The Plasmid pEX18Gm Indirectly Increases Caenorhabditis elegans Fecundity by Accelerating Bacterial Methionine Synthesis.
Plasmids are mostly found in bacteria as extrachromosomal genetic elements and are widely used in genetic engineering. Exploring the mechanisms of plasmid-host interaction can provide crucial information for the application of plasmids in genetic engineering. However, many studies have generally focused on the influence of plasmids on their bacterial hosts, and the effects of plasmids on bacteria-feeding animals have not been explored in detail. Here, we use a "plasmid-bacteria-Caenorhabditis elegans" model to explore the impact of plasmids on their host bacteria and bacterivorous nematodes. First, the phenotypic responses of C. elegans were observed by feeding Escherichia coli OP50 harboring different types of plasmids. We found that E. coli OP50 harboring plasmid pEX18Gm unexpectedly increases the fecundity of C. elegans. Subsequently, we found that the plasmid pEX18Gm indirectly affects C. elegans fecundity via bacterial metabolism. To explore the underlying regulatory mechanism, we performed bacterial RNA sequencing and performed in-depth analysis. We demonstrated that the plasmid pEX18Gm upregulates the transcription of methionine synthase gene metH in the bacteria, which results in an increase in methionine that supports C. elegans fecundity. Additionally, we found that a pEX18Gm-induced increase in C. elegans can occur in different bacterial species. Our findings highlight the plasmid-bacteria-C. elegans model to reveal the mechanism of plasmids' effects on their host and provide a new pattern for systematically studying the interaction between plasmids and multi-species.


Psychological adjustment in parents of young children with atopic dermatitis: which factors predict parental quality of life?
Bringing up children with atopic dermatitis (AD) is widely perceived as being stressful because parenting demands considerable time and energy. There have been only a few studies to assess the extent of problems experienced by the parents. To assess the psychosocial well-being of parents caring for a young child with AD and to examine the relationship between parental quality of life and disease-related and sociodemographic variables. One hundred and eighty-seven parents of young children with AD attending an inpatient rehabilitation clinic participated in the study. At admission, parents completed a set of questionnaires (assessing health-related quality of life, coping with the disease, family functioning). Dermatologists assessed disease severity using the severity scoring of AD index (SCORAD). In general, parents cope well with their situation. Compared with normal values, high rates of psychological distress were observed in a subsample of parents of children with AD. Parents of children with a higher severity of disease reported a significantly higher impact on family functioning, a greater financial burden and a higher level of disease management. Parental disease management could be predicted by the familial situation, their personal well-being and the severity of disease of their child. Differences attributed to their child's gender or age were not observed. Childhood AD has a profound impact on the emotional and social well-being of many of the parents. The results underline the importance of psychological treatment approaches designed to increase parental well-being and ability to cope with stress and social strain.


Molecular dynamics study on the adsorption and release of doxorubicin by chitosan-decorated graphene.
The safe and effective delivery of anticancer drug molecules (e.g., doxorubicin [DOX]) into target sites is of great significance in cancer therapy. Recently, considerable attention has been devoted to non-covalently functionalized graphene as a potential anticancer delivery material. Herein, molecular dynamics simulations were performed to investigate the interaction mechanism between DOX and chitosan-decorated graphene with atomic details at the molecular level. The results demonstrated that the controllable loading and release of DOX by chitosan-decorated graphene may be achieved by adjusting the solution pH (the protonation state of chitosan) and the concentration of both DOX and chitosan molecules. In particular, the bare surface of graphene can be controlled by the aggregation and dispersion of chitosan, which further affects the adsorption and release of DOX molecules.


Management of cardiogenic shock complicating acute myocardial infarction: A review.
Despite advances in percutaneous coronary interventions and their widespread use, mortality in patients presenting with acute myocardial infarction (MI) complicated by cardiogenic shock (CS) has remained very high, and treatment options are limited. Limited evidences exist, supporting many of the routinely used therapies in treating these patients. In the present article, we discuss CS complicating MI in general and an update on the currently available treatment options, including inotropes and vasopressor, coronary revascularization, mechanical circulatory support devices, mechanical complications, and long-term outcomes.


A gingival guard for crown preparation.
A device for subgingival margin preparation is presented. The gingival guard consists of a clamp attached to the high-speed handpiece supporting a stainless steel shank terminating in a sphere. The guard permits nontraumatic subgingival margin preparation.


Clinical trials: active control vs placebo--what is ethical?
The quest for effective medicines is very old. In modern times two important tools have been developed to evaluate efficacy of drugs, superiority and non-inferiority types of clinical trials. The former tests the null hypothesis of micro (the difference between a tested drug and comparator) < or = 0 against micro > 0; the latter tests the null hypothesis of micro < or = - delta against, micro > - delta, where delta is the clinical difference from the comparator. In a superiority trial, a new drug is tested against a placebo; in a non-inferiority trial, a new drug is tested against active treatment. In this paper, arguments are presented to show that a superiority trial against a placebo is scientifically sound but ethically unacceptable, whereas a non-inferiority trial against active treatment is ethically sound but scientifically not reliable. Switching from a superiority type of trial with placebo to a non-inferiority trial with an active-control--following the latest revision of Declaration of Helsinki--is in practice switching from the violation of the uncertainty principle to uncertainty of results. Given human and financial resources, it appears an academic question as to which is more unethical: to violate patients' rights or to produce results without scientific value. All presented considerations lead to the conclusion that the use of a superiority trial of design with an active control instead of placebo will satisfy scientific needs, expectation of patients, and the ancient quest for effective medicines. In the era of Good (Clinical, Laboratory, Manufacture) Practice, the attention of those performing clinical trials is focused on the procedure, not always on its essence. However even the excellent performance of a trial which is not worth doing is fruitless.


Molecular Docking and Simulation Studies of Flavanone and its Derived Compounds on PI3K-AKT Pathway Targeting against Cancer.
Flavanone compounds and their related derivatives are reported in controlling cell cycle, angiogenesis, and metastasis. Phosphoinositide 3-kinases is a major drug target. Crystalize structure of Phosphoinositide 3-kinases-Akt complex obtained from Protein Data Bank (PDBID: 3CQW) was selected as receptor protein and the binding site has been identified with PDBSum Database. Flavanone and its derivatives were retrieved using freely available existing drug databases like Drug Bank, Zinc, and PubChem. New derivatives were modified by altering the flavanone at Beta ring position. This modification would help in maintaining stable structural conformation and retaining better anticancer activity. Retrieved Flavanone derivatives from the drug database were docked against 3CQW Protein with the advanced docking tool FlexX. MD simulations of the best molecule were performed with the Desmond package by calculating nonbonding interactions such as electrostatic interaction and hydrogen bond stable and favorable conformations were calculated. These interaction studies would help identify new potential drug candidates with the help of computer-aided drug designing techniques. Natural chemicals have received a lot of attention because of their vast range of applications in human health and disease prevention without creating any negative side effects. Molecular docking is an essential approach for drug development since it allows for effective screening of potential therapeutics in a short time. We hypothesized in this paper that natural flavanone and its derivatives may be effective as Akt-1 inhibitors.


Residual image registration error by fiducial markers in accelerated partial breast irradiation using C-arm linac: a phantom study.
External beam accelerated partial breast irradiation (APBI) is an alternative treatment for patients with early-stage breast cancer. The efficacy of image-guided radiotherapy (IGRT) using fiducial markers, such as gold markers or surgical clips, has been demonstrated. However, the effects of respiratory motion during a single fraction have not been reported. This study aimed to evaluate the residual image registration error of fiducial marker-based IGRT by respiratory motion and propose a suitable treatment strategy. We developed an acrylic phantom embedded with surgical clips to verify the registration error under moving conditions. The frequency of the phase difference in the respiratory cycle due to sequential acquisition was verified in a preliminary study. Fiducial marker-based IGRT was then performed in ten scenarios. The residual registration error (RRE) was calculated on the basis of the differences in the coordinates of clips between the true position if not moved and the last position. The frequencies of the phase differences in 0.0-0.99, 1.0-1.99, 2.0-2.99, 3.0-3.99, and 4.0-5.0 mm were 23%, 24%, 22%, 20%, and 11%, respectively. When assuming a clinical case, the mean RREs for all directions were within 1.0 mm, even if respiratory motion of 5 mm existed in two axes. For APBI with fiducial marker-based IGRT, the introduction of an image registration strategy that employs stepwise couch correction using at least three orthogonal images should be considered.


