Ergonomic and behavioral interventions as the primary treatment for work-related lateral epicondylitis.
Work-related injuries (WRI) are costly to employers and the United States government due to missed days at work and medical expenses. This case report documents the results of using ergonomic and behavioral changes to address a client's symptoms due to a WRI. The client worked as an administrative assistant at a small, private medical college and presented with lateral epicondylitis. She received ergonomic and behavioral interventions to treat her injury that included modification to her work environment and education on modifying behaviors that would decrease stress and excessive work. The client reported decreased headaches with improved lighting and increased tolerance to typing with the addition of a keyboard tray, but not elimination of her chief complaints with the tray, floor mat, and behavioral changes. Some interventions that occurred at the client's desk resulted in decreased secondary symptoms. No improvements in the primary symptoms were found.


Human alloreactive CTL clones: loss and reacquisition of specific cytolytic activity can be regulated by "recombinant" interleukin 2.
In this communication, we demonstrate that human alloreactive CTL at the clonal level, can undergo reversible processes vis-a-vis lytic function: from a highly lytic phase to a nonlytic quiescent phase and back to a lytic phase. "Reversion" and reacquisition of function can be controlled by removing or adding back a chromatographically purified product of a human interleukin 2 gene (rIL 2) that appears to serve, either directly or indirectly, as a lysis-inducing signal for these CTL.


Fibrous Cap Thickness Predicts Stable Coronary Plaque Progression: Early Clinical Validation of a Semiautomated OCT Technology.
Imaging-based characteristics associated with the progression of stable coronary atherosclerotic lesions are poorly defined. Utilizing a combination of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging, we aimed to characterize the lesions prone to progression through clinical validation of a semiautomated OCT computational program. Patients with stable coronary artery disease underwent nonculprit vessel imaging with IVUS and OCT at baseline and IVUS at the 12-month follow-up. After coregistration of baseline and follow-up IVUS images, paired 5-mm segments from each patient were identified, demonstrating the greatest plaque progression and regression as measured by the change in plaque burden. Experienced readers identified plaque features on corresponding baseline OCT segments, and predictors of plaque progression were assessed by multivariable analysis. Each segment then underwent volumetric assessment of the fibrous cap (FC) using proprietary software. Among 23 patients (70% men; median age, 67 years), experienced-reader analysis demonstrated that for every 100 μm increase in mean FC thickness, plaques were 87% less likely to progress (P = .01), which persisted on multivariable analysis controlling for baseline plaque burden (P = .05). Automated FC analysis (n = 17 paired segments) confirmed this finding (P = .01) and found thinner minimal FC thickness (P = .01) and larger FC surface area of <65 μm (P = .02) and <100 μm (P = .04) in progressing segments than in regressing segments. No additional imaging features predicted plaque progression. A semiautomated FC analysis tool confirmed the significant association between thinner FC and stable coronary plaque progression along entire vessel segments, illustrating the diffuse nature of FC thinning and suggesting a future clinical role in predicting the progression of stable coronary artery disease.


Genetic organization of plasmid-mediated Qnr determinants in cefotaxime-resistant Enterobacter cloacae isolates in Korea.
Because of the strong association between qnr genes and plasmids carrying β-lactamase genes, we screened 176 clinical isolates of Enterobacter cloacae with cefotaxime MICs of ≥16 μg/mL for qnr genes. The qnrA, qnrB, and qnrS genes were detected in 18 (10.2%), 11 (6.2%), and 1 (0.56%) of the isolates, respectively. The genetic environments of the plasmids encoding these qnr genes were analyzed.


Between-subject variability and within-subject reliability of the human eye-movement response to bilateral galvanic (DC) vestibular stimulation.
Recent studies have shown that responses to surface galvanic vestibular stimulation (GVS) show substantial interindividual variation. Between-subject variability may be due to individual differences between subjects, or to the poor reliability of the test, or to differences in test details, or to host factors. The aim of the present study was to compare variability between and within subjects in binocular 3-D eye-movement responses to long-duration, maintained, large-amplitude, bilateral, bipolar, surface GVS. Subjects were seated and restrained, and in one condition fixated a small, centrally located visual target; in the other condition, testing was carried out in complete darkness. Surface GVS of 5 mA, with a rectangular waveform was delivered bilaterally for 5 min while eye movements were measured using computerised video-oculography (VTM). In the first experiment, ten subjects participated in both conditions in one session, and in the second experiment, two subjects participated in both conditions for a total of five repeated sessions. The stimulation was well tolerated by all subjects and produced a change in torsional position with the upper pole of both eyes rolling towards the anode and away from the cathode in all subjects in both conditions. Although little vertical nystagmus was evident in either condition, most subjects showed relatively strong horizontal nystagmus (slow phases towards the anode) in darkness. This study confirms previous observations that the torsional response to GVS is highly variable between subjects, whilst also showing for the first time that eye-movement responses to GVS show good within-subject repeatability. This study also demonstrates considerable between-subject variability in the relative ratios of response components (torsional and horizontal nystagmus, torsional position), whereas the relatively small within-subject variability can be characterised more by changes in the overall amplitude of the eye-movement response. Subjects show idiosyncratic oculomotor response patterns to GVS, varying slightly in absolute magnitude between sessions. Thus, GVS may be a more reliable stimulus than may have been anticipated from the literature.


Properties of the Portuguese version of the empowerment scale with mental health organization users.
This study examines the reliability and validity of the Portuguese version of the Empowerment Scale (ES) to be used in the community/psychosocial mental health field. Authors also reviewed the properties of the development and cross-cultural adaptation of the ES. Because mental health services are required to encourage empowerment and recovery-oriented interventions, adequate empowerment-oriented outcome measures are needed to evaluate services and study interventions across countries. The current research was part of a larger research project with 213 participants. A confirmatory factor analysis (CFA) was conducted to observe the ES's construct-related validity, and a reliability analysis for internal consistency. The ES concurrent validity with the recovery and psychiatric symptoms measures was also assessed using the Pearson's correlation coefficient. The CFA supported the five-factor configuration for the refined model of measure as satisfactory. The Portuguese version of the ES presented an overall satisfactory reliability (α = .79) and was positively correlated with personal recovery (r = .71) and inversely with psychiatric symptoms (r = -.22). The overall scale was considered reliable and valid to be used by Portuguese researchers and practitioners to evaluate empowering interventions in mental health services. Furthermore, in the effort to increase ES construct-related validity, this article suggests further improvements to enhance the empowerment measure.


Avian encephalomalacia in Barbados, West Indies: a description of spontaneous field cases with feed analyses.
The clinical, necropsy and histopathological findings in four natural outbreaks of encephalomalacia are reported. Feed analyses implicated low levels of vitamin E as the probable cause of the condition. Treatment with vitamin E has proved to be very effective. The instability of vitamin E in animal feed ingredients during long periods of shipment into the Caribbean may be important in the pathogenesis of the disease.


The purification and characterization of glutathione S-transferase from the hepatopancreas of the blue crab, Callinectes sapidus.
High glutathione S-transferase activity was found in the cytosol of F-cells from the hepatopancreas of the blue crab (Callinectes sapidus). Purification of glutathione S-transferase from hepatopancreas extracts by Sephadex G-200, DEAE-Sephacel, and chromatofocusing resulted in the isolation of two isozymes with isoelectric points of 5.9 and 5.7, as determined by analytical isoelectric focusing. Using 1-chloro-2,4-dinitrobenzene as the substrate the specific activities of the two purified isozymes were 222 and 182 mumol/min/mg, respectively. There was no evidence for basic transferase isozymes. In addition to 1-chloro-2,4-dinitrobenzene the purified glutathione S-transferase isozymes showed activity with p-nitrophenyl acetate, p-nitrobenzyl chloride, bromosulfophthalein, and benzopyrene oxide. Thus, both substitution and addition reactions associated with vertebrate glutathione S-transferase were found in the crab transferases. There was no when ethacrynic acid, methyl iodide, trans-4-phenyl-3-buten-2-one, 1,2-epoxy-(p-nitrophenoxy)propane, cumene hydroperoxide, and t-butyl hydroperoxide were used as substrates. The lack of peroxidase activity is of interest since this activity is commonly found in vertebrate transferase isozymes. The two transferases had a dimeric Mr of 40,800 with similar amino acid compositions and similar kinetic parameters (Vmax, Km, and pH maxima) with 1-chloro-2,4-dinitrobenzene as substrate. The two transferases could be distinguished by their isoelectric points, molecular mass of the monomers (22,300 for GST 1 and 22,300 and 22,400 for GST 2), and different inhibitor mechanisms with hematin and bromosulfophthalein.


Toluene diisocyanate: an assessment of carcinogenic risk following oral and inhalation exposure.
Although respiratory sensitization and pulmonary irritation have been the subject of particular studies with toluene diisocyanate (TDI), in recent years the potential carcinogenicity of TDI has been a reason for concern and speculation. This has arisen from the expectation that following exposure to TDI the chemical would hydrolyze at aqueous tissue surfaces to give rise to toluene diamine (TDA), a mutagen and rodent carcinogen. The chemistry of TDI suggests that the reaction with biological NH2 groups such as those on proteins, and polymerization to oligoureas, will compete with the hydrolysis reaction. This has been shown with results of in vitro studies where conjugation to protein occurs without detectable formation of TDA when protein solutions in saline are exposed to TDI vapor. Lower pH levels leading to high protonation of biological NH2 groups facilitate hydrolysis of TDI to TDA and subsequent formation of polyureas. These observations are consistent with comparative toxicokinetic studies in rats, which demonstrate significant levels of TDA following oral dosing with TDI--due to the acidic environment in the stomach--but not after inhalation. These results provide an explanation for the tumors observed in rodents after oral dosing of TDI in corn oil, but not after inhalation. Inhalation is the relevant route of human exposure for TDI and the toxicokinetics of TDI exposure at occupational exposure limits have been studied. These data provide a means by which quantitative estimates of the risk of carcinogenicity possibly resulting from the intermediate formation of TDA during TDI exposure can be obtained. Several calculations have been made, all of which lead to the conclusion that TDI exposure by inhalation at the recommended occupational limits will not give rise to significant carcinogenic risk.


