Effects of Antioxidants in Human Milk on Bronchopulmonary Dysplasia Prevention and Treatment: A Review.
Bronchopulmonary dysplasia (BPD) is a severe chronic lung illness that affects neonates, particularly premature infants. It has far-reaching consequences for infant health and their families due to intractable short- and long-term repercussions. Premature infant survival and long-term quality of life are severely harmed by BPD, which is characterized by alveolarization arrest and hypoplasia of pulmonary microvascular cells. BPD can be caused by various factors, with oxidative stress (OS) being the most common. Premature infants frequently require breathing support, which results in a hyperoxic environment in the developing lung and obstructs lung growth. OS can damage the lungs of infants by inducing cell death, inhibiting alveolarization, inducing inflammation, and impairing pulmonary angiogenesis. Therefore, antioxidant therapy for BPD relieves OS and lung injury in preterm newborns. Many antioxidants have been found in human milk, including superoxide dismutase, glutathione peroxidase, glutathione, vitamins, melatonin, short-chain fatty acids, and phytochemicals. Human milk oligosaccharides, milk fat globule membrane, and lactoferrin, all unique to human milk, also have antioxidant properties. Hence, human milk may help prevent OS injury and improve BPD prognosis in premature infants. In this review, we explored the role of OS in the pathophysiology of BPD and related signaling pathways. Furthermore, we examined antioxidants in human milk and how they could play a role in BPD to understand whether human milk could prevent and treat BPD.


Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults.
Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic drugs are commonly used to treat this condition. This is an update of a Cochrane Review first published in 2002 and last updated in 2006. To assess the effects of anticholinergic drugs compared with placebo or no treatment for treating overactive bladder syndrome in adults. We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 14 January 2020), and the reference lists of relevant articles. We updated this search on 3 May 2022, but these results have not yet been fully incorporated. We included randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug alone with placebo treatment. Two review authors independently assessed eligibility and extracted data from the included studies, including an assessment of the risk of bias. We assessed the certainty of the body of evidence using the GRADE approach. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions. We included 104 studies, 71 of which were new or updated for this version of the review. Although 12 studies did not report the number of participants, there were 47,106 people in the remainder of the included studies. The majority of the studies had insufficient information to allow judgement of risk of bias and we judged them to be unclear for all domains. Nine anticholinergic drugs were included in these studies: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium. No studies were found that compared anticholinergic drugs to no treatment. At the end of the treatment period, anticholinergics may slightly increase condition-specific quality of life (mean difference (MD) 4.41 lower, 95% confidence interval (CI) 5.28 lower to 3.54 lower (scale range -100 to 0); 12 studies, 6804 participants; low-certainty evidence). Anticholinergics are probably better than placebo in terms of patient perception of cure or improvement (risk ratio (RR) 1.38, 95% CI 1.15 to 1.66; 9 studies, 8457 participants; moderate-certainty evidence), and the mean number of urgency episodes per 24-hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, 16,875 participants; moderate-certainty evidence). Compared to placebo, anticholinergics may result in an increase in dry mouth adverse events (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, 38,368 participants; low-certainty evidence), and may result in an increased risk of urinary retention (RR 3.52, 95% CI 2.04 to 6.08; 17 studies, 7862 participants; low-certainty evidence). Taking anticholinergics may be more likely to lead to participants withdrawing from the studies due to adverse events (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, 36,943 participants; low-certainty evidence). However, taking anticholinergics probably reduces the mean number of micturitions per 24-hour period compared to placebo (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, 19,395 participants; moderate-certainty evidence). The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of anticholinergics are sustained during long-term treatment or after treatment stops.


Improving written and verbal communication skills for international medical graduates: a linguistic and medical approach.
Adapting to UK communication styles can be difficult for International Medical Graduates (IMGs). Reache Northwest provides education, training and support for internationally trained refugee and asylum seeking health professionals who are looking to return to work in the UK. A Safe and Effective Communication Skills course was designed by a team of language teachers and clinicians to provide IMGs with an understanding of the written, verbal and summarisation skills required in the UK work environment. A series of language exercises adapted to clinical situations was developed. These increased in complexity to the practical application of language skills in clinical settings using simulated patients. The combination of language and clinical tutors meant that feedback could be given from a language teacher's perspective, the clinical perspective and the cultural context. The combination of language and clinical tutors meant that analysis of communication difficulties could be made from different perspectives and detailed, specific feedback could be given to each student in these areas. Using a combined linguistic and clinical approach can provide solutions to clinical communication problems that may otherwise be missed. This strategy could be extended to cover communication areas in other contexts.


Comparison between human sperm preservation medium and TEST-yolk buffer on protecting chromatin and morphology integrity of human spermatozoa in fertile and subfertile men after freeze-thawing procedure.
The aim of this study was to identify the detrimental effect of the freeze-thaw process on chromatin integrity and morphology of human spermatozoa, and to determine whether human sperm preservation medium (HSPM) or TEST-yolk buffer (TYB) offers a better protection to spermatozoa from cryodamage after the freeze-thaw procedure. Thirty-five semen samples obtained from couples childless because of male factor infertility (subfertile men, group 1) and 25 semen samples from healthy, normal volunteers of proven fertility (group 2) were included in the study. Each semen sample was divided into 2 parts, the first part was mixed with HSPM and the other with TYB (1:1), and frozen with a controlled slow-stage freezer, before plunging into liquid nitrogen. Twelve smears from each semen sample were made before (n = 4) and after (n = 8) the freeze-thaw process. Chromatin structure was evaluated after staining using the acridine orange (AO) test, whereas morphology was analyzed according to strict criteria. The mean percentage of spermatozoa that exhibited normal morphology and intact chromatin structure was decreased after freeze-thaw in all samples treated with HSPM or TYB in comparison with the value observed in the native semen samples of both groups. However, TYB preserved chromatin and morphology significantly better than HSPM did (9.3% +/- 5.6% and 88.7% +/- 11.2% vs. 7.8% +/- 4.2% and 85.5% +/- 12.5%, respectively). Therefore, TYB could be recommended as a first choice cryoprotectant for semen preservation in order to avoid extra chromatin structure damage and morphology alterations of spermatozoa not only for patients pursuing assisted reproduction, but also for donor samples.


Breast self-examination: a new training method.
Breast self-examination is an important, well-established method of cancer detection. Some authors disagree as to its value and regard physical examination by a physician as superior. Many women, however, do not have an annual physical examination, and the majority (80%) discover their own breast cancer. Proponents find that monthly breast self-examination leads to earlier diagnosis and treatment, and to improved prognosis. Only one third of women are performing monthly breast self-examination, and most do so with inadequate technique and poor comprehension. They are unable to distinguish normal from abnormal findings, and corrective measures are necessary. Health professionals, the best source of patient instruction, should periodically recheck the patient's performance. The technique taught should be uniform and uncomplicated. A simple way to demonstrate common benign and malignant lesions is presented to improve the patient's understanding, skill, and confidence.


Using information and communication technologies to consult with patients in Victorian primary care: the views of general practitioners.
Information and communication technologies such as email, text messaging and video messaging are commonly used by the general population. However, international research has shown that they are not used routinely by GPs to communicate or consult with patients. Investigating Victorian GPs' perceptions of doing so is timely given Australia's new National Broadband Network, which may facilitate web-based modes of doctor-patient interaction. This study therefore aimed to explore Victorian GPs' experiences of, and attitudes toward, using information and communication technologies to consult with patients. Qualitative telephone interviews were carried out with a maximum variation sample of 36GPs from across Victoria. GPs reported a range of perspectives on using new consultation technologies within their practice. Common concerns included medico-legal and remuneration issues and perceived patient information technology literacy. Policy makers should incorporate GPs' perspectives into primary care service delivery planning to promote the effective use of information and communication technologies in improving accessibility and quality of general practice care.


Deep brain stimulation for trigeminal autonomic cephalalgias.
Introduction: Deep brain stimulation (DBS) of the posterior hypothalamic region (pHyr) has been shown to be efficacious for more than a half of patients suffering from trigeminal autonomic cephalalgias (TACs); nonetheless, controversies about the mechanisms of action and the actual site of stimulation have arisen in recent years.Areas covered: Firstly, a review of the most recent literature on the subject is presented, stressing the critical points that could, in the future, make a difference for optimal management of patients afflicted by these life-threating diseases. Hypothalamic functional anatomy, experimental data and pathophysiological hypotheses are reported.Expert commentary: About 32% of patients who underwent DBS for TACs are pain-free. The determination of the pHyr region seems to be crucial for the generation of pain attack in these pathologies, although other structures are involved in complex mechanisms and circuits that interact with each other. Neurophysiological data, combined with more advanced experimental models, are of primary importance regarding our understanding of what the real target is, and how to overcome the issue of refractory patients.


[Case analysis on problem-based learning of acupuncture: "a turning round before birth"].
"A turning round before birth" is a problem-based learning (PBL) case in Chinese medicine education. It focuses on malposition of fetus, through discussion on a series of questions, types and causative factors of malposition of fetus could be comprehended, diagnostic time and methods are set up, and manipulations of moxibustion at Zhiyin (BL 67) for malposition of fetus can be mastered. Mechanism on position correction is explored, and key points in application are clarified. Therefore, methods of position correction with easy, safe and effective manipulations can be popularized as well as the PBL methods in education of Chinese medicine.


Electrostatic contribution to DNA condensation--application of 'energy minimization' in a simple model in the strong Coulomb coupling regime.
The process of bending of straight DNA to a circular form in the presence of any of the mono-, di-, tri- or tetravalent counterions has been simulated in a strong Coulomb coupling environment, employing a previously developed energy minimization simulation technique. The inherent characteristics of the simulation technique allow the monitoring of the required electrostatic contribution to the bending. The curvature of the bending has been found to play a crucial role in facilitating the electrostatic attractive potential energy. The total electrostatic potential energy has been found to decrease with bending, which indicates that bending straight DNA to a circular form or to a toroidal form in the presence of neutralizing counterions is energetically favourable and is practically a spontaneous phenomenon.


