Multi-residue pesticide analysis in fruits and vegetables by liquid chromatography-time-of-flight mass spectrometry.
In this work, a new multi-residue methodology using liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS) for the quantitative (routine) analysis of 15 pesticide residues has been developed. The analytical performance of the method was evaluated for different types of fruit and vegetables: pepper, broccoli, tomato, orange, lemon, apple and melon. The accurate mass measurements were compared in different matrices at significantly different concentration levels (from 0.01 to 0.5 mg/kg) obtaining accuracy errors lower than 2 ppm, which is well within the accepted limits for elemental confirmation. Linearity of response over two orders of magnitude was demonstrated (r > 0.99). Matrix effects resulting in suppression or enhancement of the response were frequently observed, most notably in broccoli and citrus. Instrumental limits of detection (LOD) were between 0.0005 and 0.03 mg/kg depending on the commodity and pesticide studied, all being within European Union regulations for food monitoring program. Finally, the methodology was applied to the analysis of two samples from an inter-laboratory exercise. The high degree of confirmation for target pesticides by accurate mass measurements demonstrated the applicability of the method in routine analysis. This study is a valuable indicator of the potential of LC-TOF-MS for quantitative multi-residue analysis of pesticides in vegetables and fruits.


Urinary metabolic fingerprinting for amiodarone-induced phospholipidosis in rats using FT-ICR MS.
In the research and development for new therapeutic compounds, there has been a focus on detecting the changes of metabolites induced by drug administration and finding surrogate markers to assess its toxicity. We examined the suitability of urinary metabolic fingerprinting using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) for toxicological assessment in the amiodarone (AMD)-induced phospholipidosis (PLD) rat model. There were more than 400 different ion peaks detected in the negative ion mode analysis with FT-ICR MS. About 20% of the detected ions were altered more than 1.5 fold by AMD-treatment. On the scores plot of principal component analysis (PCA), the ion profiles of the treated were separated time-dependently. The loading plot revealed that the metabolites causing PCA results were m/z 178.05101, 191.01979, 192.06676, 212.00239, 258.9944 and 283.0820. The ion at m/z 178.05101 is considered to be hippurate (HA), 192.06676 is phenylacetylglycine (PAG) and 212.00239 is indican (IDN). These results indicate that PAG, IDN and HA are biomarkers for AMD-induced PLD in urinary metabolic fingerprinting using FT-ICR MS. These markers may be useful for evaluation of chemicals, which have the potential to induce PLD.


Exam cheating and academic integrity breaches during the COVID-19 pandemic: An analysis of internet search activity in Spain.
Academic institutions worldwide have had to adapt their methods of teaching and assessment due to COVID-19. In many Spanish universities exams moved online, affording students with opportunities to breach academic integrity that were not previously available to them. This paper uses the emerging research method of search engine data analysis to investigate the extent of requests for exam cheating information in Spain in the time period surrounding adjustments for the pandemic. The Internet data analytics technique is one that the paper proposes should be used more widely as an academic integrity research method. For this study, search engine activity data on exam cheating in Spain was collected and analysed for the five-year period between 2016 and 2020 inclusive. The data suggests that students are searching for information about ways to cheat in exams, including how to create cheat sheets. Most strikingly, the results show a significant increase in requests for information on cheating on online exams during the COVID-19 timeframe and the Spanish lockdown period. Based on the findings, academic institutions in other regions should be wary about the opportunities that their students have to commit exam fraud.


Influence of dietary carrot on cytostatic drug activity of cyclophosphamide and its main directly acting metabolite: induction of sister-chromatid exchanges in normal human lymphocytes, Chinese hamster ovary cells, and their DNA repair-deficient cell lines.
We have utilized an in vivo drug metabolism technique (i.e. injecting the chemical into rat and isolating plasma with metabolites from blood) for detecting the genotoxicity of indirectly acting cyclophosphamide and its directly acting metabolite phosphoramide mustard in cultures of human peripheral blood lymphocytes of normal individuals, Fanconi's anaemia (FA) and aplastic anaemia (AA) patients, wild-type Chinese hamster ovary cells (CHO) and its DNA repair-deficient mutant 43-3B cells. In addition, the influence of dietary carrot on the clastogenic activity of these 2 chemicals in all the different cell types was studied. The genotoxicity was assessed by the ability of the metabolites of these agents to induce sister-chromatid exchanges in the treated cells. A dose-dependent increase in the frequencies of sister-chromatid exchanges was observed in all cell strains following treatment with activated metabolites of cyclophosphamide or phosphoramide mustard. The sensitivity of lymphocytes from normal donors, FA and AA patients to these 2 chemicals was similar. In CHO cell lines the induced frequency of sister-chromatid exchanges was slightly higher after treatment with the metabolites of cyclophosphamide than with phosphoramide mustard. The mutant 43-3B cells responded with higher frequencies of SCEs when compared to the wild-type CHO cells, about 1.5-2-fold, at low doses. Pretreating of rats with fresh carrot juice effectively inhibited the increase in the frequencies of sister-chromatid exchanges induced by cyclophosphamide in wild-type and mutant CHO cells (P less than 0.01), and to a lesser extent in human lymphocytes (p less than 0.05). In contrast, no inhibitory effect was observed in any of these cell types in combination of dietary carrot for direct acting phosphoramide mustard on the frequency of induced sister-chromatid exchanges. The possibility that dietary carrot exerts its antimutagenic effect by affecting the processes of enzymatic activation of cyclophosphamide is discussed.


Evaluation of the monoclonal stool antigen test for Helicobacter pylori in an Asian population with dyspepsia.
Although well established in the West, stool antigen tests (SAT) are not widely used in Asia. Data on the accuracy of this test in Asia is sparse and, to date, there have been no studies looking at the more refined monoclonal SAT. The aim of this study is to validate the diagnostic accuracy of a stool antigen test, Hp STAR, for the detection of Helicobacter pylori. Consecutive new patients with dyspepsia, referred to the endoscopy unit were recruited. At endoscopy, biopsies were taken for rapid urease tests and histology. Stool specimens were collected before any therapy was given and were tested for H. pylori using the monoclonal SAT HpSTAR test. Samples were collected from 90 patients. The stool antigen results were compared with the results of rapid urease tests and histopathology, which were used together as the gold standard test in the diagnosis of H. pylori. Of the 90 patients tested, 45 were H. pylori positive and 45 were H. pylori negative. There was one false positive and one false negative test. The sensitivity, specificity, positive predictive value and negative predictive value for the Hp STAR were identical: 97.8% with a 95% confidence interval of 88.2-99.9%. The diagnostic accuracy was 97.8% with a 95% confidence interval of 92.2-99.7%. The monoclonal stool antigen test, HpSTAR is a highly accurate test for the diagnosis of H. pylori.


Topographic pattern of the rearrangement of the dystrophin gene in Japanese Duchenne muscular dystrophy.
To compare the frequency and distribution of rearrangements in the dystrophin gene in Duchenne muscular dystrophy (DMD) between Japanese DMD patients and those in North America and Europe, Southern blot analyses of the dystrophin gene were carried out in 88 probands classified as DMD. Gene rearrangements were found in 61 (69%) subjects, and they were composed of partial gene deletions in 53 (60%) probands and partial duplications in 7 (8%) probands. A total deletion of the gene was found in 1 (1%) patient. Among 53 patients with deletions, 34 (64%) had breakpoints between introns 44 and 52 and 7 (13%) had breakpoints between introns 2 and 11. Both the frequency and the distribution of gene rearrangements found in this study were similar to those reported in North America and Europe. These data suggest that there are no ethnic or racial differences in the frequency and distribution of rearrangements thought to be caused by similar mechanisms in the dystrophin gene in all human racial groupings.


Prognostic factors of endoscopic treatment of vesicoureteral reflux in spinal cord injured patients.
Vesicoureteral reflux (VUR) is an important complication in patients with spinal cord injury due to its frequency and morbidity. One of the most extended therapeutic options is endoscopic injection of obliteration substances in the urethral meatus. To analyze the prognostic factors of VUR treatment using obliterative substances in patients with spinal cord injury. A prospective study was performed in a cohort of 76 patients (age 48.9±14.4 years), of both genders, with spinal cord injuries, who underwent endoscopic treatment of the VUR during the years 2008 to 2011. In all the patients, a clinical history was obtained and a pre-operative videourodynamic study was performed. Another study was carried out at 7.32 months (standard deviation: 6.28 months) of the intervention. Treatment consisted in endoscopic injection of dextranomer/hyaluronic acid copolymer (62 cases) and polydimethylsiloxane (14). The statistical tests applied were the Fisher's exact test and the Student's T test comparing the means. Bilateral significance level was established at 95%. Resolution of VUR was achieved in 46 cases (61%). The statistically significant prognostic factors were age (younger aging cured patients), bilaterality and reflects great (greater grade in bilaterality in the cases with persistence of reflux) and presence of neurogenic detrusor overactivity (greater percentage in the cases of reflux persistence). Stress urinary incontinence (greater percentage in cured patients), contractile potency (lower percentage in cured patients) and urethral resistance (greater percentage in cured patients) were also statistically significant prognostic factors. Among the prognostic factors that affected the endoscopic treatment results of the VUR in patients with neurogenic lower urinary tract dysfunction (NLUTD), anatomical as well as functional factors were found.


Developmental toxicity in Daphnia magna induced by environmentally relevant concentrations of carbon black: From the perspective of metabolomics and symbiotic bacteria composition.
The level of carbon black (CB) pollution in the environment is rapidly increasing, owing to the increase in natural and industrial emissions. The water environment has become an important sink for CB. However, studies on CB mainly focused on its impact on air pollution and phytoremediation applications, and the toxicity mechanism of CB in aquatic organisms is relatively limited. Thus, Daphnia magna was used as a model organism to explore the developmental toxicity of environmentally relevant concentrations of CB under a full life-cycle exposure. The toxicity mechanism of CB in aquatic organisms was investigated based on metabolomic and symbiotic microbial analyses. It was found that compared with the control group, the body length of exposed D. magna decreased, while the mortality and intestinal inflammation increased with increasing concentration of CB. The normal reproductive regularity of D. magna was disturbed, and the deformity and body length of the offspring increased and decreased, respectively, after CB exposure. Metabolomic analysis showed that the urea cycle metabolic pathway of exposed D. magna was increased significantly, suggesting a perturbation of N metabolism. In addition, two eicosanoids were increased, suggesting possible inflammation in D. magna. The levels of seven phospholipid metabolites decreased that might be responsible for offspring malformations. Microbiological analysis showed that the composition of the symbiotic microbial community of D. magna was disturbed, including microorganisms involved in carbon cycling, nitrogen cycling, and biodegradation of pollutants, as well as pathogenic microorganisms. Overall, this study found that the inflammatory related metabolites and symbiotic bacterial, as well as reproductive related metabolites, were disrupted after D. magna exposed to different concentrations of CB, which revealed a possible developmental toxicity mechanism of CB in D. magna. These findings provide a scientific basis for analyzing the risks of CB in aquatic environments.


