Study of the Etiological Factors of Failures of Myringoplasty: A Observational Study.
This Study entitled "the study of the aetiological factors of failures of myringoplasty" was planned to find the various aetiological factors causing failure of myringoplasty and suggests remedial steps to improve the results in future. This observational study was carried in the Department of E.N.T, on patients who had undergone myringoplasty from Jan 2013 to June 2016. Total 905 patients operated in the above mentioned duration. 685 patients were operated during Jan 2013 to June 2015, who were studied retrospectively (only 540 came for follow up), and 220 patients were operated during June 2015 to June 2016 were studied prospectively. The patients who came to the OPD for follow up, were thoroughly reviewed and the re-perforation was seen in 53 patients. Total nine factors causing myringoplasty failure were studied, 4 factors i.e. size of perforation, site of perforation, eustachian tube function, and surgeons experience significantly affects the surgical outcome of myringoplasty while age, tympanosclerotic patch, type of anaesthesia, wet or dry graft placement, and deviated nasal septum does not affects the myringoplasty failure. For improvement of result in future, Eustachian tube dysfunction, symptomatic deviated nasal septum should be corrected before the surgery. Anterior and larger perforation should be operated by experienced surgeon.


Similarity of sli-1, a regulator of vulval development in C. elegans, to the mammalian proto-oncogene c-cbl.
Vulval induction during Caenorhabditis elegans development is mediated by LET-23, a homolog of the mammalian epidermal growth factor receptor tyrosine kinase. The sli-1 gene is a negative regulator of LET-23 and is shown here to encode a protein similar to c-Cbl, a mammalian proto-oncoprotein. SLI-1 and c-Cbl share approximately 55 percent amino acid identity over a stretch of 390 residues, which includes a C3HC4 zinc-binding motif known as the RING finger, and multiple consensus binding sites for Src homology 3 (SH3) domains. SLI-1 and c-Cbl may define a new class of proteins that modify receptor tyrosine kinase-mediated signal transduction.


Pascal laser versus conventional laser for treatment of diabetic retinopathy.
To compare the safety and efficacy of Pascal laser photocoagulation in comparison with the conventional laser photocoagulation in the treatment of diabetic retinopathy. A prospective randomized case series study was done on 120 procedures done in 120 patients divided into two main groups, group A, patients undergoing focal or modified grid macular laser and group B, patients undergoing panretinal photocoagulation (PRP). Each of the two groups were subdivided into two subgroups randomly in the first we used conventional laser photocoagulation (groups A1 and B1) and in the other we used Pascal laser photocoagulation (groups A2 and B2). Procedures in groups A1,2 and in groups B1,2 had successful outcomes. Significantly higher powers were required with the Pascal (groups A2 and B2) than with conventional laser (groups A1 and B1) (p < 0.001) in eyes that underwent PRP and focal/modified grid macular treatment with both systems. No adverse events were noted in all groups. The Pascal photocoagulator is safe, rapid, effective, with rapid learning and had short exposure time. Although the shorter pulse duration of the Pascal necessitates the use of a higher power, it is not associated with adverse effects.


How abundant are superoxide and hydrogen peroxide in the vasculature lumen, how far can they reach?
Paracrine superoxide (O2•-) and hydrogen peroxide (H2O2) signaling critically depends on these substances' concentrations, half-lives and transport ranges in extracellular media. Here we estimated these parameters for the lumen of human capillaries, arterioles and arteries using reaction-diffusion-advection models. These models considered O2•- and H2O2 production by endothelial cells and uptake by erythrocytes and endothelial cells, O2•- dismutation, O2•- and H2O2 diffusion and advection by the blood flow. Results show that in this environment O2•- and H2O2 have half-lives <60. ms and <40. ms, respectively, the former determined by the plasma SOD3 activity, the latter by clearance by endothelial cells and erythrocytes. H2O2 concentrations do not exceed the 10 nM scale. Maximal O2•- concentrations near vessel walls exceed H2O2's several-fold when the latter results solely from O2•- dismutation. Cytosolic dismutation of inflowing O2•- may thus significantly contribute to H2O2 delivery to cells. O2•- concentrations near vessel walls decay to 50% of maximum 12 μm downstream from O2•- production sites. H2O2 concentrations in capillaries decay to 50% of maximum 22 μm (6.0 μm) downstream from O2•- (H2O2) production sites. Near arterioles' (arteries') walls, they decay by 50% within 6.0 μm (4. μm) of H2O2 production sites. However, they reach maximal values 50 μm (24 μm) downstream from O2•- production sites and decrease by 50% over 650 μm (500 μm). Arterial/olar endothelial cells might thus signal over a mm downstream through O2•--derived H2O2, though this requires nM-sensitive H2O2 transduction mechanisms.


Approaches to endocrinopathic laminitis in the field: Results of a survey of veterinary practitioners in North America.
Endocrinopathic laminitis is the most common cause of laminitis in the field. Insulin has recently been implicated as a key factor in development of endocrinopathic laminitis; however, it is unclear whether diagnostic, and treatment approaches reflect insights derived from recent research. This study sought to evaluate North American veterinary practitioners' approach to endocrinopathic laminitis in the field. Demographic information, approach to diagnosis, management, and prognosis of endocrinopathic laminitis, as well as factors influencing changes in approach to laminitis were collected. To compare regional differences in approach to laminitis, results were compared to a recently published study from the United Kingdom. Findings of the present study suggest that North American practitioners have changed their approach to laminitis to more readily incorporate diagnostic testing for endocrine disease.


Coexisting role of fasting or feeding and dietary lipids in the control of gene expression of enzymes involved in the synthesis of saturated, monounsaturated and polyunsaturated fatty acids.
In the liver, maintaining lipid homeostasis is regulated by physiological and exogenous factors. These lipids are synthesized by Fasn, elongases and desaturases. Interactions in an organism among these factors are quite complex and, to date, relatively little is known about them. The aim of this study was to evaluate the coexisting role of physiological (insulin, fasting and feeding) and exogenous (dietary lipids) factors in the control of gene expression of Fasn, elongases and desaturases via Srebf-1c in liver from rats. Gene expression of encoding enzymes for fatty acid synthesis and fatty acid composition was evaluated in liver from rats in fasting and feeding (at 30, 60, 90 and 120 min after feeding) when food intake (adequate or high-lipid diet) was synchronized to a restricted period of 7h. Fasn, Scd and Fads2 were induced during 120 min after initial feeding in both dietary groups. This induction may be activated in part by insulin via Srebf-1c. Also, we showed for the first time that Elovl7 may be regulated by insulin and dietary lipids. The failure to synthesize saturated and monounsaturated fatty acids is consistent with a downregulation of Fasn and Scd, respectively, by dietary lipids. A higher content of LC-PUFAs was observed due to a high expression of Elovl2 and Elovl5, although Fads2 was suppressed by dietary lipids. Therefore, elongases may have a mechanism that is Srebf-1c-independent. This study suggests that a high-lipid diet triggers, during 120 min after initial feeding, a tight coordination among de novo lipogenesis, elongation, and desaturation and may not always be regulated by Srebf-1c. Finally, upregulation by feeding (insulin) of Fasn, Scd, Fads2 and Srebf-1c is insufficient to compensate for the inhibitory effect of dietary lipids.


Time to Antibiotic for Pediatric Oncology Patients With Febrile Neutropenia at Regional Emergency Departments.
We compared the time to antibiotic (TTA) for pediatric oncology patients with febrile neutropenia (FN) presenting at regional emergency departments (EDs) with those presenting at a pediatric referral ED, and examined its association with need for aggressive medical care. We abstracted data for pediatric oncology patients (age, <21 years) admitted for FN between August 2012 and August 2017 at a single children's hospital and compared the TTA between those referred from a regional ED across the state and those admitted via the referral ED at the children's hospital. Factors associated with delay in antibiotic administration (TTA, >60 minutes) were estimated using generalized linear modeling with generalized estimating equations (GEEs). Delay in antibiotic administration was examined for its association with the need for aggressive medical care (>1 fluid bolus, intensive care unit admission, inotropic or invasive ventilator support) within 24 hours of admission as an exploratory aim. Three-hundred eighty-nine FN admissions (regional ED, 26.7%; referral ED, 73.3%) occurred in 205 eligible patients. Median TTA was significantly (P < 0.0001) greater among patients presenting at a regional ED (117.5 minutes [range, 9-722 minutes]) vs referral ED (46 minutes [range, 6-378 minutes]). Presentation at regional ED was the only factor associated with delay in antibiotic administration (odds ratio, 9.73; 95% confidence interval, 5.37-17.63; P < 0.0001). Delay in antibiotic administration was not associated with greater need for aggressive medical care (odds ratio, 1.34; 95% confidence interval, 0.55-3.29; P = 0.5). Pediatric oncology patients with FN presenting to regional EDs have longer TTA as compared with those presenting to a referral ED at a children's hospital.


Arthro-Broström with endoscopic retinaculum augmentation using all-inside lasso-loop stitch techniques.
There is still some controversy about the augmentation of the inferior extensor retinaculum after arthroscopic anterior talofibular ligament repair. The aim of this study was to evaluate the novel arthro-Broström procedure with endoscopic retinaculum augmentation using all-inside lasso-loop stitch techniques for chronic lateral ankle instability. Thirty-four cases with grade-2 or grade-3 chronic anterior talofibular ligament lesions who underwent the novel arthro-Broström procedure with endoscopic retinaculum augmentation using all-inside lasso-loop stitch techniques were assessed retrospectively. A total of 30 cases (30 ankles) were followed up for a mean of 26.67 ± 4.19 months (range, 24-36 months). four cases were excluded due to insufficient medical records or loss of follow-up reports. The Cumberland Ankle Instability Tool scores, The Karlsson-Peterson scores and Visual Analogue Scale scores were evaluated before surgery and at the final follow-up time. Also, the results of stress fluoroscopic tests and complications were recorded. At the final follow-up, the average of the Cumberland Ankle Instability Tool scores, The Karlsson-Peterson scores and Visual Analogue Scale scores were 86.63 ± 6.69 (range, 77-100), 90.17 ± 4.64 (range, 85-100) and 0.53 ± 0.63 (range, 0-2), respectively. Moreover, the results of stress fluoroscopic tests were improved significantly after surgery. Mild keloid formation and/or knot irritation were observed in four cases. No wound infections, nerve injuries and recurrent instability were recorded. Also, no stiffness or arthritis of the subtalar joint was encountered. The arthro-Broström procedure combined with endoscopic retinaculum augmentation using all-inside lasso-loop techniques is reliable and safe due to the advantage of direct endoscopic visualization.