Role of ALOX5 in non-small cell lung cancer: A potential therapeutic target associated with immune cell infiltration.
The efficacy of immunotherapy for lung cancer is closely related to immune cell infiltration. Arachidonic acid 5-lipoxygenase (ALOX5) can activate inflammatory responses and trigger various cell death patterns; however, the relevance of ALOX5 to immune cell infiltration in lung cancer is unclear. The expression of ALOX5 in non-small cell lung cancer (NSCLC) is analyzed using an online database to explore the correlation between ALOX5 and immune cell infiltration in NSCLC and its relationship with prognosis. Differences in ALOX5 expression in NSCLC and normal lung tissues were analyzed by online databases such as TIMER, GEPIA and HPA; the UALCAN database was used to reveal the relationship between ALOX5 and clinical features; Kaplan-Meier database was applied to explore the prognostic value of ALOX5; GeneMANIA and String Website was used to explore genes and proteins associated with ALOX5 expression, respectively; the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze ALOX5 differential genes which were picked up through the TCGA database; GSEA software was applied to predict the signal pathways that ALOX5 may be involved in; and the TIMER database was used to analyze the effect of ALOX5 expression on the level of immune cell infiltration. Compared with the normal lung tissues, the ALOX5 expression was low in NSCLC tissues (P<0.05), and which affected the prognosis of lung cancer patients. The expression level of ALOX5 was related to clinical features such as sex, age, metastasis, and pathological staging in NSCLC patients (all P<0.05). The gene interaction network analysis found that the genes interacting with ALOX5 mainly included the genes related to lipid oxidation and pro-inflammatory mediators such as coactosin like protein 1 (COTL1), leukotriene C4 synthase (LTC4S), and prostaglandin endoperoxide synthase 2 (PTGS2), and the protein-protein interaction analysis results were consistent. GO and KEGG analysis found that ALOX5 was involved in the biological process of activation of immune cell function and was involved in immune response function pathways. The GSEA analysis showed that ALOX5 may activate immune responses and mediate immune-related prognosis by affecting the cytokine-cytokine receptor interactions, natural killer-mediated cytotoxicity, and T cell receptor signaling pathways. The ALOX5 mRNA expressions in lung adenocarcinoma and lung squamous cell carcinoma were positively correlated with the tumor infiltration immune cells (B cells, CD8+ T cells, CD4+ T cells, etc.) (all P<0.05), and the ALOX5 mRNA expression was positively correlated with the expression of classic T cell immune checkpoint inhibitor genes (P<0.001). The ALOX5 gene expression in NSCLC is significantly downregulated, and which can affect NSCLC prognosis and immune cell infiltration levels. ALOX5 gene may be a potential biomarker of NSCLC prognosis associated with immune cell infiltration.


Time trend of asthma prevalence among school children in Taiwan. [corrected].
The standardized International Study of Asthma and Allergies in Childhood (ISAAC) is a valid tool in assessing prevalence of asthma indices. In order to determine the time trends of childhood asthma in Taiwan, we compared data from nationwide ISAAC surveys from a very large sample of Taiwanese 12- to 15-year-old school children, using ISAAC core written and video questionnaires. The number of participants was 44,104 in 1995-96 (phase I) and 11,048 in 2001 (phase III). We found a general tendency towards an increase in lifetime prevalence of physician-diagnosed asthma and asthma symptoms between two surveys, more marked for girls than for boys. Most of the 12-month prevalence of asthma symptoms decreased among boys but stabilized among girls. When comparing different severity levels, we also noted that the decreasing trends of current symptoms were more marked with regard to severe symptoms than mild symptoms in both sexes. A combination of both improved awareness and management of asthma might in part explain this circumstance. Over the past decade in Taiwan, the lifetime prevalence of childhood asthma was increasing, more marked among girls; however, the 12-month prevalence of asthma symptoms was decreasing, mostly among boys. The exact reasons for such trends remain to be explored.


Quality of care in the oncology outpatient setting from patients' perspective: a systematic review of questionnaires' content and psychometric performance.
Cancer care is increasingly provided in the outpatient setting, requiring specific monitoring of care quality. The patients' perspective is an important indicator of care quality and needs to be assessed with well designed, psychometrically sound questionnaires. We performed a systematic literature review of currently available patient satisfaction measures for use in cancer outpatient care settings. We carried out MEDLINE/PubMed, PsycINFO, CINAHL, and Scopus searches of papers published over the past 15 years that describe cancer patient satisfaction questionnaires for use in the outpatient setting. We used the adapted COSMIN checklist to assess the quality of the questionnaires' measurement properties. A total of 6677 citations were identified and 76 relevant articles were read, of which 55 were found either not to be relevant or to provide insufficient psychometric information. The remaining 21 studies pertained to 14 patient satisfaction questionnaires. Continuity and transition, accessibility, and involvement of family/friends were less frequently addressed despite their relevance in outpatient oncology. Almost half of the psychometric studies did not provide information on item level missing data. Most internal consistency estimates (Cronbach's α) were satisfactory. Few studies reported test-retest assessment (n = 5), used confirmatory factor analysis (n = 2), or assessed fit to a graded response item response theory model (n = 3). Only three questionnaires were cross-culturally validated. Important aspects of care may be missed by current patient satisfaction questionnaires for use in the cancer outpatient setting. Additional evidence is needed of their psychometric performance, especially for cross-cultural comparative assessments.


Search for nutritional and inflammatory marker ratios to predict neutropenia in FEC therapy for breast cancer: A retrospective observational study.
Nutritional and inflammatory marker ratios are known to predict response to chemotherapy in breast cancer, but whether they predict adverse effects caused by chemotherapy remains unclear. We investigated whether nutritional and inflammatory marker ratios before starting FEC therapy (5-fluorouracil, epirubicin, and cyclophosphamide) predict grade 4 neutropenia as a serious adverse effect. 61 patients with breast cancer who started FEC therapy for the first time as preoperative or postoperative chemotherapy were studied. Relevant nutritional and inflammatory marker ratios were compared between patients who developed grade 4 neutropenia (n = 44) and those who did not (n = 17). In univariate analysis, occurrence of neutropenia was related significantly (p < 0.05) to pre-FEC-therapy white blood cell count, platelet count, neutrophil count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow prognostic score. Analysis using cutoff values obtained from receiver operating characteristic curves showed that LMR, NLR, and PLR predicted grade 4 neutropenia. However, multivariate logistic regression analysis identified no independent factor associated with grade 4 neutropenia. A post-hoc power analysis revealed an inadequate sample size. Inflammatory marker ratios, especially PLR, may predict grade 4 neutropenia caused by FEC therapy for breast cancer. Although multivariate analysis identified no independent predictive markers in this study due to inadequate sample size, further prospective large-scale research is needed to examine the usefulness of nutritional and inflammatory marker ratios for predicting adverse effects.


Squaric acid-based peptidic inhibitors of matrix metalloprotease-1.
[structure: see text] A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 microM. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 microM.


Comparison of electronic data capture (EDC) with the standard data capture method for clinical trial data.
Traditionally, clinical research studies rely on collecting data with case report forms, which are subsequently entered into a database to create electronic records. Although well established, this method is time-consuming and error-prone. This study compares four electronic data capture (EDC) methods with the conventional approach with respect to duration of data capture and accuracy. It was performed in a West African setting, where clinical trials involve data collection from urban, rural and often remote locations. Three types of commonly available EDC tools were assessed in face-to-face interviews; netbook, PDA, and tablet PC. EDC performance during telephone interviews via mobile phone was evaluated as a fourth method. The Graeco Latin square study design allowed comparison of all four methods to standard paper-based recording followed by data double entry while controlling simultaneously for possible confounding factors such as interview order, interviewer and interviewee. Over a study period of three weeks the error rates decreased considerably for all EDC methods. In the last week of the study the data accuracy for the netbook (5.1%, CI95%: 3.5-7.2%) and the tablet PC (5.2%, CI95%: 3.7-7.4%) was not significantly different from the accuracy of the conventional paper-based method (3.6%, CI95%: 2.2-5.5%), but error rates for the PDA (7.9%, CI95%: 6.0-10.5%) and telephone (6.3%, CI95% 4.6-8.6%) remained significantly higher. While EDC-interviews take slightly longer, data become readily available after download, making EDC more time effective. Free text and date fields were associated with higher error rates than numerical, single select and skip fields. EDC solutions have the potential to produce similar data accuracy compared to paper-based methods. Given the considerable reduction in the time from data collection to database lock, EDC holds the promise to reduce research-associated costs. However, the successful implementation of EDC requires adjustment of work processes and reallocation of resources.


[The feature of experimental endplate fracture in lumbar spine and its related factors].
To evaluate the feature of experimental endplate fracture in lumbar spine and its related factors. Nineteen cadaveric lumbar motion segments aged 48 - 77 years were compressed by overload to fracture the endplate and dissected into isolated vertebrae to evaluate feature of their endplate failure. Before and after failure of endplate, radiographic tests were taken on every motion segment. The bone mineral density (BMD), bone mineral content (BMC) of the vertebral body and endplate were tested respectively before endplate fracture. Among 19 motion segments, 16 were fractured and accounted for 84.2% of all and fracture featured as stellate, step, depression and intrusion. Fracture concentrated on the center or anterior of superior endplate of the inferior vertebrae in one motion segment. Failure load of endplate was positively correlated with BMD, BMC of vertebral endplate. Within one vertebral body, the BMD and BMC of its superior endplate was markedly less than that of inferior endplate, on the other hand, the difference of BMD and BMC of endplate around one disc was opposite. Fractures usually concentrate on the center or anterior part of superior endplate of one vertebrae and are hard to be identified by conventional radiographic examination. Failure load of endplate is positively correlated with BMD, BMC of vertebral body and endplate. There might be certain relationship between feature of fracture and severity of disc degeneration.