Seroreactivity to HPV-16 proteins in women with early cervical neoplasia.
Although serological reactivity to human papillomavirus type 16 (HPV-16) proteins has been demonstrated in patients with invasive cervical carcinoma, the degree of seroreactivity to these proteins in women with preinvasive disease and its relationship to the HPV type associated with the disease are unclear. We obtained sera from 27 women undergoing cone biopsy for cervical precursor lesions and 22 controls and analyzed seroreactivity by Western blot to fusion proteins containing portions of the HPV-16 E4, L1 and L2 open-reading frames (ORFs). Positives were analyzed by scanning densitometry and intensity values for each case plotted relative to controls. Cervical biopsy specimens from patients were analyzed for HPV-16 nucleic acids by DNA.DNA in situ hybridization. Mean intensity values for seroreactivity to the pATH-E4 protein approached significance (P = 0.058) and a significantly higher proportion of cases vs controls registered values over 4.0 for pATH-E4 (26% vs 4.5%; P = 0.04) and pATH-L2 (48% vs 18%; P = 0.03) proteins. A significantly higher mean intensity value for E4 was observed for cases containing HPV-16 DNA vs HPV-16 negative cases or controls. Thus, seroreactivity to HPV-16-derived proteins may be more common in women with preinvasive cervical disease, and for some protein targets (E4) may indicate a relatively type-specific response.


Inequalities and Inequities in Pediatric Respiratory Diseases.
Social inequality refers to disparities in society that have the effect of limiting a group's socioeconomic, educational, and intellectual potential. Inequity in health means any limitation to access comprehensive health services that also hinders the achievement of well-being and favorable health outcomes. Strategies for more equitable growth to eradicate global poverty would contribute to reducing health inequities and improve health care outcomes. Coordinated efforts between governments, private sector, families, and interested stakeholders are needed. This article discusses inequality and inequity in pediatric respiratory diseases, the challenges confronted, and the strategies needed to mitigate these disparities.


Long-term result of meatoplasty using inferiorly based retroauricular island pedicle flap for external auditory canal stenosis.
To characterize the long-term outcomes of meatoplasty using our new technique, inferiorly based retroauricular island pedicle flap for external auditory canal (EAC) stenosis. A long-term clinical analysis of meatoplasty for nine patients (mean age, 33 years; age range, 8-64 years) with stenotic EAC was performed. The follow-up period after meatoplasty ranged from 5 years to 14 years, with a mean duration of 8.4 years. We compared preoperative and postoperative otoscopic findings, high-resolution computed tomographic (CT) images of the EAC, and hearing levels. Otoscopic examinations demonstrated widened EAC in eight of the nine patients. There was a significant increase in the size of the EAC on postoperative CT examinations when compared with the preoperative state. The hearing outcome in all patients was variable. The postoperative air-bone gap (ABG) was closed to 10dB or less in two cases, while the other seven cases showed ABG ranging from 15.0dB to 57.5dB. We performed meatoplasty using inferiorly based retroauricular island pedicle flap for nine patients with EAC stenosis and eight of the nine patients demonstrated satisfactory patent EAC during a mean follow-up of 8.4 years.


Risk of eye diseases in osteogenesis imperfecta - A nationwide, register-based cohort study.
Osteogenesis imperfecta (OI) is a hereditary disease caused by affected collagen type 1. Collagen type 1 is an important structural component of the eye. Ocular manifestations in OI are described in literature, but little is known about the risk of eye diseases in OI. To investigate the risk of eye diseases in OI. A Danish nationwide register-based cohort study based on data from the Danish National Patient Register. All patients registered with an OI diagnosis between January 1977 and December 2018 matched 1:5 with a reference population on gender and birth month and birth year. Incidence rates (IR) per 1000 patient years and sub-hazard ratio (SHR) for any eye disease, corneal diseases, cataract, refraction disorders, vitreous haemorrhage, retinal detachment, retinopathy, angiopathy, retinal haemorrhage, retinal degeneration, retinal changes, optic nerve disorders, and traumatic eye lesions. We identified 907 OI patients (493 women) and 4535 persons (2465 women) in the reference population. The IR for any eye disease was 4.07 [95% CI 3.41-4.85] in the OI cohort and 1.96 [95% CI 1.89-2.12] in the reference cohort. The two diseases with highest incidence was cataract (2.41 [95%CI 1.93-3.03] vs 1.29 [95% CI 1.12-1.47], SHR 1.76 [95% CI 1.34-2.33]) and glaucoma (1.08 [95% CI 0.77-1.51] vs 0.42 [95% CI 0.33-0.54], SHR 2.33 [95% CI 1.55-3.53]). The absolute risk of most other eye diseases was low, but the SHR indicated a higher risk in the OI cohort compared to the reference group showing statistically increased risk of refractive disorders, vitreous haemorrhage, retinal detachment or ruptures, other retinal diseases (i.e., retinopathy, angiopathy, retinal haemorrhage, degeneration, retinal changes), and optic nerve disorders. Corneal diseases and traumatic eye lesions were not statistically significantly increased in OI-patients. Patients with OI have a higher risk of cataract, refractive disorders, glaucoma, vitreous haemorrhages, retinal detachment/ruptures, retinal diseases, and optic nerve disorders.


Upregulation of E-cadherin in bronchoalveolar lavage fluid-derived exosomes in patients with lung cancer.
Lung cancer features extremely high rates of morbidity and mortality. Bronchoalveolar lavage fluid (BALF), obtained by bronchoscopy and bronchoalveolar perfusion, can provide information on the cellular components of the lung microenvironment to assist with diagnosis and treatment of lung cancer. BALF was performed using a flexible bronchofiberscope. Exosomes were collected by ultracentrifugation. ELISA detected the amount of E-cadherin. Transmission electron microscopic, ELISA and WB were conducted to identify the existence of the exosomes. Transwell and Wound healing assays were used to detect the ability of migration and invasion. We identified the existence of exosomes in BALF. Furthermore, we observed larger amounts of E-cadherin in the BALF obtained from patients with lung cancer than in the control obtained from the healthy side of pneumonia. Exosomes from lung cancer groups promoted the migration and invasion of A549 cancer cells. The exosomes from lung cancer BALF promoted the migration and invasion of A549 cancer cells by carrying E-cadherin. E-cadherin on the surface of exosomes may act through a VE-cadherin dependent mechanism and induce lung cancer metastasis.


Stop and Play Digital Health Education Intervention for Reducing Excessive Screen Time Among Preschoolers From Low Socioeconomic Families: Cluster Randomized Controlled Trial.
High prevalence of excessive screen time among preschool children is attributable to certain parental factors such as lack of knowledge, false perception about screen time, and inadequate skills. Lack of strategies to implement screen time guidelines, in addition to multiple commitments that may hinder parents from face-to-face interventions, demands the need to develop a technology-based parent-friendly screen time reduction intervention. This study aims to develop, implement, and evaluate the effectiveness of Stop and Play, a digital parental health education intervention to reduce excessive screen time among preschoolers from low socioeconomic families in Malaysia. A single-blind, 2-arm cluster randomized controlled trial was conducted among 360 mother-child dyads attending government preschools in the Petaling district, who were randomly allocated into the intervention and waitlist control groups between March 2021 and December 2021. This 4-week intervention, developed using whiteboard animation videos, infographics, and a problem-solving session, was delivered via WhatsApp (WhatsApp Inc). Primary outcome was the child's screen time, whereas secondary outcomes included mother's screen time knowledge, perception about the influence of screen time on the child's well-being, self-efficacy to reduce the child's screen time and increase physical activity, mother's screen time, and presence of screen device in the child's bedroom. Validated self-administered questionnaires were administered at baseline, immediately after the intervention, and 3 months after the intervention. The intervention's effectiveness was evaluated using generalized linear mixed models. A total of 352 dyads completed the study, giving an attrition rate of 2.2% (8/360). At 3 months after the intervention, the intervention group showed significantly reduced child's screen time compared with the control group (β=-202.29, 95% CI -224.48 to -180.10; P<.001). Parental outcome scores also improved in the intervention group as compared with that in the control group. Mother's knowledge significantly increased (β=6.88, 95% CI 6.11-7.65; P<.001), whereas perception about the influence of screen time on the child's well-being reduced (β=-.86, 95% CI -0.98 to -0.73; P<.001). There was also an increase in the mother's self-efficacy to reduce screen time (β=1.59, 95% CI 1.48-1.70; P<.001) and increase physical activity (β=.07, 95% CI 0.06-0.09; P<.001), along with reduction in mother's screen time (β=-70.43, 95% CI -91.51 to -49.35; P<.001). The Stop and Play intervention was effective in reducing screen time among preschool children from low socioeconomic families, while improving the associated parental factors. Therefore, integration into primary health care and preschool education programs is recommended. Mediation analysis is suggested to investigate the extent to which secondary outcomes are attributable to the child's screen time, and long follow-up could evaluate the sustainability of this digital intervention. Thai Clinical Trial Registry (TCTR) TCTR20201010002; https://tinyurl.com/5frpma4b.


Induction of hybridoma growth factor (HGF), identical to IL-6, in human fibroblasts by IL-1: use of HGF activity in specific and sensitive biological assays for IL-1 and IL-6.
Human hybridoma growth factor (HGF) has been purified to homogeneity and identified with the 26kDa protein, interferon-beta 2 (IFN-beta 2), B-cell stimulatory factor-2 (BSF-2) and hepatocyte stimulatory factor (HSF). This factor, renamed interleukin-6 (IL-6), can be induced in fibroblasts by IL-1, while other cytokines are less active or inactive as inducers. The possible use of this IL-6 induction as an alternative indirect assay system for IL-1 is considered. Also, the direct HGF activity as a test IL-6 has been compared with the other biological activities of IL-6. It was concluded that the HGF assay is the most sensitive, specific and convenient test for IL-6.