Prevalence, causes and management outcome of intestinal obstruction in Adama Hospital, Ethiopia.
In Africa, acute intestinal obstruction accounts for a great proportion of morbidity and mortality. Ethiopia is one of the countries where intestinal obstruction is a major cause of morbidity and mortality. This study aims to determine prevalence, causes and management outcome of intestinal obstruction in Adama Hospital in Oromia region, Ethiopia. A hospital based cross-sectional study design was used. Data covering the past three years were collected from hospital medical records of sampled patients. The collected data were checked for any inconsistency, coded and entered into SPSS version 16.0 for data processing and analysis. Descriptive and logistic regression analyses were used. Statistical significance was based on confidence interval (CI) of 95 % at a p-value of < 0.05. 262 patients were admitted with intestinal obstruction. The prevalence of intestinal obstruction was 21.8 % and 4.8 % among patients admitted for acute abdomen surgery and total surgical admissions, respectively. The mortality rate was 2.5 % (6 of 262). The most common cause of small bowel obstruction was intussusceptions in 48 patients (30.9 %), followed by small bowel volvulus in 47 patients (30.3 %). Large bowel obstruction was caused by sigmoid volvulus in 60 patients (69.0 %) followed by colonic tumor in 12 patients (13.8 %). After controlling for possible confounding factors, the major predictors of management outcome of intestinal obstruction were: duration of illness before surgical intervention (adjusted odds ratio (AOR) = 0.49, 95 % CI: 0.25-0.97); intra-operative findings [Viable small bowel volvulus (SBV) (AOR = 0.08, 95 % CI: 0.01-0.95) and viable (AOR = 0.17, 95 % CI: 0.03-0.88)]; completion of intra-operative procedures (bowel resection & anastomosis (AOR = 3.05, 95 % CI: 1.04-8.94); and length of hospital stay (AOR = 0.05, 95 % CI: 0.01-0.16). Small bowel obstruction was more prevalent than large bowel obstruction. Intussusceptions and sigmoid volvulus were the leading causes of small and large bowel obstruction. Laparotomy was the most common methods of intestinal obstruction management. Bowel resection and anastomosis was the commonest intra-operative procedure done and is associated with postoperative complications. Wound infection in the affected area should be improved because it is the most common postoperative complication. This can be decreased by appropriate surgical technique and wound care with sterile techniques.


Endoscopic intratumoral injection of OK-432 and Langerhans' cells in patients with gastric carcinoma.
OK-432, a compound composed of penicillin-G-treated, attenuated Streptococcus pyogenes of human origin, was administered by intratumoral injection (IT) to 15 of 49 patients with Stage III gastric carcinoma, at the time of preoperative endoscopic examination. The 5-year survival rate of patients given IT was 73.3%, whereas the rate was only 36.5% in those not given IT (P less than 0.05). A study of recurrent cases revealed a significantly low incidence of peritoneal recurrence in the group on OK-432 IT (P less than 0.01). In previous work, the authors noted a favorable prognosis of patients with Stage III gastric carcinoma and with a marked infiltration of Langerhans' cells (LC) in the tumor tissues. All of the 49 in the current study were thus examined immunohistochemically, using anti-S-100 protein antibody, the objective being to clarify the relationship between OK-432 IT and the density of LC. The density of LC among those given IT was significantly increased as compared with those not given IT (P less than 0.05). The results of this study suggest that OK-432 IT may lead to augmentation of the density of LC in tumor tissues and hence prevent peritoneal recurrences in patients with Stage III gastric carcinoma.


The effect of a disease management algorithm and dedicated postacute coronary syndrome clinic on achievement of guideline compliance: results from the parkland acute coronary event treatment study.
The application of disease management algorithms by physician extenders has been shown to improve therapeutic adherence in selected populations. It is unknown whether this strategy would improve adherence to secondary prevention goals after acute coronary syndromes (ACSs) in a largely indigent county hospital setting. Patients admitted for ACS were randomized at the time of discharge to usual follow-up care versus the same care with the addition of a physician extender visit. Physician extender visits were conducted according to a treatment algorithm based on contemporary practice guidelines. Groups were compared using the primary end point of achievement of low-density lipoprotein treatment goals at 3 months after discharge and achievement of additional evidence-based practice goals. One hundred forty consecutive patients were randomized. A similar proportion of patients returned for study follow-up in both groups at 3 months (54 [79%]/68 in the usual care group vs 57 [79%]/72 in the intervention group; P = 0.97). Among those completing the 3-month visit, a low-density lipoprotein cholesterol level less than 100 mg/dL was achieved in 37 (69%) of the usual care patients compared with 35 (57%) of those in the intervention group (P = 0.43). There was no statistical difference in implementation of therapeutic lifestyle changes (smoking cessation, cardiac rehabilitation, or exercise) between groups. Prescription rates of evidence-based therapeutics at 3 months were similar in both groups. The implementation of a post-ACS clinic run by a physician extender applying a disease management algorithm did not measurably improve adherence to evidence-based secondary prevention treatment goals. Despite initially high rates of evidence-based treatment at discharge, adherence with follow-up appointments and sustained implementation of evidence-based therapies remains a significant challenge in this high-risk cohort.


Mytilus spp. as sentinels for monitoring microplastic pollution in Norwegian coastal waters: A qualitative and quantitative study.
Microplastic (MP) contamination is ubiquitous in the environment and many species worldwide have been shown to contain MP. The ecological impact of MP pollution is still unknown, thus there is an urgent need for more knowledge. One key task is to identify species suitable as sentinels for monitoring in key eco-compartments, such as coastal waters. In Norway, mussels (Mytilus spp.) have been monitored for hazardous contaminants through OSPAR since 1981. Norway has the longest coastline in Europe and adding MP to the Norwegian Mussel Watch is therefore important in a European and global context. The present study reports MP data in mussels (332 specimens) collected from multiple sites (n = 15) spanning the whole Norwegian coastline. MPs were detected at all locations, except at one site on the west coast. Among the most surprising findings, mussels from the Barents Sea coastline in the Finnmark region, contained significantly more MPs than mussels from most of the southern part of the country, despite the latter sites being located much closer to major urban areas. Only mussels from a site located very close to Oslo, the capital, contained levels similar to those observed in the remote site in Finnmark. In total an average of 1.5 (±2.3) particles ind-1 and 0.97 (±2.61) particles w.w. g-1 was found. The most common MPs were <1 mm in size, and fibres accounted for 83% of particles identified, although there was inter-site variability. Thirteen different polymeric groups were identified; cellulosic being the most common and black rubbery particles being the second. This study suggests Mytilus spp. are suitable for semi-quantitative and qualitatively monitoring of MPs in coastal waters. However, some uncertainties remain including mussel size as a confounding factor that may influence ingestion, the role of depuration and other fate related processes, and this call for further research.


Revisiting maize Brittle endosperm-2 reveals new insights in BETL development and starchy endosperm filling.
Rerouting the starch biosynthesis pathway in maize can generate specialty types, like sweet corn and waxy corn, with a drastically increasing global demand. Hence, a fine-tuning of starch metabolism is relevant to create diverse maize cultivars for end-use applications. Here, we characterized a new maize brittle endosperm mutant, referred to as bt1774, which exhibited decreased starch content but a dramatic increase of soluble sugars at maturity. Both endosperm and embryo development was impaired in bt1774 relative to the wild-type (WT), with a prominently arrested basal endosperm transfer layer (BETL). Map-based cloning revealed that BRITTLE ENDOSPERM2 (Bt2), which encodes a small subunit of ADP-glucose pyrophosphorylase (AGPase), is the causal gene for bt1774. A MuA2 element was found to be inserted into intron 2 of Bt2, leading to a severe decrease of its expression, in bt1774. This is in line with the irregular and loosely packed starch granules in the mutant. Transcriptome of endosperm at grain filling stage identified 1,013 differentially expressed genes in bt1774, which were notably enriched in the BETL compartment, including ZmMRP1, Miniature1, MEG1, and BETLs. Gene expression of the canonical starch biosynthesis pathway was marginally disturbed in bt1774. Combined with the residual 60 % of starch in this nearly null mutant of Bt2, this data strongly suggests that an AGPase-independent pathway compensates for starch synthesis in the endosperm. Consistent with the BETL defects, zein accumulation was impaired in bt1774. Co-expression network analysis revealed that Bt2 probably has a role in intracellular signal transduction, besides starch synthesis. Altogether, we propose that Bt2 is likely involved in carbohydrate flux and balance, thus regulating both the BETL development and the starchy endosperm filling.


The epithelial-specific Ets factors occupy a unique position in defining epithelial proliferation, differentiation and carcinogenesis.
The Ets family of transcription factors regulates many biological processes. Within the Ets family are a subset of proteins that have epithelial restricted expression patterns, both in tissues and cell lines. These Epithelial-specific Ets (Ese) factors, cluster into two groups based on the sequence of the Ets DNA binding domain: (i) Ese1, Ese2 and Ese3, and (ii) the more divergent, Pdef. Gene targeting and cell culture studies have demonstrated that Ese factors are important for cellular differentiation. Furthermore, the ability of Ese factors to regulate expression of genes that are markers of differentiation supports this model. Significantly, the expression profile of these Ese factors is altered in epithelial cancers relative to the respective normal tissues. It is likely that this variation in expression affects downstream target genes important for carcinogenesis such as oncogenes and tumor suppressor genes. Understanding the role of these Ese factors in normal cellular differentiation may elucidate specific mechanisms by which cancer cells can become undifferentiated.


A Comparative Study of Healthy Dietary Patterns for Incident and Fatal Digestive System Cancer.
We examined multiple dietary patterns in relation to total digestive system cancer (DSC) incidence and death. A total of 213,038 health professionals from the Health Professionals Follow-up Study (1986-2016), the Nurses' Health Study (1986-2018), and the Nurses' Health Study II (1991-2017) with no cancer diagnosis at baseline were analyzed. DSC incidence and death were estimated using time-varying Cox proportional hazards regression models. During up to 32 years of follow-up, 5,724 DSC cases accrued. Adherence to 8 healthy diet patterns was associated with a 7%-13% lower risk of DSC, particularly for digestive tract cancers. An inverse association with gastrointestinal tract cancer was also shown for all pattern scores except Alternate Mediterranean Diet and the healthful Plant-based Diet Index, with hazard ratios between 0.84 and 0.89. Inverse associations were shown for the reversed empirical dietary index for hyperinsulinemia (hazard ratio for 90th vs 10th percentile 0.64, 95% confidence interval [CI] 0.47-0.87) and the empirical dietary index associated with lower inflammation (rEDIP) (0.53, 95% CI 0.39-0.72) for stomach cancer, and for the rEDIP (0.58, 95% CI 0.37-0.92) for small intestine cancer. Among accessory cancers, the Alternate Healthy Eating Index-2010, alternate Mediterranean diet, and diabetes risk reduction diet were associated with a 43%-51% lower risk of liver cancer. The reversed empirical dietary index for hyperinsulinemia, rEDIP, and the Alternate Healthy Eating Index-2010 were inversely associated with the risk of fatal DSC. Adherence to healthy diets was associated with a lower risk of incident and fatal DSC, although the magnitude of the association varied slightly among the patterns.