A combination of Yiqiqubai granule and 308-nm excimer laser in treatment of segmental vitiligo: a prospective study of 233 patients.
To study the effect of Yiqiqubai granule combined with 308-nm excimer laser treatment for segmental vitiligo (SV). A prospective research was performed in 233 patients with SV treated in Shanghai General Hospital from 11 February 2015 to 25 August 2016, they were divided into group A (n = 75), group B (n = 78) and group C (n = 80) according to the random number table. Group A was treated with Yiqiqubai granule, group B treated with 308-nm excimer laser and group C treated with combined treatments. The treatment time lasts for 6 months. The clinical efficacy, color-reverse rate and quality of life of the three groups were assessed. After treatment, the effective rate and markedly effective rate of group C (87.5%, 51.3%) were significantly higher than group A (74.7%, 42.7%) and group B (80.8%, 47.4%) (p < .05). Color-reverse rate of group C (66.5 ± 17.6%) was much higher than group A (47.2 ± 16.4%) and group B (49.9 ± 24.2%) (p < .05). Significant differences were found among three groups after treatment in terms of embarrassment, social and work (p < .05). The combination of 308-nm excimer laser and Yiqiqubai granule in the treatment of SV has good clinical effect.


Effect of cardiac A(1) adenosine receptor overexpression on sarcoplasmic reticulum function.
We investigated the effect of A(1) adenosine receptor overexpression, which has been reported to increase myocardial tolerance to ischemia-reperfusion injury, on sarcoplasmic reticulum (SR) Ca(2+) handling. Transgenic mouse hearts (approximately 300-fold A(1) adenosine receptor overexpression) and wild-type mouse hearts were perfused in the Langendorff mode and subjected either to 80 min of aerobic perfusion or to 30 min of aerobic perfusion, 20 min of global ischemia and 30 min of reperfusion. The hearts were then homogenized and used to assay SR oxalate-supported 45Ca(2+) uptake and [3H]-ryanodine binding. Transgenic hearts showed increased resistance to ischemia-reperfusion, as shown by lower diastolic tension (1.5 +/- 0.2 vs. 2.6 +/- 0.1 g, P<0.05) and higher recovery of developed tension (45 +/- 3 vs. 30 +/- 4% of the baseline, P<0.05) following ischemia-reperfusion. Under baseline conditions, oxalate-supported 45Ca(2+) uptake was lower in transgenic hearts, owing to reduced V(max) (10.6 +/- 2.0 vs. 17.8 +/- 2.7 nmol/min per mg of protein, P<0.05), and the difference was preserved after ischemia-reperfusion (10.0 +/- 1.0 vs. 15.7 +/- 2.5 nmol/min per mg of protein, P<0.05). No significant difference in [3H]-ryanodine binding was observed. A(1) adenosine receptor overexpression is associated with a decreased rate of active Ca(2+) transport into the SR. We hypothesize that changes in SR function may cause a depletion of the SR Ca(2+) pool, which might protect from ischemic injury by delaying the development of cytosolic Ca(2+) overload during ischemia.


MiR-146a functions as a small silent player in gastric cancer.
Gastric cancer is responsible for approximately one million annual deaths worldwide. Recently, the important roles of miRNAs as vital factors in malignancy processes such as metastasis have identified. They involve in the regulation of different biological procedures such as proliferation, invasion, metastasis and cell survival. MiR-146a has an aberrant expression in different tumors and has different expressions in the gastric cancer cell lines. This microRNA can act as a tumor suppressor and/or oncogene in gastric cancer related cases. Most of the studies have confirmed that miR-146a is downregulated in human gastric cancer cell lines and tissues, significantly and that it has tumor suppressor effects in gastric cancers. On the other hand, the role of miR-146a as an oncogene has been studied in an in-vitro experiment and results showed that over- an expression of miR-146a in gastric cancer tissues inhibits apoptosis and improves cell proliferation of gastric cancer cell. MiR-146a also has been a candidate for diagnosis and prognosis in gastric cancer cases. In this review, we focus on the important roles of miR-146a in tumor genesis of gastric tissues, emphasizing on the involvement of this microRNA in diagnosis, prognosis, chemotherapy response and finally, potential therapeutic applications as an anticancer agent in inhibition of gastric cancer cell metastasis and invasion.


Calculation of absorbed dose in paediatric phantoms using Monte Carlo techniques for 18F-FDG and 99mTc-DMSA and the new TIAC.
The radiopharmaceuticals most commonly used in nuclear medicine are 18F-FDG and 99mTc-DMSA, both of which are administered to paediatric and adult patients using the same time activity coefficient. However, the IAEA recommends specific paediatric dosimetry. The aim of this work (TW) was to estimate the absorbed dose for 18F-FDG and 99mTc-DMSA using two paediatric voxel phantoms (Baby and Child) by Monte Carlo techniques. Biokinetic data for both radiopharmaceuticals were obtained from ICRP 128. In addition, the new time-integrated activity coefficient (TIAC) values from a recent publication were examined for the following organs: Brain, urinary bladder wall, liver, heart wall, and lung. The absorbed dose per injected activity (AD/IA) and effective dose per injected activity (E/IA) values were calculated for both phantoms and the results were compared with simulated data of paediatric phantoms from ICRP 128, MIRDcalc software and available literature. Regarding AD/IA in organs, differences of up to 61% and 115% were found for the Baby phantom and 120% and 167% for the Child phantom using 18F-FDG and 99mTc-DMSA, respectively. For FDG using the new TIAC, a maximum difference of 244% was observed. For E/IA, the maximum differences were 27% and 31% for the Baby and Child phantoms, respectively, for FDG and DSMA. In this study, new dosimetric data were calculated using Baby and Child phantoms and the newly recommended TIAC.


[Decision-Making Behaviour in Physician-Rating Portals: Results of a Vignette Study in the New Federal States of Germany].
The extent to which relevant information is taken into consideration in the decision process for or against the choice of certain physicians when searching for physicians via physician-rating portals is largely unknown. In particular, the question of whether longer travel distances to a doctor's office are accepted in favour of a good rating is investigated in this study. In a vignette study, 192 respondents from new German states were shown ten hits each from a fictitious search for a primary care physician. A total of 1881 choice probabilities were evaluated with cluster-corrected regressions. A good rating and a short distance to the doctor's office were the most important determinants of a positive probability of choice. Longer distances were not accepted in favour of a good rating. Arabic-sounding names strongly reduced the probability of choice, although the respondents only assigned subordinate importance to the doctors' names as a basis for decision-making. The area served by physicians in private practice does not increase if they receive good grades on rating portals. Service quality is important, but not the most important factor in the rating score.


Description of Flexiglena gen. nov. and new members of Discoplastis and Euglenaformis (Euglenida).
Environmental sampling in Poland and the United States and phylogenetic analyses based on 567 sequences of four genes (155 sequences of nuclear SSU rDNA, 139 of nuclear LSU rDNA, 135 of plastid-encoded SSU rDNA, and 138 of plastid-encoded LSU rDNA) resulted in description of the new genus Flexiglena, which has been erected by accommodating Euglena variabilis, and enriching the Discoplastis and Euglenaformis genera with five new species. Four of them have joined the Discoplastis genus, currently consisting of six representatives: D. adunca, D. angusta (=Euglena angusta), D. constricta (=Lepocinclis constricta), D. excavata (=E. excavata), D. gasterosteus (=E. gasterosteus), and D. spathirhyncha. One of them has enriched the Euglenaformis genus, currently represented by two species: Euf. chlorophoenicea (= E. chlorophoenicea) and Euf. proxima. For most studied species, the diagnostic descriptions have been emended and epitypes were designated. Furthermore, the emending of Discoplastis and Euglenaformis diagnoses was performed.


Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV.
The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women. Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled. Efavirenz concentrations were measured at 4 weeks of antiretroviral therapy initiation during pregnancy and 6 weeks post partum using validated LC-MS/MS assays. Efavirenz PK parameters were calculated using noncompartmental analysis, and within-group parameters between the 2 periods were compared. Of 25 enrolled women, 19 completed PK sampling during pregnancy and post partum. The Cmax, Cmin, AUC0-24h, and CL/F for EFV during pregnancy were similar to values at 6 weeks post partum. The pregnancy/postpartum geometric mean ratios for EFV Cmax, Cmin, AUC0-24, and CL/F were 1.10 (95% CI, 0.93-1.31), 0.88 (95% CI, 0.67-1.17), 0.84 (95% CI, 0.71-0.98), and 1.20 (95% CI, 1.02-1.40), respectively. Viral load suppression (HIV RNA <200 copies/mL) was achieved in 16 of 17 participants (94%) by the time of delivery. There was 1 maternal-to-child transmission. We found that the PK parameters of EFV 600 mg once daily during pregnancy were similar to those in the postpartum period. Our findings suggest that EFV dose adjustment during pregnancy is not necessary in our study population.


Keyworker mediated enhancement of physical health in patients with first episode psychosis: A feasibility/acceptability study.
Early intervention for people experiencing first episode psychosis is a priority, and keyworkers are vital to such services. However, keyworkers' roles in addressing first episode psychosis patients' physical health are under researched. This study addresses this knowledge gap by evaluating a keyworker-mediated intervention promoting physical health among first episode psychosis patients. The study was informed by the Medical Research Council's Framework for Complex Interventions to Improve Health. First episode psychosis participants were recruited from three Irish mental health services. The intervention was evaluated in terms of its feasibility/acceptability. Feasibility outcomes were mixed (recruitment rate = 24/68 [35.3%]; retention rate = 18/24 [75%]). The baseline sample was predominantly male (M:F ratio = 13:6; Med age = 25 y; IQR = 23-42 y). Common health issues among participants included overweightness/obesity (n = 11) and substance use (smoking/alcohol consumption [n = 19]). Participants' initial health priorities included exercising more (n = 10), improving diet (n = 6), weight loss (n = 7) and using various health/healthcare services. The intervention's acceptability was evidenced by the appreciation participants had for physical health keyworkers' support, as well as the healthy lifestyle, which the intervention promoted. Acceptability was somewhat compromised by a low-recruitment rate, variable linkages between keyworkers and general practitioners (GPs) and COVID-19 restrictions. Physical health-oriented keyworker interventions for first episode psychosis patients show promise and further evaluation of such initiatives is warranted. Future interventions should be mindful of participant recruitment challenges, strategies to enhance relationships between keyworkers and GPs, and if necessary, they should mitigate COVID-19 restrictions' impacts on care.