Early participation in an HIV cohort study slows disease progression and improves survival. The Swiss HIV Cohort Study.
Different levels of experience of physicians caring for patients with HIV infection have been found to be associated with differences in survival amongst their patients. We examined whether early participation in the Swiss HIV Cohort Study (SHCS), an ongoing prospective study with regular follow-up visits at specialized clinics, improved survival of HIV-infected patients. We studied 3553 HIV-infected individuals who joined the Swiss HIV Cohort Study (SHCS) with different levels of immunosuppression: mild (CD4 count above 500 x 106 cells L-1; n x 2038); severe (100-199 cells; n = 960); and very severe (50-99 cells; n = 555). Characteristics at different CD4 cell levels were compared and Cox proportional hazards regression was used to examine the mortality experience during a total of 16 201 person-years of follow-up. Participants joining the cohort early with mild immunodeficiency were younger, more likely to be female, and more likely to have a history of intravenous drug use. At CD4 cell counts below 200 x 106 cells L-1, they were less likely to have a history of Pneumocystis carinii pneumonia or AIDS, more likely to be on prophylaxis against P. carinii and more likely to be on antiretroviral therapy than those joining with severe or very severe immunodeficiency. For example, at the time of the first CD4 cell count in the range of 50-99 x 106 cells L-1, 8.9, 15.0 and 21.6% of participants who joined with mild, severe and very severe immunodeficiency had suffered an episode of P. carinii pneumonia. In Cox models adjusted for CD4 cell count at entry and other relevant baseline differences, mortality was increased amongst participants who joined with severe and very severe immunodeficiency. Hazard ratios (95% confidence intervals (CI)) were 1.71 (1.21-2.42) for participants with severe immunodeficiency at entry and 2.61 (1.70-4. 01) for those with very severe immunodeficiency, compared with 1.0 for those with mild immunodeficiency at entry. Individuals who were seen regularly at specialized HIV units from early stages of the infection onwards were, at comparable levels of immunodeficiency, less likely to progress to AIDS, and mortality during subsequent follow-up was reduced. This is likely to be explained by better access to prophylactic regimens and antiretroviral therapy.


Probe-based confocal laser microscopy identifies criteria predictive of active celiac sprue.
Celiac sprue is an underdiagnosed chronic intestinal inflammatory disease. Probe-based confocal laser microscopy (CLM) is a novel endoscopic technique for in vivo inspection of the intestinal mucosa that has not been evaluated in celiac sprue yet. To develop CLM criteria most predictive of celiac pathology in a prospective pilot study. Twenty-one patients (male n = 5, f = 16, mean age 52 years) with established or suspected celiac sprue, seven of whom had confirmed active disease (Marsh III) and 14 duodenal normal mucosa. CLM images from 91 duodenal sites were assessed. CLM recordings were obtained next to Argon beamer labeled areas. Biopsies were taken from the same spots for precise histological matching. After establishing histology-correlated criteria on one sample per patient, the remaining CLM recordings from the same patients were randomized and blindly evaluated. Villous atrophy and irregular appearing villi were most predictive of celiac pathology. Although the presence of crypts was diagnostic for celiac pathology, it was only recognized in 26.7% of celiac pathology sites. Using these criteria in the blinded assessment, the overall endoscopist's prediction of celiac sprue was accurate in 89.8% of all biopsy sites in 85.7% of all patients. Preliminary interobserver agreement testing villous atrophy, irregular villi, and crypts was poor (kappa 0.05 to 0.26). Probe-based CLM criteria developed in this pilot trial appear promising for the detection of active celiac sprue. Preliminary interobserver variability was high, indicating a learning curve effect. Our criteria need validation in an independent patient population.


Prediction of Preterm Delivery by Late Cervical Length Measurement after 24 Weeks.
To examine the value of the cervical length (CL) measurement at 24-30 gestational weeks in the prediction of spontaneous preterm delivery (SPD) between 30 and 34 weeks (SPD34) and between 34 and 37 weeks (SPD37). We performed a prospective cross-sectional study. CL was measured once by transvaginal ultrasound examination between 24 and 30 weeks. The study sample consisted of 1,180 low-risk singleton pregnancies. 10 women (0.85%) had a SPD34 and 60 (5.08%) had a SPD37. CL was shorter (p < 0.001) in the women who had a SPD34 (median 11 mm) compared to the women who delivered after 34 weeks (median 31 mm). CL was shorter (p < 0.001) in the women who had a SPD37 (median 22 mm) compared to the women who delivered after 37 weeks (median 31 mm). CL predicted SPD34 (OR = 0.837, R² = 0.2768, AUC = 0.9406, p < 0.001) and SPD37 (OR = 0.907, R² = 0.1085, AUC = 0.7584, p < 0.001). The model achieved a sensitivity of 70.0 and 38.3% for 10% false-positive rate for SPD34 and SPD37, respectively. CL after 24 weeks is significantly shorter in women destined to have a SPD. In low-risk singleton pregnancies CL performs very well in predicting SPD34 and adequately in predicting SPD37.


Following protein-glycosaminoglycan polysaccharide interactions with differential scanning fluorimetry.
Studies of the structural changes invoked in proteins by the binding of the glycosaminoglycan (GAG) polysaccharide portion of proteoglycans are of increasing importance to research in a wide range of fields, from biochemistry and molecular biology to biotechnology and medicine. One important aspect is the degree of stabilisation or destabilisation induced in a protein by the binding of these anionic materials, and this can affect enzyme activity, the stability of complexes, folding and the formation of aggregates, including those in neurodegenerative processes. A simple method, able to determine the effect of interactions with GAG polysaccharides on protein stability is described, based on the propensity of a fluorescent dye-Sypro™ Orange-to present differentiable fluorescence emission spectra following contact with exposed core amino acid residues. The method requires only commonly available and inexpensive equipment and is suitable for a multi-well format, allowing multiple readings to be made simultaneously.


Superior compliance with a neuromuscular training programme is associated with fewer ACL injuries and fewer acute knee injuries in female adolescent football players: secondary analysis of an RCT.
Little is known about the influence of compliance with neuromuscular training (NMT) on the knee injury rate in football. To evaluate team and player compliance with an NMT programme in adolescent female football and to study the association between compliance and acute knee injury rates. Prospective cohort study based on a cluster randomised controlled trial on players aged 12-17 years with 184 intervention teams (2471 players) and 157 control teams (2085 players). Exposure and acute time loss knee injuries were recorded. Team and player compliance was recorded by the coaches on a player attendance form. The intervention group was divided into tertiles of compliance. Injury rates were compared by calculating rate ratios (RRs) and 95% CIs using exact Poisson tests with the low-compliance tertile as reference. Seasonal compliance trends were analysed using linear regression. Players in the high-compliance tertile had an 88% reduction in the anterior cruciate ligament (ACL) injury rate (RR 0.12, 95% CI 0.01 to 0.85), whereas the rate in the control group players was not significantly different from those in the low-compliance tertile (RR 0.77, 95% CI 0.27 to 2.21). A significant deterioration occurred in team (b=-3.0% per month, 95% CI -5.2 to -0.8) and player (b=-5.0% per month, 95% CI -7.1 to -2.9) compliance over the season. Players with high compliance with the NMT programme had significantly reduced ACL injury rate compared with players with low compliance. Significant deterioration in team and player compliance occurred over the season.


The V-shaped subscapularis tenotomy for anatomic total shoulder arthroplasty.
Management of the subscapularis tendon during anatomic total shoulder arthroplasty (TSA) remains controversial. In our unit, subscapularis tenotomy is the preferred technique; however, the potential for tendon gapping and failure is recognised. The purpose of this study is to describe and provide early clinical results of a novel, laterally based V-shaped tenotomy (VT) technique hypothesised to provide greater initial repair strength and resistance to gapping than a transverse tenotomy (TT), with both clinically and radiologically satisfactory post-operative tendon healing and function. A retrospective study of patients who underwent primary TSA with VT over a three year period was performed using shoulder and subscapularis-specific outcome scores, radiographs, and ultrasound. A separate cohort of patients who underwent TSA using a subscapularis sparing approach was also reviewed to provide comparative clinical outcomes of a group with TSA and an un-violated subscapularis. Eighteen patients were reviewed at mean 30.4 months (± 11.7). Constant (78.2 ± 12.3), UCLA (8.4 ± 1.5), pain VAS (2.3 ± 2.8), and strength in internal rotation were no different from the comparison group. Likewise, neither were the clinical outcomes of range-of-motion, belly-press, lift-off, and shirt-tuck tests. One patient (5.5%) was found to have a failed subscapularis repair on ultrasound. VT during TSA appears to provide healing rates at least equal to those reported for TT, and not dissimilar from those of lesser tuberosity osteotomy. Clinical outcomes are comparable to reported results in the literature for alternative techniques, and not different from those observed here in a comparison cohort with TSA performed without violating the subscapularis tendon. VT therefore potentially offers a more effective and secure tendon repair than a traditional TT, with at least comparable clinical outcomes.


Winter is coming: Regulation of cellular metabolism by enzyme polymerization in dormancy and disease.
Metabolism feeds growth. Accordingly, metabolism is regulated by nutrient-sensing pathways that converge growth promoting signals into biosynthesis by regulating the activity of metabolic enzymes. When the environment does not support growth, organisms invest in survival. For cells, this entails transitioning into a dormant, quiescent state (G0). In dormancy, the activity of biosynthetic pathways is dampened, and catabolic metabolism and stress tolerance pathways are activated. Recent work in yeast has demonstrated that dormancy is associated with alterations in the physicochemical properties of the cytoplasm, including changes in pH, viscosity and macromolecular crowding. Accompanying these changes, numerous metabolic enzymes transition from soluble to polymerized assemblies. These large-scale self-assemblies are dynamic and depolymerize when cells resume growth. Here we review how enzyme polymerization enables metabolic plasticity by tuning carbohydrate, nucleic acid, amino acid and lipid metabolic pathways, with particular focus on its potential adaptive value in cellular dormancy.