Plasma and erythrocyte zinc, copper and selenium in cystic fibrosis.
Plasma and erythrocyte zinc, copper and selenium were measured in 20 cystic fibrosis children, aged 7 to 19 years. Mean plasma zinc and copper levels were not different from those in age-matched controls but very low zinc levels occurred sporadically. Plasma zinc concentrations were significantly lower in patients with moderate-to-severe growth retardation and with severe pulmonary disease as compared to patients without growth failure and with moderate pulmonary disease. Mean erythrocyte zinc (40.8 micrograms/g Hb +/- 9.2) and copper levels (3.56 micrograms/g Hb +/- 0.50) were very significantly increased (30.4 micrograms/g Hb +/- 5.2 and 2.73 micrograms/g Hb +/- 0.30 respectively, for age-matched controls). Mean plasma and erythrocyte selenium levels (63 ng/ml +/- 15 and 329 ng/g Hb +/- 86) were significantly lower than those in age-matched controls (82 ng/ml +/- 13 and 404 ng/g Hb +/- 116). The trace element concentrations in erythrocytes are discussed in relation to the activities of the copper- and zinc-containing enzyme superoxide dismutase and the seleno-enzyme glutathione peroxidase. We consider that more data on trace element metabolism in CF should be collected before specific supplementation is considered.


[The comparative characteristics of the antiatherogenic effect of xymedon and parmidine].
We've studied xymedon (30 mg/kg, 12 m) and parmidin (pyridinolcarbamate 30 mg/kg, 12 m.) effects on the development of experimental cholesterol atherosclerosis on rabbits. It was demonstrated that after the use of xymedon aorta damage reduces twice. Xymedon also prevents accumulation of cholesterol and fatty degeneration of the liver. Antiatherogenic effect of xymedon resulted comparable with the effect of parmidin. As it was demonstrated in the present investigation and in the previous ones in contrast to parmidin, xymedon normalizes the lipoproteins balance owing to increase of HDL cholesterol. It also has regenerative activity on endotheliocytes and immunomodulator properties. That can be of great importance for the anti-atherosclerotic effects of the medicine.


Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity.
Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction. To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation. Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months. One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat. One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.


SARS-CoV-2 Sequence Analysis during COVID-19 Case Surge, Liberia, 2021.
In June 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases surged in Liberia. SARS-CoV-2 sequences from patients hospitalized during March-July 2021 revealed the Delta variant was in Liberia in early March and was dominant in June, irrespective of geography. Mutations and deletions suggest multiple SARS-CoV-2 Delta variant introductions.


Is bilateral knee arthroscopy suitable as a day-case procedure?
A retrospective analysis of 100 out of 108 cases has been audited for suitability of bilateral knee arthroscopy as a day-case procedure. Fifty-three female and 47 male patients with age range of 15-78 years underwent bilateral knee arthroscopy. All patients had general anaesthetic and were ASA grade 1 or 2. Eight patients had more than one diagnosis and procedures. Post-operatively 68% could walk without walking aids, 1% had 1 stick and 31% needed 2 sticks and were given elbow crutches. One patient stayed overnight due to poor pain control and 1 attended A&E due to effusion. There were 5 (2.5%) major and 62 (31%) minor complications in 200 knees. Mild post-operative pain was the commonest minor complication in 52 (26%) out of 62 knees and was attributed to high number of bilateral arthritis cases in this study. Complication rate of bilateral arthroscopy is similar to unilateral arthroscopy. It is concluded that bilateral arthroscopy is safe as a day-case procedure.


Health-care practitioners' preferences for the return of secondary findings from next-generation sequencing: a discrete choice experiment.
Health-care practitioners' (HCPs) preferences for returning secondary findings (SFs) will influence guideline compliance, shared decision-making, and patient health outcomes. This study aimed to estimate HCPs' preferences and willingness to support the return (WTSR) of SFs in Canada. A discrete choice experiment estimated HCPs' preferences for the following attributes: disease risk, clinical utility, health consequences, prior experience, and patient preference. We analyzed responses with an error component mixed logit model and predicted WTSR using scenario analyses. Two hundred fifty participants of 583 completed the questionnaire (completion rate: 42.9%). WTSR was significantly influenced by patient preference and SF outcome characteristics. HCPs' WTSR was 78% (95% confidence interval: 74-81%) when returning SFs with available medical treatment, high penetrance, severe health consequences, and patient's preference for return. Genetics professionals had a higher WTSR than HCPs of other types when returning SFs with clinical utility and patient preference to know. HCPs >55 years of age were more likely to return SFs compared with younger HCPs. This study identified factors that influence WTSR of SFs and indicates that HCPs make tradeoffs between patient preference and other outcome characteristics. The results can inform clinical scenarios and models aiming to understand shared decision-making, patient and family opportunity to benefit, and cost-effectiveness.


Dose-response association between sedentary time and incident of diabetes in Chinese middle-aged and older adults: The 4C study.
To investigate the dose-response relationship of total sedentary time with incident diabetes in Chinese middle-aged and older adults. The present study followed 100,525 participants aged ≥ 40 years old from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was a prospective study conducted in 25 communities across mainland China. Associations between sedentary time and incident diabetes were assessed with Cox regression and restricted cubic splines. During a median follow-up of 3.8 years, 7,529 participants developed diabetes. After adjustment for multiple variables, high levels of sedentary time (≥ 30 h/week) was associated with increased risk for developing diabetes (hazards ratio, 1.08; 95 % confidence intervals 1.02, 1.14) compared with low levels of sedentary time (<20 h/week). Restricted cubic spline analyses revealed an inverted U-shaped relation between sedentary time with diabetes. Subgroup analyses found that the observed association remained significant in subgroup of individuals with body mass index (BMI) ≥ 25 kg/cm2 or diastolic blood pressure (DBP) ≥ 90 mm Hg. However, the significant association was diminished in participants with sufficient physical activity (PA) (P = 0.22). The multicenter, population-based, prospective study suggested an inverted U-shaped relation between sedentary time with diabetes. PA alleviated the deleterious effects associated with sedentary time.


Quality analysis of smart phone sleep apps in China: can apps be used to conveniently screen for obstructive sleep apnea at home?
Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence in China. Standard diagnosis of OSA requires polysomnography (PSG). Currently, smart phone applications (apps) are widely used as an important source of health guidance. However, the quality of the information provided by these apps has not been carefully assessed. We searched for sleep apps available in China. We designed an evaluation scale that included scientific, functionality and usability, and accountability domains. The Scientific domain included an index of 16 items to evaluate the scientific quality of the apps for their level of adherence to PSG. The functionality and usability domain included 10 items to evaluate the functions of apps and 1 item to define whether the apps needed to connect with other devices. The accountability domain included 9 items that came from the Silberg Scale to evaluate whether the information provided by apps were trustable or not. We then calculated the sum of all domains. We also evaluated the popularity of each app. A total of 2379 apps were found, and 127 met the inclusion criteria. The mean total score of the apps was 14.23 ± 3.93. The mean scores of scientific basis, functionality and usability, and accountability were 5.51 ± 2.58, 2.90 ± 1.84, and 2.90 ± 1.84. The scientific scores of apps that could connect to other devices were higher than those of apps that worked alone (mean score: 5.26 vs. 4.17, P < 0.001). The functionality and usability score was correlated with the accountability score, and the coefficient of correlation was 0.304 (P = 0.001). Apps that could connect to other devices were more scientific and powerful than those that worked alone. Multifunctional apps were more popular and reliable. Because of the low quality of sleep apps in China, more work is necessary to create an ideal app.


Coronary perfusion pressure and left ventricular hemodynamics as predictors of cardiovascular collapse following percutaneous coronary intervention.
Appropriate patient selection for mechanical circulatory support following percutaneous coronary intervention (PCI) remains a challenge. This study aims to evaluate the role of coronary perfusion pressure and other left ventricular hemodynamics to predict cardiovascular collapse following PCI. We retrospectively analyzed all patients who underwent PCI for acute coronary syndrome (ACS) from 2003 to 2016. Coronary perfusion pressure was calculated for each patient and defined as the difference in mean arterial pressure and left ventricular end diastolic pressure (LVEDP). Logistic regression analysis was performed to determine predictor of composite outcome of in-hospital mortality, myocardial infarction (MI), congestive heart failure (CHF), and cardiogenic shock. Nine hundred twenty-two patients were analyzed. Two-hundred twenty-eight (25%) presented with ST-elevation MI (STEMI) while 694 (75%) underwent PCI for unstable angina or non-Q-wave MI. The mean LVEDP was significantly higher in the STEMI patients (24 ± 9 vs. 19 ± 8 mm Hg, p < 0.05) and perfusion pressure significantly lower (68 ± 24 vs. 74 ± 18 mm Hg, p < 0.05). Eighty-seven (9.4%) reached the composite endpoint, and there was no difference between the STEMI and Not-STEMI groups. Neither LVEDP nor coronary perfusion pressure was a predictor of the composite outcome following multivariable logistic regression analysis for either STEMI or Not-STEMI patients. Increasing age, chronic renal insufficiency (CRI), CHF, and low left ventricular ejection fraction were predictors of the composite outcome for Not-STEMI patients, whereas only history of cerebrovascular accident and CRI were predictors for STEMI patients. In hemodynamically stable patients presenting with ACS, LVEDP and coronary perfusion pressure are not predictive of in-hospital cardiovascular collapse. The authors retrospectively analyzed 922 patients from a single center who underwent percutaneous coronary intervention (PCI) for acute coronary syndromes to evaluate the role of coronary perfusion pressure and other left ventricular hemodynamics to predict cardiovascular collapse following PCI. They found that neither coronary perfusion pressure nor left ventricular end diastolic pressure was predictive of in-hospital cardiovascular collapse.


