Contact sensitivity and recalcitrant wounds.
Allergic contact dermatitis is a common and under-recognized phenomenon in patients with recalcitrant wounds. There are many possible causes including components of numerous agents used to treat these wounds, such as topical antibiotics, adhesives in dressings, emollients, emulsifiers, and self-administered medicaments. Considering allergic contact dermatitis when a wound is recalcitrant is important in the management of wounds. Etiologic agents, controversies, pathogenesis, diagnosis, and management of contact sensitivity are discussed.


Identification of major dioxin-like compounds and androgen receptor antagonist in acid-treated tissue extracts of high trophic-level animals.
We evaluated the applicability of combining in vitro bioassays with instrument analyses to identify potential endocrine disrupting pollutants in sulfuric acid-treated extracts of liver and/or blubber of high trophic-level animals. Dioxin-like and androgen receptor (AR) antagonistic activities were observed in Baikal seals, common cormorants, raccoon dogs, and finless porpoises by using a panel of rat and human cell-based chemical-activated luciferase gene expression (CALUX) reporter gene bioassays. On the other hand, no activity was detected in estrogen receptor α (ERα)-, glucocorticoid receptor (GR)-, progesterone receptor (PR)-, and peroxisome proliferator-activated receptor γ2 (PPARγ2)-CALUX assays with the sample amount applied. All individual samples (n = 66) showed dioxin-like activity, with values ranging from 21 to 5500 pg CALUX-2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ)/g-lipid. Because dioxins are expected to be strong contributors to CALUX-TEQs, the median theoretical contribution of dioxins calculated from the result of chemical analysis to the experimental CALUX-TEQs was estimated to explain up to 130% for all the tested samples (n = 54). Baikal seal extracts (n = 31), but not other extracts, induced AR antagonistic activities that were 8-150 μg CALUX-flutamide equivalent (FluEQ)/g-lipid. p,p'-DDE was identified as an important causative compound for the activity, and its median theoretical contribution to the experimental CALUX-FluEQs was 59% for the tested Baikal seal tissues (n = 25). Our results demonstrate that combining in vitro CALUX assays with instrument analysis is useful for identifying persistent organic pollutant-like compounds in the tissue of wild animals on the basis of in vitro endocrine disruption toxicity.


Apoptosis of glomerular mesangial cells induced by sublytic C5b-9 complexes in rats with Thy-1 nephritis is dependent on Gadd45 gamma upregulation.
The complement C5b-9 complexes can result in cell apoptosis, but the mechanism of sublytic C5b-9-mediated glomerular mesangial cell (GMC) apoptosis in Thy-1 nephritis (Thy-1N) remains largely unclear. The Gadd45 gene is involved in the cellular response to DNA damage and can promote cell apoptosis. In this study, both Gadd45 gamma expression patterns and pathologic changes of renal tissue were examined in rat Thy-1N. Both Gadd45 gamma expression and GMC apoptosis were significantly decreased in Thy-1N rats upon the depletion of complement with cobra venom factor. Our in vitro studies showed that Gadd45 gamma over-expression increased sublytic C5b-9-induced GMC apoptosis, while Gadd45 gamma gene knockdown by siRNA greatly reduced GMC apoptosis. Moreover, Gadd45 gamma gene silencing in vivo markedly inhibited the pathologic changes in the renal tissue of Thy-1N rats. These data suggest that Gadd45 gamma gene expression is involved in regulating GMC apoptosis mediated by sublytic C5b-9 in Thy-1N.


Radical reduction of upper extremity lymphedema with preservation of perforators.
Excisional procedures have been successfully utilized by different authors in multistage treatment of upper extremity lymphedema. We have used microsurgical principles of perforator flap surgery in order to develop a one-stage procedure that enables a radical reduction of the lymphedematous tissue with preservation of the vascular supply to the overlying skin.Between March 2000 and February 2007, 11 patients affected by late stage II lymphedema underwent radical reduction of the affected tissues with preservation of perforators. Perforator vessels from the radial and posterior interosseous arteries were identified and through medial and lateral forearm incisions, skin flaps were raised off the underlying lymphedematous tissue and the affected tissue was removed off the deep fascia. At a mean follow-up of 17.8 months the average percentage reductions above and below the elbow, at the wrist, and the hand were 15.1%, 20.7%, 0.5%, and 3.6%, respectively. Statistical analysis showed significant circumference reduction above and below the elbow (P = 0.048 and 0.022, respectively) but not at the wrist and hand. There were no cases of wound breakdown, skin necrosis, or cellulitis in the postoperative period. Four patients complained of mild numbness confined to the vicinity of the surgical incisions.Microvascular principles applied to the radical excision of the subcutaneous tissue seems to offer a new promising one-stage surgical procedure in patients affected by upper extremity lymphedema that has failed conservative therapy.


Dynamic contrast-based quantization for lossy wavelet image compression.
This paper presents a contrast-based quantization strategy for use in lossy wavelet image compression that attempts to preserve visual quality at any bit rate. Based on the results of recent psychophysical experiments using near-threshold and suprathreshold wavelet subband quantization distortions presented against natural-image backgrounds, subbands are quantized such that the distortions in the reconstructed image exhibit root-mean-squared contrasts selected based on image, subband, and display characteristics and on a measure of total visual distortion so as to preserve the visual system's ability to integrate edge structure across scale space. Within a single, unified framework, the proposed contrast-based strategy yields images which are competitive in visual quality with results from current visually lossless approaches at high bit rates and which demonstrate improved visual quality over current visually lossy approaches at low bit rates. This strategy operates in the context of both nonembedded and embedded quantization, the latter of which yields a highly scalable codestream which attempts to maintain visual quality at all bit rates; a specific application of the proposed algorithm to JPEG-2000 is presented.


Pivotal Advance: eosinophil infiltration of solid tumors is an early and persistent inflammatory host response.
Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals; however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors, indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4+ T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with T helper cell type 2-dependent immune responses and that recruitment is a dynamic, ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial-restricted. It is more important that these data also show that the mechanism(s) that elicit this host response occur, independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis.


Physical Activity Types and Coronary Heart Disease Risk in Middle-Aged and Elderly Persons: The Rotterdam Study.
Physical activity is associated with decreased risk of coronary heart disease (CHD). The specific physical activity types that provide beneficial effects in an older population remain unclear. We assessed the association of total physical activity, walking, cycling, domestic work, sports, and gardening with CHD by using Cox proportional hazard models among 5,901 participants aged >55 (median age, 67) years from the prospective population-based Rotterdam Study, enrolled between 1997 and 2001. Activities were categorized into tertiles, and the lowest tertiles were used as reference. In the multivariable model, we adjusted for age, sex, smoking, alcohol consumption, education, diet, and other physical activity types. During 15 years of follow-up (median, 10.3 (interquartile range, 8.0-11.8) years), 642 participants (10.9%) experienced a CHD event. In the multivariable model, the respective hazard ratios for the medium and high categories compared with the low category were 0.79 (95% confidence interval CI): 0.66, 0.96) and 0.71 (95% CI: 0.58, 0.87) for total physical activity, 0.76 (95% CI: 0.63, 0.92) and 0.70 (95% CI: 0.57, 0.88) for cycling, and 0.81 (95% CI: 0.66, 0.98) and 0.71 (95% CI: 0.56, 0.90) for domestic work. Walking, sports, and gardening were not associated with CHD. In conclusion, in this long-term follow-up study of older adults, domestic work and cycling were associated with reduced CHD risk. Physical activity should be promoted in this population with the aim to prevent CHD.


Engineering approaches to develop the next generation of antibodies to respiratory targets.
Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) represent a significant health burden worldwide and are a major unmet medical need. Asthma affects over 300 million people and leads to 250,000 deaths per year, with an increasing prevalence particularly in developing countries. Although a large proportion of asthmatics are maintained on beta agonists and corticosteroids, there still remains a group of patients where these medicines fail to modulate symptoms and who may therefore benefit from monoclonal antibody based drugs that are aimed at controlling the disease. COPD is a cigarette smoke-driven chronic inflammatory airway disease with an increasing global prevalence. Given that current therapies fail to prevent disease progression or mortality, this patient population is also a focus for the development of monoclonal antibody therapies. At present anti-IgE (omalizumab, Xolair®) is the only monoclonal antibody based drug approved in the respiratory space for the treatment of asthma. However, an increasing number of antibodies targeting key mediators/pathways of disease are in clinical development for both asthma and COPD, including targeting the Th2 pathway for asthma (anti-IL-4/5/13) and the pro-inflammatory cytokine IL-1 for COPD. This review will examine the antibody engineering approaches used to develop the next generation of antibodies, with a focus on respiratory disease.


[Detection of malondialdehyde-DNA adduct level by 32P-postlabeling assay in normal human esophageal epithelium and esophageal squamous cell carcinoma].
To study whether the main malondialdehyde-DNA adduct (M1-dG) produced by lipid peroxidation is involved in the carcinogenesis of esophagus. DNA samples were isolated from normal esophageal epithelium (n = 32) obtained by biopsy and esophageal squamous cell carcinoma specimens (n = 30) obtained by surgery. All tissue samples came from individuals living in Linxian, Henan, a high-risk area of esophageal cancer. Contents of M1-dG adducts were detected by 32P-postlabeling method. M1-dG adducts were detectable both in the normal and cancerous tissue samples. However, normal esophageal epithelial tissues exhibited significantly lower levels of M1-dG adducts (median 3.4, range 1.7/10(8)-55.4/10(8) nucleotides) than those found in esophageal cancer tissues (median 14.1, range 1.4/10(8)-59.0/10(8) nucleotides, P < 0.0001). The adduct levels were neither associated with gender, age, tobacco smoking status or genetic polymorphism in the CYP2E1, an enzyme participating in the oxidation of ethanol to form reactive free radicals. Our findings provide evidence that DNA damage, resulted from lipid peroxidation, can accumulate in the normal human esophageal tissue and reach relatively high level in cancer tissue which suggests that M1-dG adducts may be involved in the initiation and progression of cancer with its mutagenic and carcinogenic effects.


