Endoscopic endonasal approach to pituitary adenomas: Impact on adenohypophyseal function. Study of 231 cases.
To identify presurgical and surgical factors associated with the development of hypopituitarism and its recovery after endoscopic endonasal transsphenoidal (EET) resection of pituitary adenomas (PAs). Retrospective study of patients with PAs operated by the same neurosurgeon through an EET approach in two Spanish tertiary hospitals in ten years. 242 pituitary surgeries performed in 231 patients were analyzed. In the 154 surgeries performed in 146 patients with non-functioning PAs (NFPAs), 46.8% (n=72) presented presurgical hypopituitarism. After PAs resection, 41 of these (56.9%) normalized pituitary function and 11 of 82 patients with preoperative normal function (13.4%) developed new pituitary deficits. Patients with preoperative visual impairment (OR=3.9, p=0.046) and operated in the first four years of the neurosurgeon's learning curve (OR=5.7, p=0.016) presented a higher risk of developing postoperative hypopituitarism. Of the 88 surgeries in 85 patients with functioning PAs (FPAs), 23.9% presented presurgical hypopituitarism, and 47.6% of those recovered after surgery. 9% of the cases with preoperative normal function developed new pituitary deficit/s. Diabetic patients presented a higher risk of persistence of hypopituitarism (OR=10.5, p=0.024). Patients with presurgical visual impairment (OR=30.0, p=0.010) and PAs>3cm (OR=14.0, p=0.027) had higher risk of developing new pituitary deficits. Approximately 50% of patients with PAs and preoperative hypopituitarism recover pituitary function after EET surgery. 10% of patients with normal function develop new deficits. Patients with NFPAs with visual involvement and operated in the first four years of neurosurgeon's learning curve, and FPAs patients with presurgical visual impairment and tumor size>3cm have a higher risk of postoperative hypopituitarism.


Nop9 is an RNA binding protein present in pre-40S ribosomes and required for 18S rRNA synthesis in yeast.
Proteomic analyses in yeast have identified a large number of proteins that are associated with preribosomal particles. However, the product of the yeast ORF YJL010C, herein designated as Nop9, failed to be identified in any previous physical or genetic analysis of preribosomes. Here we report that Nop9 is a nucleolar protein, which is associated with 90S and 40S preribosomes. In cells depleted of Nop9p, early cleavages of the 35S pre-rRNA are inhibited, resulting in the nucleolar retention of accumulated precursors and a failure to synthesize 18S rRNA. Nop9 contains multiple pumilio-like putative RNA binding repeats and displays robust in vitro RNA binding activity. The identification of Nop9p as a novel, essential factor in the nuclear maturation of 90S and pre-40S ribosomal subunits shows that the complement of ribosome synthesis factors remains incomplete.


Hymenolepis diminuta infection in a child living in the urban area of Rome, Italy.
We report a case of Hymenolepis diminuta infection in an Italian child affected by tuberous sclerosis. Praziquantel is the drug of choice for the treatment of H. diminuta infection. However, considering the patient's neurological disease, we decided to use not praziquantel but niclosamide, which proved equally effective.


Hepatic portocholecystostomy for biliary atresia.
Four infants with biliary atresia had gross obliteration of the common hepatic duct but residual patency of the gallbladder, cystic duct and common bile duct. The patients were treated by hepatic portocholecystostomy utilizing the extant bile ducts for biliary reconstruction. Bile drainage was achieved in all four infants. There was a conspicuous absence of postoperative cholangitis. Subsequent obstruction of the distal ducts in two patients necessitated reoperation and construction of a standard biliointestinal conduit. The other two children are surviving, jaundice-free, 5 1/2 and 5 years after operation with minimal sequelae of biliary atresia. Hepatic portocholecystostomy is a feasible surgical alternative to intestinal reconstruction in patients with biliary atresia in whom the disease is limited to the proximal extrahepatic bile ducts.


A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test.
This paper describes a new procedure for detecting effective antidepressant treatments. The procedure uses the swim-test susceptible (Susceptible) rat which has been selectively bred to show decreased struggling behavior in a swim test after exposure to a mild stressor. The ability of treatments to block this decrease in swim-test activity was assessed as a method for detecting effective antidepressants. In both male and female Susceptible rats, chronic (14-day) treatment with different antidepressant drugs delivered via osmotic minipump [i.e., three tricyclics (desmethylimipramine, imipramine, amitriptyline), two selective serotonin reuptake inhibitors (fluoxetine and sertraline), a monoamine oxidase inhibitor (phenelzine), and two atypical antidepressants (venlafaxine and bupropion)] all prevented the stress-induced decrease in swim-test struggling normally shown by these rats. Electroconvulsive shock had a similar effect. Unlike antidepressant drugs, 14-day treatment with various non-antidepressant drugs [i.e., a stimulant (amphetamine), an anxiolytic (chlordiazepoxide), an antihistamine (chlorpheniramine), and an anticholinergic (scopolamine)] did not have this effect. Antidepressant drug treatment for 1 day (i.e., acute treatment) was also ineffective in this test. The procedure described above requires use of the Susceptible rat--swim test resistant rats (i.e., rats selectively bred to be resistant to decreased swim-test activity after exposure to stressful conditions) showed no significant differences in swim-test behavior between stress and nonstress conditions after 14-day drug treatment, and randomly bred Sprague-Dawley rats did not show a decrease in swim-test activity following exposure to the mild stressor that is the basis for the test. These results suggest that the procedure described here, which uses a rat subject that has been bred for vulnerability to stressful conditions, may be a selective screening technique for effective antidepressant treatments.


Prolonged fetal bradycardia with recovery--its significance and outcome.
bradycardia lasting more than 21/2 minutes with a decrease in FHR of more than 30 b.p.m. were observed in the course of 15 monitored labors. The mean fetal pH during the 20 minutes following the bradycardia (early recovery) was significantly less than the mean pH obtained 30 minutes or more after the bradycardia (late recovery). Various types of periodic heart rate changes were observed during the early recovery period but few persisted into late recovery. Vaginal delivery occurred in 13 of 15 patients. Two cesarean sections were performed for indications unrelated to the prolonged bradycardia. The 5 minute Apgar score of all 15 neonates was 7 or greater.


The extent of perfusion-F18-fluorodeoxyglucose positron emission tomography mismatch determines mortality in medically treated patients with chronic ischemic left ventricular dysfunction.
The purpose of this study was to assess the determinants of mortality in a large group of patients with ischemic cardiomyopathy who are treated medically and the impact of the extent of viable tissue on prognosis. Whether the presence of viability drives mortality in patients with ischemic cardiomyopathy who are treated medically and whether the extent of viability is important are issues that are currently unclear. Two hundred sixty-one patients with ischemic cardiomyopathy underwent positron emission tomography (PET) for assessment of viability. Prospective follow-up was obtained. Ninety-four patients were revascularized and 167 were not. The cardiac death rate was significantly less in the revascularized patients as compared with medically treated patients (13% vs. 24%, p < 0.05). In the revascularized patients, there was a trend toward better survival in patients with viable myocardium as compared with nonviable myocardium (3.5-year survival, 85% and 75% respectively, p = NS). In the medically treated group, age (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.2 to 3.7), presence of left bundle branch block (HR 3.4, 95% CI 1.6 to 7.2) and extent of perfusion-metabolism mismatch on PET (HR 1.36, 95% CI 1.1 to 1.6) predicted cardiac death during a median follow-up period of 2.1 years. The risk of cardiac death was not significantly increased when the extent of mismatch was < or =20% (HR 0.97, 95% CI 0.46 to 2.05) but was significantly increased when the extent of mismatch was >20% (HR 3.21, 95% CI 1.38 to 7.49). Medically treated patients with ischemic cardiomyopathy and large areas of viable myocardium on PET are at high risk for cardiac death.


Short-term ursodeoxycholic acid treatment improves gallbladder bile turnover in gallstone patients: a randomized trial.
Ursodeoxycholic acid (UDCA) prevents in vitro gallbladder (GB) muscle damage caused by acute cholecystitis and reduces risk of biliary pain and complications in gallstone (GS) patients. These effects could be partially explained by the improved GB bile turnover. To assess the effect of short-term UDCA treatment on GB motility and bile turnover. Ultrasonographic (US) assessment of GB volumes was performed in 16 GS patients, in the postprandial phase, for 90 min with a time sampling of 1 min, before and after 30 days of UDCA (10 mg kg(-1) die(-1)) or placebo, randomly assigned. US data were analysed with statistical tools and with computer fluido-dynamic (CFD) software Fluent(TM) to simulate GB bile flow. After therapy, fasting volume (FV) increased from 21.6 +/- 9 to 28.2 +/- 12 mL (p < 0.001) while the ejection fraction (EF) remained unchanged (44.5 +/- 17% vs 45.1 +/- 20%; p: ns). Volumes before and after treatment were poorly correlated (0.02 < r < 0.35), unlike those in placebo patients (r > 0.6). The average GB volume was increased in 7 out of 10 patients following UDCA (range 7-67%). CFD analysis supports the finding of improved bile flow after treatment. Unlike results of conventional US parameters of GB motility, CFD analysis shows that UDCA improves GB bile turnover in GS patients.


Consequences of challenge infections with Fasciola hepatica on rat liver P450-dependent metabolism of sex hormones.
The effect of single or repetitive fluke-infections on rat liver steroid hormone metabolism was studied. Fascioliasis was induced by oral administration of 20 metacercariae of Fasciola hepatica to rats, by week-6 (mono-infected) or 12 and 6 (bi-infected), or 12, 9 and 6 (tri-infected) before killing. Total microsomal cytochrome P450 and P450 isoenzymes were measured spectrophotometrically and by Western-blot analysis, respectively. Progesterone and testosterone metabolism were quantified by normal phase high performance liquid chromatography. In control rats, progesterone and testosterone were mainly converted to 2 alpha- and 16 alpha-hydroxymetabolites. In the liver of mono-infected rats, hepatic cytochrome P450 was significantly decreased by 36-64% whereas the expression of all investigated isoenzymes was decreased by 36-82% with the exception of the unchanged P4502E1. 16 alpha- and 2 alpha-hydroxylations of progesterone and testosterone were significantly decreased by 50-90%, these decreases were correlated with those of P4502B1/2 and P4502C11 isoenzymes, respectively. In bi- and tri-infected rats, steroid hormones were metabolized similarly to control rats. The return of steroid drug metabolizing enzyme activities to control level could be related to the immune response associated to the development of the animal resistance to the parasitic infection.