The structure property and adsorption capacity of new enzyme-treated potato and sweet potato starches.
To explore a valuable new enzyme method that effectively changes the molecular structure and absorption property of potato and sweet potato starch granules, the common combination of α-amylase (AA) and glucoamylase (GA), namely AA → GA (common method as contrast), the combination of glycosyltransferase (GT) and GA, namely GT → GA, or the combination of sequential AA, GT and GA (AA → GT → GA) treatment was utilized. The results indicated that three types of enzyme treatments increased the pore size, pore volume, specific surface area and relative crystallinity of potato and sweet potato starches, resulting in a significant increment in adsorption capacities. Compared to GT → GA or AA → GA treatment, AA → GT → GA treatment had the most significant effect on the hydrolysis of starches since a lower amylose content, higher branched degree and more amount of short side chains of starches obtained using AA → GT treatment might increase the amount of GA active sites. So, GT → AA → GA treatment had the most significant absorption impact on oil, dye and heavy metal ions of starches. Compared to native starch, the adsorption capacity of GT/AA/GA-treated starches increased by about 7-21 folds. Thus, a novel GT → AA → GA treatment may be a most effective method to prepare porous potato and sweet potato starches as desirable green adsorbents.


The effect of intraventricular injections of noradrenaline, 5-hydroxytryptamine, acetylcholine and tranylcypromine on the ox (Bos taurus) at different environmental temperatures.
1. Noradrenaline, 5-hydroxytryptamine (5-HT), acetylcholine and tranylcypromine were injected or infused into the lateral ventricle of the ox. The effects of these drugs on heart and respiration rates, heat production, rectal, skin and hypothalamic temperatures and skin evaporative loss were measured when the animal was exposed to environmental temperatures ranging from -1 degrees C to +30 degrees C.2. Acetylcholine (0.001-2 mg) had no detectable effect on temperature regulation at 20 degrees C.3. In small doses (0.005-0.05 mg) 5-HT had no detectable effect. Larger doses (2-5 mg) given in a cold environment (-1 degrees C) also had no effect but the same doses given in warm environments (15-30 degrees C) caused increases in skin temperatures, skin evaporative loss and respiratory rate, and decreases in rectal and hypothalamic temperatures.4. Infusion of tranylcypromine (0.107 ml./min of a 1 in 50 solution) in a warm environment (20 degrees C) also caused a decrease in rectal temperature after a delay of 1-1(1/2) hr during which no effects were apparent.5. Noradrenaline (2 mg) had no effect on temperature regulation when injected into animals in a warm environment (30 degrees C). When injected (1 mg) into animals in a cold environment (-1 degrees C) shivering stopped and heat production and rectal and hypothalamic temperatures were decreased.6. It is concluded that intraventricular 5-HT and noradrenaline both cause a decrease in body temperature, and it is unlikely that central temperature regulation in the ox is mediated only by these two substances.


Differences in effect of early enteral nutrition on mortality among ventilated adults with shock requiring low-, medium-, and high-dose noradrenaline: A propensity-matched analysis.
Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 μg/kg/min), medium- (0.1-0.3 μg/kg/min), and high-dose (≥0.3 μg/kg/min) noradrenaline groups. We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, -2.9%; 95% confidence interval [CI], -4.5% to -1.3%) and in the medium-dose noradrenaline group (risk difference, -6.8%; 95% CI, -9.6% to -4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, -1.4%; 95% CI, -7.4%-4.7%). Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in those requiring high-dose noradrenaline.


Unlocking COVID therapeutic targets: A structure-based rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike.
There are no approved target therapeutics against SARS-CoV-2 or other beta-CoVs. The beta-CoV Spike protein is a promising target considering the critical role in viral infection and pathogenesis and its surface exposed features. We performed a structure-based strategy targeting highly conserved druggable regions resulting from a comprehensive large-scale sequence analysis and structural characterization of Spike domains across SARSr- and MERSr-CoVs. We have disclosed 28 main consensus druggable pockets within the Spike. The RBD and SD1 (S1 subunit); and the CR, HR1 and CH (S2 subunit) represent the most promising conserved druggable regions. Additionally, we have identified 181 new potential hot spot residues for the hSARSr-CoVs and 72 new hot spot residues for the SARSr- and MERSr-CoVs, which have not been described before in the literature. These sites/residues exhibit advantageous structural features for targeted molecular and pharmacological modulation. This study establishes the Spike as a promising anti-CoV target using an approach with a potential higher resilience to resistance development and directed to a broad spectrum of Beta-CoVs, including the new SARS-CoV-2 responsible for COVID-19. This research also provides a structure-based rationale for the design and discovery of chemical inhibitors, antibodies or other therapeutic modalities successfully targeting the Beta-CoV Spike protein.


Erysipelothrix rhusiopathiae Infection Associated with Swollen Head Syndrome in a Broiler Breeder Flock in North Georgia.
An unusual case of swollen head syndrome in a 55-wk-old broiler breeder flock was identified in north Georgia in the summer of 2019. The presenting complaint was elevated mortality and visibly swollen heads. Necropsy of affected birds on the farm primarily revealed signs of bacterial septicemia, with few large scab lesions near the vent area. Bacterial culture analysis identified multiple organisms, but the primary organism of interest was identified as Erysipelothrix rhusiopathiae, cultured from affected liver, lung, sinuses, and one swollen wattle of birds in the affected house. Histopathologic analysis identified gram-positive rod-shaped bacteria in the spleen and liver (consistent with bacterial septicemia) confirmed with special staining (Brown & Hopps Gram stain). These organisms were noted to be consistent with E. rhusiopathiae; E. rhusiopathiae infection in broiler breeder chickens is a rare occurrence and is primarily associated with turkeys and/or swine production systems.


Micropulse laser trabeculoplasty on Chinese patients with glaucoma or ocular hypertension: average 35 months follow-up results.
Glaucoma is a group of eye diseases that can damage the optic nerve and cause vision loss. A novel technology micropulse laser trabeculoplasty (MLT) can use duty-circle subvisible laser pulses to treat glaucoma. The aim of this study is to evaluate the efficacy of 360° MLT to alleviate intraocular pressure (IOP) in patients with glaucoma. This was a single-center prospective study on patients treated with 360° MLT using a Diode True-Yellow 577-nm Laser with MicroPulse technology. All the patients were recruited from the Department of Ophthalmology. Follow-up visits were carried out at 1 day, 1 week, 1 month, 3 months, 6 months, 18 months, and 36 months after the procedure. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), and vertical cup-to-disc ratio (C/D ratio) were measured during the follow-up. Repeated-measures analysis of variance (ANOVA) and Kaplan-Meier analysis were performed to evaluate the outcomes. A total of 39 eyes from 25 patients were included in this study (10 men/15 women). The average age of patients was 41.47 ± 14.39 years old, and the baseline IOP was 21.13 ± 7.75 mmHg. MLT significantly reduced the IOP at 1 day (range 15.61-19.01, P = 0.0218), 3 months (range 16.47-19.22, P = 0.0390), and 6 months (range 15.38-18.56, P = 0.0332) compared with the baseline. However, by the end of the study, only 21.88% of patients demonstrated a ≥ 20% IOP reduction, while seven eyes needed further laser or surgical treatment. The IOP of glaucoma patients was significantly lower than the ocular hypertension patients at 1 month (P = 0.0124), 3 months (P = 0.0004), 18 months (P = 0.0061) and 36 months (P = 0.0119). Micropulse laser trabeculoplasty reduce IOP in patients with glaucoma or ocular hypertension for a short period, but its lowering efficiency is limited up to 6 months of the follow-up period.


Molecular correlates of repolarization alternans in cardiac myocytes.
Arrhythmogenic action potential alternans (APD-ALT) is thought to arise from beat to beat alteration in cellular Ca(2+) cycling. Previously, we found that spatial heterogeneity in APD-ALT between ventricular myocytes is key to the mechanism linking APD-ALT to cardiac arrhythmogenesis. However, the cellular and molecular basis for APD-ALT is poorly understood. To test the hypothesis that spatial heterogeneities in expression and function of calcium cycling proteins underlies heterogeneities in APD-ALT, endocardial and epicardial myocytes were isolated from left ventricular free wall of 20 guinea pig hearts. APD-ALT and Ca(2+) transient alternans (Ca-ALT) were measured simultaneously as stimulus rate was increased progressively. Endocardial myocytes exhibited greater susceptibility to cellular alternans than epicardial myocytes as evidenced by a significantly lower pacing rate threshold for APD-ALT (113 +/ -9 bpm vs. 151 +/- 8 bpm, respectively, P < 0.05) and for Ca-ALT (110 +/- 8 bpm vs. 149 +/- 8 bpm, respectively, P < 0.05). APD-ALT never occurred without Ca-ALT, whereas Ca-ALT was readily induced in the absence of APD-ALT by repetitive constant action potential waveform, suggesting that Ca-ALT was not secondary to APD-ALT. Importantly, there were significant voltage-independent differences in Ca(2+) cycling between endocardial and epicardial myocytes as evidenced by weaker Ca(2+) release (32% lower Ca(2+) amplitude, and 16% longer rise time), and slower Ca(2+) reuptake (24% larger Ca(2+) decay time constant, and 9% longer Ca(2+) transient duration) in endocardial compared to epicardial myocytes. Taken together these data indicate that myocytes that are most susceptible to APD-ALT exhibit impaired Ca(2+) release and reuptake. Moreover, transmural differences in Ca(2+) cycling function was associated with significantly reduced endocardial expression of ryanodine release channel (by 22%) and SERCA2 (by 40%), suggesting a potential molecular basis for spatially heterogeneous APD-ALT. Moreover, transmural differences in expression and function of key SR Ca(2+) cycling proteins may underlie spatial heterogeneity of APD-ALT that has been closely linked to cardiac arrhythmogenesis.