Global estimates on the number of persons across the Alzheimer's disease continuum.
Global estimates on numbers of persons in early stages of Alzheimer's disease (AD), including prodromal and preclinical, are lacking, yet are needed to inform policy decisions on preventive measures and planning for future therapies targeting AD pathology. We synthesized the literature on prevalence across the AD continuum and derived a model estimating the number of persons, stratified by 5-year age groups, sex, and disease stage (AD dementia, prodromal AD, and preclinical AD). The global number of persons with AD dementia, prodromal AD, and preclinical AD were estimated at 32, 69, and 315 million, respectively. Together they constituted 416 million across the AD continuum, or 22% of all persons aged 50 and above. Considering predementia stages, the number of persons with AD is much larger than conveyed in available literature. Our estimates are uncertain, especially for predementia stages in low- and middle-income regions where biomarker studies are missing.


Glomerular diseases in children. "The Iranian experience".
A total of 411 children, aged from 0.3 to 18 years, suffering from glomerular diseases, were studied by renal biopsy between 1976 and 1985. The clinical presentation included nephrotic syndrome (79% of cases), renal failure (43%), and arterial hypertension (38%). In all, 177 cases presented with primary nephrotic syndrome; all had complicated courses and most were either corticosteroid-dependent or -resistant. Only 26.6% had minimal change disease on renal biopsy; 56.5% had focal-segmental sclerosis; and immunofluorescent deposits were observed in half of the group. Acute poststreptococcal (36 cases), mesangiocapillary (80 cases), and lupus (34 cases) glomerulonephritis occurred frequently; IgA glomerulopathy (10 cases) and haemolytic uraemic syndrome (6 cases) were uncommon. Glomerular crescents were observed in 71 cases. These observations illustrate the types of glomerular diseases seen in Iranian children.


[A rare case of suppurative mesenteric adenitis associated with intussusception in a child: a clinical case].
Some cases of suppurative mesenteric adenitis have already been described in the literature but not associated with intussusception. We describe the case of a 3-year-old boy presenting to the department of surgery at the University Hospital of Lubumbashi with bowel obstruction. He was visited elsewhere, in the previous 12 days, for diarrhea, vomiting, fever, coma and treated for cerebral malaria and blackwater fever. Surgery revealed an ileal intussusception and a suppurative mesenteric adenitis whose pyoculture revealed the presence of Enterobacter cloacae, sensitive to norfloxacin. We performed desinvagination, sucked the pus out into a syringe and excized completely the site of suppurative adenitis. The evolution of patient was good. The clinician must know that the association between suppurative mesenteric adenitis and intussusceptions exists. The diagnosis is not easy and there is the risk of developing acute peritonitis due to its fistulation in the abdominal cavity.


Creation of an atrial septal defect for acute postperfusion right ventricular failure.
Acute postperfusion right ventricular failure following mitral and aortic valve replacement in a patient with severe double-valve incompetence secondary to endocarditis is presented. The situation was reversed by creating an atrial septal defect that decompressed the right ventricle and increased left ventricular filling pressure.


Morphologic and phenotypic analysis of canine natural killer cells: evidence for T-cell lineage.
Canine natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity were studied utilizing a canine thyroid adenocarcinoma cell line and a lymphoblastoid cell line (CT-45S), respectively, as cell targets. Fractionation of peripheral blood mononuclear cells by Percoll discontinuous-gradient centrifugation resulted in a six- to sevenfold enrichment in large granular lymphocytes (LGL) in parallel with a twofold increase in NK activity (%specific lysis) in low-density fractions. Further enrichment in LGL (78 +/- 6%) and NK activity (threefold increase) was obtained by lytic treatment of low-density fractions 2 and 3 with monoclonal antibody WIG4. By means of cytolytic treatment with additional monoclonal antibodies the phenotype of canine NK cells was determined as Dly-1+, Dly-6+, 1A1+, E-11+, DT-2-, WIG4-. Some NK cells were also Ia+. NK activity was relatively radioresistant with 40% specific lysis even after irradiation with 40 Gy. Among the populations examined, the highest NK activity was found in peripheral blood mononuclear cells, followed by splenic mononuclear cells and bone marrow mononuclear cells. These results indicate that canine NK cells have the morphology of LGL, are relatively radioresistant, and express cell surface antigens suggesting a T-cell lineage.


Ecologic Momentary Assessment: Perspectives on Applications and Opportunities in Research and Practice Regarding Nutrition Behaviors.
Retrospective self-reported data have limitations, making it important to evaluate alternative forms of measurement for nutrition behaviors. Ecological momentary assessment (EMA) attempts to overcome the challenges of recalled data with real-time data collection in a subject's natural environment, often leveraging technology. This perspective piece 1) introduces the concepts and terminology of EMA, 2) provides an overview of the methodological and analytical considerations, 3) gives examples of past research using EMA, and 4) suggests new opportunities (including combining assessment and intervention) and limitations (including the need for technology) for the application of EMA to research and practice regarding nutrition behaviors.


Rapid freshening of the deep North Atlantic Ocean over the past four decades.
The overflow and descent of cold, dense water from the sills of the Denmark Strait and the Faroe Shetland channel into the North Atlantic Ocean is the principal means of ventilating the deep oceans, and is therefore a key element of the global thermohaline circulation. Most computer simulations of the ocean system in a climate with increasing atmospheric greenhouse-gas concentrations predict a weakening thermohaline circulation in the North Atlantic as the subpolar seas become fresher and warmer, and it is assumed that this signal will be transferred to the deep ocean by the two overflows. From observations it has not been possible to detect whether the ocean's overturning circulation is changing, but recent evidence suggests that the transport over the sills may be slackening. Here we show, through the analysis of long hydrographic records, that the system of overflow and entrainment that ventilates the deep Atlantic has steadily changed over the past four decades. We find that these changes have already led to sustained and widespread freshening of the deep ocean.


Relationship between gene mutation and lung cancer metastasis.
Cancer is a genetic disease occurring through a multi-step process. Many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely identified and the pathways through which they act characterized. One question that remains unanswered is whether the development of new, more specific therapeutic agents is the best way to minimize cancer morbidity and mortality in the long-term. Metastasis is the relentless pursuit of cancer to escape its primary site and colonize distant organs. Phenotypic changes during cancer progression reflect the sequential accumulation of genetic alterations, which endow cancer cells with the ability to undergo their own divergent evolution and create distinct metastatic species. In order to understand this process, it is crucial to identify genes whose alterations accumulate during cancer progression and correlate with metastatic phenotypes of cancer cells.


Potential histological discordance revealed by second review in the national rare gynecological cancer network (TMRG).
Since 2010, the network of rare malignant tumors of the ovary (TMRG) was developed to optimize the management of patients, also allowing a histological second opinion of rare ovarian tumors. The aim of this work was to study the contribution of second opinion to improve histological diagnostic accuracy on ovarian rare malignant tumors included in the TMRG database. Histological data of patients diagnosed with a rare ovarian tumor included in TMRG network over a one-year period (2018) were collected. Initial diagnoses were compared with second opinion from national gynecological pathologist experts. The modalities of histological second opinion requests were studied, as well as the histological characteristics of the tumors. The discordances were classified as minor (if the modification of histological diagnosis did not change patient management) and major (if the patient management can be modified). Of 1185 included patients, 937 matched the inclusion criteria. Full concordance between primary diagnosis and expert second opinion was reached in 611 cases (65,3%), minor discordance was seen in 114 (12,2%) and major discordance in 209 (22,3%) of cases. In systematic review requested by the network, 26% (n = 137) of cases were reported with a change in histological diagnosis, while the change concerned 44% (n = 186) of cases for a second opinion spontaneously requested by the initial pathologist. The discrepancies concerned all categories of ovarian tumors, with a majority of mucinous tumors (43% of major discordances), followed by stromal and sex-cord tumors (13.8% of major discordances) and clear cell tumors (12,4% of major discordances). This analysis confirms the diagnostic difficulty of ovarian tumors, due to their rarity and morphological heterogeneity. French pathologists are aware of these difficulties and spontaneously refer ovarian tumors with unusual histology for a second opinion and collaborate with rare tumor networks for systematic review.