Cervical meningioma masquerading as schwannoma: two cases and a review of the literature.
Two patients presenting with intradural, extramedullary, transforaminal ''dumbbell-shaped'' tumors are discussed. While imaging studies were strongly suggestive of schwannoma, both patients were diagnosed with meningioma. Presentation, imaging studies, operative intervention and pathology are described. Due to the difficulty in achieving complete resection, and the propensity for recurrence, long-term follow-up is recommended.


Structure Characterization and Anti-Rheumatoid Arthritis Activity of a Polysaccharide from Notopterygium incisum.
Notopterygium incisum is a traditional Chinese medicine that is commonly used to treat rheumatoid arthritis. Polysaccharides from N. incisum can be one of its main active components. However, there have been little investigations on N. incisum polysaccharides. A novel polysaccharide named NIP is extracted from N. incisum with a molecular weight of 2.34 × 106 Da. NIP, composed of arabinose, galactose, glucose, and galacturonic acid, is linked by methyl esterified 1,4-linked α-galacturonic acid, 1,6-linked β-galactose, 1,5-linked α-arabinose, and 1,4,6-linked β- glucose. In vitro, NIP can inhibit the NO production of LPS-stimulated RAW264.7 cells. In vivo, NIP relieves toe redness and swelling of AIA rats, reduces the release of inflammatory factors in the serum, and inhibits the activation of NF-κB and JAK/STAT3 signaling pathways. In addition, NIP can effectively decrease oxidative stress, reverse intestinal flora imbalance, and promote butyric acid-producing bacteria's proliferation to exert anti-RA activity. NIP may be recommended as a functional food that can alleviate the damage of rheumatoid arthritis.


Comparison of Locked Plating of Varus Displaced Proximal Humeral Fractures With and Without Fibula Allograft Augmentation.
To compare the clinical and radiographic outcomes between patients treated with fibula allograft-augmented locking compression fixation and patients treated with locking compression fixation alone for 2- and 3-part proximal humeral fractures with varus displacement. Retrospective review. Level 1 trauma center. One hundred two patients treated with locking plate fixation ± fibular allograft augmentation confirmed intraoperatively by visual inspection to have varus-angulated, 2- and 3-part proximal humerus fractures with at least 45 degrees of varus angulation at the neck/shaft and at least 1 cm of displacement. Proximal humerus locking plate (PHILOS; Synthes, Paoli, PA) with or without fibula allograft augmentation. Statistical analysis to determine the differences between fractures treated with locking compression fixation ± fibula allograft augmentation regarding complications, shoulder reported outcome measures, and patient ROMs (Visual Analog Score (VAS), Disabilities of the Arm, Shoulder and Hand, and Simple Shoulder Test scores). Medical comorbidities as potential risk factors for complication from surgery were also evaluated. Of 102 surgical cases, 27 were augmented with fibula allograft and 75 were not. Postoperatively, there were 16 noncatastrophic varus collapses of the fracture, 6 catastrophic varus collapses, and 5 deaths. Addition of fibula allograft did not significantly affect postoperative varus collapse, shoulder ROM, pain, or PROMs. Addition of fibula allograft to patients sustaining varus-angulated, 2- and 3-part proximal humeral fractures conferred no benefit to patient outcomes at our institution. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Two translational initiation sites in the infB gene are used to express initiation factor IF2 alpha and IF2 beta in Escherichia coli.
The gene infB codes for the two forms of translational initiation factor IF2: IF2 alpha (97 300 daltons) and IF2 beta (79 700 daltons). To determine whether the two forms differ at their N terminus, purified IF2 alpha and IF2 beta were subjected to 11 or more steps of Edman degradation. The N-terminal amino acid sequences are completely different, but match perfectly the DNA sequences at the beginning of the infB open reading frame and an in-phase region 471 bp downstream. A fusion was constructed between the proximal half of the infB gene and the lacZ gene lacking the region coding for the first eight amino acids. The fused gene expresses two products of 170 000 and 150 000 daltons, corresponding to the fused proteins IF2 alpha-beta-galactosidase and IF2 beta-beta-galactosidase, which confirms in vivo that the IF2 forms differ at their N terminus. A deletion of the 5'-non-translated region of the fused gene, including the Shine/Dalgarno ribosomal binding site, results in the expression of IF2 beta-beta-galactosidase but not IF2 alpha-beta-galactosidase. This strongly suggests that IF2 beta results from independent translation rather than from a precise proteolytic cleavage of IF2 alpha. Further evidence for initiation of protein synthesis at the putative IF2 alpha and IF2 beta start sites was sought by using an in vitro dipeptide synthesis assay. A DNA fragment containing the entire infB gene was cloned into three plasmid vectors and the resulting recombinant DNAs were used as templates in assays containing fMet-tRNA and various labelled aminoacyl-tRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)


Catheter infections as a factor in the transfer of continuous ambulatory peritoneal dialysis patients to hemodialysis.
The effect of peritoneal catheter infections on the transfer of continuous ambulatory peritoneal dialysis (CAPD) patients to hemodialysis over a 9-year period were examined. Twenty-seven percent (68/247) of all patients were transferred permanently to hemodialysis after a mean of 15 +/- 14 months of CAPD. An additional 29% transferred temporarily one or more times during the study period (mean time of peritoneal dialysis, 35 +/- 23 months). The reasons for permanent transfer to hemodialysis were catheter infections (15/68, 22%), peritonitis (13/68, 19%), catheter infections associated with peritonitis (10/68, 15%), patient preference (9/68, 13%), mechanical problems (4/68, 6%), noncompliance (7/68, 10%), inadequate clearance or ultrafiltration (6/68, 9%), with other reasons for the remainder (4/68, 6%). Temporary transfers to hemodialysis were also mainly due to catheter infections (32%), peritonitis (23%), and simultaneous catheter infections and peritonitis (24%). Catheter infection rates were much higher in the groups that permanently and temporarily were transferred to hemodialysis in comparison with those patients who remained on peritoneal dialysis. We conclude that catheter infections are a leading cause of both temporary and permanent transfer of CAPD patients to hemodialysis.


Biological and practical implications of genome-wide association study of schizophrenia using Bayesian variable selection.
Genome-wide association studies (GWAS) have identified over 100 loci associated with schizophrenia. Most of these studies test genetic variants for association one at a time. In this study, we performed GWAS of the molecular genetics of schizophrenia (MGS) dataset with 5334 subjects using multivariate Bayesian variable selection (BVS) method Posterior Inference via Model Averaging and Subset Selection (piMASS) and compared our results with the previous univariate analysis of the MGS dataset. We showed that piMASS can improve the power of detecting schizophrenia-associated SNPs, potentially leading to new discoveries from existing data without increasing the sample size. We tested SNPs in groups to allow for local additive effects and used permutation test to determine statistical significance in order to compare our results with univariate method. The previous univariate analysis of the MGS dataset revealed no genome-wide significant loci. Using the same dataset, we identified a single region that exceeded the genome-wide significance. The result was replicated using an independent Swedish Schizophrenia Case-Control Study (SSCCS) dataset. Based on the SZGR 2.0 database we found 63 SNPs from the best performing regions that are mapped to 27 genes known to be associated with schizophrenia. Overall, we demonstrated that piMASS could discover association signals that otherwise would need a much larger sample size. Our study has important implication that reanalyzing published datasets with BVS methods like piMASS might have more power to discover new risk variants for many diseases without new sample collection, ascertainment, and genotyping.


Postoperative management following supraglottoplasty for severe laryngomalacia.
To retrospectively analyze the postoperative management and care needs of patients undergoing spontaneous ventilation supraglottoplasty (SVS). Retrospective chart review. Charts of children undergoing (SVS) for severe laryngomalacia from 2007 to 2011 at a single institution were reviewed. Intraoperative and postoperative management data were collected to review the airway management, postoperative care needs, and potential complications associated with this surgery. A total of 65 patients were included in the study. Only three patients (4.5%) required more than an overnight stay in the hospital, and no patients left the operating room intubated. One patient required temporary intensive care unit observation, and the majority (78.1%) demonstrated adequate oral intake within 4 hours of surgery. Comorbidities did not portend a longer hospital stay or slower return to oral intake. SVS with cold-steel instruments is a safe and effective surgical intervention with low complication rates. This study suggests that postoperative intubation or intensive care unit monitoring may not be necessary when using these techniques.


Medication reviews are useful, but the model needs to be changed: Perspectives of Aboriginal Health Service health professionals on Home Medicines Reviews.
The Australian Home Medicines Review (HMR) program consists of a pharmacist reviewing a patient's medicines at his or her home and reporting findings to the patient's general practitioner (GP) to assist optimisation of medicine management. Previous research has shown that the complex HMR program rules impede access to the HMR program by Aboriginal and Torres Strait Islander clients. This study explores the attitudes and perceptions of health professional employees working within Aboriginal Health Services (AHSs) towards the HMR program. The goal was to identify how the HMR program might better address the needs of Aboriginal and Torres Strait Islander people. Thirty-one semi-structured interviews were conducted with health professionals at 11 diverse AHSs. Fourteen Aboriginal Health Workers (AHWs), five nurses, one manager and 11 GPs were interviewed. Interviews were recorded, de-identified and transcribed verbatim. Transcripts were coded and analysed for themes that recurred throughout the interviews. This study identified a number of barriers to provision of HMRs specific to Aboriginal and Torres Strait Islander clients. These included paternalistic attitudes of health professionals to clients, heightened protection of the GP-client relationship, lack of AHS-pharmacist relationships, need for more culturally responsive pharmacists and the lack of recognition of the AHS's role in implementation of culturally effective HMRs. Changes to the HMR model, which make it more effective and culturally appropriate for Aboriginal and Torres Strait Islander people, were recommended. Improved relationships between GPs and pharmacists, between pharmacists and AHSs, and between pharmacists and Aboriginal and Torres Strait Islander clients were identified as key to increasing HMRs for Aboriginal and Torres Strait Islander people. Aboriginal Health Services are well-placed to be the promoters, organisers, facilitators and implementers of health programs, such as HMR, for Aboriginal and Torres Strait Islander clients. Embedding a pharmacist within an AHS addresses many of the barriers to HMRs. It ensures pharmacists are culturally mentored and that they build strong relationships with health professionals and clients. The HMR program rules need to be changed significantly if medication review is to be an effective tool for improving medication safety and adherence for Aboriginal and Torres Strait Islander people.


