The usefulness of a hydrolysed fish and rice starch elimination diet for the diagnosis of adverse food reactions in cats: an open clinical trial.
Diagnosis of adverse food reaction (AFR) is based on an eight week elimination diet (ED) and is confirmed by relapse upon re-challenge with the previously fed diet. Hydrolysed EDs are commonly used for this purpose. To evaluate the commercially available hydrolysed fish protein and rice starch ED Farmina UltraHypo (FUH) for the diagnosis of feline AFR. Thirty-two nonseasonally pruritic cats. Pruritus was assessed with a new dual Visual Analog Scale, lesions with the Scoring Feline Allergic Dermatitis scale and Quality of Life with a validated questionnaire on days 0 and 56. Short-acting corticosteroids or oclacitinib were permitted during the first six weeks. Cats showing 50% pruritus and/or lesional improvement were separately challenged with their prior diet, fish and rice. Cats not responding to the study diet were fed another hydrolysed diet for two months. Twenty-five cats completed the ED: four dropped out due to vomiting and/or diarrhoea, one owing to low palatability and two were lost to follow-up. In 17 cats, pruritus improved by >50% and these underwent dietary challenges. Of these, nine reacted to their prior diet and/or fish and/or rice and were diagnosed with AFR, while eight did not relapse (and a diagnosis of AFR was considered to be doubtful). Of the eight cats in which pruritus did not improve, four underwent a second ED with no improvement. FUH may be a useful ED for the diagnosis of feline AFR, even in cats reacting to fish or rice.


Influence of enteric bacteria conditioned media on recovery of Escherichia coli O157:H7 exposed to starvation and sodium hypochlorite.
To examine the effect that starvation and sodium hypochlorite stress have on virulence of Escherichia coli O157:H7 and the influence of conditioned media on recovery of stressed cells. Escherichia coli O157:H7 was starved for 5 days then exposed to 1 microg ml(-1) sodium hypochlorite, suspended in defined media Dulbecco's Modified Eagle's Medium supplemented with conditioned media, sampled over a 12-h period; and assayed for growth, production of Shiga toxin (Stx), and attachment to HCT-8 cells. During recovery, stressed and control cells grown in conditioned media exhibited greater attachment efficiencies to HCT-8 cells then cells in DMEM alone. Production of Stx by treated cells mimicked Stx production by control cells suggesting that components of conditioned media assist in recovery. Results showed that levels of autoinducer-2 fluctuate during recovery and growth suggesting involvement of a quorum sensing mechanism during the recovery of stressed E. coli O157:H7. The recovery of stressed E. coli O157:H7 exposed to starvation conditions and HOCl is positively affected by the presence of autoinducer-2 thereby influencing virulence factor production. Food-borne pathogens in a stressed state prior to ingestion can rapidly recover in the presence of bacterial by-products; exhibiting virulence characteristics and presenting a microbial food safety hazard.


Pulmonary function in patients surviving to COVID-19 pneumonia.
The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia. Our case series consisted of 13 patients with COVID-19 pneumonia. At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014). These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern.


An integrated scale-down plant for optimal recombinant enzyme production by Pichia pastoris.
An integrated bioprocess was created in a scale-down production plant by developing a two-stage enzyme production process with Pichia pastoris, containing a cell-breeding reactor and a production reactor in combination with a three-stage downstream process. To harvest the secreted enzymes, a disc separator and a cross-flow microfiltration clear the broth from the cells. Purification with hydrophobic interaction chromatography removes other proteins, concentrates the product, and prepares the enzyme solution for lyophilization. Fully automated and broad observable multi-stage parallel process courses have been developed using industrial process control systems and at-line measurements for enzyme concentration and enzyme activity. Optimal process conditions were found by application of Design of Experiments (DoE) for the production process.


Critical review of decision support tools for sustainability assessment of site remediation options.
In Europe alone, there are more than 2,5 million potentially contaminated sites of which 14% are expected to require remediation. Contaminated soil and groundwater can cause damage to human health as well as to valuable ecosystems. Globally more attention has been paid to this problem of soil contamination in the past decades. For example, more than 58 000 sites have been remediated in Europe between 2006 and 2011. Together with this increase in remediation projects there has been a surge in the development of new remediation technologies and decision support tools to be able to match every site and its specific characteristics to the best possible remediation alternative. In the past years the development of decision support tools (DST) has evolved in a more sustainable direction. Several DSTs added the claim not only to denote effective or technologically and economically feasible remediation alternatives but also to point out the more or most sustainable remediation alternatives. These trends in the evaluation of site remediation options left users with a confusing clew of possibly applicable tools to assist them in decision making for contaminated site remediation. This review provides a structured overview on the extent decision support tools for contaminated site remediation, that claim to assist in choosing the most sustainable remediation alternative, actually include the different elements of sustainability proposed in our assessment framework. The review contains an in-depth analysis of thirteen tools specifically developed to assess the sustainability of site remediation alternatives. This analysis is based on six criteria derived from the definition of sustainable development of the Brundtland report. The six criteria were concretized by using the three pillars of sustainability, applied to site remediation according to the SuRF-UK framework, two criteria derived from Life Cycle Assessment and Cost-Benefit Analysis, and an 'User friendly' criterion. These elements come together in a framework, drafted for this study, containing six criteria covering the environmental, economic, social, time, uncertainty aspects and user friendliness of a sustainable site remediation. The main remarks uncovered by this review are the imbalance of used indicators still expressing a strong preference for the environmental aspect at the expense of the economic and social aspects of sustainability, the lack of consistency in the terminology used within the field and the failure in adapting released tools to recent legislation or scientific advancements.


Portaprival collaterals following distal splenorenal shunt. Incidence, magnitude and associated portal perfusion changes.
Collateral venous pathways develop between the high pressure portal vein and low pressure splenic vein following distal splenorenal shunt. This review of angiography in 50 patients with cirrhosis prior to and 1 year after DSRS shows that 98% developed collaterals: 72% transpancreatic, 48% transgastric, and 46% colonic. Multiple pathways developed in 64% of patients. Grading of the size of these collaterals showed that in 74% these exceeded the size of the portal and/or superior mesenteric vein. The effect of these collaterals on portal perfusion showed that 32% lost perfusion at 1 year, but significantly (P less than 0.05) more alcoholics (48%) lost perfusion than nonalcoholics (16%). The size, site and number of collaterals was not different between etiologies. Late follow-up in a subset of 32 of the patients showed no change in the site, and minimal increase in size of the collaterals at 3-11 years, with no further loss of portal perfusion. We conclude that virtually all patients develop collaterals after DSRS, these are along predictable pathways and are of significant size in the majority. However, development of collaterals per se does not equate to loss of portal venous flow, and a stable pattern is set in the first year after shunt. Characterization of these pathways will permit new approaches to minimizing their development.


Cumulative live birth rates of patients in the Peruvian Andes according to the POSEIDON criteria: a single-center retrospective analysis.
To identify low prognosis in-vitro fertilization (IVF) patients treated at Centro de Fertilidad y Ginecología del Sur (CFGS) based on the POSEIDON criteria. This retrospective study included 412 IVF patients and assessed them based on the POSEIDON criteria to describe the cumulative live birth rates seen in each group. 13.1% of patients met the POSEIDON criteria, and the proportion of cases in POSEIDON groups 1, 2, 3 and 4 were 20.4%, 31.5%, 14.8%, and 33.3%, respectively. The cumulative live birth rate for the individuals meeting the POSEIDON criteria was 25.9%, while for patients in POSEIDON groups 1, 2, 3, and 4 the rates were 45.5%, 29.4%, 25.0%, and 11%, respectively. The differences were not statistically significant due to the small number of cases. Patients belonging to the four POSEIDON groups were described at CFGS. Age and number of retrieved mature oocytes were determining parameters in the prognosis of pregnancy in IVF/ICSI patients.


The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study.
Two extracellular enzymes of the SGNH hydrolase superfamily reveal highly homologous 3D structures, but act on different substrates; one is a true phospholipase A1 from Streptomyces albidoflavus (SaPLA1, EC: 184.108.40.206, PDB code: 4HYQ), whereas the promiscuous enzyme from Streptomyces rimosus (SrLip, EC: 188.8.131.52, PDB code: 5MAL) exhibits lipase, phospholipase, esterase, thioesterase, and Tweenase activities. To get insight into binding modes of phospholipid and triglyceride substrates in both enzymes and understand their chain-length preferences, we opted for computational approach based on in silico prepared enzyme-substrate complexes. Docking procedure and molecular dynamics simulations at microsecond time scale were applied. The modelled complexes of SaPLA1 and SrLip enzymes revealed substrate accommodation: a) the acyl-chain attached to sn-1 position fits into the hydrophobic pocket, b) the acyl-chain attached to sn-2 position fits in the hydrophobic cleft, whereas c) the sn-3 bound acyl chain of the triglyceride or polar head of the glycerophospholipid fits into the binding groove. Moreover, our results pinpointed subtle amino acid differences in the hydrophobic pockets of these two enzymes which accommodate the acyl chain attached to sn-1 position of glycerol to be responsible for the chain length preference. Slight differences in the binding grooves of SaPLA1 and SrLip, which accommodate the acyl chain attached to sn-3 position are responsible for exclusive phospholipase and both phospholipase/lipase activities of these two enzymes, respectively. The results of modelling correlate with the experimentally obtained kinetic parameters given in the literature and are important for protein engineering that aims to obtain a variant of enzyme, which would preferably act on the substrate of interest.