Comparative effects of carvedilol and metoprolol on regional vascular responses to adrenergic stimuli in normal subjects and patients with chronic heart failure.
Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that alpha-adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol. Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip -3.5 U for carvedilol versus -1.2 U for metoprolol and -2.2 U for placebo, P=0.15; cold pressor test 3.1+/-8.9 U for carvedilol versus 9.0+/-2.7 U for metoprolol and 8.2+/-5.8 U for placebo, P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups. Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by alpha-adrenergic blockade.


Prognostic significance of estrogen and progesterone receptors in stage II breast cancer.
Estrogen (ER) and progesterone receptors (PgR) were evaluated in samples from primary tumors in 539 patients with stage II breast cancer participating in a randomized multicenter controlled clinical trial on adjuvant therapy. At the cut-off points of 10 fmol ER/mg protein and 30 fmol PgR/mg protein, no significant difference in recurrence-free survival (RFS) existed between premenopausal patients with receptor-positive and negative tumors, respectively. After recurrence, premenopausal patients with receptor-positive tumors had a significant longer survival than patients with receptor-negative tumors. In postmenopausal patients not treated with adjuvant tamoxifen, no correlations between RFS and receptor status were found. Patients with ER+ tumors survived longer than patients with ER-tumors. In postmenopausal patients treated with adjuvant tamoxifen, highly significant differences in RFS and in survival were observed when receptor-positive patients were compared with receptor-negative patients. No differences in survival after recurrence were registered among these patients.


Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis.
Autologous hematopoietic stem cell transplantation (aHSCT) is a highly effective treatment of multiple sclerosis (MS). It depletes autoreactive cells and subsequently renews adaptive immune cells. The possible proinflammatory potential of surviving T cells early after aHSCT has not been studied. Here, we examined the dynamics of new and surviving T cells in 27 patients after aHSCT by multidimensional flow cytometry, T cell receptor (TCR) sequencing, specificity testing, telomere length profiling, and HLA genotyping. Early after aHSCT, naïve T cells are barely detectable, whereas effector memory (EM) T cells quickly reconstitute to pre-aHSCT values. EM CD4+ T cells early after aHSCT have shorter telomeres, have higher expression of senescence and exhaustion markers, and proliferate less than those before aHSCT. We find a median TCR repertoire overlap of 26% between the early post-aHSCT EM CD4+ T cells and pre-aHSCT, indicating persistence of EM CD4+ T cells early after transplantation. The EM CD4+ TCR repertoire overlap declines to 15% at 12 months after aHSCT, whereas the naïve TCR repertoire entirely renews. HLA-DR-associated EM CD4+ T cell reactivity toward MS-related antigens decreased after aHSCT, whereas reactivity toward EBV increased. Our data show substantial survival of pre-aHSCT EM CD4+ T cells early after transplantation but complete renewal of the T cell repertoire by nascent T cells later.


Effects of cannabinoids and cocaine on the mitogen-induced transformations of lymphocytes of human and mouse origins.
The effects of delta 9-tetrahydrocannabinol (d9THC), delta 6-tetrahydrocannabinol (d6THC), and cocaine on the mitogen-induced transformations of lymphocytes of human and mouse origins were examined in an in vitro system. None of the three compounds is mitogenic in nature. The effects of the two components of marijuana on the mitogen-induced transformation are biphasic. Both compounds stimulated the lymphocyte transformation at low concentrations and inhibited mitogenesis at high concentrations. Cocaine, on the other hand, neither affected mitogen-induced lymphocyte transformations nor altered d9THC's transformation effects when both compounds were added together. Human lymphocytes and mouse splenocytes appeared to respond in similar patterns.


The human auditory brain stem as a generator of auditory evoked potentials.
Data on the size, location, and orientation of human brain stem auditory nuclei are discussed here from the point of view of the potential role of these structures in generation of the brain stem auditory evoked response. Due to reduction in size of several nuclei in the human brain stem, the structures most likely to be generators of far-field potentials are the cochlear nuclei, medial olivary nuclei, dorsal lemniscal nuclei, inferior colliculi, and their axonal projections. Consideration of the anatomy of the human auditory brain stem pathway forms the basis for a model of generation of auditory evoked potentials.


Isolation of 11 beta-hydroxylated androgens from testicular vein blood of the mature boar.
The isolation of 11 beta-hydroxyandrostenedione and 11 beta-hydroxytestosterone from testicular vein blood of the mature male domestic pig is described. Blood was collected from veins and arteries on the surface of the testes of mature boars. Steroids were extracted from plasma with SEP-PAK C18 cartridges and recovered with acetonitrile. A separation of steroids was made by high performance liquid chromatography (HPLC) using acetonitrile/water (37/63; v/v), and fractions were collected manually with detection at 254 nm. Preliminary identification was based on comparison with the HPLC retention time of an authentic steroid standard. Final characterization was achieved by means of capillary gas chromatography-mass spectrometry (GC-MS). The findings record the first evidence for the secretion of C19-11-hydroxylated steroids by normal testes in a mammalian species.


Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of non-palpable testis.
Studies were needed to evaluate the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) for diagnosing non-palpable testis, and to study the clinical usefulness of US and MRI before surgical exploration. Fifty-six patients with non-palpable testis aged 1--12 years were examined between 1993 and 2002. Forty-six patients (55 non-palpable testes) underwent US. Forty patients (47 non-palpable testes) were examined using MRI. Both US and MRI were used in 29 patients (34 non-palpable testes). We used Fisher's exact probability test to compare the results of these graphic examinations with the surgical or laparoscopic findings for the non-palpable testis. Ultrasonography had a sensitivity of 76%, a specificity of 100%, and an accuracy of 84% in the diagnosis of non-palpable testis, whereas MRI had a sensitivity of 86%, a specificity of 79%, and an accuracy of 85%. There were no statistically significant differences in the accuracy rates of US and MRI for diagnosing non-palpable testis. Laparoscopy or inguinal exploration should be performed even if these graphic examinations demonstrate the absence of a testis, because some patients with a non-palpable testis were found to be false negatives. We recommend US as the first step after clinical examination, and MRI could be performed when the US findings are negative preoperatively for a non-palpable testis.


Personal view: to treat or not to treat? Helicobacter pylori and gastro-oesophageal reflux disease - an alternative hypothesis.
Helicobacter pylori causes acute on chronic gastritis and is responsible for most peptic ulcers and gastric cancer. However, recent papers have suggested that it may protect against gastro-oesophageal reflux, Barrett's oesophagus and oesophageal cancer. Furthermore, the rapid increase in gastro-oesophageal reflux disease, Barrett's oesophagus and adenocarcinoma of the oesophagus in the developed world has been attributed by some to the falling prevalence of H. pylori. These considerations have led to the suggestion that H. pylori infection should not necessarily be treated, especially in patients with gastro-oesophageal reflux disease. Conversely, data from prospective randomized studies have shown that H. pylori eradication does not cause gastro-oesophageal reflux disease in patients with duodenal ulcer or in the normal population, nor does it worsen the outcome of pre-existing gastro-oesophageal reflux disease. Therefore, although H. pylori is negatively associated with gastro-oesophageal reflux disease, its eradication does not induce the disease. A hypothesis is presented suggesting that the increased prevalence of gastro-oesophageal reflux disease is a result of rising acid secretion in the general population, which, in turn, is a consequence of the increased linear height (a predictor of acid secretion). The greater acid secretion could also explain the decline in the prevalence of H. pylori and perhaps account for the inverse relationship between H. pylori and gastro-oesophageal reflux disease. These considerations are explored in discussing whether H. pylori infection should be treated in infected patients presenting with gastro-oesophageal reflux disease.


A sensitive rosetting method for detecting subpopulations of lymphocytes which react with alloantisera.
A procedure is described for directly estimating the proportion of mouse lymphoid cell suspensions which react with alloantisera. The method entails reacting Ig-capped lymphoid cells with alloantisera, and then assessing the uptake of alloantibodies by rosetting the lymphocytes with SRBC coated with sheep IgG specific for mouse Ig. This rosetting procedure was found to be generally more sensitive than the conventional dye exclusion microcytotoxicity test for detecting the binding of alloantibodies to lymphocytes. Furthermore, the rosette method has the advantage that, unlike the complement lysis technique, it has a low and reproducible background and lymphocyte subpopulations which react with alloantisera can be isolated.


Energy measurements and requirements of critically ill patients.
The energy expenditure of the critically ill patient is influenced by many factors, thus making it difficult to predict. Measurement of energy expenditure in mechanically ventilated patients receiving elevated oxygen concentrations requires a good understanding of the measurement technique and its limitations, whether it be the gas exchange or Fick method. More investigation is needed to better understand the determinants of energy expenditure, as well as the total energy requirements of the critically ill patient.