Follow-up of natural products isolation.
Follow-up of natural products isolation refers to re-isolation of compound(s) of interest in larger amounts for further pharmacological testing, conclusive structure elucidation, structure modifications to synthesize analogs for structure-activity relationships (SAR) studies, preformulation and formulation studies or clinical trials. In addition to conventional synthetic chemistry approaches, several other methodologies can be applied for following-up natural products isolation. This chapter outlines, with specific examples, various strategies and methods involved in follow-up of natural products isolation.


Van Nes rotationplasty as a treatment method for Ewing's sarcoma in a 14-month-old.
In recent years, the rotationplasty procedure has become popular amongst tumour surgeons as an alternative to endoprosthetic replacement or amputation. There are very few documented cases of this technique in young patients with malignancy. We describe an extremely rare case of Ewing's sarcoma in a 14-month-old boy that involved the entire length of the left femur. At initial presentation, pulmonary metastatic spread had occurred and there was no neurovascular involvement. Complete response to neo-adjuvant chemotherapy was achieved prior to performing the definitive surgical procedure. This case highlights the many reconstructive options and difficulties encountered in managing such extremely young patients with aggressive malignant disease. In this case, a complete femoral excision was necessary and various treatment options were explored. These included irradiation and re-implantation, endoprosthetic replacement and manufacturing a custom growing prosthesis. Taking future functional, psychological and social implications into consideration, we performed a total femoral excision and Van Nes rotationplasty of the tibia at our institute. Histological analysis of the tumour resection showed clear tumour margins and at 1 year clinical review, the patient demonstrates good functional outcome with no evidence of disease recurrence. Van Nes rotationplasty is a viable reconstructive option in young patients with sarcoma of the femur. We believe this to be the youngest reported case of rotationplasty in current literature.


Cell cycle regulation of hepatitis C and encephalomyocarditis virus internal ribosome entry site-mediated translation in human embryonic kidney 293 cells.
We have established stably transformed human embryonic kidney cell lines (HEK293) containing bicistronic constructs to study regulation of viral internal ribosome entry site (IRES)-mediated translation in vivo. These cells produce Renilla luciferase (Rluc) in a cap-dependent manner, while Firefly luciferase (Luc) synthesis is mediated by IRES elements. Using these cell lines, we demonstrate here that IRES-mediated translation directed by both hepatitis C (HCV) and encephalomyocarditis (EMCV) virus varies with the cell cycle. Experiments involving arrest of the cell lines at different phases of the cell cycle, release of synchronized cells from cell cycle arrest, as well as direct sorting of the cells based on position in the cell cycle have shown that the activity of the HCV and EMCV IRES elements is lowest during the G2/M phase in HEK293 cells. These results suggest that cellular trans-acting factors either stimulate viral IRES-mediated translation during G1 and S phases or repress translation during the G2/M phase in HEK293 cells.


Association of household solid fuel use and long-term exposure to PM2.5 with arthritis in middle-aged and older population in China: A cohort study.
Air pollutants are common modifiable risk factors for arthritis. To explore the longitudinal effects of air pollution on arthritis based on a cohort study in middle-aged and elder people of China. Data was obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. A total of 7449 participants aged 45 years and older were involved in our study. The generalized linear mixed models were conducted to examine the separate and joint effects of household air pollution and outdoor air pollution on arthritis, respectively. We found a strong significant association between air pollution and arthritis incidence. Individuals cooking primarily with solid fuel were more likely in higher risk of arthritis compared with cleaner fuel (OR= 1.15; 95% CI: 1.08-1.23). The group-based trajectory model identified four trajectory groups, compared with group "High-Decreasing rapidly", adjusted ORs of incident arthritis for group "Middle-Decreasing moderately", "Low-Decreasing slowly" and "Low-Stably" were 1.36 (95% CI, 1.03-1.79), 1.36 (95% CI, 1.01-1.83) and 1.81 (95% CI, 1.30-2.52), respectively. These associations were generally higher in participants younger than 65 years. In addition, solid fuel use and PM2.5 exposure had additive and multiplicative effects on arthritis. The results suggested that solid fuel use and long-term PM2.5 exposure were associated with a higher incidence of arthritis. Therefore, it is necessary to restrict solid fuel use to reduce household air pollution and make stronger environmental protection policies to reduce PM2.5 concentration.


Predictive value of cortical transit time on MAG3 for surgery in antenatally detected unilateral hydronephrosis caused by ureteropelvic junction stenosis.
In children with antenatally detected hydronephrosis caused by ureteropelvic junction (UPJ) stenosis, the main challenge is preserving renal function by identifying children who require early surgical intervention from those for whom watchful waiting may be appropriate because of the potential for spontaneous resolution without a significant loss of renal function. To assess the impact of initial cortical transit time (CTT) on technetium-99m mercaptoacetyltriglycerine (MAG3) diuretic renogram on the need for surgery in children with antenatally detected unilateral hydronephrosis caused by UPJ stenosis. We retrospectively reviewed the medical records of 33 patients with antenatally detected unilateral hydronephrosis caused by UPJ stenosis who were managed at our institution between 2006 and 2014. Delayed CTT was defined as the absence of activity in the subcortical structures within 3 min of tracer injection on a MAG3 scan. The surgical indication includes symptomatic UPJ stenosis, seriously deteriorating hydronephrosis with parenchymal thinning on serial USG, split renal function <40%, or progressive deterioration of split renal function (>5%) on a MAG3 scan. This study analyzed and compared the initial level of Society for Fetal Urology grade, anteroposterior diameter (APD), split renal function, drainage pattern on a diuretic renogram, and CTT with the need for surgery. Of the 33 children, 16 were classified into the delayed CTT group and 17 were placed in the normal CTT group. During the follow-up period (mean 31.8 months), surgery was needed in 75.0% (12/16) of patients in the delayed CTT group and in 5.9% (1/17) of those in the normal CTT group. Multivariate analysis showed that delayed CTT on initial MAG3 scan and APD on initial ultrasonography were independent predictive factors of the need for surgery. In this era of conservative management of antenatally detected hydronephrosis caused by UPJ stenosis, it is critical to identify which measurement on an image study is the most reliable for predicting the need for surgery by reflecting functional deterioration. In this study, multivariate analysis revealed that CTT on the initial MAG3 scan was an independent predictive factor of the need for surgery. In addition, CTT showed high negative predictive value for surgical need in children with antenatally detected unilateral hydronephrosis caused by UPJ stenosis. CTT on an initial MAG3 scan may be a useful predictor of the need for surgery in children with antenatally detected unilateral hydronephrosis caused by UPJ stenosis.


Enzymatic transformation of PSP toxins in the littleneck clam (Protothaca staminea).
Stemming from investigations into the relationship between toxins produced by Gonyaulax sp. and accumulated in shellfish, we wish to report enzymatic transformations of the PSP toxins to decarbamoyl derivatives in the littleneck clam (Protothaca staminea). No toxin transformations were observed in either mussels (Mytilus edulis) or in butter clams (Saxidomus giganteus). In addition, littleneck clam samples from the natural environment contained predominantly the decarbamoyl derivatives, while other shellfish species collected from the same vicinity contained the previously reported PSP toxins.


Impact of the blue-carba rapid test for carbapenemase detection on turnaround time for an early therapy against Pseudomonas aeruginosa.
To determine the turnaround time from a blue-carba result until a final microbiological report (bacterial identification plus antimicrobial susceptibility profile) and to infer the impact of an early therapeutic intervention based on the blue-carba results. Pseudomonas aeruginosa isolates were recovered from hospitalized patients from Porto Alegre, Brazil, and tested by blue-carba test. Time required for a blue-carba result, right after the sample processing, was compared with those required to get final report (specie identification and antimicrobial susceptibility profile) Isolates blue-carba positive were tested by phenotypically and genotypically for Klebsiella pneumoniae carbapenemase and metallo-β-lactamase genes. A total of 199 isolates were analyzed and 23 (11.6%) were blue-carba positive and harboring the blaSPM-1-like gene. Fifty-two (26.1%) isolates were blue-carba negative but resistant to meropenem and/or imipenem. Polymyxin B and ceftolozane/tazobactam (this latter except for SPM-1 producers) were 100% active for all P. aeruginosa isolates, a blue-carba test allow an earlier intervention or adequacy of therapy. Early adequacy can be promoted by blue-carba test for 11.6% of SPM-1-producing P. aeruginosa isolates, polymyxin B could be prior associated and ceftolozane/tazobactam withdrawn from therapy. For the remaining isolates, empirical therapy involving ceftolozane/tazobactam can be maintained with greater likelihood of adequacy. An active communication between laboratory and clinical services is necessary to better explore these earlier blue-carba results, significantly reducing the time for a first intervention.


Fatal SARS-CoV-2 infection in a renal transplant recipient.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) caused a pandemic that first discovered in Wuhan, China. While 10% of the patients have asymptomatic infection, 15-20% have lung involvement, 5-10% have multiple organ failure, and macrophage activation syndrome. Chronic respiratory diseases, diabetes mellitus, hypertension, and cancer are risk factors for mortality. Prognosis or optimal treatment strategy for renal transplant recipients in SARS-CoV-2 infection is still unknown. Besides fatal cases, there were also milder case reports. In addition, COVID-19 treatment and the maintenance immunosuppression strategy is still under debate. Antiviral therapies and drug interactions are special topics for these patients. To the best of our knowledge, favipiravir and anti-cytokine treatments have not been previously reported in a kidney transplant recipient with SARS-CoV-2 infection before. We report a case of SARS-CoV-2 infection in a kidney transplant recipient with fatal outcomes.


Roentgen stereophotogrammetry in high tibial osteotomy for gonarthrosis.
In three cases operated with high tibial osteotomy for medial gonarthrosis the exact method of roentgen stereophotogrammetry with tantalum balls as bone markers (Selvik 1974) was used to study angular and translational movement in three dimensions at the operation and during the healing period. Tibial osteotomy caused angular and translational movements even in planes where correction was not intended, and the stereo technique revealed that stability was not present when knee mobilisation started. Correlation between the stereo values and conventional radiographic measurements were best in the frontal plane (root mean square value of discrepancies 1.3 degrees). Roentgen stereophotogrammetry gives superior information compared with the conventional radiographic technique, but it is concluded that the latter has sufficient accuracy for the clinical assessment of corrections in the frontal plane.