All-or-none shortening of isolated single smooth muscle cells from different organs to acetylcholine.
1. Single smooth muscle cells from the guinea-pig taenia caecum and the fundus of guinea-pig stomach were prepared by collagenase digestion under different, mild conditions. 2. Most of the cells either from taenia caecum or from the fundus of stomach responded repeatedly, showing an all-or-none response to acetylcholine (ACh). 3. The threshold concentrations of ACh were different for the cells of the two tissues. Although individual cells showed an all-or-none response to ACh, the average responses of all the cells were graded, like that of whole tissues. 4. Thus, isolated single smooth muscle cells from different tissues and under different conditions responded to ACh in an all-or-none manner such as the twitch observed in skeletal muscle. 5. These results suggest that the isolation of cells reveals the fundamental characteristics of smooth muscle cells as excitable.


Experimental chronic epilepsy in rats: a screening method for antiepileptic drugs.
Rats were rendered epileptic by subpial injection of an FeCl3 solution. Epileptiform discharges, recorded by chronically implanted extradural electrodes, were evident within 48 h of surgery and persisted for more than 6 months. It is demonstrated that this model is useful for studying new antiepileptic agents since a series of clinically effective drugs (diazepam, clonazepam, Na phenobarbital, primidone, carbamezepine, ethosuximide, diphenylhydantoin, Na valproate, GABOB) show an activity which is does-dependent and within a range satisfactorily related to human dosages.


Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport.
The Ebola virus matrix protein VP40 plays an important role in virion formation and viral egress from cells. However, the host cell proteins and mechanisms responsible for intracellular transport of VP40 prior to its contribution to virion formation remain to be elucidated. Therefore we used coimmunoprecipitation and mass spectrometric analyses to identify host proteins interacting with VP40. We found that Sec24C, a component of the host COPII vesicular transport system, interacts specifically with VP40 via VP40 amino acids 303 to 307. Coimmunoprecipitation and dominant-negative mutant studies indicated that the COPII transport system plays a critical role in VP40 intracellular transport to the plasma membrane. Marburg virus VP40 was also shown to use the COPII transport system for intracellular transport. These findings identify a conserved intersection between a host pathway and filovirus replication, an intersection that can be targeted in the development of new antiviral drugs.


Volumetric-modulated arc therapy in postprostatectomy radiotherapy patients: a planning comparison study.
The purpose of this study was to compare postprostatectomy planning for volumetric-modulated arc therapy (VMAT) with both single arc (SA) and double arcs (DA) against dynamic sliding window intensity-modulated radiotherapy (IMRT). Ten cases were planned with IMRT, SA VMAT, and DA VMAT. All cases were planned to achieve a minimum dose of 68Gy to 95% of the planning target volume (PTV) and goals to limit rectal volume >40Gy to 35% and >65Gy to 17%, and bladder volumes >40Gy to 50% and >65Gy to 25%. Plans were averaged across the 10 patients and compared for mean dose, conformity, homogeneity, rectal and bladder doses, and monitor units. The mean dose to the clinical target volume and PTV was significantly higher (p<0.05) for SA compared with DA or IMRT. The homogeneity index was not significantly different: SA = 0.09; DA = 0.08; and IMRT = 0.07. The rectal V40 was lowest for the DA plan. The rectal V20 was significantly lower (p<0.05) for both the VMAT plans compared with IMRT. There were no significant differences for bladder V40 or rectal and bladder V65. The IMRT plans required 1400MU compared with 745 for DA and 708 for SA. This study shows that for equivalent dose coverage, SA and DA VMAT plans result in higher mean doses to the clinical target volume and PTV. This greater dose heterogeneity is balanced by improved low-range rectal doses and halving of the monitor units.


[A histopathological study on the intervertebral discs of idiopathic and paralytic scoliosis--abnormalities in transition from the notochordal nucleus to the fibrocartilaginous nucleus].
To elucidate morphologic events, 105 intervertebral discs in 22 patients with idiopathic scoliosis and 14 in four patients with paralytic scoliosis were histopathologically compared with 13 control intervertebral discs in 13 cases, including three fetuses. In control intervertebral discs, the notochordal area became smaller with age, and was almost completely occupied by fibrocartilagenous matrix at 16 years of age or more. In intervertebral discs of patients aged 19-33 with idiopathic scoliosis, many notochordal cells were seen and many areas without fibrocartilagenous matrix were found. In contrast, in intervertebral discs of patients aged 21-35 with paralytic scoliosis, there was no notochordal cells or defect of the fibrocartilagenous matrix. The results suggest an impairment of transition from the notochordal nucleus to the fibrocartilagenous nucleus in intervertebral discs in patients with idiopathic scoliosis, and that such abnormalities are related to the onset of idiopathic scoliosis.


Cytological grading of prostatic aspiration biopsy: a comparison with the Gleason grading system.
Cytological grade determined by fine needle aspiration of the prostate was compared to histological grade in 30 patients undergoing subsequent radical prostatectomy. The degree of cytological pleomorphism determined by the consensus grade of 3 observers predicted correctly the Gleason grade sum range in 80 per cent of the cases. The cytological grade was reasonably reproducible with agreement among all 3 observers in 50 per cent of the cases and between 2 of 3 observers in the remainder. The accuracy of predicting the Gleason grade sum of the radical prostatectomy specimen by cytological examination compared favorably with that achieved by histological examination of cutting needle biopsy and transurethral resection specimens reported in the literature.


Effects of cholesterol gallstone induction on gallbladder function and bile salt pool size in the prairie dog model.
The prairie dog gallstone model was used to test the following hypotheses: (1) gallbladder stasis occurs in association with gallstone formation, and (2) bile salt pool size decreases as gallstones develop. Bile salt pool sizes and the extent of equilibration of hepatic and gallbladder bile salt over the course of gallstone development were measured. No evidence for bile salt pool reduction was found, but there was significant evidence of progressively inefficient equilibration of hepatic and gallbladder bile salt very early during gallstone formation. These changes, suggestive of gallbladder stasis and observed only in the presence of cholesterol crystals in bile, persisted as cholesterol stones developed and antedated any reduction in bile salt pool size.


Involvement of Ca2+ waves in excitation-contraction coupling of rat atrial cardiomyocytes.
Two-dimensional and line-scan analyses of the early phase Ca2+ transients in rat cardiomyocytes were performed with a rapid-scanning laser confocal microscope and fluo-3 to elucidate the mechanism of activation of Ca2+ release from the sarcoplasmic reticulum in atrial myocytes which lack a well developed T-tubular network. On electrical stimulation of ventricular myocytes, Ca2+ concentration began to rise earliest at the Z-line level and became uniform throughout the cytoplasm within about 10 msec. In contrast, on stimulation of atrial myocytes, the earliest rise in Ca2+ occurred at the cell periphery and then spread to the cell interior; cytoplasmic Ca2+ became uniform after more than 30msec. The velocity of the propagation of rise in Ca2+ was 112 +/- 5.1 microm/sec (n = 10), which was similar to that of spontaneous Ca2+ waves observed in atrial and ventricular myocytes. No difference in frequency, amplitude and kinetics of spontaneous Ca2+ sparks was observed between the subsarcolemmal and central regions of atrial myocytes. Ryanodine concentration-dependently decreased the contractile force of isolated rat atrial and ventricular tissue preparations; the sensitivity was higher in atrial myocytes. The present study visualized the involvement of a propagated Ca2+-induced-Ca+ release mechanism in atrial but not ventricular myocytes. This difference may underlie some of the atrioventricular difference in response to physiological and pharmacological stimuli.


Spinal interneurone depression by DS103-282.
The depressant effect of 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiodiazole (DS103-282) on the polysynaptic excitation of interneurones in the cat spinal cord appears to be related to a postsynaptic reduction in the effectiveness of excitatory transmitters than to interference with their presynaptic release.


Assessment of Depression in Elderly. Is Perceived Social Support Related? A Nursing Home Study : Depression and Social Support in Elderly.
Geriatric depression is more common in nursing homes and social support is a mechanism that mitigates the stressors of life factors and simultaneously promotes wellness and health. The purpose of the study was to assess the levels of depression and social support among elderly in nursing homes. During the period February 2016-March 2016 170 elderly residents in nursing homes completed the Geriatric Depression Scale-15 (GDS-15) and the Multidimensional Scale of Perceived Social Support (MSPSS). Statistical analysis was conducted with IBM SPSS Statistics 23. 37, 1% of the sample had depressive symptoms. Depression is statistically correlated with age and it is affected by the years of education (p = 0.003), the number of the children (p = 0.006), whether the elderly person is bedridden or not (p < 0.001), the frequency of visits by family members (p < 0.001) and whether the elderly performs activities outside the nursing home (0.001). Higher GDS score had those who were illiterate (6.41), those with one or no children (6.82 and 6.59 respectively), the bedridden (6.70), people without visits from relatives (7.69) and without activities outside (5.64). Also, social support is affected by the family status (p < 0.001), the number of children (p < 0.001), the frequency of visits by relatives (p < 0.001) and whether the elderly performs activities outside the foundation (p < 0.008). Higher MSPSS score had those who were married (61.60), those who had four children (63.50), people who accept visits from relatives every day (64.58) and people who do activities outside the institution (58.07). The appearance of this increased rate of depression symptoms in this elderly population leads to the need for more aid social support.


Development and verification of a nomogram for predicting short-term mortality in elderly ischemic stroke populations.
Stroke is a major healthcare problem worldwide, particularly in the elderly population. Despite limited research on the development of prediction models for mortality in elderly individuals with ischemic stroke, our study aimed to address this knowledge gap. By leveraging data from the Medical Information Mart for Intensive Care IV database, we collected comprehensive raw data pertaining to elderly patients diagnosed with ischemic stroke. Through meticulous screening of clinical variables associated with 28-day mortality, we successfully established a robust nomogram. To assess the performance and clinical utility of our nomogram, various statistical analyses were conducted, including the concordance index, integrated discrimination improvement (IDI), net reclassification index (NRI), calibration curves and decision curve analysis (DCA). Our study comprised a total of 1259 individuals, who were further divided into training (n = 894) and validation (n = 365) cohorts. By identifying several common clinical features, we developed a nomogram that exhibited a concordance index of 0.809 in the training dataset. Notably, our findings demonstrated positive improvements in predictive performance through the IDI and NRI analyses in both cohorts. Furthermore, calibration curves indicated favorable agreement between the predicted and actual incidence of mortality (P > 0.05). DCA curves highlighted the substantial net clinical benefit of our nomogram compared to existing scoring systems used in routine clinical practice. In conclusion, our study successfully constructed and validated a prognostic nomogram, which enables accurate short-term mortality prediction in elderly individuals with ischemic stroke.