Neuroprotective role of naringenin on carbaryl induced neurotoxicity in mouse neuroblastoma cells.
Neuroprotective effect of naringenin against carbaryl toxicity was studied in mouse neuroblastoma cell line. Mouse neuroblastoma cells (Neuro 2A) obtained from National Center for Cell Sciences, Pune, India were either exposed to carbaryl or pre-treated with naringenin (a flavonoid prepared from grape fruit) before their exposure to carbaryl. Results were analyzed using MTT [3-4,5-Dimethylthiazol-2-yl)-2,5-diphenltetrazolium bromide] assay for cell viability, FACS (fluorescence assisted cell sorting) analysis for apoptotic and necrotic cell populations, DCFH-DA (2`,7`-dichlorofluorescin-diacetate) assay for Reactive Oxygen Species (ROS) visualization, JC-1 staining for determining mitochondrial membrane potential and real-time PCR for quantifying pro and anti-apoptotic gene expression. Exposure to naringenin resulted in better survival of Neuro 2A cells which were subsequently subjected to carbaryl toxicity. Treatment with naringenin was found to reduce the oxidative stress by decreasing the ROS and was found to maintain the integrity of mitochondrial membrane potential. It was also found to downregulate pro-apoptotic genes (BAX and Caspase-3) while upregulating anti-apototic gene (Bcl2). The results of this pilot study underline the potential of naringenin in treating carbaryl induced neurotoxicity and further studies are warranted to establish the effect of naringenin in vivo conditions.


Unforeseen cardiac involvement in McArdle's disease.
McArdle's disease (glycogen storage disease type V) is a rare autosomal recessive metabolic myopathy due to myophosphorylase deficiency. It classically manifests by exercise intolerance, leg cramps, muscle pain and occasionally exercise induced myoglobinuria. The onset of exercise intolerance is typically in the second or third decades of life. It has a specific predilection to skeletal muscle involvement, yet cardiac muscle involvement is very rare. This report describes an unusual case of a 33 year-old man with known McArdle's disease who presented with an incidental finding of severe obstructive hypertrophic cardiomyopathy.


The overexpression and clinical significance of TBX15 in human gliomas.
T-box transcription factor 15 (TBX15) is upregulated in a variety of tumors and has been reported to promote uncontrolled proliferation of tumor cells and induce tumor cells to avoid apoptosis, thus accelerating the malignant transformation of malignant tumors. However, the prognostic value of TBX15 in glioma and its relationship with immune infiltration remain unknown. In this study, we intended to explore the prognostic value of TBX15 and its link to glioma immune infiltration and examine TBX15 expression in pan-cancer using RNAseq data in TPM format from TCGA and GTEx. TBX15 mRNA and protein expressions in glioma cells and adjacent normal tissue were detected and compared by RT-qPCR and Western blot. The effect of TBX15 on survival was assessed by Kaplan-Meier Method. The correlation between TBX15 upregulation and the clinicopathological characteristics of glioma patients was assessed by using TCGA databases, and the relationship between TBX15 and other genes in glioma was evaluated by using TCGA data. The top 300 genes most significantly associated with TBX15 were selected to establish a PPI network through the STRING database. The relationship between TBX15 mRNA expression and immune cell infiltration was explored by using ssGSEA and the TIMER Database. It was found that TBX15 mRNA expression in glioma tissues was significantly higher than that in the adjacent normal tissues, and this difference was most obvious in high-grade gliomas. TBX15 expression was increased in human gliomas and associated with worse clinicopathological characteristics and poorer survival prognosis in glioma patients. In addition, elevated TBX15 expression was linked to a collection of genes involved in immunosuppression. In conclusion, TBX15 played an important role in immune cell infiltration in glioma and may prove to be a predictor of the prognosis in glioma patients.


Lipopolysaccharide represses the expression of ATP-binding cassette transporter G1 and scavenger receptor class B, type I in murine macrophages.
To investigate the regulation of cholesterol transporters, including ATP-binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor class B, type I (SR-BI), by inflammatory stimuli in macrophages. MATERIALS AND TREATMENTS: RAW 264.7 macrophages and mouse peritoneal macrophages were treated with inflammatory stimuli with or without rosiglitazone, a peroxisome proliferator activated receptor γ (PPARγ) agonist, or T0901317, a liver X receptor (LXR) agonist. Real-time PCR and Western blotting for cholesterol transporters as well as cellular cholesterol efflux to high-density lipoprotein 2 (HDL(2)) were determined. In RAW 264.7 macrophages, lipopolysaccharide (LPS) significantly reduced ABCG1 and PPARγ as well as cholesterol efflux to HDL(2). Rosiglitazone and T0901317 induced ABCA1 and ABCG1 several-fold, but LPS reduced only ABCG1. ABCG1 and SR-BI proteins, but not ABCA1, were decreased by LPS. In mouse peritoneal macrophages, LPS, tumor necrosis factor α and interleukin-1β decreased ABCG1, SR-BI, LXRα and PPARγ mRNA. The agonists increased ABC transporter expression but LPS reduced mRNA of T0901317-induced ABCA1 as well as basal and agonists-induced ABCG1. SR-BI protein was increased by rosiglitazone but LPS decreased the levels. The data suggest that inflammatory insults repress ABCG1 and SR-BI expression partly dependent on PPARγ with a minimal effect on ABCA1 expression.


Defining the Culture of Surgery.
Surgical culture is often referenced but not well defined. Recent research and changing policies in graduate medical education have influenced the training paradigm and expectations of surgical trainees. It is unclear how these changes impact surgeons' understanding of surgical culture today and how those views impact surgical training. We sought to understand surgical culture and its impact on training from the perspective of a diverse group of surgeons with varied amounts of experience. A series of semi-structured, qualitative interviews were conducted with 21 surgeons and trainees in a single academic institution. Interviews were transcribed, coded, and analyzed using directed content analysis. We identified 7 major themes that impact surgical culture. Cohorts were separated by those who had been promoted to at least associate professor (late-career surgeons) and assistant professors, fellows, residents, and students (early-career surgeons). Both cohorts similarly emphasized patient-centered care, hierarchy, high standards, and meaningful work. Late- and early-career surgeons highlighted themes differently: late-career surgeons' perceptions were informed by experience and focused on challenges, complications, humility, and work ethic, while perceptions of early-career surgeons were more individually focused and referenced being goal-oriented and self-sacrificing, and focus on education and work-life balance. Late- and early-career surgeons both emphasize that patient-centered care is core to surgical culture. Early-career surgeons expressed more themes related to personal well-being, while late-career surgeons emphasized themes related to professional accomplishment. Differences in the perceived culture can lead to strained interactions between generations of surgeons and trainees, and a better understanding of these differences would lead to improved communication and interactions between these groups, as well as better management of expectations for surgeons in their training and career.


Burnout Among Surgeons in the UK During the COVID-19 Pandemic: A Cohort Study.
Surgeon burnout has implications for patient safety and workforce sustainability. The aim of this study was to establish the prevalence of burnout among surgeons in the UK during the COVID-19 pandemic. This cross-sectional online survey was set in the UK National Health Service and involved 601 surgeons across the UK of all specialities and grades. Participants completed the Maslach Burnout Inventory and a bespoke questionnaire. Outcome measures included emotional exhaustion, depersonalisation and low personal accomplishment, as measured by the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). A total of 142 surgeons reported having contracted COVID-19. Burnout prevalence was particularly high in the emotional exhaustion (57%) and depersonalisation (50%) domains, while lower on the low personal accomplishment domain (15%). Burnout prevalence was unrelated to COVID-19 status; however, the greater the perceived impact of COVID-19 on work, the higher the prevalence of emotional exhaustion and depersonalisation. Degree of worry about contracting COVID-19 oneself and degree of worry about family and friends contacting COVID-19 was positively associated with prevalence on all three burnout domains. Across all three domains, burnout prevalence was exceptionally high in the Core Trainee 1-2 and Specialty Trainee 1-2 grades. These findings highlight potential undesirable implications for patient safety arising from surgeon burnout. Moreover, there is a need for ongoing monitoring in addition to an enhanced focus on mental health self-care in surgeon training and the provision of accessible and confidential support for practising surgeons.