[Pandora's digital box: mental disorders in cyberspace].
The emersion of the Internet did not only change human communication and information seeking, it also contributed to manifold alterations in the manifestation, perception and treatment of mental disorders. Thus, one focus of current psychological research lies on the relationship between the new medium and psychosocial functioning. This review embraces recent results on this topic following a discussion from two different perspectives: first, it poses the question, whether the Internet - due to its very specific character - is capable of creating new mental disorders and second, it asks whether rare disorders may possibly be uncovered by the Internet or if already known disorders may be sustained and intensified by the online medium. Accordingly, the first part of this review deals with the conceptual basis of problematic Internet use, Internet addiction and problematic online-gaming as an example of specific internet use. Predisposing psychosocial factors, such as social isolation, depression and compulsive behavior are reviewed as potential triggers for these new internet- related disorders. The second part however draws upon two already existing groups of psychological disorders: eating disorders in relation to Pro-Ana and Pro-Mia on the one hand and Body Integrity Identity Disorder (BIID) on the other hand. Recent research is discussed to explore the sustaining and intensifying effect of the Internet on these disorders.


Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent.
Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low beta- energy, (177)Lu [T(1/2)=6.73 days, E(beta max)=497 keV, E(gamma)=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of (177)Lu-EDTMP to collect preclinical data for starting human clinical trials. (177)Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of (177)Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. (177)Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. The protracted effective half-life of (177)Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing (177)Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior differences were observed. Toxicity studies in dogs did not show any biological adverse effects. The studies demonstrate that (177)Lu-EDTMP is a promising radiopharmaceutical that can be further evaluated for establishing as a radiopharmaceutical for human use.


Predictive Soil Provenancing (PSP): An Innovative Forensic Soil Provenance Analysis Tool.
Soil is a common evidence type used in forensic and intelligence operations. Where soil composition databases are lacking or inadequate, we propose to use publicly available soil attribute rasters to reduce forensic search areas. Soil attribute rasters, which have recently become widely available at high spatial resolutions, typically three arc-seconds (~90 m), are predictive models of the distribution of soil properties (with confidence limits) derived from data mining the inter-relationships between these properties and several environmental covariates. Each soil attribute raster is searched for pixels that satisfy the compositional conditions of the evidentiary soil sample (target value ± confidence limits). We show through an example that the search area for an evidentiary soil sample can be reduced to <10% of the original investigation area. This Predictive Soil Provenancing (PSP) approach is a transparent, reproducible, and objective method of efficiently and effectively reducing the likely provenance area of forensic soil samples.


[A short-term follow-up results of lumbar disc herniation by Coflex].
To evaluate the short term effectiveness of lumbar disc herniation by Coflex. From December 2007 to June 2008, 31 patients (16 males and 15 females) were treated by Coflex. The average age was 51.4 years (range, 33 - 70 years). The average period of follow-up was 10 months. To evaluate the short term effectiveness of lumbar disc herniation by Coflex by JOA, VAS, the conventional radiography and oswestry disability index (ODI). The average JOA score increased from 9.1 +/- 1.1 preoperatively to 26.4 +/- 1.7 at 6 month postoperatively. ODI decreased from 24.7 +/- 4.8 preoperatively to averaged 4.5 +/- 1.1 at 6 months postoperatively. The VAS score decreased from 7.9 +/- 0.8 to 3.0 +/- 0.9. The clinical symptoms after operation were improved significantly. There were statistically significant differences between the preoperative and postoperative HD (height of dorso- intervertebral discs), DS(distance across the two adjacent spinous processes), DI (distance of intervertebral foramina). The average HD increased from (7.9 +/- 1.1) mm preoperatively to (10.8 +/- 1.3) mm after operation. The average DS increased from (28.3 +/- 2.4) mm preoperatively to (36.4 +/- 1.7) mm postoperatively. The average DI changed from (18.8 +/- 1.0) mm preoperatively to (21.6 +/- 1.7) mm postoperatively. Complications occurred in 3 patients (9.6%). One case complained of persistent low back pain. One case showed opposite lower limb pain in 3 weeks after operation, and was cured after appropriate treatment. One case had the loosening of Coflex in 6 months after surgery, but did not appear related clinical symptoms. Coflex for lumbar disc herniation can increase the HD and DI significantly, and it has positive meaning for keeping height of lumbar vertebral space and treating the nerve root symptom of lumbar disc herniation.


Lean beef: impetus for lipid modifications.
Health-conscious consumers want lean beef. The beef industry has responded by physically removing much of the adipose tissue from retail products and by initiating attempts to produce--genetically and environmentally--cattle with more muscle, less external fat, and less seam fat, without sacrificing the quality dependent on the amount of marbling present. Offering lean beef that is closely or completely trimmed of external fat has improved retail beef sales. Impetus for modification of the lipid composition of bovine muscle and adipose tissue, including marbling, has resulted from the following: (a) diet/health concerns of consumers and demands for leaner beef, (b) research clarifying effects of dietary fatty acids and cholesterol on serum cholesterol levels, (c) dietary guidelines and recommendations from health organizations, and (d) dietary recommendations by physicians and dietitians to reduce beef consumption. Analysis of cholesterol content of marbling dissected from the rib (longissimus dorsi) muscle revealed that marbling contributes little to total cholesterol content. Cholesterol content of marbling was 117 mg/100 gm intramuscular adipose tissue (equivalent to about a 2 mg cholesterol contribution to a 100-gm serving of uncooked meat). The difference in fatty acid composition of lean meat and of adipose tissue is primarily in the percentage of polyunsaturated fatty acids, which is higher in lean meat. The most prevalent fatty acids in adipose tissue including marbling were: palmitic acid (24.1%), stearic acid (13.5%), and oleic acid (37.7%).


Luminescence-guided and visibly transparent solar concentrators based on silicon quantum dots.
In this work, we demonstrate a new tapered prism-shaped luminescent solar concentrator (LSC), which guides most of the luminescence toward one edge instead of four, for the solar window application. Only one Si photovoltaic (PV) strip attached to the light-emitting sidewall is needed to collect the luminescence, which further reduces PV material cost and avoids electrical mismatch. To achieve high visible transmission and mitigate reabsorption, colloidal silicon quantum dots (SiQDs) with ultraviolet-selective absorption and large Stokes shift are used as the fluorophores. With the SiQD concentration equal to 8 mg mL-1, the SiQD-LSC as a solar window can attain a power conversion efficiency (PCE) equal to 0.27%, while ensuring high average visible transmission (AVT = 86%) and high color rendering index (CRI = 94 with AM1.5G as the incident spectrum). When adjusted to front-facing, the Si PV strip can harvest not only the direct sunlight but also the concentrated SiQD fluorescence guided from the LSC. As a result, the overall solar window PCE can be increased to 1.18%, and the PCE of the front-facing Si PV strip alone can be increased by 7% due to the luminescence guided from the SiQD-LSC.


The Association of Number and Space Under Different Tasks: Insight From a Process Perspective.
We investigated the Spatial Numerical Association of Response Codes (SNARC) effect in 240 adults using a parity judgment and a magnitude classification task. Eight numbers from 1 to 9 except 5 were randomly presented one at a time, half of the participants were asked to compare these number with the target number 5 in the magnitude classification task; the other half of the participants were asked to judge whether these numbers were even or odd. It was called a phase when all eight numbers were tested; there were in total 16 phases. Detailed analyses of the changes in response times across the range of numbers and the chronological trend of the SNARC effect size over 16 phases estimated by a curvilinear regression model were reported. This phase-to-phase design and analyses provide an insight into the process of the SNARC effect in different tasks. We found that the SNARC effect emerged earlier and stayed more stable in magnitude classification task than in the parity task during the time course. Furthermore, the size of SNARC effect increased with time in the magnitude classification task, whereas it fluctuated up and down over time in the parity task. These findings indicate that the association of the number and space is dynamic and the process of the SNARC effect varies across tasks.


DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study.
Present clinical algorithms assign adjuvant chemotherapy according to prognosis, but clinical decision-making would be greatly improved if reliable predictive markers were available to identify which subsets of patients benefit most from treatment. We examined molecular markers in preserved tissue from patients with Dukes' B or C colon cancer randomised to receive, or not, adjuvant fluorouracil, and assessed each marker's prognostic and predictive value. Formalin-fixed paraffin-embedded paired normal and tumour samples were obtained from 393 patients with colon cancer from the UK AXIS trial of postoperative portal vein infusion fluorouracil versus control. We measured loss of heterozygosity (LOH) and microsatellite instability at four loci: P53 (17p13), D18S61 (18q22.3), D18S851 (18q21.1), and DP1 (5q21). The prognostic value of each marker was assessed with the log-rank test, and the predictive value by comparison of treatment hazard ratios with the chi(2) test for heterogeneity (CSH). In 228 (58%) patients informative for LOH at D18S61, this marker was significantly predictive: benefit from fluorouracil was significantly greater in patients retaining heterozygosity than in those with LOH (CSH p=0.02). Conversely, LOH at D18S61 was a significant prognostic marker of improved outcome in untreated patients. 314 (80%) patients were informative for LOH at at least one of the three 17p and 18q sites, of whom half retained heterozygosity at one or more site. The effect of chemotherapy in these patients was striking (hazard ratio 0.45, 95% CI 0.28-0.73), whereas chemotherapy had no effect in patients with no retained heterozygosity (0.91; 0.56-1.48), CSH p=0.039. Retention of heterozygosity at one or more 17p or 18q sites was associated with the ability to benefit from adjuvant fluorouracil. These results support the principle of developing molecular markers as predictive factors in treatment decisions.