Association Between Omega-3 Fatty Acid Treatment and Atrial Fibrillation in Cardiovascular Outcome Trials: A Systematic Review and Meta-Analysis.
Data on the relationship between omega-3 fatty acid (n-3 FA) therapy with atrial fibrillation (AF) have been inconsistent. We investigate the association between n-3 FA and risk for AF by pooling data from available large, cardiovascular outcome trials. We performed a systematic search on PubMed and Embase for studies on n-3 FA with AF as an outcome measure. Large (≥ 1000 participants) randomized controlled trials with ≥ 1-year follow-up period were included. The association between n-3 FA and risk of AF or stroke was assessed. Mantel-Haenszel random effects model was used to calculate risk ratios (RR) with 95% confidence intervals (CI). We then performed meta-regression to evaluate effect on AF by dose of n-3 FA therapy. A total of 8 randomized control trials encompassing 83,112 participants were included in the meta-analysis. Of these, five trials assessed a lower dose of n-3 FA (≤ 1 g daily, n = 61,096) while 3 trials assessed a higher dose (> 1 g daily, n = 22,016). In meta-analysis, a significant association was noted between n-3 FA treatment and risk of AF (4.0% vs 3.3%; RR 1.24, 95% CI 1.11-1.38, p = 0.0002). There was a modest but still significant association in the lower dose (n-3 FA ≤ 1 g daily) sub-group (RR 1.12, 95% CI 1.04-1.21, p = 0.004) and stronger association in the higher dose (n-3 FA > 1 g daily) sub-group (RR 1.51, 95% CI 1.26-1.80, p < 0.001; p-interaction between low versus high subgroups = 0.003). There was no increase in stroke risk (RR 1.04, 95% CI 0.90-1.20). Meta-regression demonstrated a significant association between dose of n-3 FA with risk for AF events (log RR 0.103, 95% CI 0.048-0.159, p < 0.001). While overall AF event rates were low, n-3 FA treatment is associated with increased risk for AF.


Vazirani-Akinosi Nerve Block Technique: An Asset of Oral and Maxillofacial Surgeon.
Vazirani-Akinosi nerve block technique is an established and a reliable technique to achieve anaesthesia in mandible with high success rate and is useful in cases where Halstead's technique fails to provide desired anaesthetic effect. A total of 140 ASA-I or ASA-II patients, both genders, between 16 and 45 years who required extraction of mandibular tooth were divided into two groups. Group A received nerve block through Halstead technique, while Group B received nerve block through Vazirani-Akinosi technique with 2% lignocaine containing 1:200,000 adrenaline. We evaluated the subjective and objective onset of anaesthesia, outcome of the injection, outcome of the aspiration and patient satisfaction. In Group A, the altered sensation was experienced at 68.70 s, while in Group B it was 92.55 s and the difference was statistically highly significant (p < 0.001) between the two groups. The mean onset of anaesthesia (measured with Electric pulp tester) in Group A was 78.36 s, while for Group B it was 104.24 s and this difference was statistically highly significant (p < 0.001). Positive aspiration was seen in 11 (15.71%) patients in Group A and in 2 (2.86%) patients in Group B. The success rate for Group A was 81.42% and for Group B it was 97.14%. Vazirani-Akinosi technique provides desirable surgical anaesthesia with relatively high success rate and lower incidence of positive aspiration and can be considered as a boon for oral and maxillofacial surgeons.


The Sociodemographic and Risk Factors for Fuchs' Endothelial Dystrophy: A Nationwide, Matched Case-Control Study in Taiwan.
This nationwide, population-based, retrospective, matched case-control study included 4334 newly diagnosed Fuchs' endothelial dystrophy (FED) patients who were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 371.57, and selected from the Taiwan National Health Insurance Research Database. The age-, sex-, and index-date-matched control group included 4334 non-FED controls selected from the Taiwan Longitudinal Health Insurance Database 2000. Ocular allergic conditions and sociodemographic conditions were examined using univariate logistic regression analyses and paired t-test was used for continuous variables. Adjusted logistic regression was used to compare the odds ratio (OR) of the FED development. Patients with ocular allergic conditions were more likely to have FED than the controls (OR = 25.50, 95% CI = 12.58-51.68, p < 0.0001) even after conditional logistic regression was conducted (adjusted OR = 25.26, 95% CI = 11.24-56.77, p < 0.0001). Regarding the sociodemographic factors, we found that more than half of the FED patients in Taiwan were aged ≥45 years old, there was an equal female-to-male ratio (1.06:1), and patients with a lower income and living in northern Taiwan had higher odds of developing FED. The results strongly support an association between ocular allergic conditions, geographic region, residential status, income, and FED.


Rhesus macaque and mouse models for down-selecting circumsporozoite protein based malaria vaccines differ significantly in immunogenicity and functional outcomes.
Non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic. A comparison of immunogenicity, fine-specificity and functional activity of two Alum-adjuvanted Plasmodium falciparum circumsporozoite protein (CSP)-based vaccines was conducted in mouse and rhesus models. One vaccine was a soluble recombinant protein (CSP) and the other was the same CSP covalently conjugated to the Qβ phage particle (Qβ-CSP). Mice showed different kinetics of antibody responses and different sensitivity to the NANP-repeat and N-terminal epitopes as compared to rhesus. While mice failed to discern differences between the protective efficacy of CSP versus Qβ-CSP vaccine following direct challenge with transgenic Plasmodium berghei parasites, rhesus serum from the Qβ-CSP-vaccinated animals induced higher in vivo sporozoite neutralization activity. Despite some immunologic parallels between models, these data demonstrate that differences between the immune responses induced in the two models risk conflicting decisions regarding potential vaccine utility in humans. In combination with historical observations, the data presented here suggest that although murine models may be useful for some purposes, non-human primate models may be more likely to predict the human response to investigational vaccines.


Metagenomic investigation of potential abortigenic pathogens in foetal tissues from Australian horses.
Abortion in horses leads to economic and welfare losses to the equine industry. Most cases of equine abortions are sporadic, and the cause is often unknown. This study aimed to detect potential abortigenic pathogens in equine abortion cases in Australia using metagenomic deep sequencing methods. After sequencing and analysis, a total of 68 and 86 phyla were detected in the material originating from 49 equine abortion samples and 8 samples from normal deliveries, respectively. Most phyla were present in both groups, with the exception of Chlamydiae that were only present in abortion samples. Around 2886 genera were present in the abortion samples and samples from normal deliveries at a cut off value of 0.001% of relative abundance. Significant differences in species diversity between aborted and normal tissues was observed. Several potential abortigenic pathogens were identified at a high level of relative abundance in a number of the abortion cases, including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Streptococcus equi subspecies zooepidemicus, Pantoea agglomerans, Acinetobacter lwoffii, Acinetobacter calcoaceticus and Chlamydia psittaci. This work revealed the presence of several potentially abortigenic pathogens in aborted specimens. No novel potential abortigenic agents were detected. The ability to screen samples for multiple pathogens that may not have been specifically targeted broadens the frontiers of diagnostic potential. The future use of metagenomic approaches for diagnostic purposes is likely to be facilitated by further improvements in deep sequencing technologies.


Isolated iliac artery aneurysm rupture causing lumbar plexopathy.
Isolated iliac artery aneurysms (IIAAs) are rare. We present a patient with lumbosacral plexopathy due to common iliac artery aneurysm rupture that presented with left monoplegia.


Angiotensin-converting enzyme inhibitor use in the year 2005.
The angiotensin-converting enzyme (ACE) inhibitor drug class is one with considerable staying power. ACE inhibitors are not only well established antihypertensive agents but also are compounds that fairly regularly provide end-organ protection. Several of the ACE inhibitors are entangled in an active debate regarding class effect. Class effect for ACE inhibitors is a hopelessly confused term because its definition is not standardized and is subject to interpretation that in many cases is self-serving. For the most part, ACE inhibitor side effects are readily identifiable, and management strategies put in place can be logical and sequential. The future of this drug class remains bright. Other drug classes, such as angiotensin receptor blockers, have narrowed-but not entirely closed-the outcomes gap that exists between these two drug classes.


An exploration of an innovative methodological approach for examining nurses' heuristic use in clinical practice.
What heuristics (reasoning strategies) do experienced critical care nurses use to assist in reasoning and making decisions about patient care? In this study, think aloud data were collected and protocol analysis was utilized to identify and describe the heuristics that permitted nurses to evaluate patient data, assess patient status, and make decisions necessary to maintain patient stability. Five heuristics were identified: pattern recognition, attending, anchoring, focused questioning, and listing. Clearer understanding of nurses' heuristic use could improve reasoning in practice, and could also provide educators with strategies to enhance the reasoning of their students.


Ectopic pulmonary cartilage and bone in domestic fowl.
The occurrence and histological appearance of ectopic pulmonary cartilage and bone in domestic fowl was investigated. Its incidence was shown to vary in different strains of birds. The structures may occur in newly hatched chicks and are similarly present in birds maintained on diets containing bonemeal and diets without it. They could not be experimentally induced by bronchial insufflation of fine bone particles. Previous theories of their genesis are discussed and it is concluded that they do not originate from either inhaled dietary bonemeal or disease processes but are probably abnormal embryonic induction of mesenchyme or cartilaginous germ cells displaced from adjacent bronchi.


Malignant Ventricular Tachycardia, Ventricular Wall Ablation, and Orthotopic Heart Transplantation.
Described herein are three patients with refractory ventricular tachycardia and one or more unsuccessful ablation procedures finally leading to orthotropic heart transplantation (OHT). The latter procedure allowed examination of the ventricular ablation sites, an unusual opportunity reported previously in few patients (all case reports). The acute ablation lesions are unique, with necrosis of the myocardial fibers adjacent to the endocardium and encircled by layers of extravasated erythrocytes in the deeper myocardial wall. All 3 patients returned to normal activities following the OHT.


Fibromyalgia complicating disease management in rheumatoid arthritis.
To evaluate frequency of fibromyalgia in rheumatoid arthritis and its effect on disease activity score. Cross-sectional study. The Indus Hospital, Karachi, from December 2010 to May 2011. All adult patients of either gender diagnosed as rheumatoid arthritis on the basis of clinical, laboratory and X-ray criteria were included in the study. The sample data was separated into two groups depending on presence or absence of fibromyalgia and 28 joint disease activity score (DAS-28) value was evaluated. There were 31 (25.83%) patients with rheumatoid arthritis and fibromyalgia (RAFM) out of the total 120. The median (IQR) age of patients was 40 (32 - 51) years. All were females. The overall female frequency was 79 (88.8%). The median (IQR) DAS-28 score in RA group was 4.9 (3.66 - 5.71), while the median (IQR) DAS-28 score in RAFM was 7.04 (6.62 - 7.64) [p < 0.0001]. The number of patient getting combination therapy of DMARD in RAFM group was 61.3% while in RA group was 42.7%. DAS-28 was found to be significantly higher in RAFM patients probably because of higher perception of pain.


Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells.
Individuals with neurofibromatosis type 1 (NF1) are predisposed to certain cancers including juvenile chronic myelogenous leukaemia (JCML). The NF1 tumour-suppressor gene encodes a protein (neurofibromin) that accelerates GTP hydrolysis on Ras proteins. Here we show that primary leukaemic cells from children with NF1 show a selective decrease in NF1-like GTPase activating protein (GAP) activity for Ras but retain normal cellular GAP activity. Leukaemic cells also show an elevated percentage of Ras in the GTP-bound conformation. JCML cells are hypersensitive to granulocyte-macrophage colony stimulating factor (GM-CSF), and we observed a similar pattern of aberrant growth in haematopoietic cells from Nf1-/- mouse embryos. These data define a specific role for neurofibromin in negatively regulating GM-CSF signaling through Ras in haematopoietic cells and they suggest that hypersensitivity to GM-CSF may be a primary event in the development of JCML.


Treatment of unscheduled bleeding in women using extended- or continuous-use combined hormonal contraception: a systematic review.
Unscheduled uterine bleeding is common among women who choose extended or continuous combined hormonal contraception and may subsequently lead to method discontinuation. This systematic review evaluates the evidence on treatments for unscheduled bleeding for women using continuous or extended combined hormonal contraception. We searched the PubMed database for peer-reviewed articles that were published in any language from inception of the database through January 2012 and were relevant to therapeutic or prophylactic treatments for unscheduled uterine bleeding during extended or continuous combined hormonal contraception use. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence. Four articles met the inclusion criteria. Evidence from two randomized controlled trials, both of fair quality, suggested that a short hormone-free interval of 3 or 4 days improved a current unscheduled bleeding episode. Evidence from one randomized controlled trial of fair quality suggested that oral doxycycline (100 mg twice daily) did not improve a current unscheduled bleeding episode. One good quality randomized controlled trial suggested that prophylactic treatment with a daily low dose of oral doxycycline (40 mg) caused earlier onset of amenorrhea in new extended combined oral contraceptive users. Limited evidence suggests that introducing a short hormone-free interval when unscheduled bleeding occurs during continuous or extended hormonal contraceptive use may reduce unscheduled bleeding days; one study suggests that twice-daily oral doxycycline initiated at the time of unscheduled bleeding is an ineffective treatment. Limited data suggest that prophylactic low-dose daily oral doxycycline may induce earlier amenorrhea among new extended combined hormonal contraceptive users.


Serum antielastase deficiency in tight-skin mice with genetic emphysema.
The tight-skin (Tsk) mouse is a model of genetically determined emphysema. The cause for the development of the lung lesion is unknown. In the present study we investigated the lung morphometry and the serum elastase inhibitory capacity (EIC) of Tsk mice. Mean interalveolar distance was significantly greater (+60%) in Tsk mice than in C57 Bl/6J, NMRI, and Balb/c mice, which have similar values. Serum of Tsk mice against mouse leukocyte elastase (MLE) has significantly lower EIC values than that of NMRI, Balb/c (-64%), and C57 Bl/6J (-50%) mice. Similar results were obtained when porcine pancreatic elastase (PPE) was used. Against human leukocyte elastase (HLE), however, there was no difference among the strains, all of which had high EIC values. Preincubation of mouse (C57 Bl/6J) serum with chloramine-T (CT) resulted in an almost complete inhibition of EIC against MLE and PPE but only in a 20% inhibition against HLE using a synthetic substrate. Using elastin Congo Red as substrate, CT inhibited EIC against MLE and PPE by approximately 70% but did not affect the EIC against HLE. These results indicate that (1) the Tsk mouse can be considered a model of severe inborn deficiency of serum antielastase activity which is associated with emphysema; and (2) MLE and PPE can be considered interchangeable in studies of serum EIC in the mouse. On the other hand, the differences between MLE and HLE preclude the use of HLE for EIC determination in this species.


CD8 T cell memory.
This review describes what is generally known about CD8 immune responses, and focus in the most recent advances in this domain. It also attempts to point to the areas where experimental evidence is contradictory or insufficient, and thus require further exploration and clarification.


Changes in the vaginal microbiota across a gradient of urbanization.
The vaginal microbiota of healthy women typically has low diversity, which increases after perturbations. Among these, lifestyle associated with certain sexual and antimicrobial practices may be associated with higher diversity. To test this hypothesis, we characterized the vaginal microbiota in the cervicovaginal and introital sites in sexually active Amerindians (N = 82) spanning urbanization, and in urban mestizos (N = 29), in the Venezuelan Amazonas. HPV status was also considered. Sampling was performed in an urban gradient from remote villages to a town, and women were individually classified by the degree of urbanization (low, medium, and high). Amerindian cervicovaginal and introital microbiota diversity were not associated with major changes in urbanization or ethnicity. There was a non-significant trend of increased diversity with urbanization, with a few taxa found overrepresented in urban Amerindians (Brevibacterium linens and Peptoniphilus lacrimalis) or mestizos (Mobiluncus mulieris and Prevotella sp.). Among all women, cervicovaginal and introital samples clustered, respectively, in four and two community state types (CSTs), where most profiles were dominated by Lactobacillus iners, Gardnerella vaginalis or were highly diverse profiles. HPV status did not associate with microbial diversity. In conclusion, no association was found between urban level and the vaginal microbiome in Amerindian women, and little difference was found between ethnicities. L. iners and high diversity profiles, associated with vaginal health outcomes, prevail in these populations.


Transitioning to Telehealth: Today's Guidelines for Future Sustainability.
The coronavirus disease 2019 pandemic has brought about many changes and catapulted telehealth into the mainstream of health care delivery. Audio and video conference health care visits have become commonplace and have impacted geographic barriers and access to care issues with the potential for care coordination in our fragmented health care delivery system. To make this dramatic shift from face-to-face health care to telehealth care, providers must learn to quickly transition to this new format. A discussion of the structure, process, and outcomes of telehealth addresses provider and consumer concerns and sets up guidelines for incorporating telehealth and patient satisfaction into your practice.


[Retroperitoneal rhabdomyosarcoma revealed by acute kidney failure in children. Report of a case].
Retroperitoneal sarcomas are rare tumors representing 0.1% to 0.2% of all malignant tumors. They are usually revealed by an abdominal mass (33%), possibly associated with pain (41%). Edema of the lower limbs is reported in 10% of cases. Acute renal failure with anuria by bilateral ureteral compression, associated with invasion of the inferior vena cava has not been previously reported.


Prevalence and severity of neurologic dysfunction in critically ill patients. Influence on need for continued mechanical ventilation.
The relative importance of neurologic dysfunction in critically ill mechanically ventilated patients has not been well studied. This study investigates the prevalence of neurologic dysfunction in critically ill mechanically ventilated patients and its influence on preventing the discontinuation of mechanical ventilation and patient outcome. Prospective study. University-based, tertiary care center. All eligible adult patients mechanically ventilated for more than 48 h were included. A total of 66 patients were evaluated. None. Two independent questionnaires, one completed by the critical care attending physician documenting the major clinical factors necessitating continued mechanical ventilation, and a second questionnaire, completed by a critical-care trained neurologist documenting neurologic status and objective cardiopulmonary status formed the basis for outcome measurements. Respiratory and physiologic data, the patient's clinical conditions, and outcome (mortality) were also included in the database. Pulmonary factors were the major reason for prolonged ventilation in only 51 percent of the patient evaluations. Neurologic status was the major factor necessitating continued mechanical ventilation in 32 percent of the patient evaluations and a significant contributing factor in an additional 41 percent. Of the neurologic factors, diminished level of consciousness was the major cause of continued ventilatory support. This was usually due to a systemic illness, rather than a primary central nervous system disorder. Mortality was significantly lower in patients who continued to require mechanical ventilation after 48 h because of neurologic factors as opposed to pulmonary factors (15 percent vs 72 percent, p = 0.002). There is a high prevalence of neurologic dysfunction in critically ill patients and this problem plays a significant role in preventing the discontinuation of mechanical ventilation. Altered mental status is a major factor necessitating continued mechanical ventilation in combined medical-surgical intensive care units.


Do the bioactive effects of platelet-rich plasma and platelet-rich fibrin influence the oral health related quality of life following impacted third molar surgery? A randomized comparative study.
To compare the effects of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) on oral health-related quality of life (OHQoL) following impacted mandibular third molar (M3) surgery. A prospective, randomized study of 50 subjects was designed. Participants were divided equally into the PRP and PRF groups. The OHQoL was assessed using the OHQoL-UK instrument preoperatively and on postoperative days (PODS) 1, 3, and 7. Categorical variables were presented as frequencies and proportions. The linear mixed model analysis was used to determine the effects of PRF and PRP on overall OHQoL with respect to time, treatment, and treatment by time-point interaction. The analysis was also performed for the physical, social, and psychological domains. Fifty subjects were analyzed. The time-point assessment of the overall OHQoL was significant within the PRP and PRF groups (P-values of 0.01 and 0.000002, respectively). The time-point analysis was also significant in both study groups at all domain levels (P < 0.05). A comparison of treatment by time-point interaction for the overall OHQoL between the study groups was insignificant (P = 0.217). Treatment by time-point interaction for OHQoL between the study groups at social and psychological domain levels was insignificant, however, at the physical domain level, PRF had a significantly better effect on OHQoL (P = 0.016). The study showed that the overall OHQoL was not significantly different between the PRP and PRF groups after M3 surgery. However, PRF had a significant influence on OHQoL at the physical domain level.


Two silencers regulate the tissue-specific expression of the collagen II gene.
Collagen II, the major component of cartilage, is synthesized primarily by chondrocytes and by certain cells in the eye. Previously, we have studied the regulatory regions of the collagen II gene by DNA transfection assays (Horton, W., Miyashita, T., Kohno, K., and Yamada, Y. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8864-8868). These studies show that both the promoter and an enhancer sequence in the first intron are required for high transcriptional activity in chondrocytes. These elements do not show significant activity in cells which do not synthesize collagen II, such as in muscle cells and fibroblasts. In this report, we have constructed plasmids containing various deletions of the promoter of the collagen II gene, fused to a reporter gene for chloramphenicol acetyltransferase (CAT) and transfected them into both chick embryonic fibroblasts and HeLa cells. We have found that silencer elements in the collagen II promoter region reduce CAT activity 11-fold in fibroblasts, while not affecting the enhancer-mediated transcription in chondrocytes. Deletions in the promoter showed that most of the silencing activity was localized in two sites, between -360 and -460 base pairs and between -620 and -700 base pairs. Furthermore, a fragment containing these two sequences in a thymidine kinase promoter CAT construct reduced the activity of the promoter in an orientation independent fashion. Sequence analysis revealed that the two silencer regions are homologous and contain consensus motifs for silencer elements found in other genes. Gel retardation experiments showed that nuclear factors from HeLa cells bind specifically to a DNA fragment containing the silencer, whereas chondrocyte nuclear extracts did not show any activity. Thus, our study indicates that the expression of the collagen II gene is controlled by both negative and positive elements to ensure that the gene is only expressed in suitable cells.