Survey of the use of therapeutic hypothermia after cardiac arrest in UK paediatric emergency departments.
To ascertain current use of therapeutic hypothermia (TH) after paediatric cardiac arrest in UK emergency departments (EDs), and views on participating in a UK randomised controlled trial (RCT) incorporating early induction of TH in ED. Anonymous web-based survey of 77 UK Emergency Medicine (EM) consultants from 28 UK EDs that see children during the period April-June 2010. 62% (48/77) of surveyed consultants responded from 21/28 (75%) EDs. All managed children post cardiac arrest. 90% (43/48) were aware of the literature concerning TH after cardiac arrest in adults. However, 63% (30/48) had never used TH in paediatric practice. All departments had at least one method of inducing TH (surface cooling; air/water blankets; intravenous cold fluid or catheters). Reasons stated for not inducing TH included no equipment available (26%; 11/42), TH not advocated by the local PICU (24%; 10/42) and not enough evidence for its use (24%; 10/42). TH was considered based on advice from the local Paediatric Intensive Care Units (68%; 17/25) or likelihood of recovery after arrest (32%; 8/25). There was strong support for a UK RCT of TH versus normothermia (85%; 40/47). The proposed RCT was felt to be ethical (87%; 40/48) with use of deferred consent acceptable (74%; 34/46). UK EM consultants are aware of TH but infrequently initiate the therapy in children for a number of reasons. Their involvement would enable early induction of TH in EDs after paediatric cardiac arrest during a UK RCT. The authors have demonstrated the availability of suitable equipment and EM consultant support for participation in such a RCT.


The Neural Metric Factorization for Computational Drug Repositioning.
Computational drug repositioning aims to discover new therapeutic diseases for marketed drugs and has the advantages of low cost, short development cycle, and high controllability compared to traditional drug development. The matrix factorization model has become the cornerstone technique for computational drug repositioning due to its ease of implementation and excellent scalability. However, the matrix factorization model uses the inner product operation to represent the association between drugs and diseases, which is lacking in expressive ability. Moreover, the degree of similarity of drugs or diseases could not be implied on their respective latent factor vectors, which is not satisfy the common sense of drug discovery. Therefore, a neural metric factorization model for computational drug repositioning (NMFDR) is proposed in this work. We novelly consider the latent factor vector of drugs and diseases as a point in the high-dimensional coordinate system and propose a generalized euclidean distance to represent the association between drugs and diseases to compensate for the shortcomings of the inner product operation. Furthermore, by embedding multiple drug (disease) metrics information into the encoding space of the latent factor vector, the information about the similarity between drugs (diseases) can be reflected in the distance between latent factor vectors. Finally, we conduct wide analysis experiments on three real datasets to demonstrate the effectiveness of the above improvement points and the superiority of the NMFDR model.


[Current therapeutic approach to cervicofacial lymphangiomas in children].
Twenty-four cases of cervicofacial lymphangioma treated between 1984 and 1991 are reported. The therapeutic approach is discussed. Because the therapeutic problem depends on whether or not the airways are involved, an endoscopic evaluation and a CT scan study should be included in the workup. In the five patients with limited lymphangiomas, complete surgical exeresis was feasible and yielded good results. Sclerosing injections are an alternative to surgery in this situation. In patients with pharyngeal or laryngeal infiltration or involvement of the mediastinum, the prognosis is extremely grim and surgery is still the mainstay of therapy despite the potential for recurrence due to the fact that only incomplete exeresis can be performed. Tracheostomy was required in two patients.


Differences in risk factors for binge eating by socioeconomic status in a community-based sample of adolescents: Findings from Project EAT.
Binge eating is prevalent across socioeconomic status (SES) groups, but it is unclear whether risk factors for binge eating vary by SES. This study examined the prevalence of several risk factors for binge eating by SES and SES as a potential moderator of these risk factors. Participants included 2,179 individuals involved in Project EAT during early/middle adolescence (EAT-I) and 5 years later during late adolescence/emerging adulthood (EAT-II). Risk ratios were computed using modified Poisson regression of incident EAT-II binge eating on EAT-I risk factors among participants of high and low SES. Interactions between each risk factor and SES were tested. Among higher SES adolescents, overweight/obesity (RR = 3.2; 95% CI: 1.8, 5.7), body dissatisfaction (RR = 2.6; 95% confidence intervals (CI): 1.2, 5.5), dieting (RR = 4.0; 95% CI: 2.0, 8.2), and family weight-teasing (RR = 2.3; 95% CI: 1.3, 4.3) predicted increased risk for binge eating. Among adolescents from low-SES backgrounds, overweight/obesity (RR = 1.5; 95% CI: 0.9, 2.5), dieting (RR = 2.2; 95% CI: 1.2, 3.9), and food insecurity (RR = 1.4; 95% CI: 0.7, 2.7) predicted increased risk for binge eating. Moderator analyses revealed that overweight/obesity, body dissatisfaction, dieting, and family weight-teasing were stronger risk factors in the high-SES group than the low-SES group; interactions with food insecurity could not be examined given the low prevalence of food insecurity in the high-SES group. Risk factors for binge eating may vary by SES, suggesting the potential utility of modifying intervention and prevention methods based on SES. In particular, the role of food insecurity must be addressed.


Correlation between Lindane Use and the Incidence of Thyroid Cancer in the United States: An Ecological Study.
The increasing rate of thyroid cancer may be attributable to endocrine disruptive chemicals. Lindane is a persistent organochlorine pesticide with endocrine disruptive properties that has been classified as carcinogenic to humans. The aim of this ecological study was to evaluate potential correlation between lindane exposure and thyroid cancer incidence in the United States (US). Data on statewide age-adjusted thyroid cancer incidence rate (per 100,000 people) was obtained from the Centers for Disease Control and Prevention for all US states for 2019. Lindane use estimates per cropland (kg/acres cropland) were then overlaid on the map of age-adjusted thyroid cancer incidence rate using ArcGIS. The trend of lindane use in the US between 1992 and 2007 was calculated using the Mann Kendall correlation test. The correlation between statewide lindane use and age-adjusted thyroid cancer incidence rates was calculated using Spearman correlation. Lindane use in the US decreased significantly between 1992 and 2007 (T = -0.617; p < 0.001). There was no statistically significant correlation between lindane use in 1992 and thyroid cancer incidence rate for any of the years between 1999 and 2019. Our results suggest that restrictions clearly seem to be effective in reducing lindane use, however, more research is needed for individual pesticides and thyroid cancer.


Smoking decreases the level of circulating CD34+ progenitor cells in young healthy women--a pilot study.
Decreased levels of circulating bone marrow-derived progenitor cells have been associated with risk factors and cardiovascular diseases. Smoking is the most important modifiable risk factor for atherosclerosis in young women. The aim of this pilot study was to assess in healthy premenopausal women without other risk factors for cardiovascular disease the influence of nicotine abuse on the number of circulating progenitor cells in relation to endothelial function. The number of endothelial progenitor cells, measured as colony-forming units in a cell-culture assay (EPC-CFU) and the number of circulating CD34 + and CD34 + /CD133 + cells, measured by flow cytometry, was estimated in 32 women at the menstrual phase of the menstrual cycle. In addition, flow-mediated dilation (FMD) was assessed as a marker for vascular function. In a subgroup of these women (n = 20), progenitor cells were also investigated at the mid-follicular and luteal phases of the menstrual cycle. Compared to non-smokers, the abundance of circulating CD34 + cells was significantly lower in smoking women in the menstrual, mid-luteal, and mid-follicular phases of the menstrual cycle. The number of CD34 + progenitor cells was revealed to have significant positive correlation with FMD in young healthy women, whereas CD34 + /CD133 + progenitor cells and EPC-CFU showed no significant correlation. The number of CD34 + progenitor cells positively correlates with FMD in young healthy women and is decreased by smoking.


Altitude-induced arterial gas embolism: a case report.
Following a rapid decompression in an altitude chamber for routine training purposes, a 38-year-old altitude chamber technician developed rapid onset of mental dullness, right arm weakness, and sensory deficits. Immediate treatment with compression therapy in a hyperbaric chamber resulted in complete resolution. Ambient pressure changes great enough to result in arterial air embolism due to an explosive or rapid decompression have been described as a potential hazard in aviation, although no actual cases of such a phenomenon have been previously reported. The aeromedical considerations of this complication are discussed.


Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.
CDK4 is amplified in > 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces senescence in cell lines and xenografts. In a phase I trial of PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label phase II study to determine the safety and efficacy of PD0332991 in patients with advanced WDLS/DDLS. Patients age ≥ 18 years experiencing disease progression while receiving systemic therapy before enrollment received PD0332991 200 mg orally once per day for 14 consecutive days in 21-day cycles. All were required to have CDK4 amplification by fluorescence in situ hybridization and retinoblastoma protein (RB) expression by immunohistochemistry (≥ 1+). The primary end point was progression-free survival (PFS) at 12 weeks, with 12-week PFS of ≥ 40% considered promising and ≤ 20% not promising. If ≥ nine of 28 patients were progression free at 12 weeks, PD0332991 would be considered active. We screened 48 patients (44 of 48 had CDK4 amplification; 41 of 44 were RB positive). Of those, 30 were enrolled, and 29 were evaluable for the primary end point. Grade 3 to 4 events included anemia (17%), thrombocytopenia (30%), neutropenia (50%), and febrile neutropenia (3%). At 12 weeks, PFS was 66% (90% CI, 51% to 100%), significantly exceeding the primary end point. The median PFS was 18 weeks. There was one partial response. Treatment with the CDK4 inhibitor PD0332991 was associated with a favorable progression-free rate in patients with CDK4-amplified and RB-expressing WDLS/DDLS who had progressive disease despite systemic therapy.


