NP gene into three different plant expression systems and comparison of expression in Nicotiana benthamiana. The highest expressing construct was selected. Expressed NP was purified by ammonium sulphate fractionation prior to histidine affinity chromatography. Purified NP was tested in an indirect ELISA to determine if the recombinant antigen was able to detect anti-CCHFV IgG in sera from convalescent patients. Plant-produced NP detected IgG antibodies against CCHFV in 13/13 serum samples from convalescent patients and 0/13 samples collected from volunteers with no history of CCHFV infection. Results were compared with commercially available immunofluorescent assays and 100% concordance was obtained between the two assays. This suggests that a full evaluation of the plant produced NP for application as a safe recombinant is warranted.


Genome-Wide Studies of Rho5-Interacting Proteins That Are Involved in Oxidant-Induced Cell Death in Budding Yeast.
Rho GTPases play critical roles in cell proliferation and cell death in many species. As in animal cells, cells of the budding yeast Saccharomyces cerevisiae undergo regulated cell death under various physiological conditions and upon exposure to external stress. The Rho5 GTPase is necessary for oxidant-induced cell death, and cells expressing a constitutively active GTP-locked Rho5 are hypersensitive to oxidants. Yet how Rho5 regulates yeast cell death has been poorly understood. To identify genes that are involved in the Rho5-mediated cell death program, we performed two complementary genome-wide screens: one screen for oxidant-resistant deletion mutants and another screen for Rho5-associated proteins. Functional enrichment and interaction network analysis revealed enrichment for genes in pathways related to metabolism, transport, and plasma membrane organization. In particular, we find that ATG21, which is known to be involved in the CVT (Cytoplasm-to-Vacuole Targeting) pathway and mitophagy, is necessary for cell death induced by oxidants. Cells lacking Atg21 exhibit little cell death upon exposure to oxidants even when the GTP-locked Rho5 is expressed. Moreover, Atg21 interacts with Rho5 preferentially in its GTP-bound state, suggesting that Atg21 is a downstream target of Rho5 in oxidant-induced cell death. Given the high degree of conservation of Rho GTPases and autophagy from yeast to human, this study may provide insight into regulated cell death in eukaryotes in general.


Sharing the wisdom of nursing by writing for publication.
Nurses share their experiences, wisdom and insights through storytelling. Writing these stories for publication can serve to extend the reach of nursing practice. Writing for publication is a skill that all nurses can develop. It could be considered a professional obligation, as well as an act of generosity. The process of writing involves selecting a topic, working through an initial draft, reviewing, revising and finally submitting for publication. For the nursing profession to contribute fully to the advancement of health care, nurses need to present themselves as competent, thoughtful leaders able to express themselves clearly and effectively. Writing for publication helps accomplish this goal.