Silencing of Rieske iron-sulfur protein using chemically synthesised siRNA as a potential biopesticide against Plutella xylostella.
Extensive applications and frequent long-term use of pesticides can affect behavioural mechanisms and physiological and biochemical aspects of insects, leading to resistance. However, insect control strategies involving a different mode of action would be valuable for managing the emergence of insect resistance. In this context, the development of RNA interference technology has brought a turning point in the creation of new biopesticides. Full-length cDNA of Rieske iron-sulfur protein (RISP) was cloned and characterised from Plutella xylostella L. Three siRNAs specific to RISP sequences were designed and chemically synthesised, and fed to P. xylostella larvae by coating cabbage leaves. This resulted in specific gene silencing of RISP, and consequently brought significant mortality of P. xylostella larvae compared with the control treatment. Silencing of RISP leads to significantly lower transcript levels of RISP compared with the control. In addition, the amount of ATP in the surviving larvae was lower than in the control. However, surviving larvae gradually recovered to normal transcript and protein levels. This is the first demonstration of the potential use of chemically synthesised siRNA in the development of new biopesticides as a mitochondrial electron transport inhibitor.


Dose escalation of three-dimensional conformal radiotherapy for locally recurrent nasopharyngeal carcinoma: a prospective randomised study.
To investigate prospectively the feasibility and efficacy of dose escalation using three-dimensional conformal radiotherapy (3D-CRT) boost technique for locally recurrent nasopharyngeal carcinoma (NPC) in a randomised study. Thirty-six patients with locally recurrent NPC (>6 months interval from previous radical radiotherapy, no cervical lymph-node involvement and no distant metastasis) were enrolled. Treatment included conventional external-beam radiotherapy to 54 Gy, followed by a 3D-CRT boost to the gross tumour region. Patients were randomised to three boost dose levels: 16 Gy, 20 Gy and 24 Gy for groups I, II and III, respectively, with 12 patients in each group. All boost doses were delivered in 4-Gy fractions and 3 fractions per week. Median follow-up was 27 months (range 14-44 months). Three-year, local-recurrence-free survival rate was significantly higher (72%) for the high-dose group III than for groups I and II (37% and 28%, respectively, P = 0.047). No significant difference was found in the 3-year overall survival rate among the three groups (72%, 59% and 82% for groups I, II and III, respectively). Three-year distant metastases rates were 17%, 0% and 18%, respectively. Skull-base invasion (P = 0.017) and pathology (P = 0.0006) correlated with overall survival. Treatment was well tolerated and no significant difference was observed among the three groups in acute and late toxicities (grade III toxicity is minimal: 17%, 17%, 0% of oral mucositis and 25%, 17%, 17% of nasopharyngeal mucositis in groups I, II, III, respectively, and 8% leukocytopenia only in group II; no grade IV toxicity occurred in any of the groups except for a fatal bleeding in group III). Re-irradiation with high-dose 3D-CRT boost technique results in high local control rate and acceptable toxicity in patients with recurrent NPC. Dose escalation to the boost volume to 78 Gy (54 Gy + 24 Gy boost) results in improved recurrence-free survival compared with lower doses.


Mechanisms of everolimus-induced glomerulosclerosis after glomerular injury in the rat.
Despite the lack of nephrotoxicity, adverse effects of the new antiproliferative immunosuppressant everolimus have been reported. By varying time point and dose of everolimus treatment as well as the degree of glomerular injury, the specific conditions and potential mechanisms leading to adverse actions in the anti-Thy1 model have been determined. Only the combination of early and high-dose everolimus treatment (1-3 mg/kg bw) with a severe glomerular lesion ('full-dose' anti-Thy1 model) caused adverse effects with a high mortality rate, progressive apoptosis, crescent formation and glomerulosclerosis. In contrast, either later start or low-dose (0.3 mg/kg bw) therapy or treatment of a less severe lesion ('reduced dose' anti-Thy1 model) appeared to be relatively safe for the glomerular architecture. The adverse effects of everolimus were linked to its marked inhibition of endothelial cell, but not necessarily mesangial cell proliferation. In addition, everolimus markedly inhibited the angiogenic cytokine vascular endothelial growth factor in nephritic glomeruli in vivo. These experimental results suggest special caution regarding the use of everolimus in all situations of severe glomerular cell injury requiring extensive capillary repair, where at least adaption to a low dose needs to be considered.


High pressure homogenization is a key unit operation in inclusion body processing.
Recombinant protein production in E. coli often leads to the formation of inclusion bodies (IBs). Although downstream processing of IBs has the reputation of being a great hurdle, advantages of IBs can be substantial. Highly pure recombinant protein with the possibility of correctly folded structures and an easy separation from cell matter are decisive factors that make IB processes so interesting. Product yield, purity and biological activity of the refolded protein are the responses to evaluate an IB process. The objective of this case study was to develop a refolding process in an integrated manner. The effects of the unit operations 1) homogenization, 2) IB wash and 3) IB solubilisation as well as their interdependencies were analyzed. We revealed interesting factor interactions between homogenization and IB wash, as well as homogenization and solubilisation, which would be overlooked if the single unit operations were investigated individually. Furthermore, we found that homogenization was a key unit operation for IB processing. By changing the conditions during homogenization only, the product yield, purity and biological activity of the refolded product was affected 2-fold, 1.2-fold and 2.5-fold, respectively.


Identification of pH-specific protein expression responses by Campylobacter jejuni strain NCTC 11168.
In this study a data dependent acquisition label-free based proteomics approach was used to identify pH-dependent proteins that respond in a growth phase independent manner in Campylobacter jejuni reference strain NCTC 11168. NCTC 11168 was grown within its pH physiological normal growth range (pH 5.8, 7.0 and 8.0, μ = ∼0.5 h-1) and exposed to pH 4.0 shock for 2 h. It was discovered that gluconate 2-dehydrogenase GdhAB, NssR-regulated globins Cgb and Ctb, cupin domain protein Cj0761, cytochrome c protein CccC (Cj0037c), and phosphate-binding transporter protein PstB all show acidic pH dependent abundance increases but are not activated by sub-lethal acid shock. Glutamate synthase (GLtBD) and the MfrABC and NapAGL respiratory complexes were induced in cells grown at pH 8.0. The response to pH stress by C. jejuni is to bolster microaerobic respiration and at pH 8.0 this is assisted by accumulation of glutamate the conversion of which could bolster fumarate respiration. The pH dependent proteins linked to growth in C. jejuni NCTC 11168 aids cellular energy conservation maximising growth rate and thus competitiveness and fitness.


Clinical efficacy of vitamin B in the treatment of mouth ulcer: a systematic review and meta-analysis.
Our study sought to determine the efficacy of vitamin B in treating mouth ulcers. The databases PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang were comprehensively searched to identify relevant articles published between 2010 and 2021. Subsequently, the clinical efficacy of vitamin B in the treatment of mouth ulcers was comprehensively and quantitatively evaluated through meta-analysis. Totally, 16 studies were finally included in the meta-analysis, including 1,534 patients. Patients who did not receive treatment were taken as controls, while those who were treated with vitamin B alone or vitamin B combined with pantothenic acid were included in the treatment group. In comparison with the control group, the effective rate was higher [odds ratio (OR) =5.24, 95% confidence interval (CI): 3.72 to 7.37, P<0.001] while the recurrence rate was lower (OR =0.194, 95% CI: 0.128 to 0.295, P<0.001) in the treatment group. Additionally, both the ulcer healing time [standardized mean difference (SMD) =-2.15, 95% CI: -2.80 to -1.50, P<0.001] and treatment time (SMD =-2.31, 95% CI: -2.67 to -1.96, P<0.001) in the treatment group were shorter than those of the control group. Vitamin B enables a higher effective rate and lower recurrence rate, accelerates ulcer healing, and shortens the course of treatment. Collectively, vitamin B has a high clinical value in treating patients with mouth ulcers.


Novel Ag3PO4/boron-carbon-nitrogen photocatalyst for highly efficient degradation of organic pollutants under visible-light irradiation.
Ag3PO4 is an indirect bandgap semiconductor with excellent photocatalytic activity. However, it has not been widely used so far for the treatment of polluted wastewaters. This scarce use in wastewater treatment can be mainly attributed to its large crystallite size, which would be due to rapid agglomeration during the synthesis process, as well as to the photo-corrosion problem affecting this material. Hence, it would be crucial to develop a photocatalytic system involving Ag3PO4 nanoparticles with enhanced properties, such as higher specific surface area and excellent photocatalytic stability. To meet this demand, a novel Ag3PO4/boron carbon nitrogen (Ag3PO4/BCN) composite photocatalyst was successfully prepared in the present study via electrostatically driven self-assembly and ion exchange processes. After characterization and assessment, it was shown that the as-prepared Ag3PO4/BCN nanocomposite photocatalyst not only contains smaller Ag3PO4 nanoparticles, but also exhibits an enhanced visible-light photocatalytic activity for Rhodamine B (RhB) Methyl Orange (MO) and Tetracycline (TC) and improved stability, without decrease after 5 cycles, compared with pure Ag3PO4 nanoparticles. Positive synergy between Ag3PO4 nanoparticles and BCN nanosheets, including the increase in the number of active adsorption sites, and the restriction of the formation of Ag due to the recombination of photogenerated electron-hole pairs in Ag3PO4 nanoparticles, are mainly responsible for the enhanced properties of the prepared catalyst. This study shows that Ag3PO4/BCN composite photocatalyst would be promising for wastewater treatment, which would be of clearly environmental and public health relevance.