Impact of initial temporary abdominal closure in damage control surgery: a retrospective analysis.
Damage control surgery has revolutionized trauma surgery. Use of damage control surgery allows for resuscitation and reversal of coagulopathy at the risk of loss of abdominal domain and intra-abdominal complications. Temporary abdominal closure is possible with multiple techniques, the choice of which may affect ability to achieve primary fascial closure and further complication. A retrospective analysis of all trauma patients requiring damage control laparotomy upon admission to an ACS-verified level one trauma center from 2011 to 2016 was performed. Demographic and clinical data including ability and time to attain primary fascial closure, as well as complication rates, were recorded. The primary outcome measure was ability to achieve primary fascial closure during initial hospitalization. Two hundred and thirty-nine patients met criteria for inclusion. Primary skin closure (57.7%), ABThera™ VAC system (ABT) (15.1%), Bogota bag (BB) (25.1%), or a modified Barker's vacuum-packing (BVP) (2.1%) were used in the initial laparotomy. Patients receiving skin-only closure had significantly higher rates of primary fascial closure and lower hospital mortality, but also significantly lower mean lactate, base deficit, and requirement for massive transfusion. Between ABT or BB, use of ABT was associated with increased rates of fascial closure. Multivariate regression revealed primary skin closure to be significantly associated with primary fascial closure while BB was associated with failure to achieve fascial closure. Primary skin closure is a viable option in the initial management of the open abdomen, although these patients demonstrated less injury burden in our study. Use of vacuum-assisted dressings continues to be the preferred method for temporary abdominal closure in damage control surgery for trauma.


Disability and Depression.
Here, Ann Cvetkovich, interviewed by Abby Wilkerson, brings Cvetkovich's influential cultural studies analysis of depression explicitly into conversation with disability studies. Cvetkovich understands "feeling bad" (a term she prefers to "depression") as a defining affective state under neoliberalism. Drawing on a distinctive historical/cultural archive, she challenges the atomism of the neoliberal medical model that frames depression and affective distress more generally as the result of faulty brain chemistry-individual organisms gone awry. Instead, she traces these common experiences to sociopolitical phenomena ranging from current neoliberal demands for productivity as exemplified in university life, to histories of colonization, slavery, and displacement. The conversation considers the value of disability frameworks for understanding mental health diagnoses and the intersections of social institutions, bodily practices, and everyday affective life.


Stresses experienced by psychiatrists and their role in burnout: a national follow-up study.
Many studies have looked at sources of stress in psychiatrists, yet the role played by different factors in the causation of burnout in psychiatrists remains unclear. We had two aims, first, to develop a predictive model for the onset of burnout. Second, we aimed to study the differences in the perception of what caused stress between psychiatrists who rated themselves high on Emotional Exhaustion compared to those who rated themselves as low on Emotional Exhaustion. A previously described questionnaire that identified stressors relevant to consultant psychiatrists was mailed out to 426 psychiatrists, with 240 replies. Scores on the Emotional Exhaustion dimension of the Maslach Burnout Inventory were available for 131 respondents. Based on an earlier literature review, the Sources of Stress Questionnaire (SOS-Q) used in the study had 45 factors, categorized into predisposing, precipitating, perpetuating and protective factors for burnout in psychiatrists. Of these, factor analysis identified 11 non-correlated factors which were used in the final analysis of this study. Four factors emerged as associated with burnout in psychiatrists in New Zealand: too much work; working long hours; an aggressive administrative environment; and lacking support from management. Two factors negatively correlated with Emotional Exhaustion were a high level of job satisfaction and/or enjoyment, and low pay compared to other countries. Most factors associated with burnout are preventable and can be managed jointly between psychiatrists and administrators. Service providers need to address burnout seriously.


Drug-Mediated Control of Receptor Valency Enhances Immune Cell Potency.
Designer T cells offer a novel paradigm for treating diseases like cancer, yet they are often hindered by target recognition evasion and limited in vivo control. To overcome these challenges, we develop valency-controlled receptors (VCRs), a novel class of synthetic receptors engineered to enable precise modulation of immune cell activity. VCRs use custom-designed valency-control ligands (VCLs) to modulate T cell signaling via spatial molecular clustering. Using multivalent DNA origami as VCL, we first establish that valency is important for tuning the activity of CD3-mediated immune activation. We then generate multivalent formats of clinically relevant drugs as VCL and incorporate VCR into the architecture of chimeric antigen receptors (CARs). Our data demonstrate that VCL-mediated VCRs can significantly amplify CAR activities and improve suboptimal CARs. Finally, through medicinal chemistry, we synthesize programmable, bioavailable VCL drugs that potentiate targeted immune response against low-antigen tumors both in vitro and in vivo. Our findings establish receptor valency as a core mechanism for enhancing CAR functionality and offer a synthetic chemical biology platform for strengthening customizable, potent, and safer cell therapies.


The contribution of copy number variants to psychiatric symptoms and cognitive ability.
Copy number variants (CNVs) are deletions and duplications of DNA sequence. The most frequently studied CNVs, which are described in this review, are recurrent CNVs that occur in the same locations on the genome. These CNVs have been strongly implicated in neurodevelopmental disorders, namely autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay (DD), but also in schizophrenia. More recent work has also shown that CNVs increase risk for other psychiatric disorders, namely, depression, bipolar disorder, and post-traumatic stress disorder. Many of the same CNVs are implicated across all of these disorders, and these neuropsychiatric CNVs are also associated with cognitive ability in the general population, as well as with structural and functional brain alterations. Neuropsychiatric CNVs also show incomplete penetrance, such that carriers do not always develop any psychiatric disorder, and may show only mild symptoms, if any. Variable expressivity, whereby the same CNVs are associated with many different phenotypes of varied severity, also points to highly complex mechanisms underlying disease risk in CNV carriers. Comprehensive and longitudinal phenotyping studies of individual CNVs have provided initial insights into these mechanisms. However, more work is needed to estimate and predict the effect of non-recurrent, ultra-rare CNVs, which also contribute to psychiatric and cognitive outcomes. Moreover, delineating the broader phenotypic landscape of neuropsychiatric CNVs in both clinical and general population cohorts may also offer important mechanistic insights.


[Investigation on Medical Device Standards].
In this paper, Medical Device Standards, including Nation standards and Professional standards are investigated. The major problems that may appear in the Medical Device Standardization are analyzed. Based on the result of the analysis, some policy suggestions on the medical device standardization are put forward, which may help the authority making policy of standardization in Medical Device.


Development to blastocyst is impaired when intracytoplasmic sperm injection is performed with abnormal sperm from infertile mice harboring a mutation in the protein phosphatase 1cgamma gene.
Idiopathic azoospermia, characterized by abnormal spermatogenesis, is commonly treated by performing intracytoplasmic sperm injection (ICSI) with sperm retrieved from testicular biopsies. However, no controlled experiments have been performed using an animal model to assess the efficacy or safety of the procedure. We have performed ICSI with testicular sperm obtained in a similar manner from testes of male mice homozygous for a null mutation in the protein phosphatase 1cgamma gene (PP1cgamma) or those of their wild-type littermates. PP1cgamma mutant testicular sperm are less resistant to sonication than are wild-type sperm and display a range of morphological abnormalities, similar to those reported for testicular sperm from idiopathic azoospermic men. PP1cgamma mutant sperm are unable to support development to the blastocyst stage, resulting in arrested development either before or just after compaction. A comparison of testicular and epididymal sperm from wild-type males revealed that the epididymal sperm caused embryos to fragment at an elevated rate. These results suggest that ICSI with any kind of testicular sperm carries an increased risk of embryo fragmentation and that abnormal testicular sperm has an added risk of embryo wastage at later preimplantation stages.


Controllable phase connectivity and magnetoelectric coupling behavior in CoFe(2)O(4)-Pb(Zr,Ti)O(3) nanostructured films.
Magnetoelectric CoFe(2)O(4)-Pb(Zr,Ti)O(3) nanostructured films with various phase connectivity patterns were prepared by a pulsed laser deposition method. It was found that the microstructure as well as the phase connectivity pattern of the film varied remarkably with the variation of phase content ratio. All composite nanofilms exhibit evident ferromagnetic and ferroelectric characteristics, as well as distinct magnetoelectric coupling behavior upon increasing the magnetic field. The correlation between the phase connectivity pattern and magnetoelectric coupling behavior for the composite nanofilm was revealed. This work provides an efficient avenue to modulate the magnetoelectric coupling behavior for the ferroelectric-ferromagnetic composite nanofilm.


Antifertility effect of Andrographis paniculata (Nees) in male albino rat.
Dry leaf powder of A. paniculata, when fed orally to male albino rats, at a dose level of 20 mg powder per day for 60 days, resulted in cessation of spermatogenesis, degenerative changes in the seminiferous tubules, regression of Leydig cells and regressive and/or degenerative changes in the epididymis, seminal vesicle, ventral prostate and coagulating gland. There was reduction in the weight and fluid content of the accessory glands. The treatment also resulted in accumulation of glycogen and cholesterol in the testis, and increased activities of lactate dehydrogenase in testis and alkaline phosphatase in testis and ventral prostate. The results suggest antispermatogenic and/or antiandrogenic effect of the plant.