Characterising two-pathogen competition in spatially structured environments.
Different pathogens spreading in the same host population often generate complex co-circulation dynamics because of the many possible interactions between the pathogens and the host immune system, the host life cycle, and the space structure of the population. Here we focus on the competition between two acute infections and we address the role of host mobility and cross-immunity in shaping possible dominance/co-dominance regimes. Host mobility is modelled as a network of traveling flows connecting nodes of a metapopulation, and the two-pathogen dynamics is simulated with a stochastic mechanistic approach. Results depict a complex scenario where, according to the relation among the epidemiological parameters of the two pathogens, mobility can either be non-influential for the competition dynamics or play a critical role in selecting the dominant pathogen. The characterisation of the parameter space can be explained in terms of the trade-off between pathogen's spreading velocity and its ability to diffuse in a sparse environment. Variations in the cross-immunity level induce a transition between presence and absence of competition. The present study disentangles the role of the relevant biological and ecological factors in the competition dynamics, and provides relevant insights into the spatial ecology of infectious diseases.


Empirical and normative ethics: a synthesis relating to the care of older patients.
The aim of this study was to synthesize the concepts from empirical studies and analyze, compare and interrelate them with normative ethics. The International Council of Nurses (ICN) and the Health and Medical Service Act are normative ethics. Five concepts were used in the analysis; three from the grounded theory studies and two from the theoretical framework on normative ethics. A simultaneous concept analysis resulted in five outcomes: interconnectedness, interdependence, corroboratedness, completeness and good care are all related to the empirical perspective of the nurse's interaction with the older patient, and the normative perspective, i.e. that found in ICN code and SFS law. Empirical ethics and normative ethics are intertwined according to the findings of this study. Normative ethics influence the nurse's practical performance and could be supporting documents for nurses as professionals.


Chrysin ameliorates 3 nitropropinoic acid induced neurotoxicity targeting behavioural, biochemical and histological alterations.
Huntington disease (HD) is an autosomal dominant inheritance neurodegenerative disorder. 3-Nitropropanoic acid (3-NP) is a mitochondrial toxin that induces HD-like symptoms and thus serves as a good experimental model of HD. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid that have multiple biological activities. The present work was aimed to evaluate the neuroprotective efficacy of Chrysin in rat brain, under the influence of 3-NP treatment, by studying neurobehavioral and biochemical alterations alongwith histo-architectural changes. Male Wistar rats (220-250 g) were used in the study and were divided into three groups following randomization. Each group comprised of nine animals. Group I animals served as control group and administered with normal saline (orally) as vehicle. Animals of Group II were treated with 3-NP for four successive days, at the dose of 20 mg/kg, intraperitoneally (i.p.). Animals that received Chrysin for the period of four consecutive days with the dose of 50 mg/kg, orally twice daily (30 min pre-treatment and 6 h post-treatment) following 3-NP administration served as Group III. After the treatment regime, animals were evaluated for neurobehavioral alterations and brain homogenates were used for estimation of neurotoxicity marker activity and neurotransmitter level along with histological assessment. The significant alteration in neurobehavioral, biochemical and neuronal structure in striatal part of brain was observed in the 3-NP administered (Group II) animals. It was observed that co-treatment of Chrysin with 3-NP treated rats the rotarod performance, grip strength, stride length as well as monoamine oxidase activity and serotonin levels were elevated. The results of this study reveal that Chrysin treatment alleviated the neurobehavioral, biochemical and histological alterations against HD symptoms in rats.


The impacts of coping style and perceived social support on the mental health of undergraduate students during the early phases of the COVID-19 pandemic in China: a multicenter survey.
An increasing number of undergraduate students in China have been reported to have psychological problems. In response to the COVID-19 pandemic, a series of preventive and control measures were implemented, which undoubtedly worsened their psychological health. Coping style and social support were probably important factors that affected the psychological well-being of undergraduate students during the pandemic. This study aimed to explore the effects of coping style and perceived social support on the psychological well-being of college students and relevant risk factors. This cross-sectional study was performed in February and March of 2020 by distributing an online questionnaire among undergraduate students from seven geographical regions across China. The questionnaire included sociodemographic information; the 21-item Depression, Anxiety and Stress Scale (DASS-21); the Perceived Social Support Scale (PSSS); and the Simplified Coping Style Questionnaire (SCSQ). For the analyses, t-tests, one-way analysis of variance (ANOVA), the Kruskal-Wallis test and multiple linear regression were utilized. The level of significance was set at P < 0.05. Among 3113 college students, the rates of anxiety, depression and stress symptoms were 13.3, 15.4 and 6.8%, respectively. Increased rates of current smoking and drinking (5.5 and 25.2%, respectively) among undergraduates were identified. The results indicated that the PSSS subscales and SCSQ subscales were significantly associated with DASS-21 scores (P < 0.001). Multiple linear regression analysis showed that active coping style and family support were protective factors while passive coping style could aggravate psychological problems among participants (P < 0.001). A remarkable number of college students adopted passive coping strategies to cope with negative feelings, such as smoking and drinking, which were detrimental to their mental health. In contrast, active coping strategies helped improve their psychological well-being. Moreover, family support was particularly important for maintaining their mental health and ameliorating mental health challenges in this major health crisis. Consequently, suitable psychointervention, routine screening for risk behaviors, and provision of further social support are needed for undergraduate students in the COVID-19 pandemic or other emergency public health events.


Genetic diversity of the msp-1, msp-2, and glurp genes of Plasmodium falciparum isolates in Northwest Ethiopia.
Determination of the genetic diversity of malaria parasites can inform the intensity of transmission and identify potential deficiencies in malaria control programmes. This study was conducted to characterize the genetic diversity and allele frequencies of Plasmodium falciparum in Northwest Ethiopia along the Eritrea and Sudan border. A total of 90 isolates from patients presenting to the local health centre with uncomplicated P. falciparum were collected from October 2014 to January 2015. DNA was extracted and the polymorphic regions of the msp-1, msp-2 and glurp loci were genotyped by nested polymerase chain reactions followed by gel electrophoresis for fragment analysis. Allelic variation in msp-1, msp-2 and glurp were identified in 90 blood samples. A total of 34 msp alleles (12 for msp-1 and 22 for msp-2) were detected. For msp-1 97.8% (88/90), msp-2 82.2% (74/90) and glurp 46.7% (42/90) were detected. In msp-1, MAD20 was the predominant allelic family detected in 47.7% (42/88) of the isolates followed by RO33 and K1. For msp-2, the frequency of FC27 and IC/3D7 were 77% (57/74) and 76% (56/74), respectively. Nine glurp RII region genotypes were identified. Seventy percent of isolates had multiple genotypes and the overall mean multiplicity of infection was 2.6 (95% CI 2.25-2.97). The heterozygosity index was 0.82, 0.62 and 0.20 for msp-1, msp-2 and glurp, respectively. There was no significant association between multiplicity of infection and age or parasite density. There was a high degree of genetic diversity with multiple clones in P. falciparum isolates from Northwest Ethiopia suggesting that there is a need for improved malaria control efforts in this region.


Structural insights into the psychrophilic germinal protease PaGPR and its autoinhibitory loop.
In spore forming microbes, germination protease (GPR) plays a key role in the initiation of the germination process. A critical step during germination is the degradation of small acid-soluble proteins (SASPs), which protect spore DNA from external stresses (UV, heat, low temperature, etc.). Inactive zymogen GPR can be activated by autoprocessing of the N-terminal pro-sequence domain. Activated GPR initiates the degradation of SASPs; however, the detailed mechanisms underlying the activation, catalysis, regulation, and substrate recognition of GPR remain elusive. In this study, we determined the crystal structure of GPR from Paenisporosarcina sp. TG-20 (PaGPR) in its inactive form at a resolution of 2.5 A. Structural analysis showed that the active site of PaGPR is sterically occluded by an inhibitory loop region (residues 202-216). The N-terminal region interacts directly with the self-inhibitory loop region, suggesting that the removal of the N-terminal pro-sequence induces conformational changes, which lead to the release of the self-inhibitory loop region from the active site. In addition, comparative sequence and structural analyses revealed that PaGPR contains two highly conserved Asp residues (D123 and D182) in the active site, similar to the putative aspartic acid protease GPR from Bacillus megaterium. The catalytic domain structure of PaGPR also shares similarities with the sequentially non-homologous proteins HycI and HybD. HycI and HybD are metal-loproteases that also contain two Asp (or Glu) residues in their active site, playing a role in metal binding. In summary, our results provide useful insights into the activation process of PaGPR and its active conformation.


Uraemic symptom burden and clinical condition in women and men of ≥65 years of age with advanced chronic kidney disease: results from the EQUAL study.
The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of ≥65 years of age with advanced CKD receiving routine nephrology care. The European QUALity study on treatment in advanced chronic kidney disease (EQUAL) study follows patients from six European countries of ≥65 years of age years whose estimated glomerular filtration rate (eGFR) dropped to ≤20 mL/min/1.73 m2 for the first time during the last 6 months. The Dialysis Symptom Index was used to assess the prevalence and severity of 33 uraemic symptoms. Data on the clinical state at baseline were collected from medical records. Prevalence was standardized using the age distribution of women as the reference. The results in women (n = 512) and men (n = 967) did not differ with age (77.0 versus 75.7 years) or eGFR (19.0 versus 18.5). The median number of symptoms was 14 [interquartile range (IQR) 9-19] in women, and 11 (IQR 7-16) in men. Women most frequently reported fatigue {39% [95% confidence interval (CI) 34-45]} and bone/joint pain [37% (95% CI 32-42)] as severe symptoms, whereas more men reported difficulty in becoming sexually aroused [32% (95% CI 28-35)] and a decreased interest in sex [31% (95% CI 28-35)]. Anaemia [73% (95% CI 69-77) versus 85% (95% CI 82-87)] was less common in women than in men, as were smoking history and cardiovascular comorbidity. However, a diagnosis of liver disease other than cirrhosis, psychiatric disease and mild malnutrition were more common among women. Women in secondary care with an incident eGFR ≤20 mL/min/1.73 m2 reported a higher symptom burden, while their clinical state was considered similar or even more favourable as compared with men.