Rapid diagnostic testing for syphilis in Arctic communities (the STAR study): a multisite prospective field diagnostic accuracy study in an intended-use setting.
We evaluated the field diagnostic accuracy of a syphilis rapid test (RDT), using serum and whole blood by non-laboratorians in two Canadian Arctic communities. We implemented a multisite prospective field evaluation wherein patients were screened by an RDT containing treponemal and non-treponemal components (Chembio DPP® Syphilis Screen & Confirm) between January 2020 and December 2021. Venous whole blood and serum were collected for rapid testing and compared with laboratory-based serology reference testing using a reverse sequence algorithm of treponemal and rapid plasma reagin (RPR) testing. Overall, 135 whole blood and 139 serum specimens were collected from 161 participants during clinical encounters. Treponemal-RDT sensitivity against a treponemal-reference standard (38/161 confirmed cases) was similar for serum (78% [95% CI: 61-90%]) and whole blood (81% [95% CI: 63-93%]). In those with RPR titres ≥1:8 (i.e. suggestive of recent/active infection), sensitivity increased to 93% (95% CI: 77-99%) for serum and 92% (95% CI: 73-99%) for whole blood. Treponemal-RDT specificity was excellent (99% [95% CI: 95-100%]) for both specimen types. Non-treponemal-RDT sensitivity against RPR was 94% (95% CI: 80-99%) for serum and 79% (95% CI: 60-92%) for whole blood. Sensitivity increased to 100% (95% CI: 88-100%) for serum and 92% (95% CI: 73-99%) for whole blood when RPR titres ≥1:8. RDT performance with whole blood was similar to that with serum. Non-laboratorians using the RDT accurately identified individuals with infectious syphilis under real-world conditions in an intended-use setting at the point of care. Implementing the RDT can eliminate treatment delays and may enhance disease control.


The differential effect of optic nerve disease on pattern and focal electroretinograms.
We studied nine cases of retrobulbar neuritis with confirmed multiple sclerosis and six cases of optic atrophy from other causes. Pattern and focal electroretinograms (macular ERGs) were recorded with high (400 cd/m2) and low (40 cd/m2) intensity stimuli. Contrast sensitivity was also measured with a simple printed test. Luminance was not markedly important. High spatial frequency contrast sensitivity was significantly correlated with pattern ERG amplitude. Pattern and focal ERG amplitude ratio was usually reduced, but the effect was not correlated with contrast sensitivity or large enough to be useful clinically. In optic atrophy the pattern ERG (PERG) was clearly more severely reduced than the focal ERG (FERG). In retrobulbar neuritis both ERGs were equally and more severely reduced even though the visual losses were less. In unilateral cases the PERG increased then decreased after the initial attack, as previously described (Arden et al., 1982). The results suggest that retinal layers beyond the ganglion cells may be affected in retrobulbar neuritis, but proximally generated, pattern-specific ERG components are selectively lost in optic atrophy.


Artificial Intelligence and Machine Learning in Sport Research: An Introduction for Non-data Scientists.
In the last two decades, artificial intelligence (AI) has transformed the way in which we consume and analyse sports. The role of AI in improving decision-making and forecasting in sports, amongst many other advantages, is rapidly expanding and gaining more attention in both the academic sector and the industry. Nonetheless, for many sports audiences, professionals and policy makers, who are not particularly au courant or experts in AI, the connexion between artificial intelligence and sports remains fuzzy. Likewise, for many, the motivations for adopting a machine learning (ML) paradigm in sports analytics are still either faint or unclear. In this perspective paper, we present a high-level, non-technical, overview of the machine learning paradigm that motivates its potential for enhancing sports (performance and business) analytics. We provide a summary of some relevant research literature on the areas in which artificial intelligence and machine learning have been applied to the sports industry and in sport research. Finally, we present some hypothetical scenarios of how AI and ML could shape the future of sports.


Glucocorticoid receptors of wild-type and variant mouse lymphoma cells.
Glucocorticoid receptors of wild-type mouse lymphoma cells and two glucocorticoid resistant variants of nt- and nti phenotypes, respectively, were investigated. Photoaffinity labelling of receptor complexes with a radiolabelled glucocorticoid of high affinity enabled us to analyse crude receptor preparations by SDS gel electrophoresis. Wild-type and nt- receptors yielded radiolabelled polypeptide bands of 98,000 mol. wt while nti receptors had a mol. wt of 42,000. Monoclonal antibodies raised against purified rat liver glucocorticoid receptors reacted with wild-type and nt- receptors but not with nti receptors. Partial proteolysis of wild-type receptors with alpha-chymotrypsin resulted in a fragment of 39,000 mol. wt which contained the steroid binding site but had increased affinity for DNA indistinguishable from nti receptors. Mild proteolysis with trypsin yielded smaller fragments which contained the steroid binding site but did not bind to DNA. A model of the wild-type receptor is discussed.


Ancestral divergence of Rickettsia bellii from the spotted fever and typhus groups of Rickettsia and antiquity of the genus Rickettsia.
The eubacterial genus Rickettsia belongs to the alpha subgroup of the phylum Proteobacteria. This genus is usually divided into three biotypes on the basis of vector host and antigenic cross-reactivity characteristics. However, the species Rickettsia bellii does not fit into this classification scheme; this organism has characteristics common to both the spotted fever group and the typhus group biotypes and also exhibits some unique features. Sequences of the 16S rRNA and 23S rRNA genes from Rickettsia rickettsii (spotted fever group), Rickettsia prowazekii (typhus group), and R. bellii were studied to determine the position of R. bellii in the rickettsial classification scheme. The 23S rRNA gene sequences described in this paper are the first 23S rRNA sequences reported for any member of the Rickettsiaceae. The 23S rRNA gene contains substantially more phylogenetic information than is contained in the 16S rRNA sequences, and the 23S rRNA gene sequence has diverged about 1.9 times faster in the three Rickettsia species which we studied. Taken together, the molecular data obtained from the two genes indicate that R. bellii is not a member of either the spotted fever group or the typhus group; rather, this organism appears to be the product of a divergence which predates the separation of the genus into the spotted fever group and the typhus group. Consequently, different combinations of the ancestral characteristics retained by R. bellii have been retained in the more derived lineages of the genus.(ABSTRACT TRUNCATED AT 250 WORDS)


Predation of oomycetes by myxobacteria via a specialized CAZyme system arising from adaptive evolution.
As social micropredators, myxobacteria are studied for their abilities to prey on bacteria and fungi. However, their predation of oomycetes has received little attention. Here, we show that Archangium sp. AC19 secretes a carbohydrate-active enzyme (CAZyme) cocktail during predation on oomycetes Phytophthora. These enzymes include three specialized β-1,3-glucanases (AcGlu13.1, -13.2 and -13.3) that act as a cooperative consortium to target β-1,3-glucans of Phytophthora. However, the CAZymes showed no hydrolytic effects on fungal cells, even though fungi contain β-1,3-glucans. Heterologous expression of AcGlu13.1, -13.2 or -13.3 enzymes in Myxococcus xanthus DK1622, a model myxobacterium that antagonizes but does not predate on P. sojae, conferred a cooperative and mycophagous ability that stably maintains myxobacteria populations as a mixture of engineered strains. Comparative genomic analyses suggest that these CAZymes arose from adaptive evolution among Cystobacteriaceae myxobacteria for a specific prey killing behavior, whereby the presence of Phytophthora promotes growth of myxobacterial taxa by nutrient release and consumption. Our findings demonstrate that this lethal combination of CAZymes transforms a non-predatory myxobacterium into a predator with the ability to feed on Phytophthora, and provides new insights for understanding predator-prey interactions. In summary, our work extends the repertoire of myxobacteria predatory strategies and their evolution, and suggests that these CAZymes can be engineered as a functional consortium into strains for biocontrol of Phytophothora diseases and hence crop protection.


Treatment of dairy wastewaters by electrocoagulation using mild steel electrodes.
The removal of COD and oil-grease from dairy wastewater was experimentally investigated using direct current (DC) electrocoagulation (EC). In the EC of dairy wastewater, the effects of initial pH, electrolysis time, initial concentration of COD, conductivity and current density were examined. The COD and oil-grease in the aqueous phase were effectively removed when iron was used as sacrificial anode. The optimum operating range for each operating variable was experimentally determined. The batch experimental results revealed that COD and oil-grease in aqueous phase was effectively removed. The overall COD and oil-grease removal efficiencies reached 98 and 99%, respectively. The optimum current density, pH and electrolysis time for 18,300 mg COD/L and 4570 mg oil-grease/L were 0.6 mA/cm2, 7 and 1 min, respectively. Mean energy consumption was 0.003 kWh/kg of COD.


Determination of cell mass and polymyxin using multi-wavelength fluorescence.
Multi-wavelength fluorescence was applied for on-line monitoring of cell mass and the antibiotic polymyxin B in Bacillus polymyxa cultivations. By varying the phosphate and nitrogen content of the medium different polymyxin-cell mass ratios could be obtained. Using this strategy, it was possible to investigate if multi-wavelength fluorescence is able to give independent prediction of the two parameters. Partial least square (PLS) regression was applied to establish mathematical relationships between off-line determined cell mass and polymyxin concentrations and on-line collected fluorescence data. For polymyxin one universal PLS model, with a correlation of 0.95 and a root mean square error of cross validation (RMSECV) of 35 mgl(-1), could be constructed. However, correlation between fluorescence and cell mass dry weight could not be established including data from all three types of cultivations. For data from each type of cultivation, separate models with high correlation and low RMSECV values were built. A large variation in cellular composition as a result of the different levels of nitrogen and phosphorus in the cultivations was the probable reason to the necessity of building three models. The results of the present investigation indicate that production of polymyxin is concomitantly regulated by phosphate and nitrogen as the highest polymyxin yield on cell mass, 0.17+/-0.01 gg(-1), was reached in the cultivations where both nitrogen and phosphate concentrations were kept low.