Pretreatment serum xanthophyll concentrations as predictors of head and neck cancer recurrence and survival.
The purpose of this study was to examine associations of pretreatment serum carotenoids, tocopherols, and quercetin with prognosis in 154 patients newly diagnosed with head and neck cancer. Pretreatment blood and health surveys were collected. Serum micronutrients were measured by high performance liquid chromatography. Data on recurrence and death were collected annually. Cox proportional hazards models measured associations of serum nutrient concentrations with recurrence and overall survival. During a median follow-up time of 37 months, there were 32 recurrences and 27 deaths. After controlling for covariates, subjects with high versus low serum xanthophyll and total carotenoid concentrations had significantly longer recurrence-free time (p = .002 and p = .02, respectively). Overall survival time was significantly longer in patients with high versus low serum xanthophyll concentrations (p = .02). Future research should evaluate the possible benefits of interventions to increase intakes of rich food sources of xanthophylls in this patient population. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1591-E1597, 2016.


Interactions of multilamellar phospholipid vesicles with bovine lymphocytes: effects of alpha-tocopherol on lymphocyte blastogenesis.
Multilamellar lipid vesicles (MLV) composed of egg yolk lecithin (EYL) suppressed the response of bovine peripheral blood lymphocytes (BPBL) to phytohemagglutinin (PHA). EYL contains 18:1 and 18:2 as the major unsaturated phospholipids. Dioleoyllecithin (DOL; cis 9) MLV did not suppress BPBL blastogenesis. Dilinoeyllecithin (DLL; cis, cis 9, 12) MLV suppressed BPBL blastogenesis. The suppressive effect could be reversed by increasing the MLV DML concentration. The addition of alpha-tocopherol (alpha-T) at 10 mole% into MLV containing DLL reversed blastogenic suppression of BPBL. MLV composed of mixed saturated phospholipids (dimyristoyllecithin and dipalmitoyllecithin) and alpha-T enhanced the BPBL blastogenic response to PHA. BPBL incubated with varying PHA concentrations (11.82-375 mg/ml) and a constant concentration (2 mumoles/ml) of MLV composed of EYL remained suppressed either when PHA and MLV were added simultaneously or when MLV were incubated for 1 hr prior to the addition of PHA. This suggests that alpha-T may act as an immunomodulator in the blastogenic response to PHA. Results suggest that alpha-T reversion of EYL suppression of BPBL blastogenesis may be due to interactions of alpha-T with unsaturated acyl chains in EYL phospholipids.


United States cosmetic ingredient labeling.
United States federal regulations require ingredient listing on cosmetics labeled after November 30, 1976. Standardized ingredient nomenclature from a reference text will be utilized to minimize confusion which might arise if various synonyms for chemical names were used. This new information on cosmetics labeling will assist physicians in the diagnosis of cosmetic-related dermatoses. It should facilitate the patch testing procedure by enabling the dermatologist to focus attention on suspect ingredients early in the evaluation. Once the identify of offending ingredients in a cosmetic has been determined for a particular patient, the individual will have the opportunity to avoid those ingredients and related ingredients in future purchases of cosmetics.


Hypoglycemic activity of the antioxidant saponarin, characterized as alpha-glucosidase inhibitor present in Tinospora cordifolia.
Tinospora cordifolia, used in anti-diabetic herbal drug preparations, was reported [12] to contain an alpha-glucosidase inhibitor, characterized as saponarin (apigenin-6-C-glucosyl-7-O-glucoside). The leaf extract had appreciable antioxidant and hydroxyl radical scavenging activities and contained the flavonoid in the range of 32.1 +/- 1.5-45.5 +/- 3.5 mg/g of dry solid. Saponarin showed mixed competitive inhibition on activities of alpha-glucosidase and sucrase of different origins. IC(50), Ki and ki' values determined were 48 muM, 8 muM and 19.5 microM respectively for intestinal maltase and 35 microM, 6 microM and 13 microM respectively for intestinal sucrase. When given orally to maltose-fed rat, saponarin showed hypoglycemic activity in the range of 20-80 mg/kg compared to 100-200 mg/kg for acarbose as reported.


Effects of Exercise Training and CPAP in Patients With Heart Failure and OSA: A Preliminary Study.
Exercise and CPAP improve OSA. This study examined the effects of exercise in patients with heart failure (HF) and OSA. Patients with HF and OSA were randomized to the following study groups: control, exercise, CPAP, and exercise + CPAP. Sixty-five participants completed the protocol. Comparing baseline vs 3 months, the mean apnea-hypopnea index (AHI) did not change significantly (in events per hour) in the control group, decreased moderately in the exercise group (28 ± 17 to 18 ± 12; P < .03), and decreased significantly more in the CPAP group (32 ± 25 to 8 ± 11; P < .007) and in the exercise + CPAP group (25 ± 15 to 10 ± 16; P < .007). Peak oxygen consumption, muscle strength, and endurance improved only with exercise. Both exercise and CPAP improved subjective excessive daytime sleepiness, quality of life, and the New York Heart Association functional class. However, compared with the control group, changes in scores on the 36-item Medical Outcomes Study Short Form Survey and Minnesota Living with Heart Failure Questionnaire were only significant in the exercise groups. In patients with HF and OSA, our preliminary results showed that exercise alone attenuated OSA and improved quality of life more than CPAP. In the landscape treatment of OSA in patients with HF, this analysis is the only randomized trial showing any treatment (in this case, exercise) that improved all the studied parameters. The results highlight the important therapeutic benefits of exercise, particularly because adherence to CPAP is low.


Surgical repair of the isolated incomplete median cleft lip.
Median cleft lip refers to a vertical cleft on the midline of the upper lip. It is a rare congenital craniofacial anomaly brought about by a fusion failure in the medial nasal prominence. A novel surgical approach to median cleft lips and their repair is reported herein, with reference to a clinical case. The patient had a cleft in the lower half of the upper lip. There were no other craniofacial anomalies in this patient other than the cleft. Within the framework of the patient's surgical treatment, a functional and cosmetically satisfactory result was achieved by performing a V-Y advancement flap on the columella base, Z-plasty in the vermillion zone, and Z pattern muscular tissue repair, without having to resort to any tissue excisions.


Santa Catharina and the origin of cloudy taenite in meteorites.
CLOUDY taenite appears as a dark-etching rim that occurs at the high nickel border of taenite fields in iron meteorites and mesosiderites. Transmission electron microscopy (TEM) shows it to consist of a foam-like association of interpenetrating single crystals of taenite and kamacite when well developed(1) with an orientation relationship between those of the Kurdjumow-Sachs and the Nishiyama(2). It occurs between compositional limits that have been reported as approximately 25-40% Ni(1) and 30-40% Ni(3). Observed taenite particle sizes range from 0.4 microm in the Estherville mesosiderite(1) to considerably less than 0.1 microm for many iron meteorites (unpublished data). The mechanism of cloudy taenite formation has not been previously explained, although it is believed(2) to be a phenomenon related to the Invar effect, which occurs in Fe-35% Ni (Invar) and several other alloy systems. Santa Catharina is a wholly taenitic anomalous iron meteorite that contains 35% Ni and 0.6% Co (ref. 4). This composition, which is very similar to that of Invar, places it well inside the range where cloudy taenite is known to form. The optical microstructure of Santa Catharina suggested that the matrix phase of the entire meteorite may consist of cloudy taenite, so I have now examined it by TEM and the results are reported here.


Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C.
Oxidative stress appears to initiate organ failure in sepsis, justifying treatment with antioxidants such as vitamin C at megadoses. We have therefore investigated the safety and efficacy of megadose sodium ascorbate in sepsis. Interventional study. Research Institute. Adult Merino ewes. Sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg). Sepsis-induced fever (41.4 ± 0.2°C; mean ± se), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial Po2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue Po2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01). Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary Po2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg). We confirmed these physiologic findings in a coronavirus disease 2019 patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours. IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.


Identification of peptides that bind to irradiated pancreatic tumor cells.
Peptides targeting tumor vascular cells or tumor cells themselves have the potential to be used as vectors for delivering either DNA in gene therapy or antitumor agents in chemotherapy. We wished to determine if peptides identified by phage display could be used to target irradiated pancreatic cancer cells. Irradiated Capan-2 cells were incubated with 5 x 10(12) plaque-forming units of a phage display library. Internalized phage were recovered and absorbed against unirradiated cells. After five such cycles of enrichment, the recovered phage were subjected to DNA sequencing analysis and synthetic peptides made. The binding of both phage and synthetic peptides was evaluated by fluorescence staining and flow cytometry in vitro and in vivo. We identified one 12-mer peptide (PA1) that binds to irradiated Capan-2 pancreatic adenocarcinoma cells but not to unirradiated cells. The binding of peptide was significant after 48 h incubation with cells. In vivo experiments with Capan-2 xenografts in nude mice demonstrated that these small peptides are able to penetrate tumor tissue after intravenous injections and bind specifically to irradiated tumor cells. These data suggest that peptides can be identified that target tumors with radiation-induced cell markers and may be clinically useful.


Amperometric immunosensor for the determination of IgA deficiency in human serum samples.
An electrochemical immunosensor for the detection of human IgA deficiency in real human blood serum has been developed. The performance of the immunosensor presents a large but sensitive dynamic range that allows the determination of non-deficient IgA levels (>70 μg/mL) as well as of severe IgA deficiencies (0.5-5.0 μg/mL). The assay architecture involves the immobilisation of a coating antibody on an electrode surface using carboxylic-ended bipodal alkane-thiol self-assembled monolayers (SAMs). The long chain bipodal SAM presents intercalated poly(ethylenglycol) groups that confer the immunosensor the ability to retain its optimum performance in very complex matrices and serum with negligible non-specific adsorption phenomena. Amperometric optimisation of the assay resulted in limits of detection of 142 ng/mL in just 30 min total assay time. Real patients' serum samples were analysed using the developed electrochemical immunosensor demonstrating an excellent correlation in terms of sensitivity and reproducibility compared with standard enzyme linked immunosorbent assays (ELISA).