Physiotherapists' experiences of early mobilization after stroke thrombolysis in England and Wales: A qualitative study.
Thrombolysis with tissue plasminogen activator is a mainstream treatment for ischemic stroke. Known risks with thrombolysis include intracerebral hemorrhage and bleeding elsewhere in the body. There are no specific recommendations for the timing of commencing mobility rehabilitation after thrombolysis. Research evidence for early mobilization (within 24 hours) after thrombolysis is sparse and little is known about physiotherapy practice in the UK. Purpose: This exploratory study aimed to investigate the experiences, including clinical decision-making of physiotherapists in England and Wales regarding early mobilization after thrombolysis. A qualitative study with interpretative paradigm using a phenomenological methodology. Semi-structured interviews were conducted with a purposive sample. Thematic analysis triangulated by participant and researcher review of resultant themes was supported by NVivo software. A reflexive diary was maintained throughout. Data saturation was reached after 14 interviews. All participants reported experience of early mobilization after thrombolysis, with no reported harm or serious incident. Themes included descriptions of practice, perceived benefits and harms, and implementation of risk assessment and management strategies. Physiotherapists describe a variety of practices with careful implementation of any early mobilization after thrombolysis. Common factors of risk assessment reported by participants could contribute to guideline development.


A systematic review of stakeholder views of selection methods for medical schools admission.
The purpose of this paper is to systematically review the literature with respect to stakeholder views of selection methods for medical school admissions. An electronic search of nine databases was conducted between January 2000-July 2014. Two reviewers independently assessed all titles (n = 1017) and retained abstracts (n = 233) for relevance. Methodological quality of quantitative papers was assessed using the MERSQI instrument. The overall quality of evidence in this field was low. Evidence was synthesised in a narrative review. Applicants support interviews, and multiple mini interviews (MMIs). There is emerging evidence that situational judgement tests (SJTs) and selection centres (SCs) are also well regarded, but aptitude tests less so. Selectors endorse the use of interviews in general and in particular MMIs judging them to be fair, relevant and appropriate, with emerging evidence of similarly positive reactions to SCs. Aptitude tests and academic records were valued in decisions of whom to call to interview. Medical students prefer interviews based selection to cognitive aptitude tests. They are unconvinced about the transparency and veracity of written applications. Perceptions of organisational justice, which describe views of fairness in organisational processes, appear to be highly influential on stakeholders' views of the acceptability of selection methods. In particular procedural justice (perceived fairness of selection tools in terms of job relevance and characteristics of the test) and distributive justice (perceived fairness of selection outcomes in terms of equal opportunity and equity), appear to be important considerations when deciding on acceptability of selection methods. There were significant gaps with respect to both key stakeholder groups and the range of selection tools assessed. Notwithstanding the observed limitations in the quality of research in this field, there appears to be broad concordance of views on the various selection methods, across the diverse stakeholders groups. This review highlights the need for better standards, more appropriate methodologies and for broadening the scope of stakeholder research.


Do You Read How I Read? Systematic Individual Differences in Semantic Reliance amongst Normal Readers.
The extent to which meaning is involved in reading aloud has proven an area of longstanding debate, and current computational models differ on this dimension. The connectionist triangle model proposes that normal individuals rely on semantic information for correct reading of words with atypical spelling-sound relationships, but to varying degrees. This proposed individual difference would account for the varying stage of decline at which patients with semantic dementia first show the reading impairment known as surface dyslexia. Recent neuroimaging data has provided validation of this view, showing that individual differences in degree of semantic reliance during exception word reading predict the amount of activation in left anterior temporal regions associated with semantic processing. This study aimed to establish the cognitive correlates of individual differences in semantic reliance during exception word reading. Experiment 1 used a subgrouping approach with 32 participants and found larger imageability and semantic priming effects specifically for exception word reading amongst high relative to low semantic reliance readers. High semantic reliance readers also tended to read nonwords more slowly than low semantic reliance readers. A second experiment used a regression approach with 129 readers and confirmed the relationship of degree of semantic reliance both to imageability effects in exception word reading and speed of nonword reading. Further, while the performance of the higher semantic readers revealed no significant association with semantic processing tasks, there was a negative relationship with rhyme processing tasks. We therefore speculate that differences in phonological abilities may be responsible for varying degrees of semantic reliance in reading aloud. This proposal accords with the results of functional imaging showing that higher semantic reliance during exception word reading corresponds to lower activation in left pre-central gyrus, an area associated with direct spelling sound mapping and phonological processing. Our results therefore establish the nature of systematic individual differences in degree of semantic involvement amongst normal readers, and suggest directions for future neuroimaging and computational modeling research to uncover their origins.


Lifestyle factors and p53 mutation patterns in colorectal cancer patients in the EPIC-Norfolk study.
The tumour suppressor p53 is one of the most commonly altered genes in colorectal cancer (CRC) development. Genetic alterations in p53 may therefore be associated with postulated lifestyle risk factors for CRC, such as red meat consumption. In the European Prospective Investigation into Cancer and Nutrition-Norfolk study, we examined whether detailed estimates of dietary and lifestyle factors measured at baseline related to later development of p53 mutations in CRCs. After 10-year follow-up, there were 185 incident CRCs of which 34% had somatic p53 mutations (p53+). We observed significantly higher mean intakes of alcohol, total meat and red meat, in the group with p53 mutations and advanced Dukes' stage disease (daily alcohol intake was 7 and 12 g for p53- and p53+ cases, respectively, P = 0.04; daily total meat intake was 69 and 100 g for p53- and p53+ cases, respectively, P = 0.03 and daily red meat intake was 39 and 75 g for p53- and p53+ cases, respectively, P = 0.01). Each 50 g/day increment in total meat intake was associated with having p53 mutations in cases with advanced Dukes' stages [odds ratio (OR): 3.43, 95% confidence interval (CI): 1.47-7.96]. Similarly, each 50 g/day increment in red meat intake was also significantly associated with having consistent p53 mutations in cases with advanced Dukes' stages (OR: 2.42, 95% CI: 1.18-4.96). These effects of total meat or red meat intake and advanced Dukes' stages were independent of age, sex, body mass index, smoking and alcohol intake. Furthermore, P values for interaction between daily total meat or red meat intake and Dukes' stages were statistically significant in multivariable models (Pinteraction < 0.001). Our results suggest that p53 mutations accelerate progression of CRC to advanced Dukes' stage in association with higher meat especially red meat intakes.


[Comparative ecology of tuberculosis and hanseniasis as they coincide endemically in tropical countries].
The authors discuss the several aspects of the co-sensibilization in the infections produced by M. Tuberculosis and M. hanseniae. Attention is called to Rabello's pioneer works written in 1935 and the subsequent works written by several Argentinian and Brazilian authors. Special emphasis is made to the experimental works in animals by Azulay. The authors discuss the aspects of competitiveness, protection and the crossed granulomatosis answers to the infections.


Arctigenin shows preferential cytotoxicity to acidity-tolerant prostate carcinoma PC-3 cells through ROS-mediated mitochondrial damage and the inhibition of PI3K/Akt/mTOR pathway.
Extracellular acidity in the tumor microenvironment contributes to chemoresistance of malignant tumors. The objective of this study was to determine anticancer effects of arctigenin, a novel anti-inflammatory lignan extracted from seeds of Arctium lappa, on acidity-tolerant prostate cancer PC-3AcT cells. The PC-3AcT cells manifested increased tolerance to low-pH media with enhanced percent cell viability and increased resistance to docetaxel compared to their parental PC-3 cells. Arctigenin alone or in combination with docetaxel induced potent cytotoxicity. Preferential sensitization of PC-3AcT cells to arctigenin was accompanied by increased cell fractions with sub-G0/G1 peak and annexin V-PE(+), increased ROS levels, decreased mitochondrial membrane potential and cellular ATP content, and inhibition of PI3K/Akt/mTOR pathway. A series of changes caused by arctigenin were efficiently reversed through reducing ROS levels by radical scavenger N-acetylcysteine, thus placing ROS upstream of arctigenin-driven cytotoxicity. Collectively, these results demonstrate that arctigenin can increase oxidative stress-mediated mitochondrial damage of acidity-tolerant PC-3AcT cells, suggesting that arctigenin might be a potential therapeutic candidate to overcome acidic-microenvironment-associated chemotherapeutic resistance in prostate cancer.


cDNA nucleotide sequence and expression of a tobacco cytoplasmic ribosomal protein L2 gene.
The ribosomal protein L2 is an essential component of the ribosomal large subunit by its relation to the peptidyl transferase reaction, subunit association and elongation factor G-GTP binding. We have isolated a 937 nucleotide long cDNA encoding a cytoplasmic ribosomal L2 protein. Its deduced protein contains 260 amino acid residues and shows 65% identity with eucaryotic RL2 but only 32% identity with the chloroplast homologue. In addition, the protein presents the PROSITE signature which matches all the 50S and 60S L2 proteins and the two residues involved in the peptidyl transferase activity. The corresponding mRNA is accumulated in young plant tissues, in growing cell suspension and in germinating seeds but is not detectable in mature plant tissues, stationary cell suspension and in dry seeds. The mRNA accumulation is correlated with the growth process. Southern blot hybridization shows that cytoplasmic ribosomal protein L2 is encoded by two types of gene which could originate from each parent. highly homologous L2 genes were also detected by Southern blots in the genomes of several monocot and dicot plant species.