Identification of an antigenic determinant of mouse lactate dehydrogenase C4.
A peptide bearing an antigenic determinant of the sperm-specific lactate dehydrogenase C4 isozyme (LDH-C4) has been isolated from a tryptic digest of the whole protein. This peptide, comprising residues 152-159 (MC152-159), reacts with rabbit anti-mouse LDH-C4. Immunization of rabbits with synthetic MC152-159 conjugated to bovine serum albumin induces an immune response which is specific for the peptide. Anti-MC152-159 IgG binds 125I-labeled mouse LDH-C4 and competition experiments demonstrate the specificity of this antigen antibody reaction.


Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion.
Genome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid recombination (SCR). To decipher the role of chromatin in eukaryotic DSB repair, here we analyze a collection of yeast chromatin-modifying mutants using a previously developed system for the molecular analysis of repair of replication-born DSBs by SCR based on a mini-HO site. We confirm the candidates through FLP-based systems based on a mutated version of the FLP flipase that causes nicks on either the leading or lagging DNA strands. We demonstrate that Rpd3L and Hda1 histone deacetylase (HDAC) complexes contribute to the repair of replication-born DSBs by facilitating cohesin loading, with no effect on other types of homology-dependent repair, thus preventing genome instability. We conclude that histone deacetylation favors general sister chromatid cohesion as a necessary step in SCR.


Developing the online survey.
Institutions of higher education are now using Internet-based technology tools to conduct surveys for data collection. Research shows that the type and quality of responses one receives with online surveys are comparable with what one receives in paper-based surveys. Data collection can take place on Web-based surveys, e-mail-based surveys, and personal digital assistants/Smartphone devices. Web surveys can be subscription templates, software packages installed on one's own server, or created from scratch using Web programming development tools. All of these approaches have their advantages and disadvantages. The survey owner must make informed decisions as to the right technology to implement. The correct choice can save hours of work in sorting, organizing, and analyzing data.


A Network-Based Analysis of Disease Complication Associations for Obstetric Disorders in the UK Biobank.
Recent studies have found that women with obstetric disorders are at increased risk for a variety of long-term complications. However, the underlying pathophysiology of these connections remains undetermined. A network-based view incorporating knowledge of other diseases and genetic associations will aid our understanding of the role of genetics in pregnancy-related disease complications. We built a disease-disease network (DDN) using UK Biobank (UKBB) summary data from a phenome-wide association study (PheWAS) to elaborate multiple disease associations. We also constructed egocentric DDNs, where each network focuses on a pregnancy-related disorder and its neighboring diseases. We then applied graph-based semi-supervised learning (GSSL) to translate the connections in the egocentric DDNs to pathologic knowledge. A total of 26 egocentric DDNs were constructed for each pregnancy-related phenotype in the UKBB. Applying GSSL to each DDN, we obtained complication risk scores for additional phenotypes given the pregnancy-related disease of interest. Predictions were validated using co-occurrences derived from UKBB electronic health records. Our proposed method achieved an increase in average area under the receiver operating characteristic curve (AUC) by a factor of 1.35 from 55.0% to 74.4% compared to the use of the full DDN. Egocentric DDNs hold promise as a clinical tool for the network-based identification of potential disease complications for a variety of phenotypes.


Mood and anxiety disorders in patients with abnormal uterine bleeding.
We aimed to investigate the prevalence of mood and anxiety disorders in patients with abnormal uterine bleeding (AUB) and the relationship between mood and anxiety disorders and AUB. 96 consecutive patients with not yet classified AUB based on the PALM-COEIN classification and 94 volunteers were included in the study. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Clinical Version. Out of 96 patients, 55 (57.3%) met the criteria for at least one diagnosis of mood and anxiety disorder. The most common psychiatric disorders in patients with AUB were major depression (n=15, 15.6%), generalized anxiety disorder (n=18, 18.8%) and obsessive compulsive disorder (n=22, 22.9%), respectively. Compared with the control group, the prevalence of any psychiatric disorder (x(2)=43.52, p=0.000), any mood disorder (x(2)=10:37, p=0.001) and any anxiety disorder (Fisher's exact test, p=0.000) was higher in patients with AUB. The presence of any mood and anxiety disorder was an independent risk factor for AUB. Mood and anxiety disorders, particularly major depression, generalized anxiety disorder and obsessive-compulsive disorder were frequently observed in patients with AUB.


Abnormal cone synapses in human cone-rod dystrophy.
Little is known of the cytopathology of photoreceptors in human inherited retinal dystrophies that initially affect the central retina, including the macula. The current study sought to determine the cytologic features of dysfunctional cone and rod photoreceptors, as well as the pattern of degeneration of the cells in representative cases of central retinal dystrophy. Comparative human tissue study. Four human donor eyes with the following forms of central retinal dystrophy: cone-rod dystrophy (CRD), central areolar choroidal dystrophy, Bardet-Biedl syndrome, and cone dystrophy-cerebellar ataxia. The cytologic features of retinal photoreceptors in these eyes were compared with those in an eye with retinitis pigmentosa and six normal human eyes. Immunocytochemistry and electron microscopy were used to evaluate the retinal histopathology in the donor eyes. Cone numbers were decreased in the case of CRD, particularly in the central and far peripheral retina, and both cone and rod outer segments were slightly shortened. Occasional degenerate cones had dense cytoplasm and pyknotic nuclei dislocated sclerad to the external-limiting membrane. The most prominent alteration in this retina was marked enlargement and distortion of the cone photoreceptor pedicles, which contained reduced numbers of synaptic vesicles. The retina with central areolar choroidal dystrophy contained a few cones with similarly abnormal synapses. However, comparable cone synapse abnormalities were not observed in the cases of Bardet-Biedl syndrome, cone dystrophy-cerebellar ataxia, retinitis pigmentosa, or in the normal retinas. The functional consequences of the cone synapse abnormalities in CRD are not known but may correlate with the electroretinographic abnormalities documented in some cases of CRD. To our knowledge, comparable synapse changes have not been noted in either rods or cones in other forms of retinal dystrophy, including retinitis pigmentosa, suggesting that different cytopathologic mechanisms may be involved.


Effects of cyclosporin A and a non-immunosuppressive analogue, O-acetyl cyclosporin A, upon the growth of parent and multidrug resistant human lung cancer cells in vitro.
We have studied the ability of cyclosporin A (CsA) and a non-immunosuppressive analogue, O-acetyl cyclosporin A (OACsA, B3-243) to inhibit the growth of human lung cancer cells in vitro. Using continuous drug exposure and the MTT colorimetric assay to determine cell growth we found that CsA produced partial growth inhibition at doses ranging from 0.5 to 3.0 micrograms ml-1 (0.4-2.4 microM). At progressively higher doses, complete growth inhibition and in situ cell lysis were seen. The P-glycoprotein expressing multidrug resistant (MDR) variant H69/LX4 of the small cell line H69/P was less sensitive to cyclosporins than the parent line, but this was not true of the non-P-glycoprotein expressing MDR variants of large cell line COR-L23 or adenocarcinoma line MOR. Sensitivity to OACsA was approximately 2-fold higher than that to CsA in most of the lines although not in the most sensitive line, COR-L88. Even in COR-L88, exposed to CsA or OACsA for 24 h, clonogenic cell survival was reduced only to 50%. There was no reduction in polyamine content of COR-L23 or COR-L88 cells following 48 h of exposure to CsA or OACsA. The effects on cell growth could not be inhibited by the addition of exogenous putrescine, nor could they be enhanced by the addition of alpha-difluoromethylorthinine. It does not appear therefore that inhibition of polyamine synthesis is the basis of the observed growth inhibition.


Dentists' knowledge, attitudes and practices toward patients with epilepsy in Hyderabad city, India.
The present study was designed to assess the knowledge, attitudes and practices about epilepsy among a group of dentists in Hyderabad city, India. All dentists registered with the local Dental Association branch were eligible to participate in this questionnaire study. Descriptive and Inferential Statistics were used. Multiple group analysis was done using Kruskal-Wallis, and Mann Whitney U Test was used for two-group comparison. The variables were taken as significant at a p value of 0.05. A total of 217 respondents with mean age of 33.16±10.4 years participated in the study. Most respondents possessed a post-graduate (Master of Dental Surgery - MDS) degree (59.4%). A convulsion or shaking was identified as the most familiar recognizable symptom of epilepsy. 84.3% of the dentists would not object to their children having association with patients with epilepsy, and 61.3% would not object to their relative marrying a person with a history of epilepsy. A large number of dentists (178; 82%) were confident to treat a person with epilepsy. 95.3% assumed that they have an ethical responsibility to treat this population. None of the practice-related questions showed any significant difference with respect to different age groups, gender or the education levels (BDS/MDS). Our study reflects that this group of Indian dentists has a fairly high knowledge and positive attitudes toward patients with epilepsy. This encouraging approach and confidence among dentists may positively influence patients with epilepsy to seek dental care.


Differential and cooperative effects of IL-25 and IL-33 on T helper cells contribute to cryptococcal virulence and brain infection.
The epithelial cell-derived cytokines IL-33 and IL-25 are important mediators in driving type-2 inflammation during C. neoformans infection. Nevertheless, the impact of these cytokines in regulating host T helper cell response during C. neoformans infection is still unclear. We observed that C. neoformans infection promoted a predominant increase of T helper cells that co-expressed IL-25 and IL-33 receptors within the lung during the late infection phase. A comparative transcriptomic analysis of effector T helper cells co-treated with IL-25 and IL-33 revealed a cooperative effect of these cytokines in promoting IL-13 gene expression. Without IL-25 receptor signaling, IL-33 treatment upregulated Th1-associated genes and genes associated with nucleotide metabolism. By contrast, IL-25 had a unique effect in enhancing type-2 cytokines IL-5 and IL-9 and chemokine CCL24, as well as genes in the pathways that are associated with L-arginine metabolisms. Interestingly, this pathogenic T helper cell population that expressed IL-25 and IL-33 receptors was greatly enriched in mice that were infected with high cryptococcal virulence and associated with fungal burdens in the brain. Therefore, our data further provide the additional function of IL-25 and IL-33 in potentiating cryptococcal brain dissemination.