Effects of resistance training on body composition and physical function in elderly patients with osteosarcopenic obesity: a systematic review and meta-analysis.
Osteosarcopenic obesity (OSO) is a complex disease commonly seen in the elderly. We found that resistance training may improve bone mineral density, skeletal muscle mass, and body fat percentage in patients with OSO. Therefore, resistance training is beneficial for elderly OSO patients and is worth being promoted. Investigate effects of resistance training on body composition and physical function in elderly osteosarcopenic obesity (OSO) patients. PubMed, Web of Science, Embase, Cochrane Library, Medline, SinoMed, CNKI, and Wanfang Database were searched from inception until October 13, 2021.Two independent researchers extracted the key information from each eligible study. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. The Cochrane Risk of Bias Tool was used to assess the risk of bias. Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the quality of the outcomes. Sensitivity analysis indicated the stability of the results. Statistical analysis was performed using Review Manager 5.3. Four randomized controlled studies meeting the inclusion criteria were included, with 182 participants. Twelve weeks of resistance training improved bone mineral density (BMD, mean difference (MD) = 0.01 g/cm2, 95% confidence interval (CI): 0.001, 0.02, P = 0.03, I2 = 0%), skeletal muscle mass (SMM, MD = 1.19 kg, 95% CI: 0.50, 1.89, P = 0.0007, I2 = 0%), Z score, timed chair rise test (TCR), and body fat percentage (BFP, MD = - 1.61%, 95% CI: - 2.94, - 0.28, P = 0.02, I2 = 50%) but did not significantly affect skeletal muscle mass index (SMI, MD = 0.20 kg/m2, 95% CI: - 0.25, 0.64, P = 0.38, I2 = 0%) or gait speed (GS). Resistance training is a safe and effective intervention that can improve many parameters, including BFP, SMM, and Z score, among OSO patients and is a good option for elderly individuals to improve their physical fitness.


Determination of aminopolycarboxylic acids in river water by solid-phase extraction on activated charcoal cartridges and gas chromatography with mass spectrometric detection. Method performance characteristics and estimation of the uncertainty.
A new sample preparation procedure to determine aminopolycarboxylic acids (ethylenediaminetetraacetic acid, EDTA, nitrilotriacetic acid, NTA, diethylenetriaminepentaacetic acid, DTPA, and cyclohexanediaminetetraacetic acid, CDTA) in river water is described. The procedure consists of the solid-phase extraction of the aminopolycaroxyllic acids on activated charcoal cartridges after increasing the ionic strength and acidifying the sample. The extract was eluted with methanol and the analytes were methylated in presence of BF3/methanol to determine them by GC with mass spectrometric detection. Recoveries were higher than 90% with good repeatabilities and inter-day precision for concentrations close to quantification limits (about 10 μg L(-1)) and higher. It has been verified that the proposed method is robust according to the Youden and Steiner test and free of matrix effects arisen from the presence of organic matter and iron(III) as deduced from statistical tests. A bottom-up approach was followed to estimate the uncertainty of the measured concentration. At concentrations close to 10 μg L(-1) the most relevant step of the method is the calculus of the interpolated concentration which has a high value of relative standard uncertainty.


Thoughts on Coronavirus Disease 2019 Based on JingFang Medicine (Classical Chinese Formula) Solutions for COVID-19.
This article aims to provide some thoughts on the prevention and treatment of Coronavirus Disease 2019 (COVID-19) from the perspective of JingFang Medicine (Classical Chinese Formula). It is believed that the vague theoretical understanding of COVID-19 in Traditional Chinese Medicine does not hinder the precise treatment of the disease by following the rule of "With this Zheng, prescribe this Fang." According to the principle of "Fang-Zheng Correlation" and the knowledge gained from the thousands of years of experience in treating febrile diseases, Xiao Chai Hu Decoction () and its modifications are recommended with the emphasis on individualized treatment. As another form of practicing "Fang-Zheng Correlation," generalized group treatment should also be paid attention to. Giving considerations to the historical medical data, Jing Fang Bai Du Powder () and Shi Shen Decoction () are recommended for group prevention treatment. Assisting the Zheng (Upright) Qi and using tonic formulas are two entirely different concepts. According to the principle of "Fang-Zheng Correlation," tonics abuse should be avoided in the prevention of COVID-19, and the using of Huang Qi ( Radix Astragali seu Hedysari) should also be very carefully done.


Glassy cell carcinoma of the cervix--a case report with review of the literature.
Glassy cell carcinoma of the uterine cervix is a rare neoplasm, first described by Gluksman and Cherry in 1956. It is a poorly differentiated adenosquamous carcinoma, comprising about 1-2% of all cervical cancers. We report a case of glassy cell carcinoma of the uterine cervix in 67-year-old female, nullipara, diagnosed two months after symptom onset, in IV-B stage of the disease according to the FIGO classification scale. Cervical smear test obtained three years previously was normal She was offered a palliative antihemorrhagic radiotherapy of the pelvis and palliative chemotherapy with paclitaxel-carboplatin combination. The patient died within six months of diagnosis. We present a case of a rare carcinoma of the uterine cervix with quick progression and poor outcome.


[Results of treatment of oral cavity mucosa cancer according to the data of the regional oncological clinic].
The results of treatment of 139 patients with mucosal cancer of oral cavity are summarized. The most effective method of treatment is combined one, including the operative intervention conduction. In 18 patients intraoperative cryoimpact on tumor was conducted, permitting to reduce the recidives frequency and to increase their life span.


Chloroquine in human milk.
Simultaneous milk and saliva samples were collected over a seven-day period from five lactating subjects after they had ingested two tablets of chloroquine sulfate (300 mg base). The samples were analyzed for chloroquine content by use of a combination of thin-layer chromatography and spectrophotometry. Regression analysis of two variables subject to error was used to determine the milk:saliva levels relationship. The Student's t test for paired data at .05 level of significance was used to evaluate the relationship between chloroquine levels in milk and saliva. The milk:saliva chloroquine concentrations ratio obtained by regression analysis was 0.89 +/- 0.08 (r = .93; P less than .05), and this compared favorably with the value of 0.99 +/- 0.07 obtained from the ratio of the AUC. There were no significant differences in the Tmax, Cmax, AUC, clearance, and elimination half-life values of chloroquine in milk and saliva (P greater than .05). Milk and saliva appear to be part of the central compartment. The amount of chloroquine estimated to be consumed by a nursling over a 24-hour period is about 0.55% of a 300-mg dose consumed by the mother. The data suggest that milk chloroquine levels can be estimated from saliva levels.


Plasma concentration following oral administration of di- and flucloxacillin in infants and children.
The bioavailability of commercial liquid preparations of di- and flucloxacillin was compared in infants and children. The plasma concentrations following a dose of 12.5 mg/kg were equal within the two age groups. Infants 0-1 months old, however, demonstrated a better absorption than older children.


Improving clinical communication of students with English as a second language (ESL) using online technology: a small scale evaluation study.
Increasingly, students with English as a second language (ESL) are enrolled in nursing degrees in English speaking countries (Wang et al., 2008). However, they may be at risk of clinical practice failure due to communication difficulties associated with unfamiliar linguistic and cultural factors (Guhde, 2003). This paper describes and evaluates an innovation to assist ESL nursing students at an Australian university develop their clinical communication skills and practice readiness by providing online learning resources, using podcast and vodcast technology, that blend with classroom activities and facilitate flexible and independent learning. The innovation builds on an intensive clinical language workshop program called 'Clinically Speaking' which has evolved through a cyclical process of ongoing research to produce resources in response to students' learning needs. Whilst uptake of the resources was modest, students of ESL as well as English speaking backgrounds (ESB) found the resources improved their clinical preparation and confidence by increasing their understanding of expectations, clinical language and communication skills. The innovation, developed with a modest budget, shows potential in developing ESL and ESB students' readiness for clinical communication, enabling them to engage in clinical practice to develop competency standards required of nursing graduates and registration authorities.


The performance of the leaf mining microlepidopteran Bucculatrix maritima (Stt.) on the salt marsh halophyte, Aster tripolium (L.), exposed to different salinity conditions.
The performance of phytophagous insects is influenced by the nutritional quality of the food plant, which may vary with environmental conditions. Hardly any information exists on food-plant mediated effects of variable soil salinity on the performance of phytophagous insects. Conspicuous differences in salinity levels, however, are found in soils of intertidal wetlands such as salt marshes and mangroves. The growth of larvae of Bucculatrix maritima, a leaf miner of the salt marsh halophyte Aster tripolium, was studied on the host plant along the salinity gradient of the Westerschelde estuary (S.W. Netherlands). In addition, its performance on A. tripolium grown on low or high salinity culture medium was investigated experimentally. Although salinity conditions significantly influenced the chemistry of the host plants, insect performance seemed almost unaffected, although near the mouth of the estuary high environmental salinities may have caused some inhibition of larval growth. The results contrast with our previous studies on the stem-borer Agapanthia villosoviridescens, which showed that growth and development was conspicuously influenced by the changing characteristics of Aster tripolium along the estuarine salinity gradient. The location-dependent qualities of halophytes in an estuary thus appear to have species-specific effects on insect performance. We hypothesize that this phenomenon contributes to the existence of non-identical distribution patterns of phytophagous insects associated with the same halophyte in an estuary.


Sodium dodecyl sulfate activation of a plant polyphenoloxidase. Effect of sodium dodecyl sulfate on enzymatic and physical characteristics of purified broad bean polyphenoloxidase.
Latent broad bean polyphenoloxidase was purified and shown to be activated by sodium dodecyl sulfate (SDS). Further characterization of the enzyme was carried out in the presence and absence of SDS. Activation of the enzyme increased in a sigmoidal manner with increasing SDS concentrations up to a maximum of 1.75 mM. The presence of SDS eliminated a low pH optimum induced by acid shocking. Increased thermolability of the enzyme was observed in the presence of SDS as well as an increased binding of [14C]dihydroxy-phenylalanine. Size exclusion chromatography on high performance liquid chromatography showed that the size and apparent molecular mass of the enzyme were slightly altered in the presence (48 kDa) versus absence (47 kDa) of SDS. Although the estimations were larger than those obtained by size exclusion techniques, no large differences in molecular weight were observed after sedimentation equilibrium of the enzyme in the presence (53.9 kDa) and absence (52.3 kDa) of SDS. Relative electrophoretic mobility and intrinsic fluorescence of tyrosine and tryptophan residues increased in a complex fashion as the SDS concentration was increased. Plateau regions in these latter experiments corresponded to concentrations of SDS needed for activation. The ability of SDS to activate the enzyme alters both its enzymatic and physical characteristics and suggests that a limited conformational change, due to binding of small amounts of SDS, may induce or initiate the activation of latent enzyme.