Polymorphism at the tetranucleotide repeat locus DYS389 in 10 populations reveals strong geographic clustering.
Several short tandem repeat polymorphism loci at the non-recombining part of the Y chromosome have been described recently and are now widely used for the investigation of the history and the diversity of man. The tetranucleotide repeat polymorphism at the DYS389 locus consists of two repetitive stretches with different numbers of (TCTG)n (TCTA)m repeat units. To study the overall variability of this locus, 768 alleles from males from 10 human populations (two sub-Saharan African, four Caucasoid and four Asian/Amerind populations) were investigated. The alleles found in the populations of different geographic origin exhibited remarkable differences in the number and arrangement of repeats in the two repetitive stretches and up to nine different sequence variants for a single fragment length have been detected. So far 53 different alleles, i.e. haplotypes, have been observed. Analysis of molecular variance (AMOVA) indicates that at least 24.5% of the total genetic variance was found between the populations and that these differences were significant in most pairwise comparisons. We propose a model, in which both founder effects and genetic drift together with single step replication slippage mutations explain the picture of haplotype diversity observed with this single locus.


Chemical and Radiation-Associated Jaw Lesions.
Osteonecrosis of the jaw is a major public health concern throughout the world. Use of radiotherapy for head and neck cancer and bone antiresorptives and antiangiogenic agents have increased its incidence. Medication-related osteonecrosis of the jaw is more common relative to other types of osteonecrosis. Osteoradionecrosis occurs despite better treatment planning and shielding to minimize collateral damage to bone. Other related necrotic lesions are secondary to usage of recreational drugs and steroids. This article provides comprehensive information about these different types of bone necrosis; provides the readers with radiographic diagnostic criteria and updates on current theories on pathophysiology of osteonecrosis.


Prevention of onychomycosis reinfection for patients with complete cure of all 10 toenails: results of a double-blind, placebo-controlled, pilot study of prophylactic miconazole powder 2%.
The objective of this 2-year, double-blind, placebo-controlled, randomized trial involving 48 participants was to determine if biweekly miconazole powder prevents onychomycosis recurrence. Intent-to-treat analysis found no significant differences in mycologic, clinical, or complete onychomycosis reinfection rates or time to reinfection. Limitations include small sample size and dosing regimen.


Phospholipid methylation in myogenic cells.
The biosynthesis of phosphatidylcholine from successive N-methylation of phosphatidylethanolamine has been implicated as a major mechanism for the transduction of several receptor-mediated signals including beta-adrenergic coupling to adenylate cyclase. In this report we demonstrate L-isoproterenol stimulation of adenylate cyclase activity in two myogenic cell lines, L8 and BC3H-1. Using a sensitive high performance liquid chromatography method for qualitative and quantitative determination of phospholipids we found an active membrane phospholipid methylation pathway in these cells. Despite beta-adrenergic simulation of adenylate cyclase no alteration in the transmethylation pathway could be demonstrated.


Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects.
1. Binding of the novel radioligand (3)H-2-(2-dimethylaminomethyl-phenylsulphanyl)-5-methyl-phenylamine ((3)H-MADAM) to the serotonin transporter (SERT) was used to characterise a range of selective serotonin re-uptake inhibitors (SSRIs) in vitro and in vivo. 2. (3)H-MADAM bound with high affinity in a saturable manner to both human SERT expressed in CHO cells (K(d)=0.20 nm (pK(d)=9.74+/-0.12), B(max)=35+/-4 fmol mg(-1) protein) and mouse cerebral cortex membranes (K(d)=0.21 nm (pK(d)=9.66+/-0.10), B(max)=50+/-24 fmol mg(-1) protein). 3. Binding of (3)H-MADAM was highly selective for SERT in vitro as demonstrated by the in vitro profile of MADAM tested at 75 different receptors, ion channels and transporters. This was further substantiated by the pharmacological profile of the binding. Hence, the binding of (3)H-MADAM was potently inhibited by SSRIs but not by selective inhibitors of noradrenaline transport and dopamine transport. Likewise, a 5-HT(2A/2C) receptor antagonist did not inhibit (3)H-MADAM binding. 4. (3)H-MADAM binding in vivo was inhibited only by compounds which also inhibited the binding of (3)H-MADAM in vitro (the SSRIs, mixed SERT/noradrenaline transport inhibitors and clomipramine), confirming the selectivity of (3)H-MADAM for SERT also in vivo. Moreover, compounds effective in inhibiting (3)H-MADAM binding were the only ones found to be active in the mouse 5-HTP potentiation test confirming the model as a behavioural correlate to in vivo 5-HT uptake. 5. Finally, it was found that a SERT occupancy of 85-95% was necessary to produce 50% of the maximum behavioural response (ED(50)).


Oral motor feeding in the neonatal intensive care unit: exploring perceptions of parents and occupational therapists.
The purpose of this qualitative study was to explore the perceptions of three occupational therapists and three parents regarding occupational therapy services provided in the neonatal intensive care unit. Data were obtained through participant interviews. Role of the occupational therapist, parent training, and time spent with parents were themes that emerged from the therapist interviews. Themes from the parent interviews included occupational therapy intervention and treatment, time spent with occupational therapist, and perceptions. A cross-case analysis addressed two common themes: amount of time spent in parent training and perceptions of training provided. Implications for occupational therapy practice in the neonatal intensive care unit are discussed.


Arsenite and cadmium, but not chromium, induce NAD(P)H:quinone oxidoreductase 1 through transcriptional mechanisms, in spite of post-transcriptional modifications.
NAD(P)H:quinone oxidoreductase (Nqo1)-mediated detoxification of quinones plays a critical role in cancer prevention. Metals alter the carcinogenicity of AhR ligands, such as TCDD, by modulating the induction of Nqo1, but the mechanism(s) remain unresolved. To decipher the molecular mechanisms involved in the alteration of Nqo1, we analyzed the effect of the metals As3+ (5 microM), Cd2+ (5 microM), and Cr6+ (25 microM) on the transcriptional activation of the Nqo1 gene and post-transcriptional modifications, in Hepa 1c1c7 cells. Both As3+ and Cd2+ induced Nqo1 mRNA in a time-dependent manner and potentiated TCDD-induced Nqo1 mRNA. Cr6+ on the other hand, completely inhibited the induction of Nqo1 mRNA by TCDD. The induction of Nqo1 mRNA by the metals was completely inhibited with the DNA transcription inhibitor actinomycin-D, indicating a requirement for de novo mRNA synthesis for the induction. Furthermore, the protein synthesis inhibitor cycloheximide decreased Nqo1 mRNA induction, suggesting a role for a labile protein in the transcriptional induction of Nqo1 mRNA by metals. Surprisingly, all three metals decreased Nqo1 mRNA stability while having no effect on Nqo1 protein half-life. Meanwhile, As3+ and Cd2+ induced constitutive Nqo1 activity and potentiated the induction by increasing concentrations of TCDD. On the other hand, Cr6+ inhibited inducible Nqo1 activity. It is apparent that metals alter Nqo1 expression at the transcriptional level, through a labile protein-mediated pathway.


Elevated levels of the pro-carcinogenic adduct, O(6)-methylguanine, in normal DNA from the cancer prone regions of the large bowel.
The pro-mutagenic lesion O(6)-methyldeoxyguanosine (O(6)-MedG), a marker of exposure to many N-nitroso compounds (NOC), can be detected in normal and tumour DNA isolated from colorectal tissue. The biological significance of this exposure is, as yet, unknown but in situ NOC formation is bacterially catalysed suggesting that NOC formation and potentially DNA alkylation will vary throughout the large bowel. To determine if O(6)-MedG levels in colorectal DNA vary within the large bowel. We studied 62 men and women undergoing surgery for colorectal tumours in the north west of England. O(6)-MedG levels were measured in paired normal and tumour DNA samples. DNA was digested to nucleosides, fractionated by HPLC, and purified O(6)-MedG quantified by a radioimmunoassay. O(6)-MedG was detected in 27 out of a total of 62 (43%) normal DNA samples and in 30 of 58 (52%) tumour DNA samples: it was present at concentrations of <0. 01-0.94 and <0.01-0.151 micromol O(6)-MedG/mol deoxyguanosine for normal and tumour DNA, respectively. Levels of O(6)-MedG in normal, but not tumour, DNA from the proximal colon were lower than those found in DNA from either the sigmoid colon (p=0.03) or rectum (p=0. 05). When the analysis was restricted to samples that contained O(6)-MedG, similar results were obtained in that O(6)-MedG levels in normal DNA were lower in the proximal colon than in the sigmoid colon (p=0.04) or rectum (p=0.03). DNA alkylation varied within the large bowel possibly due to in situ NOC formation and was highest in areas of the colon and rectum where the highest incidence of large bowel tumours occurs, suggesting that DNA alkylation may play a role in the aetiology of colorectal cancer.


Synthesis of heat shock proteins in dissociated sea urchin embryonic cells.
Embryos dissociated into cells retain the stage-specific response to heat shock. The dissociated cells, irrespectively of whether they are reaggregated or not, undergo the developmental changes in their ability to respond to heat shock, at the same time as the entire embryos. The conclusion of the present experiments is that sea urchin embryonic cells become responsive to heat shock and produce heat shock proteins even in the absence of cell interactions.


Gastrointestinal ulcerations induced by anti-inflammatory drugs in rats. Physicochemical and biochemical factors involved.
Aspirin, diclofenac, diflunisal, ibuprofen and indomethacin were given orally or intravenously to fasted or fed rats. The resulting gastric and intestinal damage was assessed using standard methods. The same drugs were administered to rats with biliary fistulas, and the fraction of drug excreted in bile was quantified using HPLC methods. We found that gastric damage occurred only in the fasted animals and was found to be dose-dependent and related to the amount (r = 0.871) and solubility (r = 0.909) of the individual drug. As far as acute gastric toxicity is concerned, neither the potency of a drug as an inhibitor of cyclo-oxygenase nor the fraction of unchanged or conjugated agent excreted in bile appeared to be relevant. Secondly, ulcerations of the small intestine occurred in fed animals only. The degree of damage was related to the amount of unchanged or conjugated drug excreted in bile and cyclo-oxygenase inhibitory potency (r = 0.873). The administered dose (within the range investigated) and drug solubility appeared not to contribute to intestinal toxicity. It is concluded that, in the rat, acute gastric and intestinal toxicity of non-steroidal anti-inflammatory drugs are due to different mechanisms. Whereas gastric toxicity is strongly influenced by the amount of drug dissolved under the pH conditions in the stomach, intestinal toxicity appears to depend on biliary excretion and enterohepatic circulation of a drug as well as on its potency as an inhibitor of prostaglandin synthesis.


Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B' subunits in active complexes and induces nuclear aberrations and a G1/S phase cell cycle arrest.
Cyclin G2, together with cyclin G1 and cyclin I, defines a novel cyclin family expressed in terminally differentiated tissues including brain and muscle. Cyclin G2 expression is up-regulated as cells undergo cell cycle arrest or apoptosis in response to inhibitory stimuli independent of p53 (Horne, M., Donaldson, K., Goolsby, G., Tran, D., Mulheisen, M., Hell, J. and Wahl, A. (1997) J. Biol. Chem. 272, 12650-12661). We tested the hypothesis that cyclin G2 may be a negative regulator of cell cycle progression and found that ectopic expression of cyclin G2 induces the formation of aberrant nuclei and cell cycle arrest in HEK293 and Chinese hamster ovary cells. Cyclin G2 is primarily partitioned to a detergent-resistant compartment, suggesting an association with cytoskeletal elements. We determined that cyclin G2 and its homolog cyclin G1 directly interact with the catalytic subunit of protein phosphatase 2A (PP2A). An okadaic acid-sensitive (<2 nm) phosphatase activity coprecipitates with endogenous and ectopic cyclin G2. We found that cyclin G2 also associates with various PP2A B' regulatory subunits, as previously shown for cyclin G1. The PP2A/A subunit is not detectable in cyclin G2-PP2A-B'-C complexes. Notably, cyclin G2 colocalizes with both PP2A/C and B' subunits in detergent-resistant cellular compartments, suggesting that these complexes form in living cells. The ability of cyclin G2 to inhibit cell cycle progression correlates with its ability to bind PP2A/B' and C subunits. Together, our findings suggest that cyclin G2-PP2A complexes inhibit cell cycle progression.


Immunogenicity of random polymers of l-glutamic acid, l-alanine and l-tyrosine in inbred hamsters.
The random terpolymer GAT has been found to be immunogenic in hamsters whereas the random copolymers GA or GT were found to be nonimmunogenic. Although no immune responses to GA or GT could be elicited, the anti-GAT antibody response contained populations inhibited specifically by GA, GT and poly-G. These data suggest that in hamsters, recognition of GAT occurs via determinants which are not present in GA or GT.


Linked patterns of interhemispheric functional connectivity and microstructural characteristics of the corpus callosum in antipsychotic-naive first-episode schizophrenia.
Many magnetic resonance imaging (MRI) studies have showed significant structural abnormalities of the corpus callosum (CC) and dysregulated interhemispheric functional connectivity (FC) in schizophrenia. Although the hemispheres are mainly linked through CC, few studies directly examined the relationship between aberrant interhemispheric FC and the white matter deficits of the CC in schizophrenia. One hundred and sixty-nine antipsychotic-naive first-episode schizophrenia patients (AN-FES) and 214 healthy controls (HCs) were recruited. Diffusional and functional MRI data were obtained for each participant, and fractional anisotropy (FA) values of the five CC subregions and interhemispheric FC for each participant were acquired. Between-group differences in these metrics were compared using multivariate analysis of covariance (MANCOVA). Moreover, sparse canonical correlation analysis (sCCA) was conducted to explore correlations of fibers integrity of the CC subregions with dysregulated interhemispheric FC in patients. Compared with HCs, the patients with schizophrenia showed significantly reduced FA values of the CC subregions and dysregulated connectivity between two cerebral hemispheres. The canonical correlation coefficients identified five significant sCCA modes between FA and FC (r > 0.75, p < 0.001), suggesting strong relationships between FA values of the CC subregions and interhemispheric FC in patients. Our findings support a key role of CC in maintaining ongoing functional communication between two cerebral hemispheres, and suggest that microstructural changes of white matter fibers crossing different CC subregions may affect special interhemispheric FC in schizophrenia.


Factors Associated With Burnout and Stress in Trainee Physicians: A Systematic Review and Meta-analysis.
Evidence suggests that physicians experience high levels of burnout and stress and that trainee physicians are a particularly high-risk group. Multiple workplace- and non-workplace-related factors have been identified in trainee physicians, but it is unclear which factors are most important in association with burnout and stress. Better understanding of the most critical factors could help inform the development of targeted interventions to reduce burnout and stress. To estimate the association between different stressors and burnout/stress among physicians engaged in standard postgraduate training (ie, trainee physicians). Medline, Embase, PsycINFO, and Cochrane Database of Systematic reviews from inception until April 30, 2019. Search terms included trainee, foundation year, registrar, resident, and intern. Studies that reported associations between stressors and burnout/stress in trainee physicians. Two independent reviewers extracted the data and assessed the quality of the evidence. The main meta-analysis was followed by sensitivity analyses. All analyses were performed using random-effects models, and heterogeneity was quantified using the I2 statistic. The main outcome was the association between burnout/stress and workplace- or non-workplace-related factors reported as odds ratios (ORs) and their 95% CIs. Forty-eight studies were included in the meta-analysis (n = 36 266, median age, 29 years [range, 24.6-35.7 years]). One study did not specify participants' sex; of the total population, 18 781 participants (52%) were men. In particular, work demands of a trainee physician were associated with a nearly 3-fold increased odds for burnout/stress (OR, 2.84; 95% CI, 2.26-3.59), followed by concerns about patient care (OR, 2.35; 95% CI, 1.58-3.50), poor work environment (OR, 2.06; 95% CI, 1.57-2.70), and poor work-life balance (OR, 1.93; 95% CI, 1.53-2.44). Perceived/reported poor mental or physical health (OR, 2.41; 95% CI, 1.76-3.31), female sex (OR, 1.34; 95% CI, 1.20-1.50), financial worries (OR, 1.35; 95% CI, 1.07-1.72), and low self-efficacy (OR, 2.13; 95% CI, 1.31-3.46) were associated with increased odds for burnout/stress, whereas younger age and a more junior grade were not significantly associated. The findings of this study suggest that the odds ratios for burnout and stress in trainee physicians are higher than those for work-related factors compared with nonmodifiable and non-work-related factors, such as age and grade. These findings support the need for organizational interventions to mitigate burnout in trainee physicians.


Implementing person-centered communication in diabetes care: a new tool for diabetes care professionals.
This study tested the clinical implementation of the CoMac Communication System, an empirically validated tool for individualized Diabetes Self-Management Education and Support (DSMES). This system provides immediate feedback and guidance to health care providers (HCPs) to facilitate speaking with persons with type 2 diabetes mellitus in language reflecting patients' own worldviews and health beliefs. This 6-month implementation science study at an accredited diabetes care clinic in a Midwestern US hospital was conducted in two phases. Phase I consisted of CoMac implementation, qualitative interviews with HCPs, and evaluation of clinic flow among the diabetes education team. Seventy-two participants received CoMac's linguistically tailored patient-centric communication; a control group of 48 did not receive this intervention. In Phase II, glycosylated hemoglobin A1c (HbA1c) levels from the first visit to the follow-up visit for each group were compared. Interviews conducted during Phase I suggested that the system can be successfully implemented into DSMES practice. Knowing individual psychosocial profiles and participants' language use allowed for more effective patient counseling. In Phase II, multiple regression analysis with HbA1c change as the dependent variable showed that the key variable of interest, treated with the CoMac intervention, had a one-tailed t-value of -1.81, with a statistically significant probability value of 0.037. Findings suggest that use of the CoMac System by diabetes care professionals has the potential for improved patient health outcomes. Patients receiving the CoMac intervention showed significantly improved HbA1c levels, suggesting that this approach has great promise for effective DSMES management.


Identification of a tumor marker chromosome by flow sorting, DNA amplification in vitro, and in situ hybridization of the amplified product.
A method combining flow sorting and molecular cytogenetic techniques for the identification of unknown marker chromosomes is described. In this study, the bladder tumor cell line J82 was used, which was known to carry a marker chromosome of the size of chromosome 7 in every cell. From the cytogenetic analysis of Q-banded metaphase cells, it was shown to be composed of approximately 40% presumably the greater part of chromosome 20 and for the rest microscopically unidentifiable material. This marker chromosome was found using flow cytometric analysis to form an independent peak and hence was suitable for isolation using dual-parameter sorting after staining with Hoechst 33258 and chromomycin A3. Subsequently, the marker was isolated by dual-parameter sorting. DNA amplification of 300 isolated chromosomes by polymerase chain reaction (PCR) using the Alu-primer Bk33 and the LINES-primer LH5 was carried out. After purification of the amplified product, a yield of 5 microns of DNA was obtained. The DNA was labelled using Bio-11-dUTP and applied to human lymphocyte metaphase cells in a suppressive in situ hybridization procedure. Fluorescence was visible over chromosome 20 and over the distal one-half of 6p. Together the fluorescent regions accounted for only approximately 60% of the marker length, indicating a possible duplication of chromosome 20 material. This was confirmed by applying bicolor in situ hybridization using chromosome 6- and 20-specific DNA libraries to metaphase cells of the J82 cells.


A novel approach to surface electromyography: an exploratory study of electrode-pair selection based on signal characteristics.
A 3×4 electrode array was placed over each of seven muscles and surface electromyography (sEMG) data were collected during isometric contractions. For each array, nine bipolar electrode pairs were formed off-line and sEMG parameters were calculated and evaluated based on repeatability across trials and comparison to an anatomically placed electrode pair. The use of time-domain parameters for the selection of an electrode pair from within a grid-like array may improve upon existing electrode placement methodologies.


Mechanistic studies of uridine diphosphate glucuronosyltransferase.
Bisubstrate reaction kinetics and product inhibition studies were used to characterize the kinetic mechanism of a partially purified uridine diphosphate glucuronosyltransferase (UDPGT). These studies indicate that the reaction most likely occurs via a random order sequential mechanism. The effect of electron withdrawing and donating groups on the rate of reaction was also determined. It was found that electron donating groups increased the rate of glucuronide conjugation. This result is consistent with nucleophilic attack of the C-1 carbon of the UDP-glucuronic acid (UDPGA) by an SN2 mechanism. This is the first direct evidence for a SN2 mechanism in UDPGT catalysis.