[Plastic Surgery in times of COVID-19 in a maximum care hospital in Berlin - Description of the situation and approaches to action for resumption of regular operation].
This article illustrates the recent developments in Plastic Surgery, which faces new challenges in the context of the COVID-19 pandemic. Using the example of a Plastic Surgery department in a maximum care clinic facility in Berlin, we show recent courses of action, that may be relevant for other hospitals and that can possibly help to handle the recent situation as well as possible further waves of infections and to create a constructive way back into Plastic Surgery routine.A view into the future also shows, that in the context of COVID-19 new tasks will challenge our discipline in clinics as well as in private practice.


Pilot study of a water load test as a measure of gastric interoception in anorexia nervosa.
Research and clinical experience suggest that individuals with anorexia nervosa (AN) have deficits in gastric interoception, which has been hypothesized to maintain restrictive eating. Behavioral water load tasks (WLTs) have the capability to noninvasively assess gastric interoception; however, to date, no studies have examined WLTs in AN. Thus, the present proof-of-concept pilot study explored the preliminary validity of a WLT in individuals with AN. Participants were n = 10 individuals with AN and n = 10 matched-control women (CW). Participants completed self-report questionnaires before and after a WLT, in which participants were asked to drink water until "completely full". Participants with AN drank significantly less water than CW (AN = 240(109.14) milliliters (ml), CW = 398.00(149.21) ml, p = 0.02, Cohen's d = 1.21), but reported greater increases in negative affect pre- to-post-WLT (p = 0.04, partial eta2 = 0.21). Correlations between WLT performance and interoceptive sensibility in AN and CW participants supported the convergent validity of the WLT. Preliminary results support the potential utility of the WLT as a behavioral measure of gastric interoception in patients with AN. Future research should examine how response to the WLT changes over the course of intervention and how results are related to treatment outcome. Level IV: Evidence obtained from multiple time series analysis such as case studies. (NB: Dramatic results in uncontrolled trials might also be regarded as this type of evidence).


Content not quantity is a better measure of muscle degeneration in whiplash.
Whiplash associated disorder (WAD) represents an enormous economic, social and personal burden. Five out of 10 people with WAD never fully recover and up to 25% continue to have moderate to severe pain-related disability. Unfortunately, clear and definitive reasons as to why half of individuals with WAD recover uneventfully and the other half do not, remain elusive. Identifying the factors that can reliably predict outcome holds considerable importance for not only WAD, but arguably for other acute musculoskeletal traumas. The precise pathology present in WAD has been controversial and often biased by outdated models. Fortunately, a combination of new measurement technology that illuminates pain processing, physical and social functioning and post-traumatic stress responses (and possibly markers of altered muscle size/shape/physiology) is providing a clearer picture of the multisystem pathophysiology in individuals with persistent WAD. The aim of this professional issues paper is to illuminate the clinical and research communities with regards to the growing body of knowledge for determining the trajectory of a patient with whiplash.


Comparison of functional outcomes and patient-reported satisfaction between titanium and absorbable plates and screws for fixation of mandibular fractures: A one-year prospective study.
The aim of this study is to compare the 1-year functional outcomes and patient-reported satisfaction in treating mandibular fractures between resorbable and titanium fixation devices. A 1-year prospective study was conducted; 41 consecutive patients presenting with mandibular fractures were included. A resorbable system was used in 21 patients, while in 20 patients a titanium fixation device was used. Functional outcome was evaluated objectively at several time points (2, 4 and 6 weeks, 3 and 6 months, and 1 year after surgery). Bite forces over molars and incisors, mouth opening distance, occlusal status, operation time, fee for implants, bone healing and plate-associated complications were evaluated. Functional and overall satisfaction was measured by patients themselves subjectively. A statistical difference was found only in maximal mouth opening and molar bite force, both greater for the titanium group in the 2-week time point, achieving comparable measurements in subsequent ones. This coincides with the patient-reported statistically lower satisfaction rates. The cost of the resorbable device was nearly 3 times more expensive than the titanium devices. Resorbable fixation can achieve stability of bone healing at 1 year postoperatively, with functional and satisfaction outcomes comparable to those associated with titanium hardware from the fourth week postoperatively, while yielding unique advantages.


Phylogeny, historical biogeography and characters evolution of the drought resistant fern Pyrrosia Mirbel (Polypodiaceae) inferred from plastid and nuclear markers.
Pyrrosia s.l. comprises ca. 60 species with a disjunct Africa/Asia and Australia distribution. The infrageneric classification of Pyrrosia s.l. is controversial based on the phylogenetic analyses of chloroplast markers and morphology. Based on the expanded taxon sampling of Pyrrosia s.l. (51 species), we investigated its phylogeny, biogeography, character evolution and environmental adaptation by employing five chloroplastid markers (rbcL, matK, psbA-trnH, and rps4 + rps4-trnS) and one single (low)-copy nuclear gene, LEAFY. Pyrrosia s.l. was divided into six major clades and eight subclades. Reticulate evolution was revealed both among clades and among species in Pyrrosia s.l. Ancestral character state optimization revealed high levels of homoplastic evolution of the diagnostic characters in Pyrrosia s.l., while the crassulacean acid metabolism pathway seems to have an independent origin. Molecular dating and biogeographic diversification analyses suggested that Pyrrosia s.l. originated no later than the Oligocene and the main clades diversified during the Oligocene and Miocene, with southern Asia, the Indo-China Peninsula and southwestern and southern China as the most likely ancestral areas. Transoceanic long-distance dispersal, rather than vicariance, contributed to the intercontinental disjunction. Diversification scenarios of Pyrrosia s.l. under geological movements and climate fluctuation are also discussed.


European data of a clinical trial with a sucrose formulated recombinant factor VIII in previously treated haemophilia A patients.
To increase the safety of antihaemophilic treatment, the production process of full-length recombinant factor VIII (FVIII) KOGENATE Bayer (Kogenate FS) has been modified. Human albumin is no longer added as stabilizer during purification and in final formulation. Instead, the new KOGENATE Bayer production process uses sucrose as a stabilizer in the formulation and adds solvent/detergent virus inactivation step. An European clinical trial was carried out in Germany and France in previously treated patients with severe haemophilia A who had more than 100 exposure days to exogenous FVIII. Pharmacokinetic data was analysed according to one-stage and chromogenic assays. Efficacy and safety during home therapy and in surgical procedures were evaluated; inhibitor formation was carefully monitored. Safety and efficacy were evaluated in 33 European patients for 24 months. Patients received more than 13 million IU KOGENATE Bayer. Over 75% of patients accrued more than 100 exposure days with the new product. Of 875 bleeding episodes, 90.7% were treated with 1 or 2 infusions and 75.8% of responses to treatment were rated as 'excellent' or 'good'. Prophylactic treatment was the most common mode of therapy (60.7% of infusions). The product was well-tolerated and FVIII recovery studies were consistent throughout the study period. Only 0.26% of adverse events were reported to be drug related. No evidence of de novo inhibitor formation was observed. Overall, KOGENATE Bayer was efficacious, safe and well-tolerated for the treatment of haemophilia A in multitransfused patients.


A comparison of alcohol consumption between lesbians and heterosexual women in an urban population.
An elevated rate of alcohol problems is believed to exist in the gay and lesbian community. However, prevalence estimates suggesting this have generally been based on convenience samples which have over-represented bar patrons and clinical sources. Recent epidemiological studies examining risk factors for AIDS have gathered information on alcohol consumption as well as sexual orientation. Data based on improved sampling methods are now available for estimating drinking rates of lesbians and gay men. This study compares the drinking patterns of heterosexual women and lesbian/bisexual women who were recruited through a random sampling design in San Francisco, CA. Contrary to previous research, no statistically significant differences in alcohol consumption and drinking patterns between these two groups were found.


Ocular steroidome in human eyes and in eyes with complex central serous chorioretinopathy (CSCR).
The exact link between systemic and ocular endogenous corticoids (steroidome) is unclear and whether the ocular steroidome is altered in CSCR eyes is unknown. The aims of this study were to analyze the human steroidome in the aqueous humor as a function of age, sex and time of the day, to correlate systemic and ocular steroidome and to analyze the ocular steroidome in long lasting complex inactive CSCR. Based on our results, we present two CSCR cases treated by the combination of oral mineralocorticoid antagonist and glucocorticoids drops. In a cross-sectional study, aqueous humor (AH) was collected between 8am and 6 pm from 50 unaffected individuals (25 men and 25 women) and from 14 patients with chronic CSCR, during cataract surgery. In addition, simultaneous serum and AH were collected from 27 individuals undergoing cataract surgery and, simultaneous AH and vitreous were collected from 9 patients undergoing cataract and vitrectomy to estimate corticoids levels in the different compartments. The steroidome was determined using a LC-MS/MS method that quantifies 13 endogenous corticoids from the gluco, mineralocorticoid and androgen pathways. In AH and vitreous, the highest corticoid level is reached by cortisol (F), that represents less than 10% of F serum level. The cortisol levels in the serum did not correlate with ocular cortisol levels. Serum and ocular cortisone (E) levels correlate, although less than 5% of circulating E reaches the eye. The only mineralocorticoids measured in the AH were corticosterone (B) and its inactive form, the 11-desoxycorticosterone (A). There was no influence of circadian rhythm on cortisol ocular levels and there was no correlation between the age or the sex and the level of F, E, A, and B. In eyes with chronic inactive CSCR, the levels of the active glucocorticoid form F was lower than in control eyes and the F/E ratio was reduced by 50% but the B/A ratio was higher indicating imbalance towards active mineralocorticoids. Base on this observation, we propose to combine an antagonist of the mineralocorticoid receptor together with topical glucocorticoids in two CSCR patients, resistant to all other treatments, with favorable outcome. Our results indicate that the ocular psteroidome is highly regulated suggesting a local metabolism of ocular corticoids. In eyes with long-lasting complex inactive CSCR, the steroidome analysis shows lower active glucocorticoids and higher active mineralocorticoids.