Selective detection of trace nitroaromatic, nitramine, and nitrate ester explosive residues using a three-step fluorimetric sensing process: a tandem turn-off, turn-on sensor.
Detection of trace quantities of explosive residues plays a key role in military, civilian, and counter-terrorism applications. To advance explosives sensor technology, current methods will need to become cheaper and portable while maintaining sensitivity and selectivity. The detection of common explosives including trinitrotoluene (TNT), cyclotrimethylenetrinitramine, cyclotetramethylene-tetranitramine, pentaerythritol tetranitrate, 2,4,6-trinitrophenyl-N-methylnitramine, and trinitroglycerin may be carried out using a three-step process combining "turn-off" and "turn-on" fluorimetric sensing. This process first detects nitroaromatic explosives by their quenching of green luminescence of polymetalloles (lambda em approximately 400-510 nm). The second step places down a thin film of 2,3-diaminonaphthalene (DAN) while "erasing" the polymetallole luminescence. The final step completes the reaction of the nitramines and/or nitrate esters with DAN resulting in the formation of a blue luminescent traizole complex (lambda(em) = 450 nm) providing a "turn-on" response for nitramine and nitrate ester-based explosives. Detection limits as low as 2 ng are observed. Solid-state detection of production line explosives demonstrates the applicability of this method to real world situations. This method offers a sensitive and selective detection process for a diverse group of the most common high explosives used in military and terrorist applications today.


Switching to bedaquiline for treatment of rifampicin-resistant tuberculosis in South Africa: A retrospective cohort analysis.
South Africa led the world with guidelines on bedaquiline (BDQ) use as a single drug substitution to manage rifampin resistant tuberculosis regimen toxicity. We examined reasons for giving BDQ in a retrospective cohort: >75% of patients were switched to BDQ for toxicity (ototoxicity or renal dysfunction) rather than drug resistance.


[Gender and the working woman in Peru].
This study identifies the peruvian women's labor conditions and its social and historical determinants due to social class, race and gender differences that influence women subordination in social structure. Bibliographic review shows that the peruvian working woman situation experienced great and deep changes in time, as a result of ideological and cultural patriarchal patterns that culminated in the current capitalist society.


The Price of Progress: Cost, Access, and Adoption of Novel Cardiovascular Drugs in Clinical Practice.
The launch of new effective and safe cardiovascular drugs has produced large gains in health outcomes for several cardiovascular conditions. But this innovation comes at the cost of rapidly increasing pharmaceutical spending and high out-of-pocket costs. In the USA, manufacturers are able to set prices according to what the market will bear rather than value to patients or society, with a complicated system of discounts and rebates obscuring the final price borne by payors. Some of these costs are passed on to patients in the form of co-payments or co-insurance, making these effective but high-cost medications unaffordable for many patients. Orphan drugs developed to treat rare diseases-for which manufactures are presented substantial financial and regulatory benefits-are particularly problematic, as they typically enter the market at very high prices compared with drugs for other indications. Systematic cost-effectiveness analyses from the healthcare sector or societal perspectives can help identify the value-based price of a medication at market entry as well as later in the lifecycle of the drug when more data on effectiveness and safety becomes available. Despite bipartisan support, legislative progress on drug pricing has been slow. Clinicians should know the cost of the drugs they prescribe frequently, use generics where feasible, and regularly discuss out-of-pocket costs with patients to pre-empt cost-related non-adherence.


Laryngeal nerve monitoring during thyroid surgery in pregnancy.
A 32-week parturient required partial thyroidectomy for suspicious carcinoma. The surgeon requested laryngeal nerve monitoring to decrease the chances of laryngeal nerve injury during surgery. After rapid-sequence induction of general anesthesia and intubation, a size 3 laryngeal mask airway was inserted posterior to the endotracheal tube and the cuff inflated with 15 mL of air. A fiberoptic bronchoscope inserted through the laryngeal mask airway provided an unhindered view of vocal cords for laryngeal nerve identification and testing during surgery. This combined technique also offered the advantages of a secured airway, as well as positive pressure ventilation in the parturient during thyroid surgery.


3D ultrasound guided navigation system with hybrid image fusion.
A prototype of a navigation system to fuse two image modalities is presented. The standard inter-modality registration is replaced with a tracker-based image registration of calibrated imaging devices. Intra-procedure transrectal US (TRUS) images were merged with pre-procedure magnetic resonance (MR) images for prostate biopsy. The registration between MR and TRUS images was performed by an additional abdominal 3D-US (ab-3D-US), which enables replacing the inter-modal MR/TRUS registration by an intra-modal ab-3D-US/3D-TRUS registration. Calibration procedures were carried out using an optical tracking system (OTS) for the pre-procedure image fusion of the ab-3D-US with the MR. Inter-modal ab-3D-US/MR image fusion was evaluated using a multi-cone phantom for the target registration error (TRE) and a prostate phantom for the Dice score and the Hausdorff distance of lesions . Finally, the pre-procedure ab- 3D-US was registered with the TRUS images and the errors for the transformation from the MR to the TRUS were determined. The TRE of the ab-3D-US/MR image registration was 1.81 mm. The Dice-score and the Hausdorff distance for ab-3D-US and MR were found to be 0.67 and 3.19 mm. The Dice score and the Hausdorff distance for TRUS and MR were 0.67 and 3.18 mm. The hybrid navigation system showed sufficient accuracy for fusion guided biopsy procedures with prostate phantoms. The system might provide intra-procedure fusion for most US-guided biopsy and ablation interventions.


Cortical proteins may provide motor resilience in older adults.
Motor resilience proteins may be a high value therapeutic target that offset the negative effects of pathologies on motor function. This study sought to identify cortical proteins associated with motor decline unexplained by brain pathologies that provide motor resilience. We studied 1226 older decedents with annual motor testing, postmortem brain pathologies and quantified 226 proteotypic peptides in prefrontal cortex. Twenty peptides remained associated with motor decline in models controlling for ten brain pathologies (FDR < 0.05). Higher levels of nine peptides and lower levels of eleven peptides were related to slower decline. A higher motor resilience protein score based on averaging the levels of all 20 peptides was related to slower motor decline, less severe parkinsonism and lower odds of mobility disability before death. Cortical proteins may provide motor resilience. Targeting these proteins in further drug discovery may yield novel interventions to maintain motor function in old age.


Risk of complications in a second pregnancy following caesarean section in the first pregnancy: a population-based study.
To estimate the risks of maternal and perinatal morbidity and mortality in a second pregnancy, attributable to caesarean section in a first pregnancy. Cross-sectional analytic study of hospital births in New South Wales, based on linked population databases. 136 101 women with one previous birth who gave birth to a singleton infant in NSW in 1998-2002. Crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for maternal and perinatal morbidity and mortality. 19% of mothers had a caesarean section in their first pregnancy. Compared with mothers who had had primary vaginal births, mothers who had had primary caesarean section and underwent labour in the second birth were at increased risk of uterine rupture (aOR, 12.3; 95% CI, 5.0-30.1; P < 0.0001), hysterectomy (3.5; 1.5-8.4; P < 0.01), postpartum haemorrhage (PPH) following vaginal delivery (1.6; 1.4-1.7; P < 0.0001), manual removal of placenta (1.3; 1.1-1.6; P < 0.01), infection (6.2; 4.7-8.2; P < 0.0001) and intensive care unit (ICU) admission (3.1; 2.1-4.7; P < 0.0001); among mothers who did not undergo labour (ie, had an elective caesarean section), there was a lower risk of PPH (0.6; 0.5-0.7; P < 0.0001) and ICU admission (0.4; 0.3-0.5; P < 0.0001). For infants there was increased risk of preterm delivery (1.2; 1.1-1.3; P < 0.0001) and neonatal intensive care unit admission following labour (1.6; 1.4-1.9; P < 0.0001) in the birth after primary caesarean section. The occurrence of stillbirth was not modified by labour. Caesarean section in a first pregnancy confers additional risks on the second pregnancy, primarily associated with labour. These should be considered at the time caesarean section in the first pregnancy is being considered, particularly for elective caesarean section for non-medical reasons.


Racial and Ethnic Disparities in Receipt of Sexual Health Care and Education Among A Nationally Representative Sample of Adolescent Females.
The USA has a high rate of adolescent pregnancy, with non-Hispanic (NH) Black and Hispanic women disproportionately affected. We sought to investigate the presence of racial/ethnic disparities in the receipt of sexual health (SRH) care and education and whether such disparities contribute to differences in sexual health outcomes for youth. We conducted a cross-sectional study of females aged 15-21 years who participated in the National Survey of Family Growth from 2008 to 2015. Multivariable logistic regression was used to measure the association between race/ethnicity and SRH outcomes after adjustment for potential confounders. Models were developed to measure whether receipt of SRH care and education served as an effect modifier on SRH outcomes. The sample included 4316 participants, representing 33.5 million females. Almost half (47.2%) received birth control services in the last 12 months; NH-Blacks (aOR 0.7 [0.5, 0.9]) and Hispanics (aOR 0.6 [0.5, 0.8]) were less likely to have obtained birth control services than NH-whites. Hispanics (aOR 1.5 [1.2, 1.9]) had a higher likelihood of receipt of condom education than NH-whites. We found that disparities in SRH outcomes were slightly mitigated after adjustment for access to SRH care and education. We identified racial/ethnic disparities in sexual health outcomes and in SRH and education; however, SRH care and education can mitigate some of these differences in sexual behaviors and outcomes. Racial/ethnic differences in sexual health outcomes may be at least partially related to the differential receipt of sexual health care and education and deserve further investigation.