Glycosyltransferase-related prognostic and diagnostic biomarkers of uterine corpus endometrial carcinoma.
Uterine corpus endometrial carcinoma (UCEC) has a strong ability of invasion and metastasis, high recurrence rate, and poor survival. Glycosyltransferases are one of the most important enzymes that coordinate the glycosylation process, and abnormal modification of proteins by glycosyltransferases is closely related to the occurrence and development of cancer. However, there were fewer reports on glycosyltransferase related biomarkers in UCEC. In this paper, based on the UCEC transcriptome data published on The Cancer Genome Atlas (TCGA), we predicted the relationship between the expression of glycosyltransferase-related genes (GTs) and the diagnosis and prognosis of UCEC using bioinformatics methods. And validation of model genes by clinical samples. We used 4 methods: generalized linear model (GLM), random forest (RF), support vector machine (SVM) and extreme gradient boosting (XGB) to screen biomarkers with diagnostic significance, and the binary logistic regression was used to establish a diagnostic model for the 2-GTs (AUC = 0.979). And the diagnostic model was validated using a GEO external database (AUC = 0.978). Moreover, a prognostic model for the 6-GTs was developed using univariate, Lasso, and multivariate Cox regression analyses, and the model was made more stable by internal validation using the bootstrap. In addition, risk score is closely related to immune microenvironment (TME), immune infiltration, mutation, immunotherapy and chemotherapy. Overall, this study provides novel biomarkers for the diagnosis and prognosis of UCEC, and the models established by these biomarkers can also provide a good reference for individualized and precision medicine in UCEC.


Automatic evaluation of arterial diameter variation from vascular echographic images.
An automatic procedure for accurate arterial diameter evaluation from B-mode images obtained by diagnostic ultrasound systems is presented. It is used for measuring brachial artery dilation following reactive hyperemia induced by forearm ischemia, which is an appropriate parameter to study endothelial function in humans. B-mode images obtained from the diagnostic ultrasound system are acquired on a personal computer as grey intensity fields (pixels). A completely automatic algorithm is then applied and the artery walls are identified by two discrete sets of points. Artery diameter is evaluated by parabolic least-square approximation. The accuracy and extensive range of applicability of the diameter evaluation procedure were demonstrated both by preliminary analytic test cases and in vivo analyses. Reproducibility of the diameter estimate was assessed by in vivo measurements. The proposed procedure permits fast and accurate analysis of large amounts of data, because it requires no action by the operator. It thus represents a valuable tool for assessment of endothelium-dependent vasodilation, especially in large, multicentric clinical trials.


Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice.
We evaluated the protective effect of dietary extra virgin olive oil (EVOO) polyphenol extract (PE) supplementation in the inflammatory response associated to chronic colitis model. Six-week-old mice were randomized in four dietary groups: standard diet (SD), EVOO diet and both enriched with PE (850 ppm) (SD+PE and EVOO+PE). After 30 days, animals that were exposed to dextran sodium sulfate (DSS) (3%) followed by 3 weeks of drinking water developed chronic colitis, which was evaluated by disease activity index (DAI) and histology. Cell proliferation was analyzed by immunohistochemical and changes in monocyte chemotactic protein (MCP)-1 and tumor necrosis factor (TNF)-α mRNA expression by quantitative real-time polymerase chain reaction. Colonic expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs), IκBα inhibitory and peroxisome proliferator-activated receptor gamma (PPARγ) were determined by western blotting. SD-DSS group showed a significant increase of DAI, histological damage and cell proliferation, as well as an up-regulation of TNF-α, MCP-1, COX-2 and iNOS proteins. p38 and JNK MAPKs phosphorylation, IκBα degradation and PPARγ deactivation were also observed. However, in DSS-treated and EVOO+PE-fed mice, DAI and cell proliferation were significantly reduced, as well as MCP-1, TNF-α, COX-2 and iNOS expression levels. In addition, this dietary group, notably down-regulated JNK phosphorylation, prevented IκBα degradation and PPARγ deactivation. These results demonstrated, for the first time, that EVOO-PE supplementation possessed marked protective effects on experimental colitis through PPARγ up-regulation and nuclear transcription factor-kappa B and MAPK signaling pathway inhibition, decreasing the inflammatory cascade. We concluded that PE-enriched EVOO diet could be a beneficial functional food on ulcerative colitis.


Chromosomal deletion and plasmid complementation of the photosynthetic reaction center and light-harvesting genes from Rhodopseudomonas capsulata.
Using in vitro interposon mutagenesis, Rhodopseudomonas capsulata strains have been constructed wherein all or part of the reaction center (RC), light-harvesting I (LHI), and light-harvesting II (LHII) structural genes have been deleted. In one series of strains, the 2778-bp ApaI fragment bearing more than 90% of the rxcA operon (promoter and structural genes coding for LHI beta, LHI alpha, RC-L and RC-M) has been deleted from the chromosome. When the rxcA operon is deleted, resultant strains possess only LHII and are photosynthetically defective. The rxcA deletion in an LHII- background results in a strain lacking all LH antennae and RC subunits. As expected this strain has no near-infrared absorption characteristic of LH or RC bacteriochlorophyll. The rxcA deletion may be complemented by a pBR322 derivative carrying the entire rxcA operon (pU21). In a second series of deletion mutants, the 2500-bp BstEII-StuI fragment, including the beta and alpha structural genes coding for LHII has been deleted from the chromosome. In the wild-type background, functional RC and LHI are synthesized. LHII may be restored in the deletion strain by conjugal transfer of the plasmid pU2 which carries the LHII operon.


Distal penile prosthesis extrusion: treatment with distal corporoplasty or Gortex windsock reinforcement.
Subcutaneous extrusion of penile prosthesis cylinders beneath the glans penis is an unusual but difficult complication of penile prosthesis. Without surgical repair, extrusion, infection, and corporeal fibrosis may ensue. Twenty-eight patients with distal corporeal extrusion were reviewed to identify the optimum treatment outcome for these penile prosthesis complications. Records of 28 men with subcutaneous distal penile prosthesis cylinder extrusion were reviewed. Mean age was 56.2 y. Etiology of erectile dysfunction was diabetes mellitus in 11, vasculogenic in 10, Peyronie's disease in five, radical pelvic surgery in five. Duration of penile prosthesis was 8-72 months (mean 42.6). No patient had penile prosthesis infection or device exposure through the skin. Distal corporoplasty was treated on 18/28 men using cylinder repositioning and direct tunica albuginea repair. Ten men underwent repair using a Gortex windsock. 8/18 corporoplasty and 6/10 windsock patients required glans fixation for treatment of hypermobile glans following cylinder relocation. In two patients with windsock repair, extrusion recurrence occurred 6 and 18 months following surgery and 1/6 had post operative infection requiring prosthesis removal. Mean surgical time for corporoplasty was 52.8 minutes while windsock reconstruction was 89.6 minutes. Distal subcutaneous penile prosthesis cylinder extrusion produces coital pain and predisposes to cylinder exposure and infection. Early repair with or without additional prosthetic materials will return penile prostheses to a normal functioning state. Distal corporoplasty with cylinder repositioning appears to be a simple, low morbidity solution to this difficult dilemma. Outcomes with distal corporoplasty result in better function, less pain, and fewer recurrences than Gortex windsock repair.


Truncated phosphonated C-1'-branched N,O-nucleosides: a new class of antiviral agents.
Truncated phosphonated C-1'-branched N,O-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology, starting from N-methyl-C-(diethoxyphosphoryl)nitrone 7. Preliminary biological assays show that β-anomers are able to inhibit HIV in vitro infection at concentrations in the micromolar range. Higher SI values with respect to AZT indicated that the compounds were endowed with low cytotoxicity.


A Mixed-Methods Research Framework for Healthcare Process Improvement.
The healthcare system in the United States is spiraling out of control due to ever-increasing costs without significant improvements in quality, access to care, satisfaction, and efficiency. Efficient workflow is paramount to improving healthcare value while maintaining the utmost standards of patient care and provider satisfaction in high stress environments. This article provides healthcare managers and quality engineers with a practical healthcare process improvement framework to assess, measure and improve clinical workflow processes. The proposed mixed-methods research framework integrates qualitative and quantitative tools to foster the improvement of processes and workflow in a systematic way. The framework consists of three distinct phases: 1) stakeholder analysis, 2a) survey design, 2b) time-motion study, and 3) process improvement. The proposed framework is applied to the pediatric intensive care unit of the Penn State Hershey Children's Hospital. The implementation of this methodology led to identification and categorization of different workflow tasks and activities into both value-added and non-value added in an effort to provide more valuable and higher quality patient care. Based upon the lessons learned from the case study, the three-phase methodology provides a better, broader, leaner, and holistic assessment of clinical workflow. The proposed framework can be implemented in various healthcare settings to support continuous improvement efforts in which complexity is a daily element that impacts workflow. We proffer a general methodology for process improvement in a healthcare setting, providing decision makers and stakeholders with a useful framework to help their organizations improve efficiency.


Guidelines for hurricane and disaster preparation for animal facilities.
Animal facilities are vulnerable to hurricanes and other natural disasters, which can endanger lives and disrupt critical animal care routines. Facility managers must therefore prepare a rigorous emergency plan that ensures human safety while considering the specific needs of all animals on site. The author presents guidelines and recommendations for disaster preparedness based on her experience at a facility in Florida, where hurricanes are relatively common. An effective plan must include a priority system, a well-trained emergency response team, efficient communication methods and concrete provisions for animals and employees.


Evaluation of narrow-band imaging in the diagnosis of sinonasal inverted papilloma.
Narrow-band imaging (NBI) can be used to differentiate benign sinonasal lesions NBI can be used in the preoperative identification of sinonasal inverted papilloma Future studies can focus on NBI for recurrent inverted papilloma and surgical margin guidance.


Adenocarcinoma of the uterine cervix, gastric-type (GAS): a review of the literature focused on pathology and multimodality imaging.
Adenocarcinoma of the uterine cervix, gastric-type (GAS) is a rare, well-differentiated subtype of HPV-independent endocervical adenocarcinoma. It classically arises in middle-aged women with symptoms, including profuse watery vaginal discharge and abnormal uterine bleeding. Given the rarity of this disease, misdiagnosis is common and prognosis remains poorly defined. Distinct pathology and imaging findings can aid in diagnosis. A literature review was performed to ascertain recurring pathologic and radiologic characteristics of GAS. Key pathologic features of GAS include cytologically benign appearing mucinous glands that infiltrate into the deep stroma and may demonstrate lymphovascular or perineural invasion. Multiple imaging modalities including transvaginal ultrasound, CT, and MRI may aid in diagnosis of GAS, which characteristically is seen as a multicystic mass with solid components. MRI in particular is the preferred imaging study because it offers the best chance of identifying a potential solid component, which is key to making the diagnosis of GAS and distinguishing it from other endocervical diseases processes. Careful attention to histopathologic and radiologic details, in conjunction with clinical correlation, is necessary to distinguish GAS from other multicystic cervical lesions.