Permeability of abnormal blood-retinal barriers in rat phototoxic retinopathy: a clinicopathologic correlation study using fluorescent markers.
Phototoxic retinopathic rats were studied by vitreous fluorophotometry (VF) and histofluorescence microscopy using NaFl and FITC-Dextran molecules of selected molecular sizes as blood-retinal barrier permeability determinants. Retinopathic rats had significantly higher VF values than normal rats at a 35 mg/kg NaFl dosage; detectable levels were not obtained with 3.5 mg/kg NaFL nor with FITC-Dextrans. However, as demonstrated by histofluorescence microscopy, NaFl and FITC-Dex 3 molecules readily passed the abnormal BRB tissues to enter neural retina and vitreous space whereas FITC-Dex 20, 40, 70 and 150 molecules did not, except under certain circumstances. These studies indicate a barrier defect of both the retinal vessels and RPE is responsible for the in vivo demonstrated permeability abnormality.


Absence of an acute insulin response predicts onset of type 2 diabetes in a Caucasian population with impaired glucose tolerance.
In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population. The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population. The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged < 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests. The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60-12.67] for absence of first insulin peak, 1.58 (95% CI 0.60-4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65-4.88) for lowest vs. highest tertile of the disposition index. In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM.


Comparison of Clinical Outcomes Between Intracapsular Implantation and Intrascleral Fixation Using the Same Model of Intraocular Lens.
To compare the clinical outcomes of intrascleral intraocular lens (IOL) fixation surgery with those of intracapsular IOL implantation in conventional cataract surgery. Twenty-one eyes of 21 consecutive patients who underwent intrascleral IOL fixation (SF group) and 21 eyes of 21 patients who underwent IOL intracapsular implantation during cataract surgery (IN group) were retrospectively enrolled. For both groups, the same model of IOL was used in all cases. For all cases in the SF group, Yamane's double-needle technique was performed. The mean corrected visual acuity (logMAR) after surgery was significantly better in the IN than in the SF group (-0.063 ± 0.12 vs 0.05 ± 0.14; p = 0.0083). The mean anterior chamber depth after surgery was significantly smaller in the IN than in the SF group (4.65 ± 0.23 mm vs 4.98 ± 0.61 mm; p = 0.0231). The amounts of tilt and decentration were also significantly smaller in the IN group (5.21°± 1.47° and 0.22 ± 0.13 mm, respectively, vs 8.8° ± 3.9° and 0.52 ± 0.35 mm, respectively; p = 0.0003 and p = 0.0007). The mean absolute refractive prediction error was significantly smaller in the IN than in the SF group (0.22 ± 0.17 D vs 0.86 ± 0.59 D; p = 0.0002). The intrascleral IOL fixation surgery proved to be highly effective. However, its clinical outcomes were slightly inferior to those of IOL intracapsular implantation, and further improvement of this surgical technique may be needed.


Reliability of retrograde atrial activation patterns during ventricular pacing for localizing accessory pathways.
Definitive localization of accessory pathways is based on atrial activation patterns during orthodromic supraventricular tachycardia when retrograde conduction occurs exclusively through the accessory pathway. In some patients, supraventricular tachycardia cannot be induced or is deleterious. To determine whether accessory pathway sites can be identified accurately during ventricular pacing, retrograde atrial activation was assessed during orthodromic supraventricular tachycardia and ventricular pacing at multiple cycle lengths in 41 patients with a single accessory pathway. To obviate retrograde fusion due to concomitant conduction through the normal atrioventricular (AV) conduction system that may obscure the location of the accessory pathway, the difference in conduction time from the site of earliest atrial activation to the His bundle atrial electrogram (delta A-SVT) was measured during orthodromic supraventricular tachycardia and compared with values observed during ventricular pacing (delta A-VP). Characteristic values for the delta A-SVT interval were identified for left lateral (66 +/- 17 ms), left posterior (50 +/- 8 ms), posteroseptal (33 +/- 7 ms), right free wall (22 +/- 15 ms) and anteroseptal (0 +/- 0 ms) accessory pathway sites. During ventricular pacing, the site with the earliest atrial electrogram was used to define the accessory pathway location only if the maximal value of the delta A-VP interval over the range of cycle lengths assessed was comparable with the value of the delta A-SVT interval characteristic of that region. Values of the delta A-SVT interval correlated closely with the maximal values of the delta A-VP interval (r = 0.91). With this approach, 40 (98%) of 41 accessory pathway sites were identified correctly during ventricular pacing.(ABSTRACT TRUNCATED AT 250 WORDS)


Spatially guided functional correlation tensor: A new method to associate body mass index and white matter neuroimaging.
Obesity causes critical health problems including cardiovascular disease, diabetes, and stroke. Various neuroimaging methods including diffusion tensor imaging (DTI) are used to explore white matter (WM) alterations in obesity. The functional correlation tensor (FCT) is a method to simulate DTI in WM using resting-state functional magnetic resonance imaging (rs-fMRI). In this study, we enhanced the FCT with additional anatomical information from T1-weighted data in a regression framework. The goal was to 1) develop a spatially guided enhanced FCT (s-eFCT) and to 2) use it to identify imaging biomarkers for obesity. We computed fractional anisotropy (FA) and the mean diffusivity (MD) from the s-eFCT. The regional FA and MD values that can explain body mass index (BMI) well were chosen. The identified regional FA and MD values were used to predict BMI values. The correlation between real and predicted BMIs was 0.57. There was no significant correlation between real and predicted DTI using the MD. The BMI predicted using FA was used to classify participants into three obesity subgroups. The classification accuracy was 57.20%. In summary, we found potential imaging biomarkers of obesity based on the s-eFCT.


Adverse drug reactions and associated factors in multidrug-resistant tuberculosis: A retrospective review of patient medical records at Mbarara Regional Referral Hospital, Uganda.
The World Health Organization pragmatic guidelines recommend shorter duration drug regimens with newer, more efficacious agents for treatment of multidrug-resistant tuberculosis. However, adverse drug reactions associated with the use of newer, second-line agents may pose a major barrier to adequate management of multidrug-resistant tuberculosis. We therefore sought to investigate the prevalence and factors associated with adverse drug reactions among patients with multidrug-resistant tuberculosis. We retrospectively reviewed patient medical records at the tuberculosis treatment unit of Mbarara Regional Referral Hospital, between January 2013 and December 2020. Medical records were included in the study, if the patients were aged ⩾18 years, tested sputum positive for multidrug-resistant tuberculosis, with adequate pharmacovigilance data documented. We assessed all documented health-related patient complaints, deranged laboratory values, and clinician suspected adverse drug reactions for scientific/clinical plausibility. Adverse drug reactions were confirmed using published and manufacturer drug references materials. A multidisciplinary clinician team was involved to decide whether to exclude or include a suspected adverse drug reaction. About 6 in 10 (67.4%; 120/178) patients experienced at least one adverse drug reactions during treatment, of which 18.3%, 14.6%, and 11.4% of adverse drug reactions affected the endocrine/metabolic, otic, and musculoskeletal body systems, respectively. Majority of the adverse drug reactions were probable and had a moderate severity. There was an upward trend in adverse drug reaction incidence between 2015 and 2019. Adverse drug reaction occurrence was associated with previous adverse drug reaction history (adjusted odds ratio = 2.85 (1.08, 7.53 at 95% confidence interval)); however, patients who were underweight (adjusted odds ratio = 0.34 (0.16, 0.69 at 95% confidence interval)) and those treated with bedaquiline-based drug regimens (adjusted odds ratio = 0.2 (0.07, 0.59 at 95% confidence interval)) were less likely to experience an adverse drug reaction. Majority of patients with multidrug-resistant tuberculosis experience at least adverse drug reaction during the course of treatment. The newer standard shorter duration drug regimens (9-12 months) may be associated with intolerable adverse drug reactions that hamper effective management of multidrug-resistant tuberculosis. There is need for more studies to assess the clinical adverse drug reaction burden associated with the implementation of shorter duration regimens.


"This behavior strikes us as ideal": assessment and anticipations of Huisman (2022).
Huisman (Psychonomic Bulletin & Review, 1-10. 2022) argued that a valid measure of evidence should indicate more support in favor of a true alternative hypothesis when sample size is large than when it is small. Bayes factors may violate this pattern and hence Huisman concluded that Bayes factors are invalid as a measure of evidence. In this brief comment we call attention to the following: (1) Huisman's purported anomaly is in fact dictated by probability theory; (2) Huisman's anomaly has been discussed and explained in the statistical literature since 1939; the anomaly was also highlighted in the Psychonomic Bulletin & Review article by Rouder et al. (2009), who interpreted the anomaly as "ideal": an interpretation diametrically opposed to that of Huisman. We conclude that when intuition clashes with probability theory, chances are that it is intuition that needs schooling.


Integrated silicon carbide electro-optic modulator.
Owing to its attractive optical and electronic properties, silicon carbide is an emerging platform for integrated photonics. However an integral component of the platform is missing-an electro-optic modulator, a device which encodes electrical signals onto light. As a non-centrosymmetric crystal, silicon carbide exhibits the Pockels effect, yet a modulator has not been realized since the discovery of this effect more than three decades ago. Here we design, fabricate, and demonstrate a Pockels modulator in silicon carbide. Specifically, we realize a waveguide-integrated, small form-factor, gigahertz-bandwidth modulator that operates using complementary metal-oxide-semiconductor (CMOS)-level voltages on a thin film of silicon carbide on insulator. Our device is fabricated using a CMOS foundry compatible fabrication process and features no signal degradation, no presence of photorefractive effects, and stable operation at high optical intensities (913 kW/mm2), allowing for high optical signal-to-noise ratios for modern communications. Our work unites Pockels electro-optics with a CMOS foundry compatible platform in silicon carbide.