A study on the use of acupoint catgut embedding in the treatment of pre-diabetes: a meta-analysis and data mining approach.
The efficacy of acupoint catgut embedding (ACE) for the treatment of pre-diabetes remains controversial. Therefore, this study investigated the clinical efficacy and acupoint selection in ACE for the treatment of pre-diabetes. Eight common databases were searched for relevant literature on ACE for pre-diabetes. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore the protocol for acupoint selection. The meta-analysis revealed that compared with conventional treatment alone, conventional treatment combined with ACE reduced the levels of glycated hemoglobin A1c [mean difference (MD) -0.45, 95% confidence interval (CI) -0.67 to -0.24%, p < 0.001], fasting blood glucose (MD -0.61 mmol/L, 95% CI -0.87 to -0.36 mmol/L, p < 0.001), 2-h postprandial glucose (MD -0.77 mmol/L, 95% CI -0.98 to -0.55 mmol/L, p < 0.001), total cholesterol (MD -0.37 mmol/L, 95% CI -0.74 to 0.00 mmol/L, p = 0.049), triglyceride (MD -0.49 mmol/L, 95% CI -0.77 to -0.20 mmol/L, p < 0.001) and low-density lipoprotein cholesterol (MD -0.23 mmol/L, 95% CI -0.33 to -0.12 mmol/L, p < 0.001), and increased high-density lipoprotein cholesterol levels (MD 0.16 mmol/L, 95% CI 0.05 to 0.27 mmol/L, p = 0.004), whereas changes in the body mass index and the adverse event rates were comparable between groups. Data mining revealed that Pishu (BL20), Weiwanxiashu (EX-B3), Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Weishu (BL21), and Taixi (KI3) were the core acupoints used in ACE for pre-diabetes. ACE can effectively improve blood glucose and lipid levels in pre-diabetes patients and has a good safety profile. ACE consisting of Pishu (BL20), Weiwanxiashu (EX-B3), Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Weishu (BL21), and Taixi (KI3), is a promising complementary strategy for the treatment of pre-diabetes.


Effects of planar and non-planar driver-side mirrors on age-related discomfort-glare responses.
In this study, we evaluated subjective nighttime discomfort-glare responses on three different types of planar and non-planar driver-side mirrors on two age groups. Fifty-six individuals (28 young [18-35 years] and 28 old [65 years and over]) participated in this experiment. Subjective discomfort-glare rating scores on three different types of driver-side mirrors were assessed utilizing De Boer's rating scale in a controlled nighttime driving environment (laboratory ambient illuminant level-l lux with headlight turned off). Three driver-side mirrors included planar "flat mirror": radius of curvature 242650.92 mm, reflectivity 0.60114, and surface reflectance 0.60568; "curved mirror": radius of curvature 1433.3 mm, reflectivity 0.21652, and surface reflectance 0.58092; "blue mirror": radius of curvature 1957.1 mm, reflectivity 0.25356, and surface reflectance 0.54585. The results indicated that with the same glare level (as measured by angle of incidence and illuminance in front of the eyes), older adults reported worse feelings of glare than their younger counterparts. Furthermore, the results indicated that both young and older adults reported worse feelings of glare for planar driver-side mirror than non-planar driver-side mirrors. These results suggest that older adults' criterion of discomfort-glare is more sensitive than their younger counterparts, and importantly, the non-planar driver-side mirrors can be beneficial in terms of reducing nighttime discomfort-glare for both the young and the elderly.


Ultracompact Nanophotonics: Light Emission and Manipulation with Metasurfaces.
Internet of Things (IoT) technology is prosperous for the betterment of human well-being. With the expeditious needs of miniature functional devices and systems for adaptive optics and light manipulation at will, relevant sensing techniques are thus in the urgent stage of development. Extensive developments in ultrathin artificial structures, namely metasurfaces, are paving the way for the next-generation devices. A bunch of tunable and reconfigurable metasurfaces with diversified catalogs of mechanisms have been developed recently, enabling dynamic light modulation on demand. On the other hand, monolithic integration of metasurfaces and light-emitting sources form ultracompact meta-devices as well as exhibiting desired functionalities. Photon-matter interaction provides revolution in more compact meta-devices, manipulating light directly at the source. This study presents an outlook on this merging paradigm for ultracompact nanophotonics with metasurfaces, also known as metaphotonics. Recent advances in the field hold great promise for the novel photonic devices with light emission and manipulation in simplicity.


Access, use and completion of a brief disaster mental health intervention among Hispanics, African-Americans and Whites affected by Hurricane Ike.
African-Americans and Hispanics are disproportionally affected by disasters. We evaluated differences in the use and completion of a web-based mental health intervention, Disaster Recovery Web (DRW), by White, African-American and Hispanic adults in the aftermath of Hurricane Ike. Approximately one year after the hurricane, a telephone survey was carried out with adults from Galveston and Chambers counties. A total of 1249 adults participated in the survey (80% White, 14% African-American and 6% Hispanic). Mental health and mental health service utilization were assessed. Whites were more likely to have previously used the Internet to obtain general health information than African-Americans or Hispanics (P < 0.001). A logistic regression was used to identify differences in the use of the Internet intervention after controlling for covariates. There were no differences in rates of non-use and dropout attrition between Whites, African-Americans and Hispanics. Thus the findings suggest that web-based mental health interventions can be used to reach African-American, Hispanic and White adults at similar rates after a disaster.


Percutaneous ethanol injection for treatment of cervical lymph node metastases in patients with papillary thyroid carcinoma.
The objective of this study was to evaluate the technique, efficacy, and side effects of percutaneous ethanol injection in patients with limited cervical nodal metastases from papillary thyroid carcinoma. Fourteen patients who had undergone thyroidectomy for papillary thyroid carcinoma presented with limited nodal metastases (one to five involved nodes) in the neck between May 1993 and April 2000. All patients had received previous iodine-131 ablative therapy with a mean total dose per patient of 7,548 MBq. Ten of the patients either were considered poor surgical candidates or preferred not to have surgery, and all were unresponsive to iodine-131 therapy. Each metastatic lymph node was treated with percutaneous ethanol injection, and patients received both clinical and sonographic follow-up. Twenty-nine metastatic lymph nodes in our 14 patients were injected. Mean sonographic follow-up was 18 months (range, from 2 months to 6 years 5 months). All treated lymph nodes decreased in volume from a mean of 492 mm(3) before percutaneous ethanol injection to a mean volume of 76 mm(3) at 1 year and 20 mm(3) at 2 years after treatment. Six nodes were re-treated 2-12 months after initial percutaneous ethanol injection because of persistent flow on color Doppler sonography (n = 4), stable size (n = 1), or increased size (n = 1). Two patients developed four new metastatic nodes during the follow-up period that were amenable to percutaneous ethanol injection. Two patients developed innumerable metastatic nodes that precluded retreatment with percutaneous ethanol injection. No major complications occurred. All patients experienced long-term local control of metastatic lymph nodes treated by percutaneous ethanol injection. In 12 of 14 patients, percutaneous ethanol injection was successful in controlling all known metastatic adenopathy. Sonographically guided percutaneous ethanol injection is a valuable treatment option for patients with limited cervical nodal metastases from papillary thyroid cancer who are not amenable to further surgical or radioiodine therapy.


Atypical relapsing course of Kawasaki disease with hemorrhagic serous effusions and hepatic dysfunction.
Kawasaki disease (KD) is a multisystem vasculitis of childhood with cardiac, renal, pulmonary and neurological complications. Hemorrhagic serous effusions, liver dysfunction and relapsing course in spite of treatment are rare. We report an atypical case of KD with a relapsing course, hemorrhagic effusions and hepatic dysfunction, that required two repeated courses of intravenous immunoglobulin (IVIG) and methylprednisolone.


Drinking games and contextual factors of 21st birthday drinking.
21st birthday celebrations are among the highest risks for alcohol use throughout emerging adulthood and celebrants often experience a range of alcohol-related consequences. The present research considered what happens when drinking games are paired with an already high-risk event (i.e., 21st birthday celebrations) and how drinking games compare with other contextual factors on 21st birthdays. Approximately four days after turning 21, 1124 college students (55% women) completed an online survey assessing alcohol use and related consequences experienced during their birthday celebrations. Participants were also asked whether drinking games and other contextual factors were associated with their celebrations. Overall, 18% of participants reported playing drinking games during their 21st birthday celebrations. These individuals reported consuming more alcohol, had higher estimated BACs, and experienced more negative consequences than those who did not play drinking games. The association between playing drinking games and alcohol use and negative consequences was stronger for men. The effect of drinking games on negative consequences was mediated through elevated BAC levels. Receiving bar specials, having drinks purchased, playing drinking games, and loud music were uniquely and significantly associated with all alcohol outcomes. Together, these results suggest that drinking games are part of a larger context of risk contributing to extreme drinking on 21st birthdays. Furthermore, these results will help to facilitate interventions that are more individually tailored to target specific contextual risks, behaviors, and events.


2-Picoline catalyst-triggered [2 + 2 + 2] cycloaddition-type reaction of acetylenedicarboxylates, aldehydes and alkenes.
2-Picoline efficiently catalyzes the formation of α,β-enones from acetylenedicarboxylates and aldehydes in the presence of alkenes, thereby leading to pyrans in moderate to good yields with complete regioselectivities. This synthetic method of pyrans is represented as a first example of catalytic and direct [2 + 2 + 2] cycloaddition of three different components under the metal-free conditions.


Pneumocystis jirovecii pneumonia in an immunocompetent patient recovered from COVID-19.
Several cases of invasive fungal diseases in patients with COVID-19 have been reported, mostly due to Aspergillus spp., with anecdotic reports of Pneumocystis jirovecii pneumonia (PJP) as co-infections in immunocompromised patients. We describe the first case of PJP in an immunocompetent patient who recovered from COVID-19 pneumonia. Our patient was hospitalized for 18 d for respiratory failure due to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pneumonia and successfully treated with continuous positive airway pressure (CPAP) respiratory support, enoxaparin, ceftaroline and intravenous 6 mg of dexamethasone for 10 d, then with oral prednisone tapering. Despite his improved radiological and clinical conditions at discharge, he was admitted again after 18 d for worsening of respiratory conditions. Upon the second admission, a high-resolution CT-scan of the chest showed the development of new ground-glass opacities and P. jirovecii was detected on bronchoalveolar lavage fluid. A therapy with trimethoprim-sulphamethoxazole 20 mg/kg and methylprednisolone 40 mg i.v. bis in die (BID) was started, with improvement of clinical, biochemical and radiological conditions. COVID-19 patients may have multiple risk factors for development of PJP, in particular lymphopaenia and use of steroids. PJP must be ruled out with direct microbiological methods in patients presenting with radiologic and clinical features of possible or probable PJP, even in immunocompetent hosts.