Preparation of hollow microsphere@onion-like solid nanosphere MoS2 coated by a carbon shell as a stable anode for optimized lithium storage.
A one-step hydrothermal method was successfully used to fabricate hollow microsphere@onion-like solid nanosphere MoS2. Then the as-prepared sS-MoS2 was decorated with a carbon shell using dopamine as a carbon source by a facile route, resulting in hollow microsphere@onion-like solid nanosphere MoS2 decorated with carbon shell (sS-MoS2@C). A synergistic effect was observed for the two-component material, leading to new electrochemical processes for lithium storage, with improved electroconductivity and structural soundness, triggering an ascending capacity upon cycling. The as-prepared sS-MoS2@C exhibits optimized electrochemical behaviour with high specific capacity (1107 mA h g(-1) at 100 mA g(-1)), superior high-rate capability (805 mA h g(-1) at 5000 mA g(-1)) and good cycling stability (91.5% of capacity retained after 100 cycles), suggesting its potential application in high-energy lithium-ion batteries.


Phase II Study With Epirubicin, Cisplatin, and Infusional Fluorouracil Followed by Weekly Paclitaxel With Metronomic Cyclophosphamide as a Preoperative Treatment of Triple-Negative Breast Cancer.
The aggressive biological behavior and the lack of target therapy prompts the search for new therapeutic approaches for triple-negative breast cancers. We evaluated the efficacy in terms of Ki-67 variation and clinical response but also the toxicity of a neoadjuvant regimen based on metronomic principles including ECF (epidoxorubicin with cisplatin on day 1 with low-dose 5-fluorouracil in continuous infusion every 21 days for 4 courses) followed by paclitaxel (90 mg/m(2)) on day 1, 8, and 15 every 28 days for 3 courses in combination with metronomic oral cyclophosphamide 50 mg/d for 12 weeks in patients with HER2-negative breast cancer (T2-T4a-d, N0-3, M0) with estrogen receptor and progesterone receptor < 10%. We enrolled 34 patients from June 2009 to May 2013. All were considered evaluable on an intention-to treat basis. The mean difference between the percentage of Ki-67 positive cells evaluated in surgical resection specimens and in pretreatment tumor core biopsy was 41% (95% confidence interval [CI], 30-51; P < .0001) for the entire population, and 22% (95% CI, 7-38; P = .0097) in patients who did not achieve pathological complete response (pCR). Responses to the treatment were obtained in 31 patients [91%] of the patients, and 19 patients (56%; 95% CI, 35-70) had a pCR. Stable disease was observed in 3 patients and none had progressive disease. Grade ≥ 3 hematologic adverse events included leukopenia in 9% (3 of 34), neutropenia in 38% (13 of 34), and anemia in 3% (1 of 34) of patients. Nonhematologic Grade ≥ 3 toxicities included only stomatitis in 1 patient. A neoadjuvant program with an ECF regimen followed by weekly paclitaxel with metronomic cyclophosphamide proved to be very effective, with high pCR rates, reduction of Ki-67, and it was associated with a low toxicity profile.


Tracheal agenesis with anomalies found in both VACTERL and TACRD associations.
Tracheal agenesis (TA) was diagnosed by endoscopy after esophageal intubation in a 34-week newborn. Diagnosis, work-up, and management approach are discussed. Similar to previous reports, this case of tracheal agenesis presented with multiple associated defects found at autopsy. Tracheal agenesis had previously been reported as a part of the VATER (vertebral defects, anal atresia, tracheoesophageal fistula and/or esophageal atresia, radial dysplasia, renal defects) and VACTERL (VATER plus cardiovascular and limb defects) associations/syndromes. More recently, cases of TA have been reported with associated anomalies described as TACRD (tracheal agenesis/atresia, complex congenital cardiac abnormalities, radial ray defects, and duodenal atresia) association/syndrome. We present a case of TA with anomalies found in both VACTERL and TACRD associations, which support the speculation that both are different manifestations of a spectrum of mesodermal dysplasia.


Sex steroid production associated with puberty is absent in germ cell-free salmon.
In all vertebrates studied so far, germ cells are not required for pubertal maturation of the gonadal steroidogenic system, subsequent development of secondary sex characteristics and reproductive behavior. To explore if the absence of germ cells affects puberty or growth in Atlantic salmon, germ cell-free (GCF), dnd knockout and wild type (WT) postsmolts were stimulated to enter puberty. No GCF fish entered puberty, whereas 66.7% (males) and 30% (females) WT fish completed or entered puberty, respectively. Expression of genes related to steroidogenesis (star, cyp17a1, cyp11β, cyp19a1a), gonadal somatic cells (insl3, amh, igf3), oocytes (bmp15), gonadotropin receptors (fshr, lhcgr), and pituitary gonadotropic cells (fshb, lhb, gnrhr4) showed an immature status and failure to up-regulate gonadal sex steroid production in male and female GCF fish was also reflected in low or undetectable plasma sex steroids (11-ketotestosterone, estradiol-17β and testosterone). A gender difference (high in females, low in males) was found in the expression of star and cyp17a1 in GCF fish. No clear difference in growth was detected between GCF and immature WT fish, while growth was compromised in maturing WT males. We demonstrate for the first time in a vertebrate that germ cells are required for pubertal activation of the somatic steroidogenic cells.


Reverse smoking and chronic obstructive lung disease.
Reverse smoking is a popular habit peculiarly prevalent among adults of southeastern coastal towns and villages of India. The smoking device is hand made. A few dried twigs of home grown tobacco are rolled crudely in a semi-dried tobacco leaf. The finished product is called 'chutta'. The average weight of the hand rolled chuttas varies between 1.5 g for the small one and 7.5 g for the big chuttas. During smoking the lighted end of the chutta is kept inside the mouth during inhalation. An average adult may smoke three to four chuttas per day. Reverse smoking was first highlighted by Reddy and Rao (1957) who reported a high occurrence of oropharyngeal carcinomas in chutta smokers. The cancerous changes were attributed to the heat generated inside the oral cavity and burning of tobacco (Reddy & Rao 1957). The present study was carried out to examine the frequency of symptoms of chronic respiratory disease and changes in lung function associated with this form of smoking habit.


Behavioral Periodicity Detection from 24 h Wrist Accelerometry and Associations with Cardiometabolic Risk and Health-Related Quality of Life.
Periodicities (repeating patterns) are observed in many human behaviors. Their strength may capture untapped patterns that incorporate sleep, sedentary, and active behaviors into a single metric indicative of better health. We present a framework to detect periodicities from longitudinal wrist-worn accelerometry data. GENEActiv accelerometer data were collected from 20 participants (17 men, 3 women, aged 35-65) continuously for 64.4 ± 26.2 (range: 13.9 to 102.0) consecutive days. Cardiometabolic risk biomarkers and health-related quality of life metrics were assessed at baseline. Periodograms were constructed to determine patterns emergent from the accelerometer data. Periodicity strength was calculated using circular autocorrelations for time-lagged windows. The most notable periodicity was at 24 h, indicating a circadian rest-activity cycle; however, its strength varied significantly across participants. Periodicity strength was most consistently associated with LDL-cholesterol (r's = 0.40-0.79, P's < 0.05) and triglycerides (r's = 0.68-0.86, P's < 0.05) but also associated with hs-CRP and health-related quality of life, even after adjusting for demographics and self-rated physical activity and insomnia symptoms. Our framework demonstrates a new method for characterizing behavior patterns longitudinally which captures relationships between 24 h accelerometry data and health outcomes.


Fever: causes and consequences.
The present review distinguishes pathogenic, neurogenic, and psychogenic fever, but focuses largely on pathogenic fever, the hallmark of infectious disease. The data presented show that a complex cascade of events underlies pathogenic fever, which in broad outline - and with frank disregard of contradictory data - can be described as follows. An invading microorganism releases endotoxin that stimulates macrophages to synthesize a variety of pyrogenic compounds called cytokines. Carried in blood, these cytokines reach the perivascular spaces of the organum vasculosum laminae terminalis (OVLT) and other regions near the brain where they promote the synthesis and release of prostaglandin (PGE2). This prostaglandin then penetrates the blood-brain barrier to evoke the autonomic and behavioral responses characteristic of fever. But then once expressed, fever does not continue unchecked; endogenous antipyretics likely act on the septum to limit the rise in body temperature. The present review also examines fever-resistance in neonates, the blunting of fever in the aged, and the behaviorally induced rise in body temperature following infection in ectotherms. And finally it takes up the question of whether fever enhances immune responsiveness, and through such enhancement contributes to host survival.


[Change in the indices of direct count of bacteria in cultures and pond water at different pH].
Experiments were carried out with the pure cultures of Pseudomonas fluorescens and Bacillus subtilis, and with pond water. The adjustment of pH of the culture or water to 8.8--9.0 facilitates the direct count of the microorganisms, and makes the results more accurate.


Factors affecting Naseptin treatment success - A prospective cohort study.
To assess patient factors to predict treatment success of Naseptin for recurrent paediatric epistaxis. This prospective cohort study of paediatric patients referred to a tertiary paediatric otolaryngology clinic with recurrent epistaxis treated with Naseptin cream and education. Patients with red flag symptoms and bleeding diathesis were omitted, along with patients with concurrent otolaryngology complaints. Statistical analysis included logistic regression analysis to assess for predictive factors contributing to treatment success. 125 of 210 patients on the waiting list met the inclusion criteria and were given a complete trial of Naseptin. 80.8% (n = 101) of patients found that the frequency and severity of epistaxis had reduced, with the remaining 19.2% (n = 24) reporting that the episodes of epistaxis remained the same and required further management (i.e., silver nitrate cautery). Five patients (4%) reported minor side effects (skin irritation etc.) with no significant adverse events reported. We found that Naseptin is a safe, well-tolerated treatment that should be trialled in most cases of recurrent paediatric epistaxis. Most children will benefit from it with complete epistaxis cessation or at least reduced frequency and severity.


Parental perceptions and attitudes toward asthma and its treatment: a controlled study.
We compared the attitudes of parents of 128 asthmatic children with those of 110 control children. The majority of both groups of parents had negative perceptions of the impact of asthma on children, but control parents were significantly more pessimistic. Control parents were also significantly more pessimistic than asthma parents about the impact of asthma on family lifestyle and relationships. In contrast, both groups were remarkably concordant in their ambivalence towards compliance with medication, recognising the necessity and efficacy of drug therapy, and yet worried about its long term effects on children. Both groups were also concordant in their readiness to give up household pets but not cigarette smoking for the sake of asthmatic children. Physician awareness of parental and community perceptions of childhood asthma may contribute to improved compliance with medications.