Reviewing a clinical decision aid for the selection of anticoagulation treatment in patients with nonvalvular atrial fibrillation: applications in a US managed care health plan database.
The Clinical Decision Aid was created to assist in selecting anticoagulant therapies for patients with nonvalvular atrial fibrillation. The aid incorporates a patient's absolute risk for stroke and bleeding, relative stroke risk reduction, and increase in relative bleeding risk to identify the agent with the lowest net risk. We describe theoretical implications of utilizing the aid at a US managed care population level. This retrospective study used claims data from a large US managed care database including enrollees in commercial and Medicare Advantage plans. The distribution of patients across each possible combination of scores on the HAS-BLED scale (evidence of hypertension, abnormal renal or liver function, stroke, bleeding, labile INR, age >65 years, and drugs or alcohol abuse or dependence) and the CHA2DS2-VASc scale (CHADS2 [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism] with additional nonmajor stroke risk factors, including age 65-74 years, female sex, and vascular disease) was generated. We assessed the correlation between the HAS-BLED and CHA2DS2-VASc scores and derived the optimal treatment options based on various bleeding ratios. Data from 48,260 patients were included in the analysis. The MAPD subset had a higher mean HAS-BLED score (2.17 vs 1.39; P < 0.001) and a higher mean CHA2DS2-VASc score (3.35 vs 2.05; P < 0.001) than did the commercial subset. Pearson coefficients suggested a moderate to strong positive correlation between the HAS-BLED and CHA2DS2-VASc scores among the commercial (0.730; P < 0.001) and MAPD (0.568; P < 0.001) enrollees. Based on a 2:1 bleeding-to-stroke risk ratio, 70.50% of patients would be recommended treatment with apixaban; 25.86%, no treatment; 3.62%, acetylsalicylic acid; and 0.01%, dabigatran 150 mg, if the Clinical Decision Aid were to be used for anticoagulant treatment selection. Evidence-based clinical decision-making tools utilizing risk assessment for recommending a treatment may be valuable for not only health care providers but also health care payers in optimizing care at the population level.


Regulation of rat maternal behavior by broadband pup vocalizations.
Pups emit a broadband vocalization ranging from 2 to 40 kHz that generally occurs when the mother sits or steps on her pups. In an earlier study (Ihnat, White, and Barfield, under review), we noted that the mother was more likely to move on the pups and step on them when she was temporarily deafened with ear plugs. This research was extended in the present study by using two different methods to prevent 2-day-old pups from emitting broadband vocalizations. In the first experiment, the female was presented with six of her pups for a 10-min test. In half the tests, the pups had been anesthetized with pentobarbital; in the other half, the pups received saline. In the second experiment, females were presented with pups whose mouths had been sealed with an adhesive substance. In a final study, pups received the adhesive substance on their ventral surface as a control. When the pups were unable to vocalize, there was an increase in the amount of time per bout that the mother spent in incidental contact with her pups; in the sham condition, however, there was no change in her behavior. In addition, the female was less likely to group all her pups within the 10-min duration of the test when the pups could not call. Since pups emit primarily broadband vocalizations in response to handling prior to 4 days of age, broadband calls appear to reduce incidental contact and facilitate retrieval into a group.


Primary small cell carcinoma of the esophagus: report of a case.
A case of esophageal small cell carcinoma successfully treated with combination therapy consisting of both pre- and postoperative chemotherapy as well as surgical resection is presented. A 74-year-old man presented with a small cell carcinoma measuring 11 cm in diameter in the lower half of his thoracic esophagus. After undergoing preoperative chemotherapy with cisplatin (25 mg, iv, days 1 through 5), the gross tumor completely regressed. However, a microscopic focus of residual cancer showing squamous cell carcinoma was found in the resected esophageal specimen. The patient received an additional two courses of postoperative chemotherapy with cisplatin (75 mg, iv monthly). He has since survived more than 9 years with no evidence of recurrent disease. We herein report a rare case of a patient with esophageal small cell carcinoma who demonstrated a complete cure.


Correction: Ultrafast photochemistry of the bc1 complex.
Correction for 'Ultrafast photochemistry of the bc1 complex' by Marten H. Vos et al., Phys. Chem. Chem. Phys., 2017, 19, 6807-6813.


Mix-and-match COVID-19 vaccines trigger high antibody response after the third dose vaccine in Moroccan health care workers.
Recent studies have shown that in individuals who have received two doses of COVID-19 vaccine, the level of IgG antibodies decreased over time. In addition, the resurgence of the epidemic due to variants has led the authorities in several countries, including Morocco, to extend the third dose to the entire adult population. In this study, we included 43 healthcare workers (HCWs) who were vaccinated with three doses. They were vaccinated with ChAdOx1 nCoV-19 for the first two doses and with BNT 162b2 or BBIBP-CorV vaccine for the third dose. Humoral response was assessed on the day of injection of the third dose of vaccine and one month after the third dose by measuring anti-receptor-binding domain (RBD) IgG levels. Seven months after the second dose, the median titer of anti-RBD IgG was higher in the group with a history of SARS-CoV-2 infection than in the group with no history of infection (1038 AU/mL vs. 76.05 AU/mL, respectively, p = 0.003). One month after the third dose, a significant increase in median level of anti-RBD in both groups was observed: from 76.05 AU/mL to 6127 AU/mL in the group with no history of infection and from 1038 AU/mL to 14,412 AU/mL in the group with history of infection. Notably, the BNT 162b2 vaccine elicits a high titer of anti-RBD antibody compared to the BBIBP-CorV vaccine. Median antibody titers were 21,991 AU/mL and 3640 AU/mL for BNT 162b2 and BBIBP-CorV vaccines, respectively (p = 0.0002). 23% of HCWs were infected with SARS-CoV-2 within the first two months after the third dose injection. However, all these patients developed mild symptoms and tested negative by RT-qPCR between 10 and 15 days after the onset of symptoms. Our findings support that the third dose of COVID-19 vaccine significantly improves the humoral response and protects against the severe disease.


Postmortem pericardial fluid sLOX-1 levels and LOX-1 immunostaining in forensic specimens: Relation to cause of death.
Lectin-like oxidized LDL receptor-1 (LOX-1) is the endothelial receptor for oxidized LDL. This receptor's extracellular domain is released into the blood as soluble LOX-1 (sLOX-1) and has been linked to ischemic heart disease (IHD), cerebrovascular diseases (CVDs), obesity, and diabetes. We recently reported that sLOX-1 fluid levels in postmortem pericardial fluid were comparable to clinical values in live patients and that significant increases in sLOX-1 were observed in patients with IHD. However, postmortem serum and urine sLOX-1 levels were higher than serum levels in living patients. Here, we conducted LOX-1 immunostaining in forensic specimens (aorta and heart) and evaluated pericardial fluid sLOX-1 in 221 medicolegal autopsy cases (67 IHD, 11 CVD, 17 inflammatory diseases, and 126 control cases) with a postmortem interval < 72 h to assess the diagnostic efficiency of postmortem pericardial fluid sLOX-1. Furthermore, we evaluated the relationships between pericardial fluid sLOX-1 and body mass index (BMI), blood HbA1c, serum C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), and low-density-lipoprotein cholesterol (LDL-C). LOX-1 immunostaining positivity was found in the aortic intima. Pericardial fluid sLOX-1 levels were considerably higher in patients with IHD and CVD. However, there were no significant differences in patients with inflammatory diseases and controls. No associations between pericardial fluid sLOX-1 and BMI, HbA1c, CRP, HDL-C, or LDL-C were found. These results indicate sLOX-1 utility in the postmortem diagnosis of IHD and CVD.


[Cystoscopic-guided laser ablation for treatment of ectopic ureteroceles in 2 female dogs].
Two female intact Labrador Retriever dogs (6 and 3 months of age, respectively) presented with a history of urinary incontinence. In both dogs, abdominal ultrasound revealed evidence of a unilateral ectopic ureterocele. Diagnosis of ureteral ectopia was established urethrocystoscopically by visualization of the ureteral orifice in the urethra, and an intramural course was confirmed via retrograde contrast fluoroscopy. Ectopic ureteral orifices were stenotic in both dogs. Cystoscopic- and fluoroscopic-guided laser ablation of the ectopic ureter were performed with a Hol:YAG laser. Following the procedure, both dogs were fully continent without any medical treatment. Cystoscopic- guided laser ablation of ureteroceles was effective and safe in these 2 dogs. Thus, this minimally invasive technique for the treatment of ectopic ureteroceles provides an alternative to surgical intervention.


Replacement of methoxatin by 4,7-phenanthroline-5,6-dione and the inability of other phenanthroline quinones, as well as 7,9-di-decarboxy methoxatin, to serve as cofactors for the methoxatin-requiring glucose dehydrogenase of Acinetobacter calcoaceticus.
Glucose dehydrogenase from A. calcoaceticus has been dissociated into apoenzyme and methoxatin coenzyme, and enzyme activity restored by replacing coenzyme with 4,7-phenanthroline-5,6-dione but not with 1,10- nor 1,7-phenanthroline-5,6-diones nor with 7,9-decarboxy methoxatin.


Laparoscopic exploration of the common bile duct with a rigid scope in patients with problematic choledocholithiasis.
The development of laparoscopic cholecystectomy as a minimally invasive approach to eliminate gallstones, in conjunction with increasingly sophisticated techniques for removal of common bile duct (CBD) stones by endoscopic sphincterotomy, has revolutionized the treatment of choledocholithiasis. We describe a new technical approach to laparoscopic exploration of the CBD after unsuccessful endoscopic stone extraction. Eleven patients were subjected to laparoscopic exploration of the CBD with choledochotomy using a rigid scope (24-Fr nephroscope) during the last 2 years. Of these patients, 10 had unsuccessful preoperative (7 cases) or intraoperative (3 cases) stone extraction, and 1 case had a single impacted stone 2.3 cm in diameter. Five patients had a single bile duct stone and 6 patients had multiple stones. The size of the stones ranged from 9.5 to 24 mm (mean = 12.6 +/- 4 mm). Balloon dilation of the papilla of Vater was done in all patients. Most of the stones were fractured and pushed into the duodenum with rigid grasping forceps but a lithotripter was required in 2 patients. Stone clearance was 100%; complications related to the procedure were not observed. After CBD clearance, primary closure of the choledochotomy was achieved in 10 patients. In 1 patient who had CBD perforation during a previous procedure, choledochotomy was closed over a T-tube. The mean operative time was 124 +/- 26.7 min (range = 84-165 min) and the mean postoperative hospital stay was 4 +/- 1.7 days (range = 3-7 days). Laparoscopic exploration of the CBD with a rigid scope is an efficacious procedure in dealing with unsuccessful endoscopic stone extraction.