Ataques de nervios in Puerto Rico: culture-bound syndrome or popular illness?
Ataque de nervious is a popular illness category among Puerto Ricans and other Latinos written about in anthropological and psychiatric literature for over thirty years. This paper discusses the issue of categorizing ataque de nervios as a "culture-bound syndrome" using data from the first community-based study of this phenomena using epidemiological methods. The paper summarizes the social and psychological correlates of ataques de nervios and provides a preliminary overview of the situations which provoke ataques and the symptoms people experience. The paper critically examines the use of the "culture-bound syndrome" framework analyzing ataques de nervios and suggests that the term "popular illness" is a more effective label for categorizing this syndrome.


Animal models of fibrotic lung disease.
Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell-cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease.


Improving Pallet Mover Safety in the Manufacturing Industry: A Bow-Tie Analysis of Accident Scenarios.
A Belgian manufacturing company uses pallet movers for internal transport. Despite the company's efforts to improve occupational safety, accidents with pallet movers remain noteworthy. In order to control occupational accidents, it is crucial to have a clear view of the potential accident scenarios that are present in a company. The bow-tie method is a way to capture and visualize these accident processes in an integrative way. Included in the bow-tie are safety barriers (both technical as organizational and human) and management delivery systems that can intervene in these accident processes. Once bow-ties are composed, they are an excellent point of departure to assign indicators to the safety barriers and management delivery systems in order to control (i.e., prevent or mitigate) accident scenarios. Two types of indicators can be distinguished. Firstly, there are general indicators that are assigned to management delivery systems interrupting multiple accident scenarios, which can yield a higher safety gain (as they intervene in multiple accident scenarios). Secondly, there are scenario-specific indicators targeting one specific accident scenario, which can be valuable as they target a specific problem in the company. For the development of the bow-ties, a multi-method design with the inclusion of different data sources was used, leading to a comprehensive overview. This makes the bow-tie analysis of internal transport with pallet movers transferable to other settings where pallet movers are used for internal transport.


Maternal MEMI Promotes Female Meiosis II in Response to Fertilization in Caenorhabditis elegans.
In most animals, female meiosis completes only after fertilization. Sperm entry has been implicated in providing a signal for the initiation of the final meiotic processes; however, a maternal component required for this process has not been previously identified. We report the characterization of a novel family of three highly similar paralogs (memi-1, memi-2, memi-3) that encode oocyte-specific proteins. A hyper-morphic mutation memi-1(sb41) results in failure to exit female meiosis II properly; however, loss of all three paralogs results in a "skipped meiosis II" phenotype. Mutations that prevent fertilization, such as fer-1(hc1), also cause a skipped meiosis II phenotype, suggesting that the MEMI proteins represent a maternal component of a postfertilization signal that specifies the meiosis II program. MEMI proteins are degraded before mitosis and sensitive to ZYG-11, a substrate-specific adapter for cullin-based ubiquitin ligase activity, and the memi-1(sb41) mutation results in inappropriate persistence of the MEMI-1 protein into mitosis. Using an RNAi screen for suppressors of memi-1(sb41), we identified a sperm-specific PP1 phosphatase, GSP-3/4, as a putative sperm component of the MEMI pathway. We also found that MEMI and GSP-3/4 proteins can physically interact via co-immunoprecipitation. These results suggest that sperm-specific PP1 and maternal MEMI proteins act in the same pathway after fertilization to facilitate proper meiosis II and the transition into embryonic mitosis.


Trajectories of Palliative Care Needs in the ICU and Long-Term Psychological Distress Symptoms.
While palliative care needs are assumed to improve during ICU care, few empiric data exist on need trajectories or their impact on long-term outcomes. We aimed to describe trajectories of palliative care needs during ICU care and to determine if changes in needs over 1 week was associated with similar changes in psychological distress symptoms at 3 months. Prospective cohort study. Six adult medical and surgical ICUs. Patients receiving mechanical ventilation for greater than or equal to 2 days and their family members. The primary outcome was the 13-item Needs at the End-of-Life Screening Tool (NEST; total score range 0-130) completed by family members at baseline, 3, and 7 days. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Post-Traumatic Stress Scale (PTSS) were completed at baseline and 3 months. General linear models were used to estimate differences in distress symptoms by change in need (NEST improvement ≥ 10 points or not). One-hundred fifty-nine family members participated (median age, 54.0 yr [interquartile range (IQR), 44.0-63.0 yr], 125 [78.6%] female, 54 [34.0%] African American). At 7 days, 53 (33%) a serious level of overall need and 35 (22%) ranked greater than or equal to 1 individual need at the highest severity level. NEST scores improved greater than or equal to 10 points in only 47 (30%). Median NEST scores were 22 (IQR, 12-40) at baseline and 19 (IQR, 9-37) at 7 days (change, -2.0; IQR, -11.0 to 5.0; p = 0.12). There were no differences in PHQ-9, GAD-7, or PTSS change scores by change in NEST score (all p > 0.15). Serious palliative care needs were common and persistent among families during ICU care. Improvement in needs was not associated with less psychological distress at 3 months. Serious needs may be commonly underrecognized in current practice.


Validation of the Swedish version of PROMIS-29v2 and FACIT-Dyspnea Index in patients with systemic sclerosis.
To evaluate the reliability, internal consistency, and construct validity of the Swedish versions of PROMIS-29 and Functional Assessment of Chronic Illness Therapy-Dyspnea (FACIT-Dyspnea) instruments in patients with systemic sclerosis (SSc). In a cross-sectional study, consecutive SSc patients completed a paper-based survey. Internal consistency was assessed using Cronbach's alpha. Test-retest reliability was tested employing weighted Kappa (Kw) and intra-class correlation coefficient (ICC). Construct validity was evaluated by hypotheses testing using RAND-36, MRC Dyspnea score, Scleroderma Health Assessment Questionnaire (SHAQ) and clinical measurements. Forty-nine patients (86% female; 73% limited cutaneous SSc) completed the survey. The mean disease duration was 11 years and mean SHAQ was 0.5. Internal consistency and test-retest reliability were good with the exception of PROMIS-29 anxiety. PROMIS-29, FACIT-Dyspnea, and Functional limitation showed strong correlations to corresponding RAND-36 domains (|rs|=0.67 to -0.85). Relevant PROMIS-29 domains, FACIT-Dyspnea and Functional limitation correlated strongly to SHAQ and VAS overall disease severity (|rs|=0.60 to -0.75). Ceiling effects (>15%) were found in six PROMIS-29 domains and in both FACIT-Dyspnea and Functional limitations. Four (4/5) hypotheses were confirmed. PROMIS-29 and FACIT-Dyspnea meet the requirements for reliability and have adequate construct validity in Swedish patients with SSc.Implications for rehabilitationPROMIS-29v2 and Functional Assessment of Chronic Illness Therapy-Dyspnea (FACIT-Dyspnea) Index are patient outcome measures that gain increasing interest for the evaluation of patient with rheumatologic diseases.PROMIS-29v2 and FACIT-Dyspnea Index meet the requirements for reliability and have adequate construct validity compared to legacy measures in Swedish patients with systemic sclerosis.Translation and validation of PROMs is important for studies of rare diseases in multi-center collaborations.


Correlation between bulk- and surface chemistry of Cr-tanned leather and the release of Cr(III) and Cr(VI).
About 1-3% of the adult general population in Europe is allergic to chromium (Cr). The assessment of the potential release of Cr(III) and Cr(VI) from leather is hence important from a human health and environmental risk perspective. The Cr(VI) content in leather was recently restricted in the European Union. The aim of this study was to assess possible correlations between the bulk and surface chemistry of leather, released Cr(III) and Cr(VI), and capacities of co-released leather specific species to reduce and complex released Cr. Four differently tanned leathers were characterized by scanning electron microscopy with energy dispersive spectroscopy, X-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and the diphenylcarbazide colorimetric method. Their characteristics were compared with results on Cr(III) and Cr(VI) release into artificial sweat (ASW, pH<6.5) and phosphate buffer (PB, pH 7.5-8.0), measured by means of spectrophotometry and atomic absorption spectroscopy. Co-released leather-specific species were shown to reduce Cr(VI), both in ASW and in PB. Their reduction capacities correlated with findings of the surface content of Cr and of released Cr. Leather samples without this capacity, and with less aromatic surface groups visible by ATR-FTIR, revealed Cr(VI) both at the surface and in solution (PB).


Statin Therapy May not Effect NLR and MPV Levels in Patients With Hypercholesterolemia: A Retrospective Study.
Statins may exert pleiotropic effects in coronary artery disease (CAD), diabetes mellitus, and familial hypercholesterolemia. We evaluated the effects of statins on the neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) in 261 consecutive patients with hypercholesterolemia having CAD or at high cardiovascular (CV) risk and 50 healthy participants who were retrospectively included in this study. Patients were treated with 10 to 80 mg atorvastatin or 10 to 40 mg rosuvastatin for 24 weeks according to baseline levels of cholesterol, triglycerides, and CV risk. Baseline NLR and MPV were significantly higher in patients with CAD or at high risk compared to the control group (1.89 [0.37-6.78]) vs 1.44 [0.75-2.41], P < .001 and 8.8 [6.27-18.6] vs 8.45 [6-11] fL, P = .038, respectively). The NLR, MPV, and lipid parameters were also compared in the patient group after statin treatment for 24 weeks. Lipid levels decreased but the NLR and MPV did not change significantly after the statin therapy. Further studies are needed to clarify the effect of statin therapy on NLR and MPV in patients with CAD or at high CV risk.