Marine microorganisms for synthesis of metallic nanoparticles and their biomedical applications.
Nanotechnology has become one of the most in demand technologies applied in different fields of science. Metallic nanoparticles synthesis using marine microorganisms has been received global attention due to their extensive applications in biomedical science. The use of marine microbes for metallic nanoparticles synthesis is eco-friendly, time saving, and inexpensive. An eco-friendly method is essential to minimize waste and protect environment. Recently, marine microorganisms are recognized an eco-friendly and efficient way to utilize as potential biofactories for synthesis of metallic nanoparticles. Here, we discuss and detail the possible uses of different marine microorganisms including bacteria, fungi and microalgae for metallic nanoparticle synthesis and those nanoparticles applications as antimicrobial and anticancer agents. In addition, different parameters that cause changes on nanoparticles shape and morphology are also highlighted.


[Effect on medical practices after health insurance application for "H. pylori gastritis"].
Eradication therapy for H. pylori infected gastritis became the health insurance application in Japan in 2013. It will seem that the conception of "the chronic gastritis" greatly changes from now on in Japan. "The chronic gastritis" will be classified in H. pylori gastritis and functional dyspepsia in the near future. On the other hand, it is expected that the process of the gastric cancer detection survey greatly changes too. It seems that the ABC checkup using the blood will be carried out in place of Barium examination. A decrease in gastric cancer mortality is expected as things mentioned above from now on.


An evaluation of the API ZYM system as a means of classifying spirochaetes associated with swine dysentery.
Thirty-one strains of spirochaetes from pigs and two strains from poultry were tested in the API ZYM enzyme system. The spectrum of enzymatic reactions provided a means of differentiating between strains related to swine dysentery and strains not so related from pigs. The numerical coding system simplified the interpretation of the results.


Fibrin-coated collagen fleece versus absorbable dural sealant for sellar closure after transsphenoidal pituitary surgery: a comparative study.
Various surgical methods to prevent postoperative cerebrospinal fluid (CSF) leaks during transsphenoidal surgery have been reported. However, comparative studies are scarce. We aimed to compare the efficacy of a fibrin-coated collagen fleece (TachoSil) versus a dural sealant (DuraSeal) to prevent postoperative CSF leakage. We perform a retrospective study comparing two methods of sellar closure during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenoma resection: TachoSil patching versus DuraSeal packing. Data concerning diagnosis, reconstruction technique, and surgical outcomes were analyzed. The primary endpoint was postoperative CSF leak rate. We reviewed 198 consecutive patients who underwent 219 EETS for pituitary adenoma from February 2007 and July 2018. Intraoperative CSF leak occurred in 47 cases (21.5%). A total of 33 postoperative CSF leaks were observed (15.1%). A reduction of postoperative CSF leaks in the TachoSil application group compared to the conventional technique using Duraseal was observed (7.7% and 18.2%, respectively; p = 0.062; Pearson exact test) although non-statistically significant. Two patients required lumbar drainage, and no revision repair was necessary to treat postoperative CSF rhinorrhea in Tachosil group. Fibrin-coated collagen fleece patching may be a valuable method to prevent postoperative cerebrospinal fluid (CSF) leaks during EETS for pituitary adenoma resection.


Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor.
The low-density lipoprotein receptor-related protein (Lrp)-5 functions as a Wnt coreceptor. Here we show that mice with a targeted disruption of Lrp5 develop a low bone mass phenotype. In vivo and in vitro analyses indicate that this phenotype becomes evident postnatally, and demonstrate that it is secondary to decreased osteoblast proliferation and function in a Cbfa1-independent manner. Lrp5 is expressed in osteoblasts and is required for optimal Wnt signaling in osteoblasts. In addition, Lrp5-deficient mice display persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. These results implicate Wnt proteins in the postnatal control of vascular regression and bone formation, two functions affected in many diseases. Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation.


The influence of opening statement/closing argument organizational strategy on juror verdict and damage awards.
This study examines the influence of the organizational strategy used to structure opening statements and closing arguments on presentation effectiveness in a simulated civil trial. Two organizational structures, a narrative and a legal-expository format, were manipulated to produce a 2 (plaintiff organizational strategy) x 3 (defense organizational strategy) experimental design. Results indicate that a mixed organizational strategy (narrative opening/legal-expository closing) is more effective for the plaintiff than a strict narrative strategy, and either a mixed or strict legal-expository organizational strategy is more effective than a strict narrative strategy for the defense.


Evaluation of planned treatment breaks during radiation therapy for anal cancer: update of RTOG 92-08.
Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study. Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure were estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test. Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity. No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts.


Modified edge-to-edge technique for correction of congenital mitral regurgitation in infants and children.
Since 2008, 28 patients with congenital mitral regurgitation have undergone mitral valve repair with a modified edge-to-edge technique at our institution. The regurgitant mitral leaflet was sutured with a pledget-reinforced, horizontal mattress suture with No. 4-0 polypropylene on the ventricle side and a pledget-reinforced mattress suture with Gore-Tex sutures (W.L. Gore & Associates, Flagstaff, AZ) and Dacron pledgets (Chest, Shanghai) placed on the anterior and posterior annulus corresponding to the edge-to-edge suturing site. Early results are encouraging, but a longer follow-up is needed.


Sound spectrographic analysis of pain cry in preterm infants.
Sound spectrographic cry analysis was performed on 302 cries of 48 preterm infants born at 30-37 gestational weeks. The cries were recorded during the first week of life and thereafter weekly until the infants were discharged. The control series comprised 54 cries from 27 fullterm healthy infants. The results showed that the cries of the smallest prematures compared with the controls were shorter, more high-pitched, and included bi-phonation and glide more often. The cry characteristics changed with increasing conceptual age and the older the child the more the cry pattern resembled that of the fullterm. The cries of the preterm infants when they had reached 38 conceptual weeks were similar to those of newly born fullterm infants. The results indicate that the gestational age should be taken into consideration in cry analysis.


Surgically Amenable Childhood Cancers: An Overview of the Burden and Challenges of Management in Low- and Middle-Income Countries.
The World Health Organization's Global Initiative for Childhood Cancer was launched to decrease the disparities in childhood cancer outcomes and improve treatments for childhood cancer in resource-limited settings. Low-grade glioma, retinoblastoma, and Wilms tumors are among the index cancers included in this global initiative, as these cancers represent a large percentage of childhood tumors and are curable with cost-effective, evidence-based interventions. Herein, we discuss the global childhood tumor burden, the status of pediatric cancer surgery capacity and services around the world, and the strategic considerations for building pediatric surgical oncology capacity.


The Use and Misuse of Historical Controls in Regulatory Toxicology: Lessons from the CLARITY-BPA Study.
For many endocrine-disrupting chemicals (EDCs) including Bisphenol A (BPA), animal studies show that environmentally relevant exposures cause harm; human studies are consistent with these findings. Yet, regulatory agencies charged with protecting public health continue to conclude that human exposures to these EDCs pose no risk. One reason for the disconnect between the scientific consensus on EDCs in the endocrinology community and the failure to act in the regulatory community is the dependence of the latter on so-called "guideline studies" to evaluate hazards, and the inability to incorporate independent scientific studies in risk assessment. The Consortium Linking Academic and Regulatory Insights on Toxicity (CLARITY) study was intended to bridge this gap, combining a "guideline" study with independent hypothesis-driven studies designed to be more appropriate to evaluate EDCs. Here we examined an aspect of "guideline" studies, the use of so-called "historical controls," which are essentially control data borrowed from prior studies to aid in the interpretation of current findings. The US Food and Drug Administration authors used historical controls to question the plausibility of statistically significant BPA-related effects in the CLARITY study. We examined the use of historical controls on 5 outcomes in the CLARITY "guideline" study: mammary neoplasms, pituitary neoplasms, kidney nephropathy, prostate inflammation and adenomas, and body weight. Using US Food and Drug Administration-proposed historical control data, our evaluation revealed that endpoints used in "guideline" studies are not as reproducible as previously held. Combined with other data comparing the effects of ethinyl estradiol in 2 "guideline" studies including CLARITY-BPA, we conclude that near-exclusive reliance on "guideline" studies can result in scientifically invalid conclusions.


Three case reports of West Nile virus neuroinvasive disease: lessons from real-life clinical practice.
Despite being an uncommon cause of meningoencephalitis, West Nile virus (WNV) recently provoked significant outbreaks throughout Europe. West Nile neuroinvasive disease (WNND) is associated with significant morbidity and mortality in older and compromised individuals, while its diagnosis may be demanding for the clinician. Here discussed are three cases of WNND with a focus on the diagnostic challenges they presented due to atypical clinical presentation and laboratory findings. Between July and September 2020 three patients presented to our attention with signs and symptoms compatible with meningoencephalitis. Among routine procedures, they underwent lumbar puncture and imaging. In the absence of microbiological isolates, biological samples were sent for serology and NAATs for WNV. Following diagnosis, the patients gradually recovered and were discharged either home or to rehabilitation facilities. The laboratory findings here discussed, in particular CSF parameters, are only partially consistent with those described in the literature, which highlights the need for further research. While serology and NAATs on blood and urine appear the most reliable techniques in the diagnostic work-up of WNND, utility of NAATs on CSF specimens is limited by the kinetics of WNV viremia in biological fluids. This report underlines that WNND should always be included in the differential diagnosis of meningoencephalitis during WNV transmission period.


Improved in vitro light activation and assay systems for two spinach chloroplast enzymes.
An improved system for the in vitro light activation of the chloroplast enzymes fructose-1,6-bisphosphatase and NADP-dependent malate dehydrogenase is described. Through the presence of the monothiol beta-mercaptoethanol in the reaction mixtures the activated forms of the enzymes can be stabilized and their activity determined spectrophotometrically.