Molecular dosimetry of hepatic aflatoxin B1-DNA adducts: linear correlation with hepatic cancer risk.
An analysis of hepatic aflatoxin B1-DNA adduct (HADA) concentrations in rats and trout demonstrated that the hepatic cancer risk was linearly and quantitatively related in both species. Additionally, the adduct-risk correlation for short-term exposure accurately predicted chronic exposure risk in trout. Although rat and trout liver cells differ substantially in their nuclear DNA content, they appeared to experience similar cancer risks at a given HADA concentration. This may indicate that the liver nuclei of both species contain a similar number of an equivalent protooncogene(s). This analysis also provided a possible basis for the use of adduct measurements for estimating human cancer risk. The minimum human virtual safe dose for aflatoxin was estimated to be 0.264 ng/kg/day on the basis of this approach.


Influence of pelvic osteotomy on birth canal size.
Six pelvic osteotomies (Salter, Sutherland, Steel, Tönnis, Chiari, and periacetabular) were performed on the right hemipelvis of adult female pelvic plastic models. Each pelvis underwent conventional X-ray and computed tomographic digital pelvimetry before and after osteotomy. The change in the anteroposterior and transverse dimensions at the inlet, midpelvis, and outlet were calculated. None of the osteotomies significantly decreased the inlet. The Salter and Sutherland osteotomies decreased the midpelvis to borderline low. The Salter, Sutherland, and Steel osteotomies significantly decreased the pelvic outlet. These changes correlated closely with those in living patients. Much of this decrease is nullified when the osteotomy is performed prior to the pubertal growth spurt.


Genetic determination of polygalacturonase production in wild-type and laboratory strains of Saccharomyces cerevisiae.
The genetic determination of polygalacturonase (PG) production in Saccharomyces cerevisiae was studied by biochemical and classical genetic techniques. Crosses of PG+ strains with PG- strains showed that in the haploid wild-type-derived strain, two structural genes were involved in the production of a hydrolysis halo on plates with polygalacturonic acid. However, in the case of PG+ laboratory strain IM1-8b, the phenotype was controlled by only one structural gene although the analysis of PG- IM1-8b mutants demonstrated the existence of at least two complementation groups. All these genetic results were assessed biochemically by means of cation-exchange chromatography. Two enzymes were separated in the wild-type strain, and only one in the laboratory strain. The three enzymes had different Km values, molecular masses, and optimal pHs for activity.


Genome-wide identification of the BASS gene family in four Gossypium species and functional characterization of GhBASSs against salt stress.
Bile acid sodium symporter (BASS) family proteins encode a class of sodium/solute symporters. Even though the sodium transporting property of BASSs in mammals was well studied, their sodium transportability and functional roles in plant salt tolerance remained largely unknown. Here, BASS family members from 4 cotton species, as well as 30 other species were identified. Then, they were designated as members of BASS1 to BASS5 subfamilies according to their sequence similarity and phylogenetic relationships. There were 8, 11, 16 and 18 putative BASS genes in four cotton species. While whole-genome duplications (WGD) and segmental duplications rendered the expansion of the BASS gene family in cotton, BASS gene losses occurred in the tetraploid cotton during the evolution from diploids to allotetraploids. Concerning functional characterizations, the transcript profiling of GhBASSs revealed that they not only preferred tissue-specific expression but also were differently induced by various stressors and phytohormones. Gene silencing and overexpression experiments showed that GhBASS1 and GhBASS3 positively regulated, whereas GhBASS2, GhBASS4 and GhBASS5 negatively regulated plant salt tolerance. Taken together, BASS family genes have evolved before the divergence from the common ancestor of prokaryotes and eukaryotes, and GhBASSs are plastidial sodium-dependent metabolite co-transporters that can influence plant salt tolerance.


Clinical Presentation and Characteristics of Hand and Wrist Ganglion Cysts in Children.
Ganglion cysts are the most common mass of the hand or wrist. In adults, ganglions have a female predilection and are commonly located in the dorsal wrist. However, their presentation in children has not been well reported. This investigation sought to describe the presentation of pediatric ganglion cysts in a prospective cohort. A multicenter prospective investigation of children (aged ≤18 years) who presented with ganglion cysts of the hand or wrist was conducted between 2017 and 2019. The data collected included age, sex, cyst location, hand dominance, pain, and patient-reported outcomes measurement information system (PROMIS) scores for upper-extremity (UE) function. The patients were divided into cohorts based on age, cyst location, and cyst size. Multivariable analyses were performed to identify factors predictive of worse UE function and higher pain scores. A total of 173 patients with a mean age of 10.1 ± 5.3 years and female-to-male ratio of 1.4:1 were enrolled. The dorsal wrist was the most commonly affected (49.7%), followed by the volar wrist (26.6%) and flexor tendon sheath (18.5%). In older patients, dorsal wrist ganglions were more common than tendon sheath cysts (11.9 ± 4.1 years vs 6.2 ± 5.8 years) and were larger (86.7% were >1 cm) than cysts in other locations (34.5% were >1 cm). Patients aged >10 years reported higher pain scores, with 21.5% of older patients reporting moderate/severe pain scores versus 5.0% of younger children. This cohort of patients had an average PROMIS UE function score of 47.4 ± 9.5, and lower PROMIS scores were associated with higher pain scores. Ganglions in pediatric populations, which most commonly affect the dorsal wrist, demonstrate a female predilection. In younger children, cysts are smaller and more often involve the volar wrist or flexor tendon sheath. Older children report higher pain scores. Pediatric ganglion cysts do not appear to result in a clinically meaningful decrease in UE function. Diagnostic II.


A joint model for nonlinear longitudinal data with informative dropout.
Subject withdrawal from a study (also called dropout, or right censoring), is common in late phase clinical trials. A number of methods dealing with dropouts have been used in practice, the most common being "last observation carried forward" (LOCF). Many of these methods, including LOCF, can result in biased estimates of the efficacy or potency of the drug, especially in the modeling context. If the likelihood of dropout is correlated to the underlying unobserved data, the dropout is informative and should not be ignored in the modeling process. The topic of informative dropout in the context of longitudinal data has received much attention in the statistical literature, in the setting of linear and generalized linear models. We extend the approach to nonlinear models. The dropout hazard, as well as the longitudinal data, is modeled parametrically. Parameters are estimated by maximizing the approximate joint likelihood as implemented in the software NONMEM. Using data from actual clinical trials, we explore the impact of the dropout model on the ability of the joint model to predict observed longitudinal data patterns.


Histopathologic spectrum of oral erythema multiforme.
The histopathologic tissue patterns found in twenty-five patients with oral erythema multiforme were as variable as the clinical appearances. The biopsies served an important role in ruling out malignancy, dysplasia, and other classified diseases. While all of the specimens were designated as showing nonspecific inflammatory reactions, in many biopsy specimens there were sufficient characteristic connective tissue and epithelial changes to suggest a tissue diagnosis consistent with the clinical diagnosis of erythema multiforme.


Guided graded exercise self-help for chronic fatigue syndrome: Long term follow up and cost-effectiveness following the GETSET trial.
The GETSET trial found that guided graded exercise self-help (GES) improved fatigue and physical functioning more than specialist medical care (SMC) alone in adults with chronic fatigue syndrome (CFS) 12 weeks after randomisation. In this paper, we assess the longer-term clinical and health economic outcomes. GETSET was a randomised controlled trial of 211 UK secondary care patients with CFS. Primary outcomes were the Chalder fatigue questionnaire and the physical functioning subscale of the short-form-36 survey. Postal questionnaires assessed the primary outcomes and cost-effectiveness of the intervention 12 months after randomisation. Service costs and quality-adjusted life years (QALYs) were combined in a cost-effectiveness analysis. Between January 2014 and March 2016, 164 (78%) participants returned questionnaires 15 months after randomisation. Results showed no main effect of intervention arm on fatigue (chi2(1) = 4.8, p = 0.03) or physical functioning (chi2(1) = 1.3, p = 0.25), adjusting for multiplicity. No other intervention arm or time*arm effect was significant. The short-term fatigue reduction was maintained at long-term follow-up for participants assigned to GES, with improved fatigue from short- to long-term follow up after SMC, such that the groups no longer differed. Healthcare costs were £85 higher for GES and produced more QALYs. The incremental cost-effectiveness ratio was £4802 per QALY. The short-term improvements after GES were maintained at long-term follow-up, with further improvement in the SMC group such that the groups no longer differed at long-term follow-up. The cost per QALY for GES compared to SMC alone was below the usual threshold indicating cost-effectiveness, but with uncertainty around the result.


Recent Advances in the Chemistry and Biology of Bakuchiol and its Derivatives: An Updated Review.
Bakuchiol is a meroterpene natural product distributed in various plants. It possesses several biological activities particularly anticancer. A large number of analogs have been prepared by various researchers by targeting several positions such as phenolic -OH, ethenyl and isopropylidene groups present in the bakuchiol to develop potent therapeutic agents with improved pharmaceutical properties. The present review describes the isolation, organic synthetic schemes, chromatographic study, and biological activities of bakuchiol reported till date. Further, the review also provides an insight into the skin care effects of bakuchiol and structure-activity relationship studies of reported derivatives. Moreover, the biosynthetic pathway of bakuchiol has also been described. All the articles published on bakuchiol revealed that bakuchiol and its analogs possess a remarkable potential for the development of potent anticancer and several other therapeutic agents. The reported synthetic schemes can be utilized for the industrial production of bakuchiol. Finally, we believe that this review will provide important information to the researchers interested in the chemistry and biology of Bakuchiol.


Therapeutic embolization for vascular lesions of the head and neck. Report of 2 cases.
Vascular lesions of the head and neck are relatively rare. 2 cases are presented in which superselective therapeutic embolization with nonabsorbable materials was successfully carried out.


Site-specific intestinal DMT1 silencing to mitigate iron absorption using pH-sensitive multi-compartmental nanoparticulate oral delivery system.
Iron is a nutrient metal, but excess iron promotes tissue damage. Since iron chelation therapies exhibit multiple off-target toxicities, there is a substantial demand for more specific approaches to decrease iron burden in iron overload. While the divalent metal transporter 1 (DMT1) plays a well-established role in the absorption of dietary iron, up-regulation of intestinal DMT1 is associated with iron overload in both humans and rodents. Hence, we developed a novel pH-sensitive multi-compartmental particulate (MCP) oral delivery system that encapsulates DMT1 siRNA and validated its efficacy in mice. Using the gelatin NPs coated with Eudragit® L100-55, we demonstrated that DMT1 siRNA-loaded MCPs down-regulated DMT1 mRNA levels in the duodenum, which was consistent with decreased intestinal absorption of orally-administered 59Fe. Together, the Eudragit® L100-55-based oral siRNA delivery system could provide an effective strategy to specifically down-regulate duodenal DMT1 and mitigate iron absorption.