Structural and evolutionary characterization of the human sorbitol dehydrogenase gene duplication.
We have established that two very closely homologous human sorbitol dehydrogenase sequences lie within 0.5 Mb on Chromosome 15. We have defined the relative orientation of SORD1 and SORD2 genes with respect to both the centromere and each other and established their exact chromosome location. In addition, we have identified polymorphic variants in the locus, which may be useful, in association studies to predict predisposition to clinical problems resulting from decreased conversion of cellular sorbitol to fructose. To define the evolutionary relationship of these human genes, SORD from the marmoset was also sequenced for comparison. Marmoset SORD, which appears to be a single gene in this species, shows significantly less homology with either SORD1 or SORD2 than they do with each other, suggesting that the human homologs represent a recent gene duplication event. A hypothesis is presented to explain the retention of the redundant SORD2 sequence in the human genome.


Integrity of the National Resident Matching Program for Radiation Oncology: National Survey of Applicant Experiences.
The aim of this study was to examine the experiences of radiation oncology applicants and to evaluate the prevalence of behaviors that may be in conflict with established ethical standards. An anonymous survey was sent to all 2013 applicants to a single domestic radiation oncology residency program through the National Resident Matching Program (NRMP). Questions included demographics, survey of observed behaviors, and opinions regarding the interview and matching process. Descriptive statistics were presented. Characteristics and experiences of respondents who matched were compared with those who did not match. Questionnaires were returned by 87 of 171 applicants for a 51% response rate. Eighty-two questionnaires were complete and included for analysis. Seventy-eight respondents (95.1%) reported being asked at least 1 question in conflict with the NRMP code of conduct. When asked where else they were interviewing, 64% stated that this query made them uncomfortable. Forty-five respondents (54.9%) reported unsolicited post-interview contact by programs, and 31 (37.8%) felt pressured to give assurances. Fifteen respondents (18.3%) reported being told their rank position or that they were "ranked to match" prior to Match day, with 27% of those individuals indicating this information influenced how they ranked programs. Half of respondents felt applicants often made dishonest or misleading assurances, one-third reported that they believed their desired match outcome could be improved by deliberately misleading programs, and more than two-thirds felt their rank position could be improved by having faculty from their home institutions directly contact programs on their behalf. Radiation oncology applicants report a high prevalence of behaviors in conflict with written NRMP policies. Post-interview communication should be discouraged in order to enhance fairness and support the professional development of future radiation oncologists.


What would you do? If your colleague's a thief.
In an earlier issue, a doctor told you about a friend accused of stealing supplies. Here's what you told us you'd do in his place.


Cross-cultural perspectives on patient teaching.
Patient education for individuals of different cultures provides the professional nurse an opportunity to make a difference in the increasingly complex and changing problems in our bureaucratic society. Use of therapeutic relationships, indeed, can blend two worlds. Although we never can fully predict a patient's response to health teaching, we are likely to be much more effective if we understand and draw from the cultural context in which the patient is enmeshed.


Insights into pH-modulated interactions between native potato starch and cyanidin-3-O-glucoside: Electrostatic interaction-dependent binding.
Potato starch (PS), a natural and structured semicrystalline polymer, exhibits a distinct capacity to bind cyanidin-3-O-glucoside (C3G) at different pH values (3, 5, and 7). In this study, levels of NaCl (0.05%, 0.5%, and 5%, w/v) were introduced as electrostatic disturbing agents to the PS-C3G complexes to quantitatively reveal the role electrostatic interactions played in the binding at different pH conditions. The binding rate dropped from 31.60% to 2.19% as the pH value shifted from 3 to 7, indicating a decreasing affinity from C3G to PS. Further zeta potentials showed the possibility of electrostatic interactions in the PS-C3G complexes at pH 3 as well as screened charges in the presence of NaCl. The binding rate at pH 3 then exhibited a progressive decline to a final approximate one-third as the concentration of NaCl increased, which implied that the electrostatic interactions constituted the primary two-thirds of the driving forces involving complex stability at pH 3. The results of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, however, showed that hydrogen bonds had a negligible effect on the binding of C3G to PS at all pH conditions. Finally, the confocal laser scanning microscopy (CLSM) images, particle size and color differences were consistent with the change in the binding rate. Overall, electrostatic interactions were considered the key pH-modulated interactions between PS and C3G at different pH conditions.


Food, Medicine, and Function: Food is Medicine Part 2.
The food we eat becomes the basic building blocks of our biology. A poor diet creates poor-functioning cells, tissues, organs, and biological systems and leads to disease. A nutrient-rich whole foods diet does the opposite. Inflammation is a common denominator in most chronic diseases, and our modern-day lifestyle is primarily to blame. An overload of processed foods, sugar, starch, and exposure to toxic chemicals damages our mitochondria, overwhelms our detox organs, creates oxidative stress, hormonal and mood imbalances, cognitive decline, and so much more. Functional Medicine treats disease by removing what is causing damage and providing the body with what it needs to repair itself to regain proper functionality.


A review of the pelvic organ prolapse quantification system in China.
Unified staging systems for pelvic organ prolapse (POP) have been established. We examined the application of the POP quantification (POP-Q) system in China by examining its use in scientific journal articles. Relevant articles were identified by searching the Sinomed database using the terms: uterus prolapse, cystocele, proctocele, prolapse, and pelvic floor; limited to Chinese core journals in obstetrics and gynecology, from January 2004 to December 2014. We analyzed systems for grading POP severity and the adoption of POP-Q in different article categories and hospitals of different levels. For the last decade, with two 5-year groups (2005-2009; 2010-2014), the χ(2) test was used to evaluate inter-group differences. In a total of 429 articles, 331 included a staging system, 70.7% of which used POP-Q. The POP-Q system first appeared in 2004 in China, was reported in 50% of articles in 2007, and its highest use occurred in 2012 (89.5%). In 234 POP-Q system-utilizing reports, operative treatment and basic research accounted for 73.1% and 14.0% respectively. POP-Q usage increased from 2005-2009 to 2010-2014 in surgery-related articles (54.2% vs 85.2%; P = 0.000). The proportion of reports using POP-Q in level I, II, and III hospitals was 20.0%, 35.4%, and 77.8% respectively. The POP-Q system, first used in 2004 in China, is now the most commonly used grading system, with surgery reports and level III hospitals accounting for the largest proportion of POP-Q applications.


Bile acid and lysolecithin concentrations in the stomach of patients with gastric ulcer: before operation and after treatment by highly selective vagotomy, Billroth I partial gastrectomy and truncal vagotomy and pyloroplasty.
Bile acid and lysolecithin concentrations in the stomach were measured in normal subjects and in patients with gastric ulcer (GU) before operation and more than 1 year after highly selective vagotomy, Billroth I partial gastrectomy (PG) and truncal vagotomy and pyloroplasty. Before operation, patients with GU had significantly (P less than 0.001) higher bile acid concentrations in the stomach than normal people. After highly selective vagotomy, bile acid concentrations were significantly lower than in preoperative GU patients and were also significantly lower than in patients after PG, but were still higher than in normal people. Postprandial and peak lysolecithin concentrations after highly selective vagotomy were significantly lower than after partial gastrectomy. The therapeutic effect of highly selective vagotomy in the surgical treatment of GU may be due not only to reduced acid-peptic 'attack' on the gastric mucosa, but also to reduced duodenogastric reflux of 'bile'.


Ketamine Enhances Intranasal Dexmedetomidine-Induced Sedation in Children: A Randomized, Double-Blind Trial.
To compare the efficacy of intranasal dexmedetomidine and dexmedetomidine-ketamine premedication in preschool children undergoing tonsillectomy. We enrolled 66 children with American Society of Anesthesiologists physical status I or II, aged 3-7 years undergoing tonsillectomy. Patients were randomly allocated to receive intranasal premedication with either dexmedetomidine 2 μg kg-1 (Group D) or dexmedetomidine 2 μg kg-1 and ketamine 2 mg kg-1 (Group DK). The primary outcome was the sedation level assessed by the Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) 30 min after intervention. The minimal clinically relevant difference in the MOAA/S score was 0.5. Secondary outcomes included sedation onset time, parental separation anxiety, acceptance of mask induction, emergence time, emergence delirium, postoperative pain intensity, length of stay in the post-anesthesia care unit (PACU), and adverse effects. At 30 min after premedication, the MOAA/S score was lower in Group DK than in Group D patients (median: 1.0, interquartile range [IQR]: 1.0-2.0 vs median: 3.0, IQR: 2.0-3.0; P<0.001), with a median difference of 1.0 (95% confidence interval [CI]: 1.0-2.0, P<0.001). Patients in Group DK showed considerably faster onset of sedation (15 min, 95% CI: 14.2-15.8 min) than Group D (24 min, 95% CI: 23.2-24.8 min), with a median difference of 8.0 min (95% CI: 7.0-9.0 min, P<0.001). Both parental separation and facemask acceptance scores were lower in Group DK than in Group D patients (P=0.012 and P=0.001, respectively). There was no significant difference in emergence time, incidence of emergence delirium, postoperative pain scores, and length of stay in the PACU between the two groups. Intranasal premedication with a combination of dexmedetomidine and ketamine produced better sedation for pediatric tonsillectomy than dexmedetomidine alone.


Overexpressed thioredoxin compensates Fanconi anemia related chromosomal instability.
The cause of the molecular defect of Fanconi anemia (FA) remains unknown. Cells from patients with FA exert an elevated spontaneous chromosomal instability which is further triggered by mitomycin C. The induced lability is reduced by overexpression of thioredoxin which is not the case for spontaneous instability. However, both are eliminated by overexpression of thioredoxin cDNA with an added nuclear localization signal. This implies that thioredoxin is lacking in the nuclei of FA cells. The total thioredoxin content in all FA cells tested is reduced. The resultant lack of nuclear thioredoxin can be the explanation for the major symptomatology in FA. Since thioredoxin is known to be the reactive cofactor of ribonucleotid reductase its shortcoming reduces the supply of deoxyribonucleotides thus hindering the DNA and replication repair with resultant chromosomal breaks. Furthermore, depression of tyrosine hydroxylase, the key enzyme of melanine synthesis, could be the basis for the pathognomotic 'café au lait' spots of FA. The observation of thioredoxin reduction in FA cells permits insight into the molecular phathophysiology of FA.