Off-axis aberrations improve the resolution limits of incoherent imaging.
The presence of off-axis tilt and Petzval curvature, two of the lowest-order off-axis Seidel aberrations, are shown to improve the Fisher information of two-point separation estimation in an incoherent imaging system compared to an aberration-free system. Our results show that the practical localization advantages of modal imaging techniques within the field of quantum-inspired superresolution can be achieved with direct imaging measurement schemes alone.


Connecting and feeling: Associations between social factors and emotions in nine countries.
We aimed to explore the distribution of positive and negative emotions across nine low-, middle- and high-income countries; and the association between social factors and these emotions. Data were drawn from the SAGE and the COURAGE studies, with 52,553 participants. Emotions were assessed through the day reconstruction method.Sociodemographic characteristics and social factors were also measured. Multiple linear regressions were performed. Finland, China and African countries showed significantly lower scores on the negative emotions, whereas positive emotions were more homogeneous across countries. Loneliness was positively associated with negative emotions and negatively associated with positive ones; frequent social participation was related with higher scores in positive emotions; and lower trust with higher levels of feeling rushed, irritated, depressed and less calm. The extent to which each emotion was felt varied across countries, but there seems to exist an association of social factors with the emotions.


Micromachining of a bimorph Pb(Zr,Ti)O3 (PZT) cantilever using a micro-electromechanical systems (MEMS) process for energy harvesting application.
We designed and fabricated a bimorph Pb(Zr,Ti)O3 (PZT) cantilever with an integrated Si proof mass to obtain a low resonant frequency for an energy harvesting application. The cantilevers were fabricated on the micro-electromechanical systems (MEMS) scale. A mode of piezoelectric conversions were d31 and d33 mode in cantilever vibration Therefore, we designed and fabricated a single cantilever with d31 unimorph, d31 bimorph, d33 unimorph, and d33 bimorph modes. Finally, we fabricated a device with beam dimensions of about 5,400 microm x 480 microm x 14 microm (< +/- 5%), and an integrated Si proof mass with dimensions of about 1,481 microm x 988 microm x 450 microm (< +/- 5%). In order to measure the d31 and d33 modes, we fabricated top and bottom electrodes. The distance between the top electrodes was 50 microm and the resonant frequency was 89.4 Hz. The average powers of the d31 unimorph, d31 bimorph, d33 unimorph, and d33 bimorph modes were 3.90, 9.60, 21.42, and 22.47 nW at 0.8 g (g = 9.8 m/s2) and optimal resistance, respectively.


Efficacy of delafloxacin against the biothreat pathogen Bacillus anthracis.
To evaluate the in vitro activity and in vivo efficacy of delafloxacin against Bacillus anthracis, the causative agent of anthrax. MICs were obtained according to CLSI guidelines for 30 virulent isolates and 14 attenuated antibiotic-resistant strains. For the in vivo efficacy study, mice were administered delafloxacin (30-62.5 mg/kg) subcutaneously, or ciprofloxacin (30 mg/kg) intraperitoneally beginning at either 24 or 48 ± 1 h post-challenge (post-exposure prophylaxis) and continued every 12 h for 14 days with study termination on day 30. The mean inhaled dose in the study was approximately 103 × LD50 equivalents, and the range was 87-120 × LD50. Delafloxacin (MIC90 = 0.004 mg/L) was 16-fold more potent than ciprofloxacin (MIC90 = 0.06 mg/L) against a 30-strain set of virulent B. anthracis. Against a panel of attenuated antibiotic-resistant strains, delafloxacin demonstrated potency ≥128-fold over that observed with ciprofloxacin. When evaluated in vivo, mice treated with all delafloxacin doses tested at 24 h post-challenge demonstrated equivalent survival compared with mice treated with the positive control ciprofloxacin. Because of the high challenge dose of spores, mice treated at 48 h showed rapid and high mortality in all groups including the positive control. Surviving animals in all delafloxacin- and ciprofloxacin-treated groups (24 and 48 h) showed complete splenic clearance of infection and <2.2 × 103 cfu/g lung tissue. Given the high bar set by the 100 × LD50 challenge dose in this study, the results from delafloxacin treatment are promising for the treatment of inhaled anthrax.


Activity of the Chlamydomonas chloroplast rbcL gene promoter is enhanced by a remote sequence element.
The chloroplast gene rbcL encodes the large subunit of ribulose bisphosphate carboxylase. In Chlamydomonas reinhardtii, this gene is transcribed more actively than any other protein-encoding chloroplast gene studied to date. To delineate the rbcL gene promoter, chimeric reporter genes containing fragments of the 5' region of the rbcL gene fused to the coding sequence of the bacterial uidA gene, encoding beta-glucuronidase, were stably introduced into the chloroplast genome of Chlamydomonas by microprojectile bombardment. The relative transcription rates of endogenous and introduced genes were determined in transgenic cell lines in vivo. The basic rbcL promoter is located within the region of the gene extending from positions -18 to +63, taking position +1 as the site of initiation of transcription. A chimeric reporter gene containing only the basic promoter is transcribed only 1-15% as actively as the endogenous rbcL gene, depending on the conditions under which cells are grown and tested. However, a chimeric gene containing rbcL sequences extending to position +170 or beyond is transcribed at about the same rate as the endogenous gene. Deletion of the sequence between positions +170 and +126, well within the protein-encoding region, reduces the rate of transcription to that of reporter genes with the basic promoter alone.


Simulation-Based Training to Improve Clinical Pharmacist Self-Efficacy in the Management of a Rapidly Decompensating Patient.
Background: The optimal training method to prepare pharmacists as an integral rapid response team or cardiopulmonary arrest responders is poorly described. This study assessed the utility of simulation-based training (SBT) as a training technique for clinical pharmacists. Objective: This study aimed to determine if attending SBT is associated with an improvement in self-efficacy. Methods: This single-center, prospective, interventional cohort study offered three simulations to clinical pharmacists over the course of seven months at a 957-bed quaternary care academic medical center. Pharmacists who participated in at least one simulation were categorized in the intervention group and were compared to pharmacists who did not attend a simulation. All participants were asked to complete a 19-question self-efficacy survey in the form of a 100-point scale, a 15-question multiple-choice knowledge assessment, and a perception survey in the form of 4-point Likert scale administered at baseline and following the conclusion of the SBT. Results: Forty-four clinical pharmacists participated; 20 in the intervention group and 24 in the control group. Median change in self-efficacy score improved significantly in the intervention group compared to the control group (14.3 vs 2.3, P = .009). Median change in perception score improved significantly (2 vs 0, P = .046). Knowledge score did not change significantly from baseline. Conclusion: Simulation-based training improved clinical pharmacist self-efficacy and perceptions in the care of rapidly decompensating patients. These findings support SBT as a viable modality of training clinical pharmacists for the management of rapidly decompensating patients.


Rhegmatogenous retinal detachment following femtosecond laser-assisted cataract surgery.
Rhegmatogenous retinal detachment (RRD) following femtosecond laser-assisted cataract surgery (FLACS) has not been reported till date. We described the first case of RRD after FLACS. A 29-year-old male presented with complaints of sudden, painless dimness of vision in the left eye (LE) for the past 2 days. He was operated for refractive lens exchange in both eyes for high myopia using FLACS 3 months back. On examination, his LE vision was perception of light and accurate projection of rays with fundus showing bullous RRD. His right eye fundus was absolutely normal with 20/20 vision. A 25-gauge vitrectomy was performed in LE. The retina was settled with silicone oil (1300 centistokes) endotamponade. After 4 weeks, the patient gained 20/60 vision in LE with attached retina under silicone oil. RRD is a potential complication following FLACS and thus frequent follow-ups are required for high-risk patients after FLACS.


The function and regulation of heat shock transcription factor in Cryptococcus.
Cryptococcus species are opportunistic human fungal pathogens. Survival in a hostile environment, such as the elevated body temperatures of transmitting animals and humans, is crucial for Cryptococcus infection. Numerous intriguing investigations have shown that the Hsf family of thermotolerance transcription regulators plays a crucial role in the pathogen-host axis of Cryptococcus. Although Hsf1 is known to be a master regulator of the heat shock response through the activation of gene expression of heat shock proteins (Hsps). Hsf1 and other Hsfs are multifaceted transcription regulators that regulate the expression of genes involved in protein chaperones, metabolism, cell signal transduction, and the electron transfer chain. In Saccharomyces cerevisiae, a model organism, Hsf1's working mechanism has been intensively examined. Nonetheless, the link between Hsfs and Cryptococcus pathogenicity remains poorly understood. This review will focus on the transcriptional regulation of Hsf function in Cryptococcus, as well as potential antifungal treatments targeting Hsf proteins.


Migrated Hem-o-Lok clips in the ureter: a rare cause of recurrent urinary tract infection.
Erosion of surgical materials into the adjacent organs following surgical procedures is a rare complication. Migrations of these surgical materials into the urinary tract like pelvicalyceal system, ureter and bladder have been reported following various urological procedures. We present a case of migrated Hem-o-Lok clips into the ureter following a laparoscopic partial nephrectomy for angiomyolipoma of the left kidney presented with recurrent urinary tract infection. The case was managed with ureteroscopic removal of clips. The patient is asymptomatic on last follow-up.


Endogenous and exogenous attention in patients with conversion paresis.
Endogenous and exogenous attention of patients with conversion paresis was investigated using Posner's 'covert orienting of visual attention' task. In the light of previous evidence showing that inhibition of higher-level control functions plays a role in conversion paralysis (e.g., Marshall, Halligan, Fink, Wade, & Frackowiak, 1997), patients were expected to display weaker cue effects in the endogenous condition and weaker inhibition of return (IOR) in the exogenous condition. Eight patients with conversion paresis in one or more limbs and eight healthy controls were administered the attention task in a verbal response condition and in a limb response condition in which subjects responded with each limb separately. When responding verbally, patients showed relatively weakened endogenous cue effects on a 150-ms stimulus onset asynchronicity (SOA) and no IOR in the exogenous condition. Comparable effects emerged when patients responded with affected limbs but not when they responded with unaffected limbs. The findings suggest impairment in voluntary attention. High-level inhibition is suggested to interfere with the orientation to stimuli that prime responses with affected limbs. The fact that similar results were found for verbal responses is interpreted as supporting the view that attention deficits are manifested on a high, abstract level of cognitive processing.