Variability of neonatal premedication practices for endotracheal intubation and LISA in the UK (NeoPRINT survey).
The NeoPRINT Survey was designed to assess premedication practices throughout UK NHS Trusts for both neonatal endotracheal intubation and less invasive surfactant administration (LISA). An online survey consisting of multiple choice and open answer questions covering preferences of premedication for endotracheal intubation and LISA was distributed over a 67-day period. Responses were then analysed using STATA IC 16.0. Online survey distributed to all UK Neonatal Units (NNUs). The survey evaluated premedication practices for endotracheal intubation and LISA in neonates requiring these procedures. The use of different premedication categories as well as individual medications within each category was analysed to create a picture of typical clinical practice across the UK. The response rate for the survey was 40.8 % (78/191). Premedication was used in all hospitals for endotracheal intubation but overall, 50 % (39/78) of the units that have responded, use premedications for LISA. Individual clinician preference had an impact on premedication practices within each NNU. The wide variability on first-line premedication for endotracheal intubation noted in this survey could be overcome using best available evidence through consensus guidance driven by organisations such as British Association of Perinatal |Medicine (BAPM). Secondly, the divisive view around LISA premedication practices noted in this survey requires an answer through a randomised controlled trial.


[Factors associated with unsuccessful treatment of patients with drug-sensitive tuberculosis in Paraguay].
To determine the factors associated with the unsuccessful treatment of patients diagnosed with drug-sensitive tuberculosis (TB) in Paraguay. Retrospective cohort study, with data collected from the national program between January 2016 and March 2017. Unsuccessful treatment was defined as patients who were lost to follow-up, failed treatment, or died. Factors associated with unsuccessful treatment were determined using Poisson regression; the adjusted relative risk (RR) and 95% confidence interval (95% CI) were estimated by health region. A total of 3 034 cases were studied: 2 189 (72.1%) were successfully treated (cured: 1 221 [40.2%], complete treatment: 968 [31.9%]) and 845 (27.9%) were unsuccessfully treated (treatment failure: 40 [1.3%], loss to follow-up: 466 [15.4%] and deaths: 339 [11.2%]). Factors associated with unsuccessful treatment were masculine sex 1.28 (1.14- 1.42), indigenous descent 1.3 (1.09- 1.54), lack of report of area of residence 1.27 (1.02- 1.57), TB/HIV coinfection 1.97 (1, 63- 2.38), illicit drug addiction 1.38 (1.16- 1.63), alcohol consumption 1.25 (1.02- 1.52), previous treatment 1.23 (1.10- 1.38) and lack of treatment monitoring data 4.92 (3.69- 6.56). Being deprived of liberty 0.65 (0.47- 0.89) and TB/diabetes comorbidity 0.80 (0.67- 0.95) were considered protective factors. Paraguay has a high percentage of unsuccessful treatment in almost the entire country, without reaching the target proposed by the World Health Organization. Associated risk factors such as HIV, consumption of legal and illicit drugs, and being indigenous highlight the need to revise the treatment strategies with an inter-institutional approach.


FTO inhibits oxidative stress by mediating m6A demethylation of Nrf2 to alleviate cerebral ischemia/reperfusion injury.
Current therapies are of limited efficacy in cerebral ischemia/reperfusion (I/R) injury. Based on the important role of oxidative stress in cerebral I/R injury, this study aimed to explore how the N6-adenosine methylation (m6A) demethylase FTO affects oxidative stress. Middle cerebral artery occlusion/reperfusion (MCAO/R)-induced rat model and oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced SH-SY5Y cells were established as in vivo and in vitro model, respectively. The neurological score of rats was measured, and the volume of cerebral infarction was measured by TTC staining. The levels of FTO, nuclear factor-erythroid 2-related factor (Nrf2), and the activity of m6A demethylase FTO were detected. The m6A methylation level of Nrf2 mRNA was detected by MeRIP experiment. Flow cytometry and MTT assay were used to detect apoptosis and proliferation in vitro. TUNEL assay was used to detect apoptosis in brain tissues. FTO and Nrf2 expressions were decreased in the MCAO/R rat brain tissues and OGD/R SH-SY5Y cells, while the m6A methylation level of Nrf2 mRNA was significantly increased. Overexpression of FTO upregulated Nrf2 expression by decreasing the m6A methylation level of Nrf2 mRNA. m6A binding protein YT521-B homology (YTH) domain family protein 2 (YTHDF2) promoted the degradation of Nrf2 by promoting the m6A methylation level of Nrf2 mRNA. Furthermore, SH-SY5Y cell apoptosis was increased and cell viability was decreased after the addition of methyltransferases METTL 3/14, thus blocking FTO to protect SH-SY5Y cells from oxidative stress injury. In vivo, overexpression of FTO decreased the area of cerebral ischemia infarction and the extent of cell apoptosis. In conclusion, FTO increases Nrf2 expression by mediating m6A demethylation of Nrf2 mRNA, thereby inhibiting oxidative stress response and ultimately alleviating cerebral I/R injury.


Targeted PEG-poly(glutamic acid) complexes for inhalation protein delivery to the lung.
Pulmonary delivery is increasingly seen as an attractive, non-invasive route for the delivery of forthcoming protein therapeutics. In this context, here we describe protein complexes with a new 'complexing excipient' - vitamin B12-targeted poly(ethylene glycol)-block-poly(glutamic acid) copolymers. These form complexes in sub-200nm size with a model protein, suitable for cellular targeting and intracellular delivery. Initially we confirmed expression of vitamin B12-internalization receptor (CD320) by Calu-3 cells of the in vitro lung epithelial model used, and demonstrated enhanced B12 receptor-mediated cellular internalization of B12-targeted complexes, relative to non-targeted counterparts or protein alone. To develop an inhalation formulation, the protein complexes were spray dried adopting a standard protocol into powders with aerodynamic diameter within the suitable range for lower airway deposition. The cellular internalization of targeted complexes from dry powders applied directly to Calu-3 model was found to be 2-3 fold higher compared to non-targeted complexes. The copolymer complexes show no complement activation, and in vivo lung tolerance studies demonstrated that repeated administration of formulated dry powders over a 3 week period in healthy BALB/c mice induced no significant toxicity or indications of lung inflammation, as assessed by cell population count and quantification of IL-1β, IL-6, and TNF-α pro-inflammatory markers. Importantly, the in vivo data appear to suggest that B12-targeted polymer complexes administered as dry powder enhance lung retention of their protein payload, relative to protein alone and non-targeted counterparts. Taken together, our data illustrate the potential developability of novel B12-targeted poly(ethylene glycol)-poly(glutamic acid) copolymers as excipients suitable to be formulated into a dry powder product for the inhalation delivery of proteins, with no significant lung toxicity, and with enhanced protein retention at their in vivo target tissue.


Molecular cloning and partial characterization of ribosomal RNA genes from Trypanosoma cruzi.
To further analyze the organization of the nuclear rDNA locus in Trypanosoma cruzi, genomic recombinant plasmid clones were constructed and isolated after hybridization with rRNA molecules as hybridization probes. Approximately 11 kilobase pairs from the cistron were cloned in three recombinant plasmids carrying adjacent genomic fragments. Restriction mapping and Southern hybridization experiments performed on these clones indicate the following relative arrangement of the mature rRNA coding sequences: 18S (2.46 kb), S3 (197 b), 24S alpha (2.02 kb), S1 (261 b), 24 beta (1.66 kb), S2 (217 b) and S6 (90 b). Neither S4 (141 b) nor S5 (110 b) sequences were found within these genomic clones. Nevertheless genomic Southerns suggest a linkage of S4 towards the 3' end of this genetic system.


Perceived religiousness is protective for colorectal cancer: data from the Melbourne Colorectal Cancer Study.
The perceived or self-reported degree of 'religiousness' was obtained by interview from 715 colorectal cancer patients and 727 age/sex matched community controls, as part of a large, comprehensive population-based study of colorectal cancer incidence, aetiology and survival (The Melbourne Colorectal Cancer Study) conducted in Melbourne, Australia. Self-reported or perceived 'religiousness', as defined in the study, was a statistically significant protective factor [relative risk (RR) = 0.70, 95% confidence interval (CI) = 0.6-0.9, P = 0.002]. This statistically significant protection remained after the previously determined major risk factors found in the study, namely a family history of colorectal cancer, dietary risk factors, beer consumption, number of children and age at birth of the first child, were statistically corrected for (P = 0.004). There was no association between Dukes' staging of the cancer and perceived degree of 'religiousness' (P = 0.42). Although self-reported or perceived 'religiousness' was associated with a median survival time of 62 months compared with 52 months in those self-reporting as being 'non-religious', this difference was not statistically significant (P = 0.64).


Correlation between size and external temperature in four rat tumours after treatment with cytostatic agents.
The reduction in size of four experimental tumours (ISIS 130 and ISIS 208 immunocytomas, S 437 mammary adenocarcinoma, S 447 colon adenocarcinoma) was investigated in LOU rats under the influence of cytostatic agents belonging to different classes (5-fluorouracil, methotrexate, vinblastine, cisplatin, doxorubicin, cyclophosphamide). External tumour and rectal temperatures were measured at the same time, twice daily, during the whole experiment. With the rectal temperature of the rats kept constant, the reduction in tumour dimensions following chemotherapy correlated via a linear relationship with the duration and degree of tumour hypothermia for the three tumours S 437, ISIS 208, ISIS 130. However, for the same reduction in tumour volume following chemotherapy, the duration and degree of transient tumour hypothermia varied according to the type of tumour and cytostatic agent studied. There was not correlation between the decrease in size of S 447 and external tumour hypothermia. Even when the reduction in tumour size was statistically significant, the hypothermic tumour phase after drug administration was not sufficient to be significant, except for vinblastine. However, the temperature of this slowly growing tumour before chemotherapy was particularly low. The measurement of the degree and duration of external tumour hypothermia of tumours following chemotherapy would represent a new physiological technique for measuring the efficacy and duration of action of cytostatic agents.


Inhibition of 5'-chloro-5'-deoxyadenosine on phosphoinositide and protein phosphorylation in swine platelets.
To study the effects of adenosine on the phosphorylation of phosphoinositides and proteins in platelets. In the presence of Mg2+ and/or Ca2+, swine thrombocytic membranes were incubated with [gamma-32P]ATP at 30 degrees C for 3 min and the incorporations of 32P into phospholipids or proteins were measured. 5'-Chloro-5'-deoxyadenosine decreased the formation of phosphatidylinositol 4-phosphate and phosphatidylinositol 4, 5-bisphosphate [IC50 71 and 75 (95% confidence limits 60-85 and 62-90) mumol.L-1, respectively], behaving as a competitive inhibitor to ATP, and inhibited the phosphorylation of pleckstrin (the major protein kinase C substrate) and myosin light chain [IC50 75 and 82 (95% confidence limits 62-90 and 66-102) mumol.L-1, respectively]. Adenosine affects the phosphoinositide signaling pathway in platelets, which helps to clarify the inhibition of adenosine on platelet activation.