The Cross-Regulation Between Autophagy and Type I Interferon Signaling in Host Defense.
The production of type I interferons (IFNs) is one of the hallmarks of intracellular antimicrobial program. Typical type I IFN response activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, which results in the transcription of plentiful IFN-stimulated genes (ISGs) to establish the comprehensive antiviral states. Type I IFN signaling should initiate timely to provoke innate and adaptive immune responses for effective elimination of the invading pathogens. Meanwhile, a precise control must come on the stage to restrain the persistent activation of type I IFN responses to avoid attendant toxicity. Autophagy, a conserved eukaryotic degradation system, mediated by a number of autophagy-related (ATG) proteins, plays an essential role in the clearance of invading microorganism and manipulation of type I responses. Autophagy modulates type I IFN responses through regulatory integration with innate immune signaling pathways, and by removing endogenous ligands of innate immune sensors. Moreover, selective autophagy governs the choice of innate immune factors as specific cargoes for degradation, thus tightly monitoring the type I IFN responses. This review will focus on the cross-regulation between autophagy and type I IFN signaling in host defense.


Effects of l-arginine supplementation associated with continuous or interval aerobic training on chronic heart failure rats.
Chronic heart failure (CHF) is related with exercise intolerance and impaired nitric oxide (NO) production, which can lead to several functional capacity alterations. Considering the possible superiority of aerobic interval training compared to continuous training and the capacity of l-arginine to restore the NO pathway, the aim of the present study was to investigate whether these treatments are beneficial to exercise capacity, muscle mass preservation and hemodynamic, inflammatory and oxidative stress parameters in CHF rats. Thirty-eight male Wistar rats post 6weeks of myocardial infarction (MI) surgery were randomly assigned into 6 CHF groups: sedentary (SED, n=6); SED+Arg (n=7); ACT (n=8); ACT+Arg (n=5); AIT (n=7); AIT+Arg (n=5). Exercise test capacity (ETC) was performed pre and post 8weeks of intervention. Supplemented rats received Arg (1g/kg) by oral gavage (7×/week). Exercise training was performed on a rat treadmill (5×/week). Hemodynamic variables, tissue collection, congestion, inflammatory cytokines, and oxidative parameters were evaluated at the end of protocols. All trained groups showed a superior exercise capacity compared to SED groups on the post-intervention test (p<0.0001). Pulmonary congestion was attenuated in AIT and AIT+Arg compared with the SED group (p<0.05). Left ventricular end-diastolic pressure (LVEDP) was lower in ACT+Arg, AIT, and AIT+Arg groups than SED group (p<0.05). Association of AIT with Arg supplementation was able to improve hemodynamic responses (left ventricular systolic pressure (LVSP), systolic blood pressure (SBP), +dP/dtmax, and -dP/dtmax (p<0.05), likewise, decrease muscular and renal lipid peroxidation and tumor necrosis factor (TNF)-α, and increase interleukin (IL)-10/TNF-α plasmatic levels (p<0.01). Groups that associated aerobic exercise with Arg supplementation (ACT+Arg and AIT+Arg) revealed higher gastrocnemius mass compared to the SED group (p<0.01). Both aerobic training protocols were capable to improve aerobic capacity, and the association with Arg supplementation was important to attenuate muscle loss. Moreover, interval training associated with Arg supplementation elicits greater improvements in hemodynamic parameters, contributing to reduction in pulmonary congestion, and demonstrated particular responses in the inflammatory profile and in the antioxidant status.


Interaction of small G proteins with photoexcited rhodopsin.
Bovine rod outer segment (ROS) membranes contain in addition to the heterotrimeric G protein transducin, several small GTP-binding proteins (23-27 kDa). Furthermore, these membranes contain two substrate proteins (about 22 and 24 kDa) for botulinum C3 ADP-ribosyltransferase known to ADP-ribosylate small G proteins in any mammalian cell type studied so far. Most interestingly, [32P]ADP-ribosylation of ROS membrane small G proteins by C3 is regulated by light and guanine nucleotides in a manner similar to pertussis toxin-catalyzed [32P]ADP-ribosylation of the alpha-subunit of transducin. These findings suggest that not only the heterotrimeric G protein transducin but also the C3 substrate small G proteins present in ROS membranes interact with photoexcited rhodopsin and thus contribute to its signalling action.


Comorbid depression and treatment of anxiety disorders, OCD, and PTSD: Diagnosis versus severity.
Although anxiety and depression are highly comorbid disorders, it remains unclear whether and how a concurrent depression affects the outcome of anxiety treatment. Using anonymized routine outcome monitoring (ROM) data of 740 patients having received specialized treatment for an anxiety disorder, OCD, or PTSD, this study investigates whether a comorbid diagnosis of depression and/or self-reported depression severity levels relate to the patients' improvement following anxiety treatment. The results show that both the patients with and those without comorbid depression had profited similarly from the anxiety, OCD, or PTSD treatment, regardless of whether depression was merely diagnosed prior to treatment or based on self-reported severity (and assuming a smallest effect size of interest of d = 0.35/r = .2). Importantly, the post-treatment reductions in self-reported depressive symptoms were strongly and positively related to the reductions in self-reported anxiety symptoms and disorder-related disability. Causal inferences cannot be made due to the retrospective cross-sectional design. The outcomes obtained in a naturalistic patient sample support current treatment guidelines recommending evidence-based treatment for anxiety disorders, OCD, and PTSD in patients with and without a comorbid depression. Future treatment studies are recommended for investigate the (bi)directionality of anxiety and depressive symptoms throughout treatment.


The epidemiology of eating disorders: genetic, environmental, and societal factors.
The aim of this review was to summarize the literature to date regarding the sociodemographic, environmental, and genetic correlates of eating disorders (EDs) in adults. A keyword search was entered into Scopus (SciVerse, Elsevier) to identify relevant articles published in English up until June 2013. Articles were assessed against a range of a priori inclusion and exclusion criteria. A total of 149 full-text articles were found to be eligible for the review and included 86 articles with data on sociodemographic correlates, 57 on environmental correlates, and 13 on genetic correlates. Female sex, younger age, sexual and physical abuse, participation in esthetic or weight-oriented sports, and heritability were found to be most consistently associated with higher ED prevalence and incidence. Conversely, ethnicity, socioeconomic status, education, and urbanicity did not appear to have strong associations with ED epidemiology. More community-based research, with an equal representation of males, needs to be conducted to confirm the current findings and provide evidence for emerging factors that may be related to EDs.


Dynamic and static stretching on hamstring flexibility and stiffness: A systematic review and meta-analysis.
Hamstring injuries are one of the most common types of damage in sports. Insufficient flexibility and high stiffness are important reasons for it. Stretching is often used in warm-up activities before exercises to increase flexibility, among which dynamic stretching (DS) and static stretching (SS) are the most widely used. The effects of these two stretching techniques on the flexibility or stiffness of the hamstring still need to be clarified. This study aimed to compare the short-term, medium-term, and long-term effects of DS and SS on improving hamstring flexibility and stiffness via a meta-analysis of RCTs. RCTs were identified from PubMed, Cochrane Library, Web of Science, and PEDro from inception to July 28, 2022. The methodological quality was evaluated using the PEDro scale. The mean difference and 95% confidence interval of the outcome variables before and after stretching were calculated and the extracted data were quantitatively processed using a random or fixed effects model. A total of 27 RCTs and 606 participants were included. In terms of improving the ROM of the hamstring, there was no significant difference in the acute (MD, -0.70, 95% CI, -1.54 to 0.14; Z = 1.63, P > 0.05) and sub-acute effects (MD, 1.71, 95% CI, -2.80 to 6.22; Z = 0.74, P > 0.05) between a single bout of SS and DS, while the acute (MD, -5.13, 95% CI, -7.65 to -2.61; Z = 3.99, P < 0.05) and sub-acute effects (MD, -5.30, 95% CI, -6.33 to -4.27; Z = 10.04, P < 0.05) of multiple bouts of SS was superior to DS; There was no significant difference in the medium-term effect between the two stretching techniques (MD, 3.48, 95% CI, -2.57 to 9.53; Z = 1.13, P > 0.05), but the long-term effect of SS was better than DS (MD, - 10.40, 95% CI, -10.97 to -9.83; Z = 35.57, P < 0.05). Regarding the length of the hamstring, the acute (MD, -0.41, 95% CI, -1.09 to 0.26; Z = 1.20, P > 0.05) and sub-acute effects (MD, -0.73, 95% CI, -1.69 to 0.22; Z = 1.51, P > 0.05) of a single bout of DS and SS were similar. Two studies have compared the effects on hamstring stiffness, with one showing similar effects, and the other showed that DS was superior to SS. One study showed no difference in the magnitude of change in improving passive torque. No studies explored the effect of DS and SS on hamstring myofascial length. Only one study demonstrated no significant difference in hamstring thickness. A single bout of DS and SS have similar short-term effects in improving hamstring ROM and length, while multiple bouts of SS can significantly improve hamstring ROM compared to DS. DS and SS showed similar effects on hamstring myofascial length.


Impact of the junior doctors' industrial action on the emergency eye department in a large tertiary ophthalmic hospital: the Manchester experience.
To assess the impact of the junior doctors' industrial action on one of the largest emergency eye departments (EED) in the United Kingdom. We compared staff allocation, patient presentation, time in streaming, time in the department, the Manchester Triage System (MTS) score, number of eye emergencies and follow-up care of patients who attended the EED in the Manchester Royal Eye Hospital (MREH) during the 3-day industrial action (13-15 March 2023) compared with control periods 2 weeks before and 2 weeks after the industrial action. During the industrial action, there were almost 1.5 times more staff allocated to EED with a near doubling of the senior workforce. There was no difference in patient presentation, MTS score, number of eye emergencies or patient follow-up during the industrial action. However, patients had significantly less time in streaming (p < 0.001) and in the department (p < 0.001) during the industrial action compared to control periods. Emergency ophthalmic patient care was not compromised during the industrial action due to the reallocation of the workforce to EED. The results of this study may help in the planning of ophthalmic eye-care services in the event of future industrial actions.