[Toxic activity of Legionella pneumophila: current findings and prospects].
The AA. report the personal contributions and the recent findings of other investigators dealing with the toxic activities of Legionella pneumophila, the causative agent of Legionnaires' Disease. From the results of some tests (particularly Limulus endotoxin assay, pyrogenic reaction, skin Shwartzman reaction) there is an increasing evidence that Legionella pneumophila possesses some of the in vitro and in vivo biological properties associated with endotoxins of Gram negative bacteria, even if to a different of potency in different strains. However, the exact roles of an endotoxin and other bacterial products (e.g. haemolysins) as a pathogenetic mediators of the pathophysiological events of the disease remain to be determined.


Comparing contents of functional outcome measures in stroke rehabilitation using the International Classification of Functioning, Disability and Health.
To examine the content of outcome measures that are frequently used in stroke rehabilitation and focus on activities and participation, by linking them to the International Classification of Functioning, Disability and Health (ICF). Method. Constructs of the following instruments were linked to the ICF: Barthel Index, Berg Balance Scale, Chedoke McMaster Stroke Assessment Scale, Euroqol-5D, Functional Independence Measure, Frenchay Activities Index, Nottingham Health Profile, Rankin Scale, Rivermead Motor Assessment, Rivermead Mobility Index, Stroke Adapted Sickness Impact Profile 30, Medical Outcomes Study Short Form 36, Stroke Impact Scale, Stroke Specific Quality of Life Scale and Timed Up and Go test. Results. It proved possible to link most constructs to the ICF. Most constructs fitted into the activities and participation component, with mobility being the category most frequently covered in the instruments. Although instruments were selected on the basis of their focus on activities and participation, 27% of the constructs addressed categories of body functions. Approximately 10% of the constructs could not be linked. The ICF is a useful tool to examine and compare contents of instruments in stroke rehabilitation. This content comparison should enable clinicians and researchers to choose the measure that best matches the area of their interest.


Emerging treatments for soft tissue sarcoma of adults.
Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal tissues. Patients can present with a localised tumour (primary or local recurrence) at different sites (e.g., extremity, abdomen) or metastatic disease, which may require different treatment strategies. Is the surgical resection of a localised sarcoma enough or is it better to give an additional treatment like adjuvant and/or preoperative radiotherapy and/or chemotherapy? Which chemotherapy should be selected in the first or second line situation? Do new treatment options exist, such as targeted therapies? This review provides answers to some of these questions. To decide on consecutive treatment steps, it is important to know as many relevant factors as possible at first presentation. Therefore, the first part of this review discusses the specific characteristics and prognostic factors of importance for treatment planning. A short summary of current therapy strategies and existing standards is then given. The main body of the review summarises information on new and emerging clinical compounds for patients with soft tissue sarcoma of adults, including recent developments of targeted therapy.


Infective endocarditis following gastrointestinal and genitourinary procedures: an argument in favour of prophylaxis.
In the 2007 American Heart Association guidelines, gastrointestinal (GI) and genitourinary (GU) procedures were removed from the indications for infective endocarditis (IE) prophylaxis. The purpose of this study was to estimate the contribution of GI and GU procedures to the occurrence of IE in order to appreciate whether this removal was justified. Among 212 episodes of IE prospectively collected during 7 y, 20 cases (9%) had invasive GI and GU procedures and 17 (8%) had dental interventions within 3 months before IE diagnosis. Enteric organisms (predominantly Enterococcus faecalis) were significantly more common in the GI and GU group than in all other patients, whereas viridans streptococci, the most common pathogen in the dental group, were absent from the GI and GU group. This unique combination of pathogens in the GI and GU group is highly suggestive of a true association between the procedure and IE. Hence, GI and GU procedures pose a non-negligible risk of acquisition of IE. Consequently, it is proposed here, that adults at high risk of IE who undergo surgical GI and GU procedures, receive prophylaxis that includes an anti-enterococcal agent.


Transgene insertion affects transcription and epigenetic modification of flanking host sequence in transgenic pigs.
Transgenic technology has been used for years to study gene function, produce important proteins, and generate models for the study of human diseases. However, the efficiency of producing transgenic animal lines that retain normal function is extremely low. The low efficiency can be mainly attributed to the integrated transgene. A further understanding of the effects of transgene integration on transcription and epigenetic modification of the host genome would improve the transgenic efficiency. Therefore, we utilized three transgenic pigs produced by SCNT expressing GFP, to identify alterations of transcription, DNA methylation and histone acetylation resulting from integration of the GFP gene. Multiple copies of the transgene integrated into a single site of the three transgenic pigs were verified by TAIL—PCR and the integration sites were different in each pig. We observed that the integrated transgene frequently resulted in significantly low transcription of flanking sequences in various tissues of transgenic pigs in comparison with wild—type pigs. Corresponding with the low transcription, DNA hypermethylation and loss of acetylation of histone H3 and H4 were detected. Our results demonstrate that the abnormal transcription and epigenetic modification of sequences flanking the transgene were not correlated with the expression of the transgene. However, the disturbance caused by the insertion of the transgene, was dependent upon the integration site. This suggests that some sequences in the host genome could permit integration and expression of transgene without causing defects in the host.


Simultaneous venous gangrene in both lower and upper limbs. A case report.
Cancer-related venous gangrene is an extremely rare paraneoplastic syndrome. Here, we present the case of a woman, who suffered from cervical cancer of the uterus and was admitted to our Clinic with venous gangrene in both the right lower and upper limbs. Neither the anticoagulant therapy, nor thrombolysis, succeeded in improving her clinical condition. Cancer is one of the most important causes of venous thromboembolism. Venous gangrene is rarely seen in these patients. Despite adequate therapy, venous gangrene in some very rare occasions may progress to affect further limbs. Mortality in these patients remains very high.


Acute restraint stress and corticosterone transiently disrupts novelty preference in an object recognition task.
The object recognition task is a procedure based on rodents' natural tendency to explore novel objects which is frequently used for memory testing. However, in some instances novelty preference is replaced by familiarity preference, raising questions regarding the validity of novelty preference as a pure recognition memory index. Acute stress- and corticosterone administration-induced novel object preference disruption has been frequently interpreted as memory impairment; however, it is still not clear whether such effect can be actually attributed to either mnemonic disruption or altered novelty seeking. Seventy-five adult male Wistar rats were trained in an object recognition task and subjected to either acute stress or corticosterone administration to evaluate the effect of stress or corticosterone on an object recognition task. Acute stress was induced by restraining movement for 1 or 4h, ending 30 min before the sample trial. Corticosterone was injected intraperitoneally 10 min before the test trial which was performed either 1 or 24h after the sample trial. Four-hour, but not 1-h, stress induced familiar object preference during the test trial performed 1h after the sample trial; however, acute stress had no effects on the test when performed 24h after sample trial. Systemic administration of corticosterone before the test trial performed either 1 or 24h after the sample trial also resulted in familiar object preference. However, neither acute stress nor corticosterone induced changes in locomotor behaviour. Taken together, such results suggested that acute stress probably does not induce memory retrieval impairment but, instead, induces an emotional arousing state which motivates novelty avoidance.


Nonlinear interactions between electromagnetic waves and electron plasma oscillations in quantum plasmas.
We consider nonlinear interactions between intense circularly polarized electromagnetic (CPEM) waves and electron plasma oscillations (EPOs) in a dense quantum plasma, taking into account the electron density response in the presence of the relativistic ponderomotive force and mass increase in the CPEM wave fields. The dynamics of the CPEM waves and EPOs is governed by the two coupled nonlinear Schrödinger equations and Poisson's equation. The nonlinear equations admit the modulational instability of an intense CPEM pump wave against EPOs, leading to the formation and trapping of localized CPEM wave pipes in the electron density hole that is associated with a positive potential distribution in our dense plasma. The relevance of our investigation to the next generation intense laser-solid density plasma interaction experiments is discussed.