Combination treatment with high-dose vitamin C and alpha-tocopherol does not enhance respiratory-tract lining fluid vitamin C levels in asthmatics.
Oxidative stress plays a significant role in allergic airway inflammation. Supplementation with alpha-tocopherol (alone or combined with ascorbate/vitamin C) has been assessed as an intervention for allergic airway diseases with conflicting results. Enhancing levels of airway antioxidants with oral supplements has been suggested as an intervention to protect individuals from the effect of inhaled oxidants, although it is unclear whether supplementation changes tocopherol or vitamin C levels in both serum and airway fluids. Our objective was to obtain pilot safety and dosing data from 14 allergic asthmatic volunteers examining the effect of daily combination oral therapy with 500 mg alpha-tocopherol (alpha T) and 2 g vitamin C for 12 wk. We examined serum and airway fluid and cellular levels of alpha- and gamma-tocopherol (gamma T) and vitamin C to plan for future studies of these agents in asthma and allergic rhinitis. Six volunteers completed 12 wk of active treatment with alpha T and vitamin C and 8 completed placebo. Blood and sputum samples were obtained at baseline and at 6 wk and 12 wk of therapy and were analyzed for alpha T, gamma T, and vitamin C levels in the serum, sputum supernatant, and sputum cells. Combination treatment increased serum vitamin C and significantly decreased sputum alpha T and serum gamma T levels. No changes were found in sputum supernatant or sputum cell vitamin C or serum alpha T levels in the active treatment group. In conclusion, supplementation with alpha T and high-dose vitamin C does not augment vitamin C levels in the respiratory-tract lining fluid.


Redundant representations are required to disambiguate simultaneously presented complex stimuli.
A pedestrian crossing a street during rush hour often looks and listens for potential danger. When they hear several different horns, they localize the cars that are honking and decide whether or not they need to modify their motor plan. How does the pedestrian use this auditory information to pick out the corresponding cars in visual space? The integration of distributed representations like these is called the assignment problem, and it must be solved to integrate distinct representations across but also within sensory modalities. Here, we identify and analyze a solution to the assignment problem: the representation of one or more common stimulus features in pairs of relevant brain regions-for example, estimates of the spatial position of cars are represented in both the visual and auditory systems. We characterize how the reliability of this solution depends on different features of the stimulus set (e.g., the size of the set and the complexity of the stimuli) and the details of the split representations (e.g., the precision of each stimulus representation and the amount of overlapping information). Next, we implement this solution in a biologically plausible receptive field code and show how constraints on the number of neurons and spikes used by the code force the brain to navigate a tradeoff between local and catastrophic errors. We show that, when many spikes and neurons are available, representing stimuli from a single sensory modality can be done more reliably across multiple brain regions, despite the risk of assignment errors. Finally, we show that a feedforward neural network can learn the optimal solution to the assignment problem, even when it receives inputs in two distinct representational formats. We also discuss relevant results on assignment errors from the human working memory literature and show that several key predictions of our theory already have support.


Effect of inbreeding on pollen tube growth in diploid and tetraploid Chamerion angustifolium: Do polyploids mask mutational load in pollen?
Deleterious recessive mutations are an important determinant of fitness (mutational load) in the sporophytic phase of plants and a major cause of inbreeding depression; however, their role in gametophyte function is less well documented but may account for variation in pollen tube growth and siring ability, especially between diploid and polyploid plants, which can mask the load. We investigated the role of mutational load in pollen performance using the perennial polyploid Chamerion angustifolium by comparing tube growth of pollen, in styles and in growth medium, from inbred (selfed) and outbred diploids to that of inbred and outbred tetraploids. Pollen from tetraploids is expected to mask deleterious mutations more effectively in the outbred condition but reveal them after inbreeding. In contrast, gametophytes from diploids should express the same genetic load in inbred or outbred plants. Pollen tube growth measured in growth medium was highest in outbred tetraploids and generally lower in inbred than outbred plants. The effect of selfing was significant in pollen from tetraploids but not diploids. The differential effect of selfing was also evident in the proportion of pollen reaching the base of styles, but the ploidy × pollination interaction was not significant. Selfing also had a negative effect on sporophyte fitness but was greater in diploids than tetraploids. Pollen performance is influenced by the expression of mutational load, which is masked in polyploids. This effect may partly explain strong siring success of tetraploids in this species.


Action-selection perseveration in young children: Advances of a dynamic model.
This study presents an empirical test and dynamic model of perseverative limb selection in children of 14-, 24-, and 36-months old (N = 66 in total). In the experiment, children repeatedly grasped a spoon with a single hand. In two separate conditions, the spoon was presented either four times on their right side or four times on their left side. In both conditions, following this training, the spoon was presented on midline for two more trials. This setup enabled us to determine whether children's limb selection was influenced by their prior choices in the task (i.e., perseveration). Individual children's handedness was determined in a third condition consisting of nine object presentations (laterally or on midline). A dynamic model for limb selection is presented combining external input, motor memory, and preferences. The model was used to simulate the experiment and reproduced the results, including the age-related changes.


Alternative splicing of transcription factors in plant responses to low temperature stress: mechanisms and functions.
Transcription factors play a central role in the gene regulatory networks that mediate various aspects of plant developmental processes and responses to environmental changes. Therefore, their activities are elaborately regulated at multiple steps. In particular, accumulating evidence illustrates that post-transcriptional control of mRNA metabolism is a key molecular scheme that modulates the transcription factor activities in plant responses to temperature fluctuations. Transcription factors have a modular structure consisting of distinct protein domains essential for DNA binding, dimerization, and transcriptional regulation. Alternative splicing produces multiple proteins having different structural domain compositions from a single transcription factor gene. Recent studies have shown that alternative splicing of some transcription factor genes generates small interfering peptides (siPEPs) that negatively regulate the target transcription factors via peptide interference (PEPi), constituting self-regulatory circuits in plant cold stress response. A number of splicing factors, which are involved in RNA binding, splice site selection, and spliceosome assembly, are also affected by temperature fluctuations, supporting the close association of alternative splicing of transcription factors with plant responses to low temperatures. In this review, we summarize recent progress on the temperature-responsive alternative splicing of transcription factors in plants with emphasis on the siPEP-mediated PEPi mechanism.


Studies of binding by sulfonylureas with glyoxal- and methylglyoxal-modified albumin by immunoextraction using affinity microcolumns.
Diabetes is characterized by elevated levels of blood glucose, which can result in the modification of serum proteins. The modification of a protein by glucose, or glycation, can also lead to the formation of advanced glycated end-products (AGEs). One protein that can be modified through glycation and AGE formation is human serum albumin (HSA). In this study, immunoextraction based on polyclonal anti-HSA antibodies was used with high-performance affinity microcolumns to see how AGE-related modifications produced by glyoxal (Go) and methylglyoxal (MGo) affected the binding of HSA to several first- and second-generation sulfonylureas, a class of drugs used to treat type II diabetes and known to bind to HSA. With this approach, it was possible to use a single platform to examine drug interactions with several preparations of HSA. Each applied protein sample could be used over 20-50 experiments, and global affinity constants for most of the examined drugs could be obtained in less than 7.5 min. The binding constants measured for these drugs with normal HSA gave good agreement with global affinities based on the literature. Both Go- and MGo-related modifications at clinically relevant levels were found by this method to create significant changes in the binding by some sulfonylureas with HSA. The global affinities for many of the drugs increased by 1.4-fold or more; gliclazide and tolazamide had no significant change with some preparations of modified HSA, and a small-to-moderate decrease in binding strength was noted for glibenclamide and gliclazide with Go-modified HSA. This approach can be adapted for the study of other drug-protein interactions and alternative modified proteins by altering the antibodies that are employed for immunoextraction and within the affinity microcolumn.


Inhibition of gastric H+,K(+)-ATPase and acid secretion by cassigarol A, a polyphenol from Cassia garrettiana Craib.
The effects of cassigarol A, a naturally occurring polyphenol, on gastric H+,K(+)-ATPase and gastric acid secretion were studied. Cassigarol A inhibited H+,K(+)-ATPase and K-stimulated p-nitrophenyl phosphatase from hog gastric mucosa with 50% inhibition of 1.2 x 10(-6) and 6.3 x 10(-6) M, respectively. The kinetic study showed that the inhibition of H+,K(+)-ATPase by cassigarol A was competitive with respect to ATP and non-competitive with respect to K+. Cassigarol A inhibited both H+,K(+)-ATPase-mediated proton transport and 2-deoxy-D-glucose-induced acid secretion. On the other hand, cassigarol A acetate, in which phenolic hydroxy groups are acetylated, was not effective in the inhibition of enzyme activity and acid secretion. These results indicate that cassigarol A is a potent inhibitor of gastric H+,K(+)-ATPase, that the anti-secretory activity of cassigarol A is related to the inhibition of H+,K(+)-ATPase and that an important moiety of cassigarol A in the interaction with the enzyme is the phenolic hydroxy groups.