Compliance With Opioid Disposal Following Opioid Disposal Education in Surgical Patients: A Systematic Review.
The present opioid epidemic in the United States is a significant cause for concern in healthcare. In 1995, the concept of pain was introduced as the fifth vital sign. Since then, the sales of opioids have increased dramatically, as have the number of opioid deaths. The misuse and diversion of retained opioids following surgical procedures contribute to the problem. The objective of this project was to review the latest scholarly work and evaluate the findings related to patient education and disposal of opioid medications to decrease opioid misuse and increase disposal. A systematic review. The systematic search strategy included PubMed, Ovid Technologies (OVID), and Cumulative Index of Nursing and Allied Health Literature (CINAHL) electronic databases. A total of 4 randomized controlled trials (RCTs), 2 quasi-experimental studies, and 2 quality improvement projects met the criteria for inclusion. The studies found that as many as 92% of patients had leftover unused opioids. The retention rate of opioids among surgical patients was found to be 33 to 95%. When educational material was provided about disposal, the studies found that the disposal rate was as high as 71%. Patient education about opioid misuse, diversion, and disposal are essential topics that need to be addressed with patients and caregivers.


Complete genome sequence of Arthrobacter sp. ZXY-2 associated with effective atrazine degradation and salt adaptation.
An atrazine-degrading strain Arthrobacter sp. ZXY-2 was originally isolated from Jilin Pesticide Plant (China). Strain ZXY-2 demonstrated excellent atrazine degradation performance and saline tolerance. Here we report the complete genome sequence of strain ZXY-2 contained a circular chromosome and five circular plasmids encoding for the mechanism of salt adaptation and pollutant degradation.


Diversion of opioid maintenance treatment medications and predictors for diversion among Finnish maintenance treatment patients.
Diversion (i.e. selling or giving away) of opioid maintenance treatment (OMT) medications is a challenge that concerns many units providing OMT worldwide and tools for prevention are needed. The object of this study was to examine the prevalence and predictors for diversion of the OMT medications buprenorphine-naloxone (BNX) and methadone (MET) among Finnish OMT patients. A cross-sectional study was conducted among all Finnish OMT patients of whom 60% (n=1508) participated. The data were collected by anonymous questionnaires distributed through all OMT units in Finland. To evaluate predictors for diversion, we used binominal regression analysis with unadjusted and adjusted ORs. Selling and/or giving away of OMT medication was used as a dependent variable and explanatory variables were gender, age, duration of OMT, type of OMT medication and dose, dispensation method of OMT medication, place of residence and intravenous use of any intoxicating drugs during the past six months. Of all 1508 respondents, 7% (n=100) had sold and 12% (n=169) had given their OMT medication to others, 57% for money and 23% in exchange for other drugs. In multivariate analysis, predictors associated with diversion were BNX as OMT medication (OR 2.76, 95% CI 1.76-4.33), low (<9.0mg/day) BNX dose (OR 1.74, 95% CI 1.01-2.98), intravenous use of intoxicating drugs during the past six months (OR 4.48, 95% CI 3.13-6.43) and increasing length of OMT (OR 1.01, 95% CI 1.01-1.02). Age, place of residence or unsupervised pharmacy distribution of BNX were not associated with diversion. In order to reduce diversion, more interventions are needed to support patients to stop concurrent substance abuse. Increasing control measures, for example, increased supervision, are unlikely to prevent diversion. Given that sub-optimal dosing of BNX increases the risk of diversion, more attention should be paid to providing patients with an optimal medical dose.


The impact of the mass media on obstetricians' behavior in Norway.
Little is known about how physicians and hospitals respond to the risk of being negatively exposed in the mass media. We assume that newspapers will cover events more closely in the areas where they have most of their circulation. Within such areas the likelihood of negative publicity increases. The research question is whether obstetricians respond to negative newspaper coverage by choosing the least risky method of delivery, i.e. Caesarean section. This was tested on a large set of data from the Medical Birth Registry of Norway for the period 2000-2011. The Registry contains detailed medical information about all deliveries, for both the mother and the infant. This set of data was merged with a set of data that contained information about newspaper coverage for the municipalities in which all hospitals were located. Altogether, more than 620 000 deliveries in 46 municipalities were included in the study. The data were analyzed using a hospital fixed effects regression. The main result was that newspaper coverage had a significant positive effect on the probability of having a Caesarean section. Several supplementary analyses supported the main finding. Altogether, our results indicate that obstetricians are sensitive to the risk of being exposed in the mass media. This is likely to be because obstetricians care about their reputation.


A new bisphosphonate, BM 21.0955, prevents bone loss associated with cessation of ovarian function in experimental dogs.
We previously found that bone loss occurs as soon as 1 month after ovariohysterectomy (OHX) in beagle dogs. Indirect evidence pointed to an early dramatic increase in bone resorption. To verify this hypothesis and evaluate the effects of a newly developed bisphosphonate, BM 21.0955 (Boehringer Mannheim), 36 beagle dogs were subjected to OHX and 12 dogs were sham operated (Sham). OHX dogs were divided into six groups (n = 6 each) and received subcutaneous injections of vehicle or BM 21.0955 at various doses (0.1, 0.3, 1, 10, and 100 micrograms/kg/day) for 1 month. Sham dogs were given vehicle (n = 6) or BM 21.0955 (1 microgram/kg/day, n = 6). Iliac crest biopsies and blood drawings were done at baseline and at month 1. OHX dogs given vehicle exhibited a decrease in cancellous bone volume associated with an increase in erosion depth and a decrease in serum levels of 1,25-dihydroxyvitamin D. BM 21.0955 prevented the bone loss at a dose > or = 1 microgram/kg and the increase in erosion depth and the decrease in serum levels of 1,25-(OH)2D at a dose > or = 0.3 microgram/kg. No osteomalacia was observed at any dose of BM 21.0955. Bone turnover was reduced only when BM 21.0955 was administered at doses of 10 or 100 micrograms/kg. There were no changes in body weight or serum levels of calcium, phosphorus, creatinine, parathyroid hormone, or osteocalcin in all groups. The increase in erosion depth in OHX dogs given vehicle proves that the early rapid bone loss after cessation of ovarian function is related to an increase in osteoclastic activity. The antiosteoclastic activity of BM 21.0955 at a dose > or = 1 microgram/kg prevents this increase and preserves bone volume. The absence of any signs of osteomalacia at any dose confers a relatively wide therapeutic margin to BM 21.0955. BM 21.0955 at a dose > or = 10 micrograms/kg also acts as an inhibitor of bone turnover. This is not observed at a dose of 1 microgram/kg, at least after 1 month of administration.


Resistant hypertension and target organ damage.
Cardiovascular (CV) complications such as myocardial infarction, heart failure, stroke and renal failure are related to both the degree and the duration of blood pressure (BP) increase. Resistant hypertension (RH) is associated with a higher risk of CV complications and a higher prevalence of target organ damage (TOD). The relationship between CV disease and TOD can be bidirectional. Elevated BP in RH may cause CV structural and functional alterations, and the development or persistence of left ventricular hypertrophy, aortic stiffness, atherosclerotic plaques, microvascular disease and renal dysfunction, may render hypertension more difficult to control. Specifically, RH is related to several conditions, including obesity, sleep apnea, diabetes, metabolic syndrome and hyperaldosteronism, characterized by an overexpression of humoral and hormonal factors that are involved in the development and maintenance of TOD. Optimal therapeutic strategies, including pharmacological treatment and innovative invasive methodologies, have been shown to achieve adequate BP control and induce the regression of TOD, thereby potentially improving patient prognosis.


Sexual function and pelvic floor disorders.
Sexual wellbeing is an important aspect of women's health. Female sexual dysfunction is multifactorial and involves physical, social and psychological dimensions. Dysfunction may result from lack of sexual desire, sexual pain or arousal, and orgasmic problems. Sexual dysfunction is common and increases with age and pelvic floor disorders such as urinary incontinence and pelvic organ prolapse. Surgical treatment of pelvic floor disorders has been poorly studied but has the potential to improve sexual satisfaction or to cause sexual difficulties. New instruments such as condition-specific sexual questionnaires have recently been developed and will help us to better evaluate the results of incontinence and prolapse surgery on sexual function.


Nutrition, mood and behaviour: a review.
To conduct a critical review of recent empirical research regarding mood, behaviour and nutrition factors including essential fatty acids, macronutrients, micronutrients and food additives. A literature search of databases Medline, PsycInfo, CINAHL and Embase up to October 2008. The search emphasised empirical research published in the last 10 years and also included older literature. Studies in both adults and children were addressed. Research into omega-3 fatty acids has been substantial but evidence for their potential in treating mood and behaviour is modest. In comparison, there has been much less research into carbohydrate and protein intakes and little evidence for their ability to influence mood and behaviour. Recent trials with food additives suggest their removal from the diet may benefit susceptible children with hyperactivity disorders. Micronutrient supplementation appears to improve mood only in those who were initially deficient in micronutrients. More stringent research designs such as longitudinal studies and the use of biologically inert placebos within randomised controlled trials are needed before supplemental use of omega-3 fatty acids to treat disorders of mood and behaviour can be recommended. Caution is advised regarding the indiscriminate use of diets free of artificial food additives in managing hyperactivity disorders, as they may place an undue burden on individuals and their families. Should omega-3 fatty acid supplementation or the elimination of certain food additives be established as effective, they may provide cost-effective, accessible and well-tolerated adjuncts to standard psychiatric treatments for mood and behavioural disturbances.


Transmission Electron Microscopy Studies of Dengue Viruses.
Despite the advancement of molecular biology techniques, morphological studies using transmission electron microscopy (TEM) are still being of great importance to elucidate some aspects of viral structures, morphogenesis, and pathogenesis. In relation to dengue viruses (DENV), several studies report the use of TEM to obtain a clearer definition of viral morphology, the events involved in its morphogenesis, aspects of pathogenesis, and cell tropism. In this chapter, the main technical protocols and their respective reagents for studies of DENV infection by TEM are described, both in cell culture and in biological tissue samples.


Traditional Chinese therapy initiates oral feeding in a stroked woman after three years of nasogastric tube feeding.
Banxia Houpu Tang, a traditional Chinese medicine, helped in initiating oral feeding in a stroke patient, after three years of nasogastric tube feeding. This Chinese medicine has potential in eliminating the need for nasogastric feeding and for physical restraints in geriatric individuals after a stroke.