Impact of intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell and nerve fibre layer thickness in Neovascular age-related macular degeneration.
To compare the effects of monotherapy with intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell layer (RGCL) and retinal nerve fibre layer (RNFL) in patients with naïve neovascular age-related macular degeneration (nAMD). This is a retrospective cohort study with three-groups comparison. 83 patients and 97 eyes on continuous monotherapy with an intravitreal anti-vascular endothelial growth factor (anti-VEGF) were followed for 24 months and divided into three groups according to anti-VEGF (aflibercept: 25 eyes, ranibizumab: 34 eyes, bevacizumab: 38 eyes). Main outcome measures included: RGCL and RNFL thickness, best corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV) and the presence of intraretinal fluids (IRF), subretinal fluids (SRF) and retinal pigment epithelial atrophy (RPE-atrophy). All outcome measures were recorded at the time of the first injection, 1 and 2 years after treatment and compared longitudinally and between groups. The mean age was 79 ± 7 years. The RGCL thickness, MV, CMT and the presence of IRF and SRF decreased significantly within all three medication groups (p < 0.05 for all) with no significant difference between groups over the 2-year follow-up period (p > 0.10 for all). The decrease in RNFL thickness was not significant within or between the groups after a 2-year follow-up (p > 0.055 for all). RPE-atrophy increased significantly after 2 years in all three groups (p < 0.028 for all) with no significant difference between groups at all three time points (p > 0.307 for all). BCVA was comparable between the three groups over the 2-year follow-up period (p > 0.22 for all). Monotherapy with intravitreal aflibercept, bevacizumab and ranibizumab was associated with comparable significant decreases in RGCL thickness, CMT, MV, IRF and SRF in naïve nAMD patients during the first 2 years of treatment. Furthermore, no significant differences either in BCVA or RNFL thickness were observed between the three intravitreal anti-VEFGs during the first 2 years of treatment.


Heart failure as a metabolic problem.
Chronic heart failure (CHF) remains an important and increasing public health care problem. Not until recently it has been recognised that CHF is a chronic progressive disorder affecting different physiological and metabolic pathways. Nowadays CHF is reviewed as the consequence of an interplay of haemodynamic, neurohormonal, immunological, and endocrine mechanisms, initially thought to have beneficial adaptive effects for the organism to compensate the heart's inability to pump properly. However, these secondary changes eventually contribute to further deterioration of CHF. This review focuses on metabolic features observed in patients with CHF and discusses immunological and neuroendocrine aspects and their potential contribution to the pathogenesis of CHF. The overall evidence suggests that advanced CHF is a multifactorial metabolic syndrome that can lead to cardiac cachexia and then carries a very poor prognosis. Joint efforts of cardiologists, endocrinologists, and immunologists are required to develop therapeutic strategies able to improve the metabolic status of CHF patients.


Abandoned Air Force base redesigned as rehabilitation center.
Renovation of a three-story hospital and construction of new one-story units consolidated scattered services and provided a barrier-free design for patients.


[Blood donation in urban areas].
Medical and technical developments increase the difficulty to provide sufficient safe blood for all patients in developed countries and their sociodemographic and societal changes. Sufficient national blood supply remains a reached, however still actual, challenge. Tomorrow is prepared today: the management of blood donation programs both in line with these developments and with social marketing strategies is one of the keys to success. If the main components of this organization are well known (mobile blood drives in various appropriate environments, and permanent blood donation centers) their proportions in the whole process must evolve and their contents require adaptations, especially for whole blood donation in urban areas. We have to focus on the people's way of life changes related to increasing urbanization of the society and prominent position taken by very large cities. This requires targeting several goals: to draw the attention of the potential blood-giving candidate, to get into position to collect him when he will decide it, to give meaning and recognition to his "sacrifice" (give time rather than donate blood) and to give him desire and opportunity to come back and donate one more time. In this strategy, permanent blood centers in urban areas have significant potential for whole blood collection, highlighted by the decrease of apheresis technology requirements. This potential requires profound changes in their location, conception and organization. The concept of Maison Du Don (MDD) reflects these changes.


ERβ may contribute to the maintaining of radial glia cells polarity through cadherins during corticogenesis.
Laminar organization of neurons in cerebral cortex is essential for normal brain function. Radial glial cells (RGCs), are highly polarized cells that serve as neuronal progenitors and as scaffolds for neuronal migration during construction of the cerebral cortex. Cadherins (E-cadherin and N-cadherin)-based adherins junctions, which anchor apical end-feet of adjacent RGCs to each other at the ventricular surface contribute to sustain the polarity and adhesion of RGCs, therefore affect production of RGCs and radial migration. Estrogen is a steroid hormone and contributes to the organizational sexual differentiation of the brain. We have previously demonstrated that ERβ expression in the cerebral cortex during corticogenesis and contribute to cerebral cortex development. This has been further confirmed by studies from estrogen receptor β knockout (ERβKO) mice, in which lack of ERβ in mice induced abnormal development of cerebral cortical structure, retarded migration of the neurons, and abnormal morphology of RGCs with truncated or less organized radial processes. These indicate that estrogen via ERβ affects RGCs development. Moreover, phenotype analysis in the ERβKO mice has confirmed that estrogen activation ERβ influence the polarity of epithelial tissue and structure integrity by modulating the level of cadherins (E-cadherin and N-cadherin). Thus, we propose that ERβ maybe affect the maintaining the polarity of RGCs through cadherins.


Experimental aluminum encephalomyelopathy. Relationship to human neurodegenerative disease.
Alzheimer's disease has a complex pathogenesis and is a devastating neurologic disorder, predominantly of the elderly human population. Neuronal cell loss and neuritic pathology are a major neuropathologic feature of Alzheimer's disease, but there is no established mechanism to explain the degenerative process. The development of suitable animal systems would be of great value in helping to understand the basic mechanisms underlying the disease. We propose that the aluminum maltolate-treated elderly rabbit is a potentially useful animal system to model Alzheimer's disease neurofibrillary pathology. Details of such an experimental aluminum encephalopathy produced in the rabbit are discussed, along with other aspects of aluminum-induced neurodegeneration.


Antagonism by idazoxan at low dose but not high dose, of the natriuretic action of moxonidine.
1. Recent studies concerning the imidazoline receptor have utilized idazoxan as a specific imidazoline receptor antagonist. The aim of the present study was to describe the in vivo effects of various doses of idazoxan on renal function, in the presence and absence of moxonidine, an I1 imidazoline receptor agonist. 2. In anaesthetized, unilaterally nephrectomized (7 to 10 days) Sprague Dawley rats, an intrarenal infusion of moxonidine (3 nmol kg-1 min-1) increased urine flow rate, sodium excretion and osmolar clearance without altering free water clearance. Pretreatment with intravenous idazoxan at 0.1 and 0.3 mg kg-1 produced a dose-related decrease in the renal actions of moxonidine. However, a higher dose of idazoxan (1 mg kg-1) was not as effective as the 0.3 mg kg-1 dose in blocking the effects of moxonidine. 3. In a separate series of experiments, the direct renal actions of idazoxan alone were investigated. Idazoxan at 0.3 mg kg-1 failed to alter urine flow rate and sodium excretion. However, idazoxan at 1 mg kg-1 produced a significant increase in urine flow rate and sodium excretion in association with an increase in osmolar clearance. 4. These results do not prove but are consistent with low doses of idazoxan antagonizing the sites stimulated by moxonidine (renal imidazoline receptors). However, at higher doses, idazoxan may function as a partial agonist and/or interact with other receptors to increase urine flow rate, independent of imidazoline receptor blockade. These studies underscore the importance of the dose of idazoxan administered when this antagonist is used as a tool to investigate imidazoline receptors.


Immunometabolism regulates TCR recycling and iNKT cell functions.
Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that express an invariant T cell receptor (TCR), which recognizes glycolipid antigens presented on CD1d molecules. These cells are phenotypically and functionally distinct from conventional T cells. When we characterized the metabolic activity of iNKT cells, consistent with their activated phenotype, we found that they had much less mitochondrial respiratory capacity but increased glycolytic activity in comparison to naïve conventional CD4+ T cells. After TCR engagement, iNKT cells further increased aerobic glycolysis, which was important for the expression of interferon-γ (IFN-γ). Glycolytic metabolism promoted the translocation of hexokinase-II to mitochondria and the activation of mammalian target of rapamycin complex 2 (mTORC2). Inhibiting glycolysis reduced the activity of Akt and PKCθ, which inhibited TCR recycling and accumulation within the immune synapse. Diminished TCR accumulation in the immune synapse reduced the activation of proximal and distal TCR signaling pathways and IFN-γ production in activated iNKT cells. Our studies demonstrate that glycolytic metabolism augments TCR signaling duration and IFN-γ production in iNKT cells by increasing TCR recycling.


Expression of MIF and TNFA in psoriatic arthritis: relationship with Th1/Th2/Th17 cytokine profiles and clinical variables.
Psoriatic arthritis (PsA) is an autoimmune inflammatory disease associated with psoriasis. The cause of this pathology is still unknown, but research suggests the diseases are caused by a deregulated cytokine production. MIF is a cytokine associated with immunomodulation of Th1, Th2, and Th17 cytokine profiles in inflammatory diseases. Based on this knowledge, the aim of this study was to determine the association of MIF and TNFA expression with Th1, Th2, and Th17 cytokine profiles in serum levels of PsA patients. A cross-sectional study was performed in 50 PsA patients and 30 control subjects (CS). The cytokine profiles were quantified by BioPlex MagPix system and the mRNA expression levels by real-time PCR. TNFA mRNA expression was 138.81-folds higher in PsA patients than CS (p < 0.001). Regarding MIF mRNA expression, no significant differences were observed; however, a positive correlation was identified between MIF mRNA expression and PsA time of evolution (r = - 0.53, p = 0.009). An increase of Th1 (IFNγ: PsA = 37.1 pg/mL vs. CS = 17 pg/mL, p < 0.05; TNFα: PsA = 24.6 pg/mL vs. CS = 9.8 pg/mL, p < 0.0001) and Th17 cytokine profiles (IL-17: PsA = 6.4 pg/mL vs. CS = 2.7 pg/mL, p < 0.05; IL-22: PsA = 8.4 pg/mL vs. CS = 1.8 pg/mL, p < 0.001), were found in PsA patients. Th2 cytokines were not significantly different in both groups. In conclusion, a high expression of TNFA mRNA, as well as an increase of Th1 and Th17 cytokine profiles evaluated by IFNγ, TNFα, IL-17, and IL-22 cytokines, was observed in PsA patients.