Octopamine enhances neuromuscular transmission in developing and adult moths, Manduca sexta.
The effect of octopamine on neuromuscular transmission was examined in developing and adult Manduca sexta. Intracellular recordings were made from the dorsal longitudinal muscle (DLM), superfused with solutions containing DL-octopamine or other amines. In untreated adult moths and pharate adults nearly ready to enclose (stage Day 19), stimulation of the motor nerve evokes a large excitatory junction potential (EJP), an active membrane response, and a twitch. In adults and Day 19 animals DL-octopamine (10(-7) to 10(-4)M) has no effect on the amplitude and rise-time of the electrical response in normal saline, but 10(-6) to 10(-4) M DL-octopamine increases the amplitude of the excitatory junction potential recorded in saline containing one-third the normal calcium concentration. Immature (Day 16) muscle, which normally produces only small EJPs following stimulation of its motor nerve, responds to 10(-6) to 10(-4) M DL-octopamine by an increase in the EJP above threshold for an active membrane response and a contraction. When the muscle has developed sufficiently to spike and contract in response to nerve stimulation in the absence of exogenous octopamine (Days 17 and 18), application of DL-octopamine increases the maximum rate at which the muscle contracts in response to each stimulus in a train (designated the maximum following frequency, MFF). The threshold dose for an effect on the MFF of Day 18 immature moths is less than 10(-10) M. At this stage 10(-8) M DL-octopamine increases the MFF four-fold. The effect on the MFF is dose-dependent over the range 10(-10) M to 10(-6) M. The biogenic amines DL-epinephrine, DL-norepinephrine, tyramine, DL-phenylethanolamine, 2-phenylethylamine, and dopamine, applied at concentrations of 10(-8) or 10(-4) M, do not change the MFF. Both DL-synephrine (10(-8) M) and serotonin (10(-7) M) mimic the action of 10(-10) M DL-octopamine on the MFF. The action of DL-octopamine (10(-7) M) is blocked by phentolamine (10(-4)M) but not by propranolol (10(-4)M). The octopamine content of hemolymph was determined with a radioenzymtic assay. The concentration of octopamine in the hemolymph increases 3.6-fold, from 5 X 10(-8) M on Day 18 (duration of adult development is 19 days) to 1.85 X 10(-7) M one day following eclosion.(ABSTRACT TRUNCATED AT 400 WORDS)


Retinal thickness measurement and evaluation of natural history of the diabetic macular edema through optical coherence tomography.
1) Diagnose, through optical coherence tomography (OCT) exam, the occurrence of diabetic macular edema in patients with diabetic retinopathy and visual acuity of 20/40 or better, by measuring the foveal center point thickness, during one year. 2) Evaluate the edema natural history, during this period, associating the center point thickness with hemoglobin A1c and changes in visual acuity. 3) Correlate the obtained results with the control group. A prospective study was done, of a sample of 30 patients with diabetic macular edema and visual acuity of 20/40 or better. Measurements of the best corrected visual acuity, hemoglobin A1c level, biomicroscopy with 78-diopter lens, fluorescein angiogram and optical coherence tomography were made. The retinal thickness was selected as the main variable. Besides descriptive statistics, additional tests were applied to analyze the results and determine the correlation between these variables, such as t-Student, Chi-Square, Tukey and ANOVA. The relation of optical coherence tomography with visual acuity and hemoglobin A1c was studied through linear regression. It was found that there is no significant difference between patients and normal individuals, for the variables age and gender. The values of center point thickness found for men were greater than those for women, showing the influence of gender on that thickness. As many as 83.33% of the diabetic patients with clinically significant macular edema presented moderate non-proliferative diabetic retinopathy (NPDR), 10% presented mild NPDR and 6.66% severe non-proliferative diabetic retinopathy. Patients under combined treatment of insulin and oral hypoglycemiant presented influence on the results of center point thickness (through OCT) and visual acuity. The mean duration of diabetes was 9.63 years. Values of center point thickness were always found greater for patients than those for normal eyes. Levels of hemoglobin A1c did not have influence on the center point thickness data, whereas values of visual acuity were significantly correlated with it. This study presents the optical coherence tomography applicability in the detection and semiologic evaluation of diabetic macular edema in patients with visual acuity 20/40 or greater, during one year, showing the retinal thickening in the early stages of diabetic retinopathy. Further, it evidenced the correlation between the increase in foveal thickness and the reduction in visual acuity. Levels of hemoglobin A1c did not influence the center point thickness data. An early detection of clinically significant macular edema leads us to a redefinition of the real meaning of incipient retinopathy and can prevent further significant reduction of vision.


Longitudinally Measured Fibrinolysis Factors are Strong Predictors of Clinical Outcome in Patients with Chronic Heart Failure: The Bio-SHiFT Study.
This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). A median of 9 (interquartile range [IQR] 5-10) serial, tri-monthly blood samples per patient were prospectively collected in 263 CHF patients during a median follow-up of 2.2 (IQR 1.4-2.5) years. Seventy patients (cases) reached the composite endpoint of cardiac death, heart failure hospitalization, left ventricular assist device, or heart transplantation. From all longitudinal samples, we selected baseline samples in all patients and the last two samples before the event in cases or the last sample available in event-free patients. Herein, we measured plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and soluble urokinase plasminogen activator surface receptor (suPAR). Associations between temporal biomarker patterns during follow-up and the cardiac event were investigated using a joint model. Cases were on average older and showed higher New York Heart Association class than those who remained event-free. They also had lower blood pressures, and were more likely to have diabetes, renal failure, and atrial fibrillation. Longitudinally measured PAI-1, uPA, and suPAR were independently associated with adverse cardiac events after correction for clinical characteristics (hazard ratio [95% confidence interval]) per standard deviation increase of 2.09 (1.28-3.45) for PAI-1, 1.91 (1.18-3.24) for uPA, and 3.96 (2.48-6.63) for suPAR. Serial measurements of tPA were not significantly associated with the event after correction for multiple testing. Longitudinally measured PAI-1, uPA, and suPAR are strongly associated with adverse cardiac events during the course of CHF. If future research confirms our results, these fibrinolytic factors may carry potential for improved, and personalized, heart failure surveillance and treatment monitoring.


Mobilizing Against Measles: Physicians Face the Worst National Outbreak in Decades.
Measles - a deadly disease the U.S. Centers for Disease Control and Prevention (CDC) declared eradicated in America in 2000 - has made an unwelcome return in 2019. The anti-vaccine movement is weakening Texas' ability to withstand outbreaks, but there are still many things physicians can do to work with patients and communities to improve vaccination rates.


Development of a beta-lactamase reporter gene assay for metabotropic glutamate receptor 1 by using coexpression of glutamate transporter.
mGluR1 antagonists have been postulated to be novel CNS drugs, including antipsychotics. Toward this end, the authors developed a beta-lactamase reporter assay to identify mGluR1 antagonists. beta-Lactamase has several interesting features for high-throughput screening, including very high sensitivity and less well-to-well variation than other reporter enzymes. mGluR1-expressing Chinese hamster ovary (CHO) cells with the beta-lactamase gene under control of the nuclear factor of activated T cells (NFAT) promoter (CHO-NFAT-bla-hmGluR1b) exhibited very high basal activity, resulting in an inadequate signal-to-basal (S/B) ratio. Coexpression of glutamate/aspartate transporter (GLAST) with mGluR1 in the cell line (CHO-NFAT-bla-hmGluR1b-GLAST) dramatically decreased basal activity and improved the S/B ratio (from 2- to 20-fold). The contribution of GLAST to lowering basal activity and increasing the S/B ratio was validated by the expression level of GLAST mRNA and by a GLAST inhibitor. Antagonistic activities of known mGluR1 antagonists in the beta-lactamase reporter assay were comparable with those in the conventional Ca(2+) mobilization assay. The Z' factor of the beta-lactamase reporter assay was 0.89 under optimized conditions. Taken together, the beta-lactamase reporter assay with CHO-NFAT-bla-hmGluR1b-GLAST could be a novel high-throughput assay for mGluR1 antagonist screening. This is the first description of a successful beta-lactamase reporter assay among all mGluR subtypes.


Determination of aculeatisides based on immunoassay using a polyclonal antibody against aculeatiside A.
An enzyme-linked immunosorbent assay (ELISA) was developed for determination of aculeatisides. Aculeatiside A was conjugated with bovine serum albumin (BSA) for immunization. The ratio of hapten in an antigen conjugate was determined by matrix-assisted laser desorption/ionization TOF mass spectrometry. Polyclonal antibody was developed in rabbits against an aculeatiside A-BSA conjugate. The antibody was specific for aculeatiside A and aculeatiside B. The range of the immunoassay extended from 100 ng ml(-1) to 5 pg ml(-1) of aculeatisides. Good correlation between ELISA and HPLC methods was obtained when crude extracts of plant samples were analyzed. The optimized ELISA was found to be applicable to the determination of total aculeatisides in various plant samples.


Integrative Assessment of Reduced Listeria monocytogenes Susceptibility to Benzalkonium Chloride in Produce Processing Environments.
For decades, quaternary ammonium compounds (QAC)-based sanitizers have been broadly used in food processing environments to control foodborne pathogens such as Listeria monocytogenes. Still, there is a lack of consensus on the likelihood and implication of reduced Listeria susceptibility to benzalkonium chloride (BC) that may emerge due to sublethal exposure to the sanitizers in food processing environments. With a focus on fresh produce processing, we attempted to fill multiple data and evidence gaps surrounding the debate. We determined a strong correlation between tolerance phenotypes and known genetic determinants of BC tolerance with an extensive set of fresh produce isolates. We assessed BC selection on L. monocytogenes through a large-scale and source-structured genomic survey of 25,083 publicly available L. monocytogenes genomes from diverse sources in the United States. With the consideration of processing environment constraints, we monitored the temporal onset and duration of adaptive BC tolerance in both tolerant and sensitive isolates. Finally, we examined residual BC concentrations throughout a fresh produce processing facility at different time points during daily operation. While genomic evidence supports elevated BC selection and the recommendation for sanitizer rotation in the general context of food processing environments, it also suggests a marked variation in the occurrence and potential impact of the selection among different commodities and sectors. For the processing of fresh fruits and vegetables, we conclude that properly sanitized and cleaned facilities are less affected by BC selection and unlikely to provide conditions that are conducive for the emergence of adaptive BC tolerance in L. monocytogenes. IMPORTANCE Our study demonstrates an integrative approach to improve food safety assessment and control strategies in food processing environments through the collective leveraging of genomic surveys, laboratory assays, and processing facility sampling. In the example of assessing reduced Listeria susceptibility to a widely used sanitizer, this approach yielded multifaceted evidence that incorporates population genetic signals, experimental findings, and real-world constraints to help address a lasting debate of policy and practical importance.