A second Zn(II)(2)Cys(6) transcriptional factor encoded by the YNA2 gene is indispensable for the transcriptional activation of the genes involved in nitrate assimilation in the yeast Hansenula polymorpha.
Nitrate assimilation genes encoding a nitrate transporter (YNT1), nitrite reductase (YNI1), a Zn(II)(2)Cys(6) transcriptional factor involved in nitrate induction (YNA1) and the nitrate reductase (YNR1) are clustered in the yeast Hansenula polymorpha. A second gene, termed YNA2 (yeast nitrate assimilation), was located seven nucleotides away from the 3' region of YNR1 gene. The cluster is flanked by an ORF encoding a protein with similarity to glutathione-S-transferase on the YNT1 side and an ORF with similarity to Saccharomyces cerevisiae Rad3p on the YNA2 side. The disruption of YNA2 confers the resulting null mutant strain with inability to grow in nitrate. The YNA2 gene encodes a putative protein of 618 residues bearing in the N-terminus the consensus sequence Cys-X(2)-Cys-X(6)-Cys-X(5-16)-Cys-X(2)-Cys-X(6-8)-Cys characteristic of the Zn(II)(2)Cys(6) transcriptional factors. YNA2 is therefore a member of the H. polymorpha nitrate assimilation gene cluster which is transcribed in the opposite direction to the rest of the members. Yna2p shares about 27% similarity with the H. polymorpha Yna1p Zn(II)(2)Cys(6) transcriptional factor involved in nitrate induction. Unlike the wild-type, the yna2::URA3 strain showed no expression of the nitrate assimilation genes when incubated in nitrate for 2 h. With regard to YNA2 expression, similar YNA2 transcript levels were observed in ammonium and in ammonium plus nitrate, but about a four-fold higher expression was observed in nitrate. However, this induction by nitrate of the YNA2 gene was not observed in the Deltayna1::URA3 strain. On the contrary, the pattern of YNA1 expression was the same in the wild-type as in the yna2::URA3 strain, indicating that YNA2 does not affect YNA1 expression.


End-user experiences with two incident and injury reporting systems designed for led outdoor activities - challenges for implementation of future data systems.
Injury and incident (near miss) prevention is heavily dependent upon robust and high-quality data systems. Evaluations of surveillance systems designed to report factors associated with incidents and injuries are essential to understand their value, as well as to improve their performance and efficiency. Despite, this there have been few such evaluations published in the peer-review literature. The attitudes and experiences of industry representatives who used one of two variants of an incident and injury surveillance system to collect injury and incident data for the led outdoor activity setting were obtained through an online self-report survey following a 12-month trial. Survey respondents were 18 representatives of 33 organisations who were users of a comprehensive incident reporting and surveillance system - the Understanding and Preventing Led Outdoor Accidents Data System Software Tool (UPLOADS-ST) - and six out of 11 users of a modified system (UPLOADS-Lite). The survey collected information on user experiences in relation to system training, accessibility, ease of use, security, feedback and perceived value to the sector of collating and reporting data across organisations. Only four UPLOADS-ST responding users found the system easy to use and just three considered entering incident reports to be easy. However, many considered the training on reporting incidents to be sufficient and that the incident reports contained relevant details. Fewer than half of respondents (seven for UPLOADS-ST, three for UPLOADS-Lite) believed entering data was a good use of staff time and resources. Nonetheless, a majority of respondents (seven for UPLOADS-ST, five for UPLOADS-Lite) found the reporting format easy to read and felt the information provided was useful for their organisation. Usability barriers to incident reporting were identified, particularly for UPLOADS-ST, including time constraints and user friendliness. The majority of users believed aggregating and reporting incident and injury data across organisations would be of value in making the led outdoor activity sector safer. Improving the utility of the surveillance systems will assist in ensuring their sustainability in the led outdoor activity sector.


Early sleep after action observation and motor imagery training boosts improvements in manual dexterity.
The systematic observation and imagination of actions promotes acquisition of motor skills. Furthermore, studies demonstrated that early sleep after practice enhances motor learning through an offline stabilization process. Here, we investigated behavioral effects and neurodynamical correlates of early sleep after action observation and motor imagery training (AO + MI-training) on motor learning in terms of manual dexterity. Forty-five healthy participants were randomized into three groups receiving a 3 week intervention consisting of AO + MI-training immediately before sleeping or AO + MI-training at least 12 h before sleeping or a control stimulation. AO + MI-training implied the observation and motor imagery of transitive manual dexterity tasks, whereas the control stimulation consisted of landscape video-clips observation. Manual dexterity was assessed using functional tests, kinematic and neurophysiological outcomes before and after the training and at 1-month follow-up. AO + MI-training improved manual dexterity, but subjects performing AO + MI-training followed by early sleep had significantly larger improvements than those undergoing the same training at least 12 h before sleeping. Behavioral findings were supported by neurodynamical correlates during motor performance and additional sleep-dependent benefits were also detected at 1 month follow-up. These findings introduce a new approach to enhance the acquisition of new motor skills or facilitate recovery in patients with motor impairments.


A systematic review and meta-analysis on complications of transanal total mesorectal excision.
Transanal total mesorectal excision (TaTME) is a surgical approach for treating mid to low rectal cancer as well as other colorectal diseases. Since the procedure is difficult to master, perioperative complications of TaTME should be examined precisely, especially during the early implementation phase of this procedure. The primary aim of this review was to determine a pooled morbidity and anastomotic leakage (AL) rate after TaTME surgery, and the secondary aim was to show the completeness of reporting of complications among the included studies, as well as the correlation between completeness and reported incidence of complications. A systematic review of literature was conducted using Medline, Embase and Cochrane databases, searching for observational studies reporting on complications after TaTME. Studies published between 1 January 2010 and 15 October 2019 were included. Meta-analysis on the proportion of morbidity, AL and intraoperative complications was performed. Forty-one studies (2446 TaTME cases), consisting of 27 noncomparative studies and 14 comparative studies, were included, after screening 1711 possible studies. The pooled rates of overall morbidity and AL were 30.0% (95% CI 26.4%-34.0%) and 6.8% (95% CI 5.2%-8.9%), respectively. Subgroup analysis showed that the morbidity rate in studies that reported 30-day results (35.5%; 95% CI 31.8%-39.4%) was significantly higher than the rate in studies that did not define the follow-up length for complications (23.4%; 95% CI 17.8%-30.1%; p = 0.003). The rates of intraoperative urethral injury, rectal injury, vaginal injury and bladder injury were 0.3% (95% CI 0.1%-1.7%), 0.4% (95% CI 0.1%-2.2%), 0.3% (95% CI 0.1%-0.8%) and 0.3% (95% CI 0.1%-1.7%), respectively. This meta-analysis shows that pooled perioperative complication rates were within acceptable ranges. However, the significant difference in overall morbidity rate between the studies with 30-day results and the studies without a specified follow-up time, indicates a large under-reporting of complications in many studies.


The reliability of distinguishing primary versus secondary negative symptoms.
The objective appearance of negative symptoms in schizophrenia and other psychotic disorders may be a direct reflection of a primary neural abnormality or may be secondary to a variety of factors such as neuroleptic side effects, depression, positive symptoms, or environmental understimulation. Although there is a consensus that it is important to be able to disentangle "primary" versus "secondary" negative symptoms, optimal strategies for doing so remain unclear. Concerns have been raised about making this distinction based on clinical judgment because of potential low reliability in the absence of extensive training and/or highly specialized rating scales. This is particularly important in terms of the application of DSM-IV criteria for schizophrenia, in which negative symptoms play a prominent role. In the context of the DSM-IV schizophrenia field trial project, we examined the reliability of making the primary versus secondary distinction in a multicenter sample of 462 subjects with nonorganic psychotic disorders. Each subject was assessed by two raters, half in an interrater design (i.e., conjoint interviews) and half in a test-retest design (i.e., independent interviews by two raters conducted 1 day apart). All raters used the same semistructured interview instrument, which included an abbreviated version of the Scale for the Assessment of Negative Symptoms (SANS). In addition to the usual SANS ratings, raters were asked to indicate their judgment as to whether the symptom was primary, secondary, or unknown (inadequate information to assess). No formal training was provided. Reliability, as quantified by kapp, indicated only a fair degree of agreement ranging from 0.48 to 0.68 for interrater reliability (median, 0.50) and 0.34 to 0.66 for test-retest reliability (median, 0.38). Negative symptoms were rated as primary approximately twice as often as secondary, and raters believed they had adequate information to make this distinction based only on cross-sectional evaluation in all but 10% of the cases. These data suggest that the primary versus secondary distinction should not be incorporated into the application of operationalized diagnostic criteria. Implications are discussed in terms of balancing reliability and validity in the assessment of negative symptoms.


Insights into the highly efficient treatment of dyeing wastewater using algal bloom derived activated carbon with wide-range adaptability to solution pH and temperature.
Here, a low-cost acid-base and temperature tolerant algal bloom derived activated carbon (ABAC) was successfully prepared to remove rhodamine B (RhB) from water. The ABAC exhibited maximum adsorption capacity of RhB (1101 ± 11 mg/g), higher than that of laboratory-prepared rape straw activated carbon (176 ± 5 mg/g) and commercial activated carbon (489 ± 5 mg/g). It is attributed to larger surface area and mesoporous structure of the ABAC. Furthermore, the effective adsorption of RhB by using ABAC was achieved at a wide range of solution pH (3.2-10.8) and temperature(25-50 °C). The mass transfer resistance of RhB adsorption process well depicted by Langmuir model was controlled by external mass transfer. The adsorption process involved both secondly chemisorption (H-bonds and π-π interaction) and dominated physisorption. Four dyes in river water were efficiently removed. This work provides a promising approach for developing high-absorption biomass materials for actual dye wastewater treatment.