Trichothecene chemotypes ofFusarium graminearum isolated from corn in Hungary.
Twenty three strains ofFusarium graminearum isolated from corn were screened for their ability to produce type A and B trichothecenes and zearalenone (ZEA) on the solid substrate rice grains in the dark at 28 °C for 21 days. Toxin analyses were made with HPLC technique. Of 23 total isolates, 10 produced deoxynivalenol (DON), 4 produced DON and nivalenol (NIV), 1 produced DON and 15 acetyl-DON (15-ADON), 1 produced NIV and 4-acetyl-NIV (4-ANIV) and 1 produced NIV. Of 23 totalF. graminearum isolates, 20 produced ZEA. These results suggest that strains ofF. graminearum, prevailing in Hungarian corn growing regions, might belong to DON-and NIV-chemotypes. This is the first report demonstrating that DON-, DON-NIV-, DON-15-ADON-, NIV-4-ANIV and NIV-producingF. graminearum isolates are distributed in Hungary.


Germany: toxicology information on the World Wide Web.
Following a brief introduction to the history of toxicology in Germany, this article deals with institutions concerned with toxicological information and research in Germany. The web addresses, responsibilities and main topics of federal authorities, federal state authorities, institutions for statutory accident insurance and prevention, non-university and university research institutes, funding institutions, scientific societies, industry representatives and poison information centers are described and links are given to databases provided on the web sites of these institutions.


Mosaicism for c.431_454dup in ARX causes a mild Partington syndrome phenotype.
A common in frame duplication in ARX (c.431_454dup24) was found in a five year-old boy who presented with mild Partington syndrome. The duplication was detected by PCR amplification followed by fragment length analysis and was located in exon 2 spanning the two polyalanine tracts commonly seen to expand. Detection of the duplication by DNA sequencing was difficult due to preferential sequencing of the normal allele, demonstrating the superiority of fragment length analysis in mosaic cases. The clinical symptoms were mild to moderate developmental delay with only the hand dystonia to suggest Partington syndrome. This patient is the first male reported to be mosaic for the duplication, and his clinical features are subtle. This study shows that in males with a phenotype of mild Partington syndrome and in heterozygous females fragment length analysis should be preferred over DNA sequencing.


Short-term effects of meteorological factors, air pollution, and sunspot on childhood hand, foot, and mouth disease in Tianjin, China: a new time series regression, 2014-2018.
This study is aimed at defining the relationship between a set of environmental factors and childhood HFMD and then at estimating the related effect. The 16 environmental factors included meteorological, air pollution, and sunspot. A traditional TSR modified by using susceptible-infectious-recovery models and distribution lag nonlinear model was applied to estimate the short-term effects of daily environmental factors on children HFMD occurrence in 2014-2018 with adjustment of potential confounding factors. A total of 70,027 children aged 0-15 years with HFMD were enrolled. No significant effect was observed for daily sunspot numbers and average visibility. We found positive effects of the ambient average temperature, with an approximately m-shaped curve of the overall cumulative relationship, peaking at 25.6 °C with a relative risk (RR) of 1.45 (95% confidence intervals 1.21-1.73). The largest RR value of hot effect was achieved on the current day and then decreased by 2 days (total group, male group, and scatter group) or 1 day (female group and nursery group), and the effect lasted about 6 to 8 days from the lag 4 or lag 6 day. A greater association of temperature with HFMD for the female group and the scattered group was observed. This study suggests that ambient average temperature might be a risk factor for children HFMD in Tianjin. Further studies are warranted to confirm these findings.


Reinventing rural care. In the move from volume to value, ensuring rural health care's viability will benefit all providers.
It's time to rethink the way rural health care is funded and delivered.


Design of N-Methyl-d-Glucamine-Based Resorcin[4]arene Nanoparticles for Enhanced Apoptosis Effects.
The addition of specific chemical groups in a macrocycle structure influences its functional properties and, consequently, can provide new possibilities, among which are aggregation properties, water solubility, biocompatibility, stimuli response, biological activity, etc. Herein, we report synthesis of new resorcin[4]arene with N-methyl-d-glucamine groups on the upper rim and n-decyl chains on the lower rim, an investigation of its self-assembly behavior in aqueous media, and its use as a building block for the formation of drug nanocontainer. N-methyl-d-glucamine fragments in the resorcin[4]arene structure promote higher stability in solutions, simplification of self-aggregation, and increased biological activity. Antimicrobial and hemolytic activity assessment revealed that this resorcin[4]arene obtained is nontoxic. The study of cell penetration was carried out with both free and encapsulated doxorubicin (DOX). Surprisingly, DOX-loaded macrocycle aggregates are more efficient in causing apoptosis in human cancer cell line. Conceivably, this knowledge will help in the rational design of DOX combination for novel drug-administration strategies in cancer treatment.


[Unruptured brain aneurysms: when to screen and when to treat?].
The detection rate of intracranial aneurysms has increased with the improved availability of non-invasive imaging methods. Moreover, persons who have relatives with intracranial aneurysms increasingly demand imaging to rule out aneurysms. To deal with these problems, radiologists require basic knowledge regarding the detection and treatment of unruptured intracranial aneurysms. The prevalence of aneurysms in the normal population is 2 - 3 %. It increases to 4 - 10 % in persons with one relative with an aneurysm and to about 20 % in persons with two relatives with an aneurysm. The average natural rupture risk is estimated to be 5 % within 5 years of detection. In the individual case it depends on several variables that are discussed here. According to the literature, the risk of endovascular aneurysm treatment is about 5 %. On the basis of these data, the benefit of MRA screening needs to be discussed individually with the patient.


[Electron microscope study of the plasmid DNA from various strains of Treponema pallidum].
Electron microscopic investigation and electrophoretic analysis of DNA from two cultural strains of pale treponemes (Treponema pallidum VIII and Treponema pallidum Reiter) allowed us to identify the circular molecules of plasmid DNA their size evaluated as 7 to 8 MD. Side by side with the molecules of this size the electron microscopic pictures of the plasmid DNA of both strains of pale treponemes show small superspiralized molecules of plasmid DNA. According to electrophoretic data the size of this DNA is evaluated as two thousand base pairs.


Acupuncture therapy for gastric ulcer: A protocol for systematic review and meta-analysis.
Gastric ulcer (GU) is a clinically common disease of the digestive system that adversely affects patients' quality of life and work ability. Although some articles have reported that acupuncture can improve the clinical symptoms of GU, the efficacy of acupuncture has not been scientifically or methodically evaluated. This study aimed to evaluate the effectiveness and safety of acupuncture for the treatment of patients with gastric ulcers. The following electronic databases will be searched from the respective dates of database inception to March 23, 2021: The Cochrane Library, Web of Science, EMBASE, MEDLINE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang database, the Chinese Scientific Journal Database, and other sources. Randomized controlled trials comparing acupuncture with other interventions or sham acupuncture were included. Two independent researchers will perform article retrieval, duplication removal, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyzes, subgroup analysis, and/or descriptive analyses will be performed based on the included data conditions. The protocol of this study systematically assessed the effectiveness and safety of acupuncture for gastric ulcer patients. The primary outcome was the effective rate, and the secondary outcomes included negative conversing rate of Helicobacter pylori infection, untoward effect, recurrence rate, quality of life, and symptom scores. This study provides evidence of whether acupuncture is an effective and safe intervention for gastric ulcers. CRD42021251067.


Improving quality of life in ageing populations: what can volunteering do?
The year 2011 was declared the 'European Year of Volunteering' to recognise the contribution volunteers make to society. Such cross-national events reflect the high profile of volunteering and political imperatives to promote it. The purpose of this review is to provide a comprehensive review of current knowledge (articles published between 2005 and 2011) regarding the role of volunteering in improving older people's quality of life (QoL) and to identify areas requiring further research. Volunteering was defined as an activity that is freely chosen, does not involve remuneration and helps or benefits those beyond an individual's immediate family. Our search identified 22 studies and 5 review articles that addressed the benefits of volunteering on older people's quality of life. Most of the research had been conducted in the United States, Canada and Australia using data from longitudinal studies. The majority of the studies concluded that there is a positive association between older people's quality of life and engagement in volunteering. Due to the study designs and the heterogeneity of the research, causality is difficult to demonstrate and the knowledge the studies bring to the subject is variable. This review shows that volunteering may help to maintain and possibly improve some older adults' quality of life. However, there are still major gaps in our understanding of who actually benefits, the social and cultural context of volunteering and its role in reducing health and social inequalities.


Ultrasonographic Measurement of the Achilles and Supraspinatus Tendon Thicknesses in Patients with Chronic Lead Exposure.
The study aimed to assess tendon thickness in patients with chronic occupational lead exposure by using ultrasonography. Twenty-seven male workers (mean age 32.9 ± 6.2 years, range 25-44 years) with occupational lead exposure and 27 age- and body mass index (BMI)-matched healthy male subjects (mean age 33.1 ± 5.6 years, range 25-44 years) were enrolled. Ultrasonographic measurements were obtained from the supraspinatus and Achilles tendons by using a linear probe (5-10 MHz). Mean Achilles tendon values at long axis (p = 0.034) and tendon cross-sectional area (p = 0.013) were significantly smaller in the lead-exposed group than the control group. On the other hand, no significant difference was found regarding the thickness of the supraspinatus tendon (p > 0.05). Our preliminary results imply that subjects with occupational lead exposure have smaller Achilles tendons than healthy subjects. Chronic lead exposure may affect the tendons due to reduction of collagen synthesis. Further studies are definitely needed to confirm our initial findings.


Plasma cholesteryl ester fatty acids in 3- and 12-year-old Finnish children.
Risk factors associated with coronary heart disease were surveyed in a multicentre study carried out in 1979 among children living in different parts of Finland. The survey included analyses of plasma lipids and cholesteryl ester (CE) fatty acids as well as a dietary interview by a 48-hour recall method. The present report gives the plasma fatty acid compositions obtained from 181 3-year-old and 226 12-year-old children and their relations to dietary factors and other plasma lipids. The mean percentages (+/- SD) of CE linoleate in the 3- and 12-year-old children were 49.2 +/- 5.2 and 5.10 +/- 51.0%, respectively. Differences in CE fatty acid composition between the various regions of Finland were relatively small, but there was a trend to higher proportions of polyunsaturated fatty acids in western and urban compared with eastern and rural communities. Among different dietary constituents the daily intake of margarine + oils or butter had the greatest effect on plasma CE fatty acid composition. There was a highly significant positive correlation between the dietary P/S ratio and the percentage of CE linoleate in plasma.