Successful treatment of chronic knee pain following localization by a sigma-1 receptor radioligand and PET/MRI: a case report.
The ability to accurately diagnose and objectively localize pain generators in chronic pain sufferers remains a major clinical challenge since assessment relies on subjective patient complaints and relatively non-specific diagnostic tools. Developments in clinical molecular imaging, including advances in imaging technology and radiotracer design, have afforded the opportunity to identify tissues involved in pain generation based on their pro-nociceptive condition. The sigma-1 receptor (S1R) is a pro-nociceptive receptor upregulated in painful, inflamed tissues, and it can be imaged using the highly specific radioligand 18F-FTC-146 with PET. A 50-year-old woman with a 7-year history of refractory, left-knee pain of unknown origin was referred to our pain management team. Over the past several years, she had undergone multiple treatments, including a lateral retinacular release, radiofrequency ablation of a peripheral nerve, and physical therapy. While certain treatments provided partial relief, her pain would inevitably return to its original state. Using simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) with the novel radiotracer 18F-FTC-146, imaging showed increased focal uptake of 18F-FTC-146 in the intercondylar notch, corresponding to an irregular but equivocal lesion identified in the simultaneously acquired MRI. These imaging results prompted surgical removal of the lesion, which upon resection was identified as an inflamed, intraarticular synovial lipoma. Removal of the lesion relieved the patient's pain, and to date the pain has not recurred. We present a case of chronic, debilitating knee pain that resolved with surgery following identification of the pathology with a novel clinical molecular imaging approach that detects chronic pain generators at the molecular and cellular level. This approach has the potential to identify and localize pain-associated pathology in a variety of chronic pain syndromes.


An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.
A single enzyme found in both Drosophila and mammalian cells is able to selectively bind and degrade transforming growth factor (TGF)-alpha and insulin, but not EGF, at physiological concentrations. These growth factors are also able to inhibit binding and degradation of one another by the enzyme. Although there are significant immunological differences between the mammalian and Drosophila enzymes, the substrate specificity has been highly conserved. These results demonstrate the existence of a selective TGF-alpha-degrading enzyme in both Drosophila and mammalian cells. The evolutionary conservation of the ability to degrade both insulin and TGF-alpha suggests that this property is important for the physiological role of the enzyme and its potential for regulating growth factor levels.


Outcomes in the elderly patient following enhanced recovery pathways for elective lower-limb arthroplasty surgery.
Enhanced recovery pathways (ERPs) have been shown to reduce both morbidity and mortality, as well as length of stay, in very elderly patients undergoing joint replacement surgery. However, their impact on patient-reported outcome measures (PROMs) in this vulnerable cohort of patients has not previously been investigated. Oxford Hip and Knee Scores were collected pre- and postoperatively for patients undergoing joint replacement surgery at Wrexham Maelor Hospital, along with data on patient demographics. Of the 646 who had total hip replacements, 32 (4.95%) were aged 85 years or over, and of the 875 who had total knee replacements, 39 (4.46%) were aged 85 years or over. Similarly to younger patients, those over the age of 85 years saw a benefit in the outcome at 6 months and 24 months following elective hip and knee arthroplasty on an ERP. This was reflected by a significant increase in the outcome scores at 6 months postoperatively in both age groups undergoing either a total hip replacement or total knee replacement. We found no detrimental effect of ERPs on PROMs data in older patients. In fact, these patients saw a similar benefit in outcome following elective hip and knee arthroplasty as the younger cohort.


Genetic make-up of arthropod vectors.
A better understanding of the molecular aspects of arthropod vector biology and the processes that determine pathogen transmission can lead to the development of novel or improved control methods for vectors and vector-borne diseases. The 'omics' era provides unprecedented opportunities to explore these aspects of vectors and the diseases which they transmit. This review aims to summarise recent developments in the field of vector genomics and to provide basic insight into the application of functional genetic tools such as RNA interference, RNA sequencing and genetic transformation in vector control development.


The interdisciplinary generalist curriculum project: a national medical school demonstration project.
The United States is facing the challenge of producing more generalists for the physician workforce. The Primary Care Organizations' Consortium (PCOC) has responded by focusing on how medical education can be modified to enhance and support medical students' interest in and commitment to generalism early in their training. Evolving from PCOC's developmental work, the five-year Interdisciplinary Generalist Curriculum (IGC) Project was developed to encourage the nation's schools of medicine and colleges of osteopathic medicine to implement interdisciplinary generalist curricula in the preclinical years. Funded by the Division of Medicine in the Bureau of Health Professions of the Health Resources and Services Administration (HRSA), the IGC Project has successfully developed and implemented a nationally competitive medical school demonstration project. Thirty-three schools submitted proposals for an IGC Project award; nine were selected for site visits, from which five were chosen to receive three-year awards. Rigorous attention to creating and maintaining an interdisciplinary focus has characterized the first phase of the IGC Project. Shared leadership among the Executive Committee's project director and two project codirectors and parity in representation among the three disciplines of family medicine, internal medicine, and pediatrics on the Advisory Committee have formed a critical foundation for interdisciplinary functioning within the project. Growing national interest in generalist training and other funding initiatives have contributed to acceptance of the IGC Project. The high level of interest in the IGC Project and the successful interdisciplinary collaboration during the first phase would indicate that the interdisciplinary process can be replicated to move the nation's medical education institutions toward the production of needed generalist physicians.


Long-term effects of a standardized feedback-driven quality improvement program for timely reperfusion therapy in regional STEMI care networks.
Current European Society of Cardiology guidelines state that repetitive monitoring and feedback should be implemented for ST-elevation myocardial infarction (STEMI) treatment, but no evidence is available supporting this recommendation. We aimed to analyze the long-term effects of a formalized data assessment and systematic feedback on performance and mortality within the prospective, multicenter Feedback Intervention and Treatment Times in STEMI (FITT-STEMI) study. Regular interactive feedback sessions with local STEMI management teams were performed at six participating German percutaneous coronary intervention (PCI) centers over a 10-year period starting from October 2007. From the first to the 10th year of study participation, all predefined key-quality indicators for performance measurement used for feedback improved significantly in all 4926 consecutive PCI-treated patients - namely, the percentages of patients with pre-hospital electrocardiogram (ECG) recordings (83.3% vs 97.1%, p < 0.0001) and ECG recordings within 10 minutes after first medical contact (41.7% vs 63.8%, p < 0.0001), pre-announcement by telephone (77.0% vs 85.4%, p = 0.0007), direct transfer to the catheterization laboratory bypassing the emergency department (29.4% vs 64.2%, p < 0.0001), and contact-to-balloon times of less than 90 minutes (37.2% vs 53.7%, p < 0.0001). Moreover, this feedback-related continuous improvement of key-quality indicators was linked to a significant reduction in in-hospital mortality from 10.8% to 6.8% (p = 0.0244). Logistic regression models confirmed an independent beneficial effect of duration of study participation on hospital mortality (odds ratio = 0.986, 95% confidence interval = 0.976-0.996, p = 0.0087). In contrast, data from a nationwide PCI registry showed a continuous increase in in-hospital mortality in all PCI-treated STEMI patients in Germany from 2008 to 2015 (n = 398,027; 6.7% to 9.2%, p < 0.0001). Our results indicate that systematic data assessment and regular feedback is a feasible long-term strategy and may be linked to improved performance and a reduction in mortality in STEMI management.


[Echomorphology of the prostate].
The echogenic structures of 1983 transrectal sonographies of the prostate were analysed. In addition, 93 dissected prostates were investigated in waterbath in order to correlate sonographic and morphological structures. Compared to the normal gland, hyperplastic nodules are of the same density or slightly echodenser, rarely also with a poorer echo. In about 60% the inner gland can be delineated. Although 52% of the carcinomas show the same echodensity as diffuse hyperplasia, diagnosis is still possible by further criteria. In only 13% no carcinomas were detectable. 18% of the carcinomas were differentiated by poor echogenicity. The diagnostic value is discussed.


Iron metabolism in non-anemic myasthenia gravis patients: A cohort study.
The association of iron metabolism parameters with disease severity and outcome in myasthenia gravis (MG) patients has not been reported. This study was conducted to determined clinical factors including iron metabolism parameters correlated with disease severity and future outcome in non-anemic immunotherapy-naïve MG patients first receiving immunotherapy. One hundred and ten patients were included at baseline to explore predictor variables associated with disease severity represented by variables derived from MG activities of daily living (MG-ADL) score using multivariate logistic regression, after which 103 and 98 patients were included respectively in multivariate survival analyses at 6-month and 12-month follow-up to identify predictors for minimal manifestation status (MMS) after starting immunotherapy. Higher ferritin level was independently associated with higher risk of severe generalized disease in non-anemic immunotherapy-naïve MG patients. Total iron binding capacity <250 μg/dL and the interval between onset and immunotherapy <1 year were independent predictors for MMS at 6-month and 12-month follow-up after initiating immunotherapy. Transferrin <2.00 g/L was an independent predictor for MMS at 12-month follow-up. Iron metabolism parameters might be promising biomarkers for evaluating disease severity and guiding therapeutic decision in MG patients.