Comparative study of the Kumada, Negishi, Stille, and Suzuki-Miyaura reactions in the synthesis of the indole alkaloids hippadine and pratosine.
The total synthesis of hippadine by a tandem metalation/cross-coupling/lactamization strategy was investigated starting from either 7-bromoindole or a 6-halogenated methyl piperonate. The Kumada and Negishi cross-coupling reactions failed to provide any of the desired product. However, the Stille and Suzuki reactions furnished hippadine in low yields starting from the electron-deficient methyl 6-iodo- and 6-bromopiperonate, respectively. Starting from the metalated indole, only the Suzuki reaction occurred, affording hippadine in 67-74% and pratosine in 62% isolated yield.


Internal and external mycoflora of the American dog tick, Dermacentor variabilis (Acari: Ixodidae), and its ecological implications.
Scopulariopsis brevicaulis, the anamorph of Microascus brevicaulis (Microascaceae, Ascomycota), has been identified in the body contents of the tick Dermacentor variabilis. After topical application of the fungal inoculum, tick mortality was marked. This is the first account describing the internal mycoflora of D. variabilis with a novel technique used to recover potential biological control agents.


Alterations in N-linked oligosaccharides of glycoproteins during rat liver regeneration.
[3H]Mannose-labeled glycopeptides in the slices after partial hepatectomy were characterized by column chromatography using Sephadex G-50, DE-52 and Con A-Sepharose, and further by digestion with alpha-mannosidase and endo-beta-N-acetylglucosaminidase H. They contained both 'complex type' and 'high-mannose type' oligosaccharides. A higher proportion of 'complex type' oligosaccharides was contained in regenerating liver 24 h after partial hepatectomy than in control. This tendency was increased gradually with time and was most pronounced at 144 h. In our previous studies, the activities of microsomal N-acetylglucosaminyltransferase towards endogenous and exogenous acceptors at 144 h after partial hepatectomy were shown to exceed most prominently that in control. No differences in the oligosaccharides were observed at 240 h when the deficit of liver had been restored. The oligosaccharides of glycopeptides in the incubation media were mostly 'complex type' and the differences between regenerating liver and control were observed only at 144 h. These results suggest that oligosaccharide processing of glycoproteins is regulated at the transfer step of peripheral N-acetylglucosamine to core oligosaccharides 144 h after partial hepatectomy, and that these alterations in oligosaccharides of glycoproteins may be related to hypertrophy and hyperplasia of hepatic cells in liver regeneration.


Natural course of lid wiper epitheliopathy (LWE) in symptomatic contact lens wearers.
To establish the time course of lid wiper epitheliopathy (LWE) in established CL wearers after a single day (6-10 h) of daily disposable contact lens (CL) wear, the following day post-CL removal and 1-week after CL discontinuation. Twenty-one symptomatic (CLDEQ-8 score ≥ 12) habitual wearers of MyDay® silicone hydrogel daily disposable were included. LWE staining was assessed prior to CL wear (Visit 1, V1) using semi-automated analysis after instillation of two drops of 1 % lissamine green (10 μL) that were applied to the superior bulbar conjunctiva. LWE measurements were repeated after 6-10 h of continuous CL wear (Visit 2, V2), post-CL removal the following day (Visit 3, V3) and after 1-week CL discontinuation (Visit 4, V4). At each visit, ocular symptoms were evaluated using the SPEED-8 questionnaire and set of 0-100 visual analogue scales (VAS). LWE showed no significant changes after 6-10 h of continuous CL wear (p = 0.536), post-CL removal the following day (p = 0.677) or following 1-week of CL discontinuation (p = 0.478). Analysis revealed a significant improvement in symptomatology between V1 and V2 (SPEED-8, p < 0.01) and also improvements in the 0-100 VAS scores between V2 and V4 for average daily dryness (p < 0.01), end-of-day dryness (p < 0.01) and frequency of end-of-day dryness (p < 0.05). The present data suggest that the etiology of LWE is multifactorial and the sole intervention of temporarily discontinuing CL wear does not lead to resolution of these clinical signs.


Outbreak of healthcare-associated bacteremia caused by Burkholderia gladioli due to contaminated multidose vials with saline solutions in three Croatian hospitals.
Burkholderia gladioli has been associated with infections in patients with cystic fibrosis, chronic granulomatous disease, and other immunocompromising conditions. The aim of this study was to better depict the outbreak of healthcare-associated bacteremia caused by B. gladioli due to exposure to contaminated multidose vials with saline solutions. An environmental and epidemiologic investigation was conducted by the Infection Prevention and Control Team (IPCT) to identify the source of the outbreak in three Croatian hospitals. During a 3-month period, 13 B. gladioli bacteremia episodes were identified in 10 patients in three Croatian hospitals. At the time of the outbreak, all three hospitals used saline products from the same manufacturer. Two 100-ml multidose vials with saline solutions and needleless dispensing pins were positive for B. gladioli. All 13 bacteremia isolates and two isolates from the saline showed the same antimicrobial susceptibility patterns and pulsed-field gel electrophoresis profile, demonstrating clonal relatedness. When an environmental pathogen causes an outbreak, contamination of intravenous products must be considered. Close communication between the local IPCT and the National Hospital Infection Control Advisory Committee is essential to conduct a prompt and thorough investigation and find the source of the outbreak.


Effects of very long (up to 10 years) proton pump blockade on human gastric mucosa.
Long-term use of proton pump inhibitors (PPI) has been reported to worsen oxyntic mucosa gastritis and the resulting gland atrophy has been considered a potential risk factor for neoplastic changes in the gastric mucosa. The present study examines the effect of extended continuous PPI treatment for up to 10 years on the exocrine and endocrine stomach of patients with acid-related diseases of the upper GI tract. Biopsies from the antral and oxyntic mucosa taken at regular time intervals were examined for gastritis, atrophy, intestinal metaplasia, Helicobacter pylori and argyrophil cells and correlated to serum gastrin levels. A general amelioration of antral gastritis without relevant changes of atrophy or intestinal metaplasia, contrasted with the worsening of gastritis and gland atrophy seen in the oxyntic mucosa of reflux esophagitis (but not gastric or duodenal ulcer) patients in the presence of H. pylori infection. In association with PPI- induced hypergastrinemia, argyrophil cell hyperplasia (but not dysplasia or neoplasia) developed in the oxyntic mucosa. The present results outline the milder pretreatment pattern and higher proneness to PPI-related, H. pylori-restricted worsening of oxyntic mucosa gastritis in reflux esophagitis compared to gastric ulcer or duodenal ulcer patients. In addition, they confirm a substantial safety of long-term PPI therapy as concerns neoplastic changes in the exocrine and endocrine human stomach.


Nursing knowledge and practices regarding subcutaneous fluid administration.
To describe the evidence in the literature regarding the knowledge and practices of the nursing team about subcutaneous administration of drugs and fluids in adults. Integrative review of the literature using the descriptors "nursing", "hypodermoclysis", "drug administration routes", "adult health," and "knowledge," in English, Spanish, and Portuguese, with no publication deadline. Of the 569 articles found, eight made up the sample. A predominance of international journals (75%) with more than five years of publication (62.5%). The analysis of the methodological characteristics showed a predominance of literature reviews (25%), quantitative studies (62.5%), cross-sectional studies (50%), and non-experimental studies (50%). Although it is an old technique with proven efficacy, hypodermoclysis is still little used, a puzzling fact due to its advantages and indications for any age. descrever as evidências, na literatura, sobre os conhecimentos e as práticas da equipe de enfermagem na administração de medicamentos e de fluidos por via subcutânea no adulto. revisão integrativa da literatura utilizando os descritores enfermagem, hipodermóclise, vias de administração de medicamentos, saúde do adulto e conhecimento; nos idiomas inglês, espanhol e português, sem data limite de publicação. Dos 569 artigos encontrados, oito compuseram a amostra. predomínio de revistas internacionais (75%) e com mais de cinco anos de publicação (62,5%). Ao analisarem-se as características metodológicas, predominaram: revisões de literatura (25%), estudos quantitativos (62,5%), estudos transversais (50%) e não-experimentais (50%). apesar de se tratar de uma técnica antiga com eficácia comprovada, a hipodermóclise ainda é pouco utilizada, fato incoerente pelas suas vantagens e suas indicações para qualquer idade.


Evaluation of a mobile team dedicated to behavioural disorders as recommended by the Alzheimer Cooperative Valuation in Europe joint action: observational cohort study.
Preventing behavioural crises appears to be crucial to promote quality of life of the patient-caregiver dyad, to reduce inappropriate hospitalizations and to delay institutionalization. The Alzheimer Cooperative Valuation in Europe promotes mobile care to prevent patients from severe behavioural and psychological symptoms in dementia. This study assessed the potential efficacy of a mobile team for Alzheimer's disease on hospitalization sparing and behavioural disorder reduction. A cohort study was set up from 1 January 2012 to 31 December 2013 by the Clinical and Research Memory Centre of Lyon (France). It included patients with behavioural and psychological symptoms living at home or in a nursing home. An interview explored the alternative patient pathways used by general practitioners (GPs) if the mobile team had not existed (hospitalization sparing). The Neuropsychiatry Inventory score was assessed at inclusion and 30 days later. The sample included 424 consecutive patients with Alzheimer's disease or related disorders and behavioural disorders at any cognitive and functional stage of the disease, taken in charge by the mobile team. Amongst the 424 patients (84.0 ± 7.2 years), 220 (51.9%) hospitalizations were considered by their GPs and 181 (82.3%) were avoided. The Neuropsychiatric Inventory score declined after mobile team intervention (45.8-29.9, P < 0.001). Sleep and appetite disorders, endangered situation and caregiver burnout were associated with higher risk of hospitalization at 30 days. The mobile team for Alzheimer's disease allows a high proportion of hospitalizations related to behavioural disorders to be avoided and may help to reduce behavioural disorders.