Diagnostic accuracy of multislice computed tomography coronary angiography is improved at low heart rates.
Assess the effect of heart rate on diagnostic accuracy for the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). About 120 patients (105 males; 59+/-11 years) with suspected coronary artery disease who underwent conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA (Sensation 16, Siemens, Germany), with the following protocol: collimation 16 x 0.75 mm, gantry rotation time 420 ms, feed/rotation 3.0 mm, kV 120, mAs 400-500. The protocol for contrast material administration was 100 ml of Iodixanol (Visipaque 320 mg l/ml, Amersham, UK) at 4 ml/s and the delay was defined with a bolus tracking technique. In all patients the mean heart rate (HR) during the scan was used as a criteria to divide the population in two groups of 60 patients each. In one group (Low HR) the 60 patients with lower heart rates, and in the other group (High HR) the patients with higher heart rates. In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (>or=50% lumen reduction) was evaluated in vessels >or=2 mm of diameter using quantitative CA as reference standard. The difference in diagnostic accuracy were compared with a Chi(2) test and a p<0.05 was considered significant. There was no significant difference between the two groups regarding age, gender, weight, mean intravascular attenuation, and calcium score. Overall 1,310 (652 for Low HR and 658 for High HR) segments with 219 (105 for Low HR and 114 for High HR) significant lesions were available for the analysis. The average heart rate was 52+/-4 HU and 63+/-5 HU for Low HR and High HR, respectively (p<0.001). The sensitivity and specificity were 92 and 96% for Low HR and 90 and 92% for High HR (p<0.05). There were 22 vs. 44 false positives, and 8 vs. 12 false negatives in the Low HR and High HR, respectively. Increasing HR significantly deteriorates diagnostic accuracy in MSCT-CA.


Effectiveness of disease-specific self-management education on health outcomes in patients with chronic obstructive pulmonary disease: An updated systematic review and meta-analysis.
To update a previously published systematic review on the effectiveness of self-management education (SME) for patients with chronic obstructive pulmonary disease (COPD). Electronic databases were accessed (from inception to July 2016) to find relevant randomized controlled trials. Studies that compared SME with routine methods of care in COPD patients were retrieved. Both data synthesis and descriptive analysis were used for outcome assessment (e.g. quality of life and healthcare utilization). Twenty-four studies were included. Data synthesis showed better quality of life among COPD patients receiving SME. Significant reductions in COPD-related hospital admissions and emergency department visits were identified in the SME group. SME may positively affect the reduction of COPD patients' emotional distress. No significant reduction in smoking rate and mortality rate was observed between groups. No clear evidence supports the improvement of pulmonary functions, dyspnea, and nutritional status in COPD patients with the use of SME. SME can be a useful strategy to improve quality of life and disease-specific knowledge in patients with COPD. It also reduces respiratory-related hospital admissions and emergency department visits in COPD patients. Inclusion of SME as one of the key components for the comprehensive management of COPD is encouraged.


Relationship between carbamazepine concentrations in plasma and saliva in man as determined by liquid chromatography.
The concentration of carbamazepine in plasma and saliva was determined in 7 subjects receiving carbamazepine. Plasma and saliva samples were assayed was an excellent linear relationship between carbamazepine concentrations in saliva and plasma (r = 0.991, p less than 0.001) over a plasma concentration range of 0.2--8.0 microgram/ml. The saliva/plasma ratio for carbamazepine was 0.26 +/- 0.02 (S.D.). Since carbamazepine binding to plasma proteins is in the order of 75%, the saliva concentration seems to reflect the concentration of the free drug in plasma. There is very little intrasubject and intersubject variation in the concentration ratio of carbamazepine. This study demonstrates that carbamazepine determination in saliva is a convenient method for optimizing blood levels of patients as well as for the study of pharmacokinetic properties.


Laboratory twinning to build capacity for rabies diagnosis.
In 2009, the UK's OIE Reference Laboratory for rabies, based at the APHA in Weybridge, was awarded a project to twin with the Changchun Veterinary Research Institute in the People's Republic of China to help the institute develop the skills and methods necessary to become an OIE Reference Laboratory itself. Here, Tony Fooks, Trevor Drew and Changchun Tu describe the OIE's twinning project and the success that has since been realised in China.


The role of N-type Ca2+ channels in regulating excitability of guinea-pig sympathetic neurones.
Ca2+ entry through voltage-gated channels activated during the action potential modifies neuronal excitability by activating several types of K+ channel. We have determined the effects of Ca2+ influx through N-type Ca2+ channels in sympathetic paravertebral neurones of the guinea-pig, using the specific antagonist, omega-conotoxin GVIA. Blockade of large conductance (BK) Ca2(+)-activated K+ channels slowed action potential repolarization but did not affect the peak amplitude of the conductance (gKCal) underlying the afterhyperpolarization. Blockade of small conductance (SK) Ca2(+)-activated K+ channels decreased gKCal but did not affect action potential repolarization. Blockade of N-type Ca2+ channels slowed action potential repolarization and reduced the peak amplitude of gKCa1. We conclude that Ca2+ entry via N-type channels activates both BK and SK channels in guinea-pig sympathetic neurones. This differs from our previous observations in rat sympathetic neurones.


Feasibility and Safety of n-Butyl Cyanoacrylate-Lipiodol-Iopamidol as an Alternative Liquid Embolic Material.
To evaluate the feasibility and safety of n-butyl cyanoacrylate (NBCA)-Lipiodol-Iopamidol (NLI) as a liquid embolic material. In vitro, the ratio of NLI components was adjusted and the configuration of the mixtures was assessed visually in saline. In vivo, 14 wide-necked aneurysms were created on the common carotid and external iliac arteries of four female swine. Under balloon occlusion, 12 aneurysms were embolized with NLI prepared at a NBCA-Lipidol-Iopamidol ratio of 2:3:1 (NLI231), and two were embolized with NBCA-Lipiodol (NL) prepared at a NBCA-Lipiodol ratio of 1:2 (NL12) as a trial group. We performed angiography to evaluate the effectiveness of embolization and adhesion of the embolic material to the balloons or microcatheters. In vitro, NLI231 (33% NBCA) was considered to be the optimal ratio for aneurysm embolization based on its configuration and stability. In vivo, embolization using NLI231 was successful and no adhesion between the embolic material and the balloons or microcatheters was observed in all 12 aneurysms. Embolization with NL12 was impossible in the other two aneurysms due to leakage and adhesion of NL. The configuration of NLI changed at each ratio. NLI231 is a feasible and safe liquid embolic material for balloon-assisted embolization of wide-necked aneurysms in swine.


Use of a single silastic chest drain following thoracotomy: initial evaluation.
It is standard practice to use multiple large bore semi-rigid chest tubes to drain the pleural cavity following thoracic procedures. These can cause pain and discomfort at the insertion site. We describe our experience with the use of a single small silastic drain following thoracotomy. From November 2001 to November 2003, size 19-F silastic chest tubes (Blake drains) were used for drainage of the pleural cavity in 37 patients at our institution. The patients ranged in age from 18 to 81 years (mean 65). The operations included 22 lobectomies, two bilobectomies, 10 wedge resections, and three other procedures. Total drainage in each patient ranged from 420 to 5440 mL (mean 1387 mL). Tubes were left in place for an average of 4.3 days (range 1-12). The average postoperative length of stay was 7.6 days (range 3-44, median 5). Three patients required insertion of an additional tube for dislodgement, persistent air leak, and bronchopleural fistula, respectively. These complications occurred among the first 15 patients in the present series. None of the patients had persistent pleural effusion. Subjectively, these tubes were more comfortable for the patients and were easier to remove. The use of a single, small silastic chest drains following thoracotomy may be safe and effective in draining both fluid and air, though an additional tube may be necessary for persistent leaks.


Comparison between commercial heparin, low molecular weight heparin and pentosan polysulfate on hemostasis and platelets in vivo.
The effect of commercial heparin (MW 15000; 60 U/kg), low molecular weight heparin (MW 4500, 60 U/kg), sodium pentosan polysulfate (PZ-68) in doses of 0.5, 1, 2 and 5 mg/kg and 1 mg/kg combined with dextran 70 (0.5 g/kg) on microvascular hemostasis and platelet activity in vivo was investigated in the microcirculation of rabbit mesentery and ear chamber, respectively. Low molecular weight heparin did not alter the hemostasis: nonetheless, commercial heparin and PZ-68 interfered with the hemostatic mechanism by decreasing the stability of the hemostatic plug. This abnormality was more apparent in the venular than in the arteriolar system. Both heparins exhibited a trend towards an increase in platelet reactivity and the reverse was observed following the administration of PZ-68.


Goals, beneficiaries, and indicators of waterfront revitalization in Great Lakes Areas of Concern and coastal communities.
Cleanup of Great Lakes Areas of Concern (AOCs) restores environmental benefits to waterfront communities and is an essential condition for revitalization. We define waterfront revitalization as policies or actions in terrestrial waterfront or adjacent aquatic areas that promote improvements in human socioeconomic well-being while protecting or improving the natural capital (the stocks of natural assets, biodiversity) that underlies all environmental, social, and economic benefits. Except for economic measures such as development investments, visitation rates, or commercial activity, evidence of waterfront revitalization in the Great Lakes is mostly anecdotal. We offer a perspective on waterfront revitalization that links indicators and metrics of sustainable revitalization to community goals and human beneficiaries. We compiled environmental, social, economic, and governance indicators and metrics of revitalization, many of which are based on or inspired by Great Lakes AOC case studies and community reutilization or sustainability plans. We highlight the role of indicators in avoiding unintended consequences of revitalization including environmental degradation and social inequity. Revitalization indicators can be used in planning for comparing alternative designs, and to track restoration progress. The relevancy of specific indicators and metrics will always depend on the local context.


Beyond matrix stiffness: targeting force-induced cancer drug resistance.
During tumor progression, mechanical abnormalities in the tumor microenvironment (TME) trigger signaling pathways in cells that activate cellular programs, resulting in tumor growth and drug resistance. In this review, we describe mechanisms of action for anti-cancer therapies and mechanotransduction programs that regulate cellular processes, including cell proliferation, apoptosis, survival and phenotype switching. We discuss how the therapeutic response is impacted by the three main mechanical TME abnormalities: high extracellular matrix (ECM) composition and stiffness; interstitial fluid pressure (IFP); and elevated mechanical forces. We also review drugs that normalize these abnormalities or block mechanosensors and mechanotransduction pathways. Finally, we discuss current challenges and perspectives for the development of new strategies targeting mechanically induced drug resistance in the clinic.