Endoscopic scoring indices for evaluation of disease activity in ulcerative colitis.
Endoscopic assessment of mucosal disease activity is routinely used to determine eligibility and response to therapy in clinical trials of ulcerative colitis. The operating properties of the existing endoscopic scoring indices are unclear. A systematic review was undertaken to evaluate the development and operating characteristics of endoscopic scoring indices for the evaluation of ulcerative colitis. We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2016. We also searched references and conference proceedings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organization). Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated endoscopic indices for evaluation of ulcerative colitis disease activity were considered for inclusion. Eligible participants were adult patients (> 16 years), diagnosed with ulcerative colitis using conventional clinical, radiologic and endoscopic criteria. Two authors independently reviewed the studies identified from the literature search. These authors also independently extracted and recorded data on the number of patients enrolled; number of patients per treatment arm; patient characteristics including age and gender distribution; endoscopic index; and outcomes such as reliability (intra-rater and inter-rater), validity (content, construct, criterion), responsiveness and feasibility. Any disagreements regarding study inclusion or data extraction were resolved by discussion and consensus with a third author. Risk of bias was assessed by determining whether assessors were blinded to clinical information and whether assessors scored the endoscopic index independently. We also assessed the methodological quality of the validation studies using the COSMIN checklist MAIN RESULTS: A total of 23 reports of 20 studies met the pre-defined inclusion criteria and were included in the review. Of the 20 included validation studies, 19 endoscopic scoring indices were assessed, including the Azzolini Classification, Baron Score, Blackstone Endoscopic Interpretation, Chinese Grading System of Ulcerative Colitis, Endoscopic Activty Index, Jeroen Score, Magnifying Colonoscopy Grade, Matts Score, Mayo Clinic Endoscopic Subscore, Modified Baron Score, Modified Mayo Clinic Endoscopic Subscore, Osada Score, Rachmilewtiz Endoscopic Score, St. Mark's Index, Ulcerative Colitis Colonoscopic Index of Serverity (UCCIS), endoscopic component of the Ulcerative Colitis Disease Activity Index (UCDAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Witts Sigmoidoscopic Score and Watson Grade. The individuals who performed the endoscopic scoring were blinded to clinical and/or histologic information in ten of the included studies, not blinded to clinical and/or histologic information in one of the included studies, and it was unclear whether blinding occurred in the remaining nine included studies. Independent observation was confirmed in four of the included studies, unclear in five of the included studies, and non-applicable (since inter-rater reliability was not assessed) in the remaining eleven included studies. The methodological quality (COSMIN checklist) of most of the included studies was rated as 'good' or 'excellent'. One study that assessed responsiveness was rated as 'fair'. The inter-rater reliability of nine endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Endoscopic Activity Index, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS, UCEIS, Watson Grade was assessed in seven studies, with estimates of correlation, ƙ, ranging from 0.44 to 0.97. The iIntra-rater reliability of seven endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS and UCEIS was assessed in three studies, with estimates of correlation, ƙ, ranging from 0.41 to 0.86. No studies assessed content validity. Three studies evaluated the criterion validity of three endoscopic scoring indices including the Rachmilewitz Endoscopic Score, Magnifying Colonoscopy Grade and the UCCIS. These indices were correlated with objective markers of disease activity including albumin, blood leukocytes, C-reactive protein, fecal calprotectin, hemoglobin, mucosal interleukin-8 concentration and platelet count. Correlation estimates ranged from r = -0.19 to 0.83. Thirteen endoscopic scoring indices were tested for construct validity in 13 studies. Estimates of correlation between the endoscopic scoring indices and other measures of disease activity ranged from r = 0.27 to 0.93. Two studies explored the responsiveness of four endoscopic scoring indices including the Mayo Endoscopic Subscore, Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS. One study concluded that the Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS had similar responsiveness for detecting disease change in ulcerative colitis. The other included study concluded that the UCEIS may be the most accurate endoscopic scoring tool. None of the included studies formally assessed feasibility. While the UCEIS, UCCIS and Mayo Clinic Endoscopic Subscore have undergone extensive validation, none of these instruments have been fully validated and only two studies assessed responsiveness. Further research on the operating properties of these indices is needed given the lack of a fully-validated endoscopic scoring instrument for the evaluation of disease activity in ulcerative colitis.


Alginate-PEG sponge architecture and role in the design of insulin release dressings.
Wound healing is a natural process involving several signaling molecules and cell types over a significant period of time. Although current dressings help to protect the wound from debris or infection, they do little in accelerating the healing process. Insulin has been shown to stimulate the healing of damaged skin. We have developed an alginate sponge dressing (ASD) that forms a hydrogel capable of providing a moist and protective healing environment. By incorporating insulin-loaded poly(d,l-lactide-co-glycolide) (PLGA) microparticles into ASD, we successfully stabilized and released insulin for up to 21 days. Insulin release and water absorption and transfer through the ASD were influenced by altering the levels of poly(ethylene glycol) (PEG) in the dressing matrix. Bioactivity of released insulin can be maintained for at least 10 days, demonstrated using a human keratinocyte migration assay. Results showed that insulin-loaded PLGA microparticles, embedded within PEG-ASD, functioned as an effective long-term delivery platform for bioactive insulin.


Early virologic failure in a pilot study evaluating the efficacy of therapy containing once-daily abacavir, lamivudine, and tenofovir DF in treatment-naive HIV-infected patients.
Previous investigational data using abacavir (ABC), lamuvidine (3TC), and zidovudine has suggested the possibility of triple nucleoside analogue reverse transcriptase inhibitors (NRTI) therapy as an option in the treatment of HIV infection. We performed a pilot study to assess the potency of once daily ABC+ 3TC+ tenofovir (TDF) in the treatment of HIV-infected naive patients. CD4 and HIV-viral load (VL) were followed monthly. Patients were considered to be nonresponder/failing if there was no reduction in VL by >/= 2 log(10) by week 8 and/or a rebound in VL after initial suppression. Resistance testing was then obtained. Nineteen patients naive to antiretroviral therapy (3 women and 16 men) were enrolled, of whom, 2 did not return (withdrew from study at week 2). Median VL and CD4 count at baseline were 147,167 copies per milliliter (5.16 log(10); [range, 7650->750,000]) and 277 cells/mm(3) (range, 59-598). Eight patients had VL > 100000 at baseline. Of 17 patients eligible for follow-up, 5 (27%) were responders (virologic success). Twelve patients (63%) were considered nonresponders and/or with virologic failure. The study was prematurely interrupted because of a high rate of treatment failure. Resistance testing available for 11 nonresponders (58%) showed: 2 patients with wild-type, 5 patients with M184V (reducing susceptibility to 3TC and ABC), 4 patients with M184V+K65R (K65R is responsible for reducing susceptibility to ABC, 3TC and TDF), and none with K65R alone. In conclusion, the combination of ABC, 3TC and TDF cannot be recommended for the initial regimen in HIV treatment-naive patients.


Human urinary trypsin inhibitor, urinastatin, prevents pancreatic injuries induced by pancreaticobiliary duct obstruction with cerulein stimulation and systemic hypotension in the rat.
The protective effects of human urinary trypsin inhibitor against pancreatic injuries in multifactor-related experimental model of acute pancreatitis were evaluated. Experimental study. Acute pancreatitis was induced by short-termed (1-hour) pancreatico-biliary duct obstruction with cerulein stimulation (30 minutes; 0.2 microgram/kg per hour) and systemic hypotension (30 minutes; 30% reduction of mean arterial pressure) in rats. In this model, the protective effects of UTI against pancreatic injuries were evaluated at a dose of 10,000 U/kg per hour. In this model, significant increases in portal serum amylase, cathepsin B and malate dehydrogenase levels were observed as compared with the control rats. The redistribution of cathepsin B from the lysosomal to the zymogen fraction and activation of trypsinogen were also observed. Moreover, the increased lysosomal and mitochondrial fragility as well as impaired pancreatic adenylate energy metabolism were noted. The therapeutic administration of human urinary trypsin inhibitor had significant protective effects against these pancreatic injuries. Furthermore, the combined prophylactic and therapeutic administration of human urinary trypsin inhibitor had more significant protective effects than only therapeutic treatment. These results suggest the importance of timing and of selecting a pertinent protease inhibitor, such as urinary trypsin inhibitor, in the treatment of pancreatitis.


Lack of effect of warfarin on L-thyroxine metabolism.
The effect of a single 50 mg dose of warfarin sodium on thyroxine monodeiodination was examined in eight healthy human subjects. There was no evidence that warfarin inhibits 5'-monodeiodination, although such inhibition exists in rats.


Changes in the Results of the Subjective Visual Vertical Test After Endolymphatic Sac Drainage for Intractable Meniere's Disease.
To investigate otolithic function before and after endolymphatic sac drainage (ELSD) for Meniere's disease (MD) by using the subjective visual vertical test (SVV) in the upright and tilted positions. Eighteen patients with definite unilateral MD diagnosed in accordance with the American Academy of Otolaryngology Head and Neck Surgery criteria in 1995 and Barany Society criteria in 2015 were included. SVV in the upright position and the head-tilt position was performed preoperatively and on postoperative days 1, 5, 8, 28, and 112. Changes in the results of SVV in the upright position (UP-SVV) and head-tilt perception gain (HTPG) after surgery were measured. The average UP-SVV values significantly changed from 0.05° by the affected side before surgery to 2.5° by the unaffected side on the fifth postoperative day, followed by recovery to the normal range by the eighth postoperative day. The HTPG values for the unaffected side showed the maximum increase on postoperative day 5 during the present study period, although the values in the affected side did not alter significantly. ELSD for MD is a surgical treatment that involves less risk of otolith function damage and abnormalities in gravitational cognition. SVV in the head-tilt position could be one of the neuro-otologic examinations used to easily understand the vestibular compensatory process.


Syncope: therapeutic approaches.
Syncope is a common clinical problem characterized by transient, spontaneously self-terminating loss of consciousness with complete and prompt recovery; the cause is insufficiency of cerebral oxygen/nutrient supply most often due to a transient fall of systemic arterial pressure to levels below those tolerated by cerebrovascular autoregulation. Careful and thorough evaluation of the cause of syncope is warranted in all patients. Determining that certain individuals are at "low mortality risk" is inadequate; syncope, although often benign from a mortality perspective, tends to recur, is associated with risk of physical injury, diminishes quality-of-life, and might lead to restriction from employment or avocation. However, the diagnostic evaluation and treatment of syncope is challenging for many reasons. First, syncope is only 1 of many causes of transient loss of consciousness. Second, the patient's symptoms are fleeting, and the patient is generally fully recovered when seen in the clinic; only infrequently are there helpful physical findings. Third, spontaneous events are often unwitnessed by medical professionals; consequently, the medical history of symptom events is usually a "second-hand" or "third-hand" story. Finally, there is often an excessive sense of diagnostic "urgency" that tends to result in a rush to undertake multiple poorly considered "diagnostic" testing procedures; a deliberate approach based on initial risk stratification is more likely to reap the dual rewards of a correct diagnosis and initiation of effective treatment in a cost-effective manner.