Influence of a reduced CO2 environment on the secretion yield, potency and N-glycan structures of recombinant thyrotropin from CHO cells.
A consistent increase of approximately 60% in the secretion yield of CHO-derived hTSH was observed by changing cell culture CO2 conditions from 5% CO2 to an air environment. The overall quality of the products obtained under both conditions was evaluated in comparison with a well-known biopharmaceutical (Thyrogen). The N-glycans identified were of the complex type, presenting di-, tri- and tetra-antennary structures, sometimes fucosylated, 86-88% of the identified structures being sialylated at variable levels. The three most abundant structures were monosialylated glycans, representing approximately 69% of all identified forms in the three preparations. The main difference was found in terms of antennarity, with 8-10% more di-antennary structures obtained in the absence of CO2 and 7-9% more tri-antennary structures in its presence. No remarkable difference in charge isomers was observed between the three preparations, the isoelectric focusing profiles showing six distinct bands in the 5.39-7.35 pI range. A considerably different distribution, with more forms in the acidic region, was observed, however, for two native pituitary preparations. All recombinant preparations showed a higher in vivo bioactivity when compared to native hTSH. Different production processes apparently do not greatly affect N-glycan structures, charge isomer distribution or bioactivity of CHO-derived hTSH.


Incidence of diabetic eye disease among migrants: A cohort study of 100,000 adults with diabetes in Denmark.
To examine the incidence rates of any and referable diabetic retinopathy (DR) among migrants in Denmark. Nationwide clinical data on diabetes patients followed since 2005 were analysed. Patients were classified according to country of origin into six groups: Denmark, other Europe, Sub Saharan Africa, Middle East/North Africa, Asia, and America/Oceania. A total of 93,780 or 110,897 patients without any (including unspecific diagnoses) or referable (proliferative) DR at baseline were analyzed. We estimated event rates and hazard ratios (HRs) for incidence of any and referable DR according to country of origin. After an average follow-up of 3.59 years 6727 had incident any DR and 4747 patients had referable DR. Compared to people of Danish origin, migrants from the Middle East/North Africa and Asia had a higher risk of any and referable DR after adjustment for age, sex, body mass index, smoking status, types and duration of diabetes, clinic type (general practice vs outpatient clinic), HbA1c, blood pressure and lipid levels. The associations remained significant after further adjustment for frequency of eye screening. Migrants from the Middle East/North Africa and Asia were at increased risk of developing any and referable DR compared to native Danes, and these differences were not fully explained by differences in underlying clinical, diabetic and cardiometabolic risk factors.


Retinoic acid and 2,3,7,8-tetrachlorodibenzo-p-dioxin selectively enhance teratogenesis in C57BL/6N mice.
TCDD is one of the most toxic man-made compounds and an extremely potent teratogen in mice. Many of its toxic symptoms resemble those seen during vitamin A deficiency. Vitamin A and its derivatives, such as alltrans-retinoic acid (RA), are also teratogenic in mice, as well as many other species. Both TCDD and RA produce cleft palate in susceptible strains of mice. However, while TCDD produces hydronephrosis, RA does not, and TCDD does not produce limb bud defects while RA does. To determine whether TCDD and RA would enhance or antagonize the teratogenic effects of the other compound, C57BL/6N dams were treated po on Gestation Day (gd) 10 or 12 with 10 ml corn oil/kg containing TCDD (0-18 micrograms/kg), RA (0-200 mg/kg), or combinations of the two chemicals. Dams were killed on gd 18 and toxicity and teratogenicity assessed. Coadministration of TCDD and RA had no effect on maternal or fetal toxicity beyond what would be expected by either compound alone. Cleft palate was induced by RA at lower doses on gd 10 than on gd 12, but by TCDD at lower doses on gd 12 than on gd 10. Sensitivity to TCDD-induced hydronephrosis was similar on both gd 10 and 12. The limb bud defects were only observed when RA was administered on gd 10, not when given on gd 12. No other soft tissue or skeletal malformations were related to administration of TCDD or RA. No effect of TCDD was observed on the incidence or severity of limb bud defects induced by RA, nor did RA influence the incidence or severity of hydronephrosis induced by TCDD. However, the incidence of cleft palate was dramatically enhanced by coadministration of the xenobiotic and vitamin. On both gd 10 and 12, the dose-response curves for cleft palate induction were parallel, suggesting some similarities in mechanism between the two compounds. However, combination treatment resulted in a synergistic response that varied with the stage of development and was tissue specific.


Management of relapse in acute promyelocytic leukaemia treated with up-front arsenic trioxide-based regimens.
The standard of care for patients with acute promyelocytic leukaemia (APL) relapsing after front-line treatment with arsenic trioxide (ATO)-based regimens remains to be defined. A total of 67 patients who relapsed after receiving ATO-based up-front therapy and were also salvaged using an ATO-based regimen were evaluated. The median (range) age of patients was 28 (4-54) years. While 63/67 (94%) achieved a second molecular remission (MR) after salvage therapy, three (4·5%) died during salvage therapy. An autologous stem cell transplant (auto-SCT) was offered to all patients who achieved MR, 35/63 (55·6%) opted for auto-SCT the rest were administered an ATO + all-trans retinoic acid maintenance regimen. The mean (SD) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received auto-SCT versus those who did not was 90·3 (5·3)% versus 58·6 (10·4)% (P = 0·004), and 87·1 (6·0)% versus 47·7 (10·3)% (P = 0·001) respectively. On multivariate analysis, failure to consolidate MR with an auto-SCT was associated with a significantly increased risk of relapse [hazard ratio (HR) 4·91, 95% confidence interval (CI) 1·56-15·41; P = 0·006]. MR induction with ATO-based regimens followed by an auto-SCT in children and young adults with relapsed APL who were treated with front-line ATO-based regimens was associated with excellent long-term survival.


Intraparenchymal vs extracranial ventricular drain intracranial pressure monitors in traumatic brain injury: less is more?
Management of severe traumatic brain injury has centered on continuous intracranial pressure (ICP) monitoring with intraparenchymal ICP monitors (IPM) or extracranial ventricular drains (EVD). Our hypothesis was that neurologic outcomes are unaffected by the type of ICP monitoring device. We reviewed 377 adult patients with traumatic brain injury requiring ICP monitoring. Primary outcome was Glasgow Outcome Score (GOS) 1 month after injury. Secondary outcomes included mortality, monitoring-related complications, and length of ICU and hospital stay. There were 253 patients managed with an IPM and 124 with an EVD. There was no difference in Glasgow Outcome Score (2.7 ± 1.3 vs 2.5 ± 1.3, p = 0.45), mortality (30.9% vs 32.2%, p = 0.82), and hospital length of stay (LOS) (15.6 ± 12.4 days vs 16.4 ± 10.7 days, p = 0.57). Device-related complications (11.9% vs 31.1%, p < 0.001), duration of ICP monitoring (3.8 ± 2.6 days vs 7.3 ± 5.6 days, p < 0.001), and ICU LOS (7.6 ± 5.6 days vs 9.5 ± 6.2 days, p = 0.004) were longer in the EVD group. Age, opening ICP, and size of midline shift were independent predictors for neurologic outcomes and mortality, when type and severity of brain injury, as well as overall injury severity were controlled for. Duration of ICP monitoring and opening ICP were independent predictors for hospital LOS and the former predicted prolonged ICU stay. Device-related complications were affected by type of device. Use of EVDs in adult traumatic brain injury patients is associated with prolonged ICP monitoring, ICU LOS, and more frequent device-related complications.


The use of a monosaccharide linkage group in a heterologous solid-phase enzyme immunoassay for phenytoin.
The preparation is described of monosaccharide-hapten derivatives containing a galactosyl linkage group which bears little structural resemblance to the straight-chain hydrocarbons commonly used for attaching haptens to proteins for use as immunogens. These derivatives are readily synthesised and are coupled to enzymes under mild conditions to produce bridge-heterologous enzyme immunoassays. The use of beta-galactosidase-monosaccharide-phenytoin derivatives in the development of sensitive phenytoin enzyme immunoassays is described and the assays are compared with hapten-heterologous, site-heterologous and homologous phenytoin enzyme immunoassays prepared using other phenytoin derivatives. This technique has application in the development of immunoassays for haptens which have only one functional group to which linkage groups can be attached for covalent coupling of the hapten to proteins.


Simvastatin and preparation of polyunsaturated phospholipids produce similar changes in the phospholipid composition of high-density lipoproteins during hypercholesterolemia.
We studied the phospholipid composition of high-density lipoproteins in patients with coronary heart disease and hypercholesterolemia treated with simvastatin (Zocor, inhibitor of the key enzyme of cholesterol synthesis) and preparation of polyunsaturated phospholipids (lipostabil forte). Simvastatin produced a hypolipidemic effect and modulates the phospholipid composition of high-density lipoproteins (similarly to lipostabil forte). These changes contribute to functional activity of high-density lipoproteins in the reverse cholesterol transport.


Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center.
Restricted use of third-generation cephalosporins and fluoroquinolones has been linked to a reduced incidence of hospital-acquired infections with multidrug-resistant bacteria. We implemented an intensified antibiotic stewardship (ABS) programme in the medical service of a university hospital center aiming at a reduction by at least 30% in the use of these two drug classes. The ABS programme was focused on the 300-bed medical service. Prescription of third-generation cephalosporins was discouraged, whereas the use of penicillins was encouraged. Monthly drug use density was measured in WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient days, to evaluate trends before (01/2008 to 10/2011) and after starting the intervention (1/2012 to 3/2013). The effect was analysed using interrupted time-series analysis with six non-intervention departments as controls. Following initiation of the ABS intervention, overall antibiotic use in the medical service declined (p < 0.001). There was a significant intervention-related decrease in the use of cephalosporins and fluoroquinolones (p < 0.001) outperforming the decreasing baseline trend. Trend changes observed in some of the control departments were smaller, and the difference between trend changes in the medical service and those in control departments were highly significant for overall use and cephalosporin use reductions (p < 0.001) as well as for the increasing use of penicillins (p < 0.001). Mean use density levels (in RDD per 100 patient days) dropped for cephalosporins from 16.3 to 10.3 (-37%) and for fluoroquinolones from 17.7 to 10.1 (-43%), respectively. During the same period, the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures for antibiotics in the medical service compared to control services minus programme costs indicated initial net cost savings likely to be associated with the programme. An intensified ABS programme targeting cephalosporin und fluoroquinolone use in the setting of a large academic hospital is feasible and effective. The intervention may serve as a model for other services and hospitals with a similar structure and baseline situation.