Gpn2 and Rba50 Directly Participate in the Assembly of the Rpb3 Subcomplex in the Biogenesis of RNA Polymerase II.
RNA polymerase II (RNAPII) is one of the central enzymes in cell growth and organizational development. It is a large macromolecular complex consisting of 12 subunits. Relative to the clear definition of RNAPII structure and biological function, the molecular mechanism of how RNAPII is assembled is poorly understood, and thus the key assembly factors acting for the assembly of RNAPII remain elusive. In this study, we identified two factors, Gpn2 and Rba50, that directly participate in the assembly of RNAPII. Gpn2 and Rba50 were demonstrated to interact with Rpb12 and Rpb3, respectively. An interaction between Gpn2 and Rba50 was also demonstrated. When Gpn2 and Rba50 are functionally defective, the assembly of the Rpb3 subcomplex is disrupted, leading to defects in the assembly of RNAPII. Based on these results, we conclude that Gpn2 and Rba50 directly participate in the assembly of the Rpb3 subcomplex and subsequently the biogenesis of RNAPII.


Effects of Iranian Economic Reforms on Equity in Social and Healthcare Financing: A Segmented Regression Analysis.
One of the main objectives of the Targeted Subsidies Law (TSL) in Iran was to improve equity in healthcare financing. This study aimed at measuring the effects of the TSL, which was implemented in Iran in 2010, on equity in healthcare financing. Segmented regression analysis was applied to assess the effects of TSL implementation on the Gini and Kakwani indices of outcome variables in Iranian households. Data for the years 1977-2014 were retrieved from formal databases. Changes in the levels and trends of the outcome variables before and after TSL implementation were assessed using Stata version 13. In the 33 years before the implementation of the TSL, the Gini index decreased from 0.401 to 0.381. The Gini index and its intercept significantly decreased to 0.362 (p<0.001) 5 years after the implementation of the TSL. There was no statistically significant change in the gross domestic product or inflation rate after TSL implementation. The Kakwani index significantly increased from -0.020 to 0.007 (p<0.001) before the implementation of the TSL, while we observed no statistically significant change (p=0.81) in the Kakwani index after TSL implementation. The TSL reform, which was introduced as part of an economic development plan in Iran in 2010, led to a significant reduction in households' income inequality. However, the TSL did not significantly affect equity in healthcare financing. Hence, while measuring the long-term impact of TSL is paramount, healthcare decision-makers need to consider the efficacy of the TSL in order to develop plans for achieving the desired equity in healthcare financing.


Electromagnetic field (EMF) effects on channel activity of nanopore OmpF protein.
In this study, the effects of nonionizing electromagnetic fields (EMF; 925 MHz) on the OmpF porin channel have been characterized at the single-channel level. Channel activity was recorded in real time by the voltage clamp method. Our results showed an increase in the frequency of channel gating and voltage sensitivity. The effects of EMF lasted for several milliseconds after the field source was terminated. However, the conductance levels of channels did not change significantly. Thermal effects of EMF on single-channel properties are a possible cause, based on theoretical evaluation of results that were comparable to those seen in conventional experiments at different temperatures. We conclude that EMF affects both the dynamics and conformation of the channel, either directly by affecting critical amino acid side-chain arrangement, or indirectly, via the electrolyte or the lipid membrane.


Predictive value of a short dietary questionnaire for changes in serum lipids in high-risk Utah families.
Dietary questionnaires and serum cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol determinations were completed for 1239 subjects aged greater than or equal to 20 at each of two separate screenings. The mean time between screenings was 2.5 y. After correcting for potential confounding variables, reduction of a measure of dietary cholesterol and saturated fatty acids assessed by two simple questions was a significant independent predictor of reduction in total cholesterol in serum (p less than 0.005). Initial body mass index (BMI) and change in BMI were highly significant predictors of initial values and changes in total cholesterol, triglycerides, and HDL cholesterol in serum. Reduction of dietary saturated fatty acid and cholesterol was significantly correlated with initial serum cholesterol levels, which suggest that serum cholesterol screening may be an important motivating factor for dietary change. Important public health and research implications of these findings are discussed.


[Calcifying epithelioma in the neck: report of one case].
Calcifying epithelioma is one kind of benign tumour,which rarely happens in the neck. The clinical diagnosis of calcifying epithelioma is difficult and misdiagnosis is common. This paper reported one case of calcifying epithelioma in the neck, and discussed its clinical features and therapy based on literature review.


Disposition of salicylic acid in analbuminemic rats.
To clarify the role of albumin in the dispositions of drugs by in vivo experiment, analbuminemic rats were used and plasma-level analyses and whole-body autoradiography following intravenous administration of 14C-salicylic acid were carried out. The distribution volume of salicylic acid in analbuminemic rats (650 +/- 33 ml/kg) was remarkably larger than that in normal rats (180 +/- 3 ml/kg) (p less than 0.01). Whole-body autoradiograms demonstrated that transfer of salicylic acid from the blood to the liver, muscle and brain, especially to the liver, may be increased in analbuminemic rats. The increased distribution may be explained by the lack of plasma albumin, since the distribution of salicylic acid depends in part on plasma albumin binding. The total body clearance of salicylic acid in analbuminemic rats (12.2 +/- 1.4 ml/min/kg) was about 3.2 times that in normal rats (3.8 +/- 0.1 ml/min/kg) (p less than 0.01), suggesting that metabolic clearance and/or renal clearance is enhanced in analbuminemic rats. Increased extraction by the liver and/or the kidney due to increased free fraction in total (bound and unbound) plasma salicylic acid assumed to be responsible for this result.


Genome editing in human hematopoietic stem and progenitor cells via CRISPR-Cas9-mediated homology-independent targeted integration.
Ex vivo gene correction of hematopoietic stem and progenitor cells (HSPCs) has emerged as a promising therapeutic approach for treatment of inherited human blood disorders. Use of engineered nucleases to target therapeutic transgenes to their endogenous genetic loci addresses many of the limitations associated with viral vector-based gene replacement strategies, such as insertional mutagenesis, variable gene dosage, and ectopic expression. Common methods of nuclease-mediated site-specific integration utilize the homology-directed repair (HDR) pathway. However, these approaches are inefficient in HSPCs, where non-homologous end joining (NHEJ) is the primary DNA repair mechanism. Recently, a novel NHEJ-based approach to CRISPR-Cas9-mediated transgene knockin, known as homology-independent targeted integration (HITI), has demonstrated improved site-specific integration frequencies in non-dividing cells. Here we utilize a HITI-based approach to achieve robust site-specific transgene integration in human mobilized peripheral blood CD34+ HSPCs. As proof of concept, a reporter gene was targeted to a clinically relevant genetic locus using a recombinant adeno-associated virus serotype 6 vector and single guide RNA/Cas9 ribonucleoprotein complexes. We demonstrate high levels of stable HITI-mediated genome editing (∼21%) in repopulating HSPCs after transplantation into immunodeficient mice. Our study demonstrates that HITI-mediated genome editing provides an effective alternative to HDR-based transgene integration in CD34+ HSPCs.


Evaluating models for polycaprolactone crystallization via simultaneous rheology and Raman spectroscopy.
The crystallization of a polymer melt is characterized by dramatic structural and mechanical changes that significantly impact the processing conditions used to generate industrially-relevant products. Relationships between crystallinity and rheology are necessary to simulate and monitor the effect of processing conditions on the properties of the final product. However, separate measurements of crystallinity and rheology are difficult to correlate due to differences in sample history, geometry, and temperature. Recently, we have developed a rheo-Raman microscope for simultaneous rheology, Raman spectroscopy, and polarized reflection-mode optical measurements of soft materials, which allows for quantitative crystallinity measurements through features in the Raman spectrum. In this work, we apply this technique to monitor the isothermal crystallization of polycaprolactone to probe the relationship between structure, crystallinity, and rheology. Both crystallinity and the shear modulus vary over comparable timescales, but the birefringence increases much earlier in the crystallization process. We directly plot rheological parameters as a function of crystallinity to probe a range of suspension-based and empirical models relating the complex modulus to crystallinity, and we find that the previously developed models cannot describe the crystallinity-modulus relationship over the crystallization process. By developing a suspension-based model we can fit the complex modulus over the crystallization range. The crystallization process is characterized by a critical percolation fraction and a single scaling exponent.


Achieving weight loss and avoiding obesity.
The effect of the vast variety of nutrients on metabolic outcome and health is complex. A large number of factors play a role in the type and quantity of food consumed in free-living conditions. It is therefore obvious that prescribing a restrictive diet regimen that favours 1 or 2 nutrients at the expense of the others is a poor tool to manage long-term health and weight.


Synthesis and Aggregation Behavior of Chiral Naphthoquinoline Petroporphyrin Asphaltene Model Compounds.
The synthesis of structurally relevant compounds that model the chemical behavior and supramolecular aggregation of the asphaltenes, the most polar and metal-rich fraction of heavy petroleum, has been extended to include fusions of important petroleum biomarkers. The synthetic protocol features a multicomponent reaction to form a dyad composed of a fused steroidal naphthoquinoline, followed by a pyrrole cyclocondensation reaction to incorporate the dyad into a chiral triad containing a NiII -porphyrin substituent. This synthetic protocol has been used to prepare large molecules that represent both "continental" and "archipelago" models of asphaltene composition. The steroid-naphthoquinoline-porphyrin triads have been studied by UV/Vis and circular dichroism (CD) spectroscopies, and the results suggest that the naphthoquinoline core, a tetrahydro[4]helicene, adopts a helical conformation, producing a CD signal electronically related to the characteristic Soret absorption band of the porphyrin subunit. Finally, supramolecular aspects of asphaltene aggregation have been examined on a molecular level through analysis of axial coordination of pyridine to the Ni-porphyrin. The relative affinity of pyridine for binding to the Ni center of the porphyrin is evaluated by comparing binding propensities in a series of sterically differentiated substituted porphyrins.