Human papillomavirus and herpes virus DNA are not detected in benign and malignant prostatic tissue using the polymerase chain reaction.
Fresh prostatic tissue removed at the time of surgery was assayed for the presence of human papillomavirus (HPV) types 6, 11, 16, 18 and 33 and herpes and varicella-zoster viruses (HV) using DNA amplification followed by specific hybridization. Thirty samples representing both benign and malignant prostatic disease were assayed. Although appropriate amplimers were present for beta globulin gene indicating successful extraction of DNA, no HPV or HV amplimers could be obtained with appropriate primers. We conclude that HPV and HV are not routinely found in human prostate.


Eye position prediction in the case of nystagmus and refixations.
Nystagmus is a condition in which the eyes move in an uncontrolled fashion. These eye movements confound attempts to identify patient fixation, as desired eye positions cannot be maintained. We aim to estimate the eye positions in the case of refixations and superimposed uncontrolled motion. By incorporating saccade detection and resetting our estimation algorithms, we are able to track the nystagmus motion independently of fixation direction. We employ our algorithm on data collected from patients with latent/manifest-latent and pendular nystagmus conditions.


Surgical-site infection after hip fracture surgery: preoperative full-body disinfection compared to local disinfection of the surgical site-a population-based observational cohort study.
Swedish national guidelines recommend full-body disinfection (FBD) with 4% chlorhexidine before hip fracture surgery to prevent surgical-site infection (SSI) despite little evidence. Our objective was to compare preoperative FBD with local disinfection (LD) of the surgical site regarding SSI incidence. All patients with hip fracture, operated at a hospital in Sweden, January 1, 2018 to December 31, 2019 were included. Patients in 2018 (n = 237) were prepared with FBD and patients in 2019 (n = 259) with LD. Primary outcome was SSI and secondary outcome was SSI and/or death. We adjusted for potential confounders with logistic regression. The adjusted analysis was performed in two models to enable assessment of variables that lacked either outcome; in the first model, these variables were not adjusted, and the second model was restricted to a sub-population not affected by respective variables. There were 16 (6.8%) cases of SSI in 2018 and 8 (3.1%) cases in 2019. FBD (2018) compared to LD (2019) presented an adjusted OR of 1.9 (95%CI 0.8-4.9, P = 0.16) respectively 2.0 (95%CI 0.8-5.1, P = 0.14) in the two models of the logistic regression. In addition, 40 (16.9%) patients in 2018 and 29 (11.2%) patients in 2019 had the combined outcome of SSI and/or death, adjusted OR 1.6 (95% CI 0.9-2.8, P = 0.08) respectively 1.7 (95% CI 0.9-2.9, P = 0.06). We found a non-significant increased risk of SSI 2018 compared to 2019 after adjustment. Randomized control trials are needed. Nonetheless, results suggest that LD is not inferior to FBD regarding SSI prevention, meaning patients could potentially be spared substantial pain.


Chemopreventive effects of 5-amino salicylic acids on inflammatory bowel disease-associated colonic cancer and colonic dysplasia: a meta-analysis.
To study the effects of 5-amino salicylic acids (5-ASAs) on the incidence rates of inflammatory bowel disease (IBD)-associated colonic cancer (IBDACa) and colonic dysplasia (IBDADys), as well as to evaluate the chemopreventive effects of 5-ASAs on IBDACa/Dys. Searches for officially published clinical studies on the effects of 5-ASAs on the chemoprevention of IBDACa/Dys were conducted in both foreign-language databases, including PubMed (Medline), EMCC, OVID, and the Cochrane Library, and Chinese databases, including Wanfang, Weipu (VIP), and CNKI, as well as using Google Scholar. For literature matching the selection criteria, the statistical software RevMan was employed to calculate odds ratio (OR) values and 95% confidence intervals (CIs). Sub-group analysis was performed for different study design types and IBD types. A total of fourteen papers were included in this study. The results of the analysis showed that compared with patients not using 5-ASAs, patients using 5-ASAs showed only 49% of the occurrence rate of IBDACa and IBDADys, OR = 0.49 (95% CI: 0.33-0.73). The OR of ulcerative colitis (UC) patients using 5-ASAs exhibiting UCCa/Dys was 0.44 (95% CI: 0.26-0.76). The use of 5-ASAs exerts a chemopreventive effect against IBDACa/Dys.


Clinical characteristics determining the mode of presentation in patients with acute coronary syndromes.
The purpose of this study was to examine clinical characteristics of patients with acute coronary syndromes to identify factors that influence the mode of presentation. In acute coronary syndromes, presentation with myocardial infarction or unstable angina has major prognostic implications, yet clinical factors affecting the mode of presentation are not well defined. A prospective cohort study was made of 1,111 patients with acute coronary syndromes. Baseline demographic, clinical and biochemical data were compared in groups with myocardial infarction (n = 633) and unstable angina (n = 478). The risk of myocardial infarction relative to unstable angina was increased by age >70 years (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.33 to 3.66), male gender (OR 1.56; CI 1.13 to 2.16) and cigarette smoking (OR 1.49; CI 1.09 to 2.03). A rise in admission creatinine from the 10th to the 90th centile of the distribution also increased the odds of myocardial infarction (OR 1.30; CI 1.05 to 1.94). Conversely, the risk of myocardial infarction relative to unstable angina was reduced by previous treatment with aspirin (OR 0.37; CI 0.27 to 0.52), hypertension (OR 0.64; CI 0.47 to 0.86) and previous acute coronary syndromes (OR 0.36; CI 0.26 to 0.51) and revascularization procedures (OR 0.36; CI 0.21 to 0.62). The clinical presentation of acute coronary syndromes may be influenced by various factors that have the potential to influence the coagulability of the blood, the collateralization of the coronary circulation and myocardial mass. Myocardial infarction is favored by cigarette smoking, advanced age and renal impairment, while unstable angina is favored by treatment with aspirin, hypertension, previous revascularization and previous coronary syndromes.


Self-inactivating, all-in-one AAV vectors for precision Cas9 genome editing via homology-directed repair in vivo.
Adeno-associated virus (AAV) vectors are important delivery platforms for therapeutic genome editing but are severely constrained by cargo limits. Simultaneous delivery of multiple vectors can limit dose and efficacy and increase safety risks. Here, we describe single-vector, ~4.8-kb AAV platforms that express Nme2Cas9 and either two sgRNAs for segmental deletions, or a single sgRNA with a homology-directed repair (HDR) template. We also use anti-CRISPR proteins to enable production of vectors that self-inactivate via Nme2Cas9 cleavage. We further introduce a nanopore-based sequencing platform that is designed to profile rAAV genomes and serves as a quality control measure for vector homogeneity. We demonstrate that these platforms can effectively treat two disease models [type I hereditary tyrosinemia (HT-I) and mucopolysaccharidosis type I (MPS-I)] in mice by HDR-based correction of the disease allele. These results will enable the engineering of single-vector AAVs that can achieve diverse therapeutic genome editing outcomes.


Anterior rectal wall excision for endometriosis using the circular stapler.
Endometriosis involving the rectum is rare but is associated with significant symptoms that are best relieved by resection of the involved segment of rectum. Resection necessitates either a segmental or anterior rectal wall excision with sutured closure. Application of a circular stapling device allows an alternative technique to resect endometriosis in this area. Following laparoscopic ablation of endometriosis elsewhere in the pelvis, the rectum must be mobilized around disease present on the anterior rectal wall. This will involve lateral and anterior extraperitoneal rectal dissection; the latter dissection mobilizing the vagina from the rectum by a sufficient length necessary to allow imbrication of the diseased area. Insertion of a circular stapler per anus allows the diseased area to be imbricated into the stapler, resulting in simultaneous excision and closure of the anterior rectal wall. Thirty patients with anterior rectal wall endometriosis, estimated at <2 cm in diameter and not involving > one-third of the total circumference of the rectum, have undergone successful management using this technique. Morbidity occurred in four patients, with one patient requiring further surgery. Laparoscopic disc excision of deposits of endometriosis involving the anterior rectal wall can be safely performed utilizing the circular stapler without the need for open surgery, and with low morbidity.


The structure of networks that produce the transformation from grid cells to place cells.
Since grid cells were discovered in the medial entorhinal cortex, several models have been proposed for the transformation from periodic grids to the punctate place fields of hippocampal place cells. These prior studies have each focused primarily on a particular model structure. By contrast, the goal of this study is to understand the general nature of the solutions that generate the grids-to-places transformation, and to exploit this insight to solve problems that were previously unsolved. First, we derive a family of feedforward networks that generate the grids-to-places transformations. These networks have in common an inverse relationship between the synaptic weights and a grid property that we call the normalized offset. Second, we analyze the solutions of prior models in terms of this novel measure and found to our surprise that almost all prior models yield solutions that can be described by this family of networks. The one exception is a model that is unrealistically sensitive to noise. Third, with this insight into the structure of the solutions, we then construct explicitly solutions for the grids-to-places transformation with multiple spatial maps, that is, with place fields in arbitrary locations either within the same (multiple place fields) or in different (global remapping) enclosures. These multiple maps are possible because the weights are learned or assigned in such a way that a group of weights contributes to spatial specificity in one context but remains spatially unstructured in another context. Fourth, we find parameters such that global remapping solutions can be found by synaptic learning in spiking neurons, despite previous suggestions that this might not be possible. In conclusion, our results demonstrate the power of understanding the structure of the solutions and suggest that we may have identified the structure that is common to all robust solutions of the grids-to-places transformation.


Pharmacological effects of harmine and its derivatives: a review.
Harmine is isolated from the seeds of the medicinal plant, Peganum harmala L., and has been used for thousands of years in the Middle East and China. Harmine has many pharmacological activities including anti-inflammatory, neuroprotective, antidiabetic, and antitumor activities. Moreover, harmine exhibits insecticidal, antiviral, and antibacterial effects. Harmine derivatives exhibit pharmacological effects similar to those of harmine, but with better antitumor activity and low neurotoxicity. Many studies have been conducted on the pharmacological activities of harmine and harmine derivatives. This article reviews the pharmacological effects and associated mechanisms of harmine. In addition, the structure-activity relationship of harmine derivatives has been summarized.