Propolis-Based Nanostructured Lipid Carriers for α-Mangostin Delivery: Formulation, Characterization, and In Vitro Antioxidant Activity Evaluation.
α-Mangostin (a xanthone derivative found in the pericarp of Garcinia mangostana L.) and propolis extract (which is rich in flavonoids and phenols) are known for their antioxidant properties, making them potential supplements for the treatment of oxidative stress-related conditions. However, these two potential substances have the same primary drawback, which is low solubility in water. The low water solubility of α-mangostin and propolis can be overcome by utilizing nanotechnology approaches. In this study, a propolis-based nanostructured lipid carrier (NLC) system was formulated to enhance the delivery of α-mangostin. The aim of this study was to characterize the formulation and investigate its influence on the antioxidant activity of α-mangostin. The results showed that both unloaded propolis-based NLC (NLC-P) and α-mangostin-loaded propolis-based NLC (NLC-P-α-M) had nanoscale particle sizes (72.7 ± 1.082 nm and 80.3 ± 1.015 nm, respectively), neutral surface zeta potential (ranging between +10 mV and -10 mV), and good particle size distribution (indicated by a polydispersity index of <0.3). The NLC-P-α-M exhibited good entrapment efficiency of 87.972 ± 0.246%. Dissolution testing indicated a ~13-fold increase in the solubility of α-mangostin compared to α-mangostin powder alone. The incorporation into the propolis-based NLC system correlated well with the enhanced antioxidant activity of α-mangostin (p < 0.01) compared to NLC-P and α-mangostin alone. Therefore, the modification of the delivery system by incorporating α-mangostin into the propolis-based NLC overcomes the physicochemical challenges of α-mangostin while enhancing its antioxidant effectiveness.


Positron emission tomography and in vivo measurements of tumour perfusion and oxygen utilisation.
The advent of positron emission tomography has provided the clinical investigator with a tool for performing noninvasive (patho)-physiological measurements in humans. The method has been used extensively in the study of cerebral and cardiovascular disease. Oncological applications have been described by a more limited number of centres and have mainly concentrated on cerebral tumours. The first part of this review discusses principles of positron emission tomography and requirements for performing quantitative studies. The second part describes results of one of the most important quantitative techniques: the measurement of tumour blood flow and oxygen metabolism.


Kinetics and mechanism of proton transfer between disubstituted benzoic acids and carbinol base of crystal violet in chlorobenzene.
An investigation on the detailed kinetics of proton transfer between a set of di- and monofluoro- and chloro- (2,3-, 2,5-, 2,6-, 3,5-, 2-, and 3-) benzoic acids (HA) and Crystal Violet carbinol base in chlorobenzene favors a mechanism in terms of fast equilibrium between HA and D to form a H-bonded complex, D...HA, followed by rate-limiting proton transfer along the H-bond to form the colored ion pair DH+A- under the combined influence of monomer HA catalyst, nonreactive cyclic dimer (HA)2 inhibitor, and hyperacidic homoconjugated complex H(HA2) catalyst through a transition state with nearly 60% charge separation.


Correction to: Effects of Internet Cognitive-Behavioral Therapy on Depressive Symptoms and Surrogates of Cardiovascular Risk in Human Immunodeficiency Virus: A Pilot, Randomized, Controlled Trial.
[This corrects the article DOI: 10.1093/ofid/ofaa280.].


Type II focal cortical dysplasia: Ex vivo 7T magnetic resonance imaging abnormalities and histopathological comparisons.
In the present report, the correlations between ex vivo high-resolution imaging and specific histological and ultrastructural patterns in type II focal cortical dysplasia (FCD) have been studied to explain the differences in the magnetic resonance imaging (MRI) detection of dysplasia and to contribute to the presurgical imaging evaluation of this pathology. Surgical specimens from 13 patients with FCD IIa/b were submitted to 7T MRI scanning, and then analyzed histologically and ultrastructurally to compare the results with the MRI findings. Region of interest (ROI)-based measures on T2-weighted images (T2wi) were quantitatively evaluated in the lesion and in adjacent perilesional gray and white matter. Matched histological sections and 7T T2wi showed that the core of the lesion was characterized by patchy aggregates of abnormal cells and fiber disorganization related to inhomogeneity of intracortical signal intensity. The quantitative approach on T2wi can help to distinguish the lesions and perilesional areas even in a clinical MRI-negative case. The ultrastructural study showed that the strong signal hyperintensity in the white matter of FCD IIb was related to a dysmyelination process associated with severe fiber loss and abnormal cells. Less severe histopathological features were found in FCD IIa, thus reflecting their less evident MRI alterations. We suggest that white matter abnormalities in type IIb FCD are due to defects of the myelination processes and maturation, impaired by the presence of balloon cells. To reveal the presence and the border of type II cortical dysplasia on MRI, a quantitative ROI-based analysis (coefficient of variation) is also proposed.


Effect of Electronic Outreach Using Patient Portal Messages on Well Child Care Visit Completion: A Randomized Clinical Trial.
Outreach messages to patients overdue for well child care (WCC) can be delivered different ways (ie, telephone calls and text messages). Use of electronic health record patient portals is increasingly common but their effectiveness is uncertain. To determine the effectiveness of patient portal outreach messages, with and without the date of the last WCC, on the scheduling and completion of WCC visits and completion of vaccinations. An intention-to-treat, multigroup, randomized clinical trial was conducted at 3 academic primary care practices from July 30 to October 4, 2021. The population included predominantly non-Hispanic Black, low-income children (age, 6-17 years) whose parent had an active portal account. Participants were randomized to the standard message, tailored message, or no message (control) group. Two messages were delivered to those in the message groups. Outcomes included WCC visit scheduled within 2 weeks of the first intervention message, WCC visit completed within 8 weeks (primary outcome), and receipt of COVID-19 vaccine within 8 weeks. Nine hundred forty-five patients participated (mean [SD] age, 9.9 [3.3] years, 493 [52.2%] girls, 590 [62.4%] non-Hispanic Black, 807 [85.4%] publicly insured). Scheduling rates were 18.4% in the standard message group (adjusted risk ratio [aRR], 1.97; 95% CI, 1.32-2.84) and 14.9% in the tailored message group (aRR, 1.57; 95% CI, 1.02-2.34) compared with the control group (9.5%). Well child care visit completion rates were 24.1% in the standard message group (aRR, 1.92; 95% CI, 1.38-2.60) and 19.4% in the tailored message group (aRR, 1.52; 95% CI, 1.06-2.13) compared with the control group (12.7%). Among eligible children, rates of receiving the COVID-19 vaccine were 16.7% in the standard message group compared with 4.8% in the tailored message (aRR, 3.41; 95% CI, 1.14-9.58) and 3.7% in the control groups (aRR, 4.84; 95% CI, 1.44-15.12). In this randomized clinical trial, outreach messages delivered via electronic health record patient portals increased the rates of scheduling and completing WCC visits and receiving the COVID-19 vaccine, providing a useful tool to help restore WCC in populations whose care was delayed during the pandemic. ClinicalTrials.gov Identifier: NCT04994691.


Optimization of the culture conditions for production of Polyhydroxyalkanoate and its characterization from a new Bacillus cereus sp. BNPI-92 strain, isolated from plastic waste dumping yard.
The aim of this study was to optimize the culture conditions for production, recovery and characterization of polyhydroxyalkanoate (PHA) from potential Bacillus cereus strain BNPI-92. Cost effective carbon sources such as crude oil (CO), rice bran (RB), sugar cane molasses (SCM) and wheat bran (WB) were evaluated for PHA production using the isolate. Higher cell dry weight (CDW) (g/L), PHA concentration (P conc.) (g/L) PHA contents (PC) (%) and PHA synthesis rate (PSR) were obtained from Glucose (60.67% w/v) as a carbon source at 37 °C and pH 7 using Taguchi DOE methods. The polymer was characterized by FTIR and its functional groups (C=O) (1719.41 cm-1 wavenumber) was a characteristic feature of PHB polymer. For 1HNMR, signals of methyne (CH) (5.28 ppm), methylene (-CH2-) (2.45 ppm) and methyl (CH3) (1.27 ppm) and copolymers were predicted. Copolymers such as P (3HB-co-3 HV) and P(3HB-co-3HHX) i.e. characteristic feature of PHB were obtained from a sample of glucose, WB, and RB, respectively. XRD pattern also confirmed the presence of PHA. The major compounds obtained from GC/MS analysis of the polymer recovered from the isolate BNP-92 were 2-butenoic acid, methyl ester (8.6%), ethyl cyclopropanecarboxylate (45.99%), 1-Undecanol (10.18%) which corresponds to and have produced from PHA after thermal degradation.


Metastatic laryngeal carcinoma as a cause of progressive ophthalmoplegia.
We have described a patient with primary laryngeal carcinoma who had bilateral progressive ophthalmoplegia. Repeated studies of cerebrospinal fluid and initial radiologic examinations failed to provide a diagnosis. Sphenoidal sinusotomy and biopsy were necessary to confirm the diagnosis of metastatic laryngeal carcinoma--a previously unreported phenomenon.


Carotid-cavernous fistulas.
Carotid-cavernous fistulas (CCFs) are vascular shunts allowing blood to flow from the carotid artery into the cavernous sinus. The characteristic clinical features seen in patients with CCFs are the sequelae of hemodynamic dysfunction within the cavernous sinus. Once routinely treated with open surgical procedures, including carotid ligation or trapping and cavernous sinus exploration, endovascular therapy is now the treatment modality of choice in many cases. The authors provide a review of CCFs, detailing the current classification and clinical management of these lesions. Therapeutic options including conservative management, open surgery, endovascular intervention, and radiosurgical therapy are presented. The complications and treatment results as reported in the contemporary literature are also reviewed.


Identification and patterns of synapsis of the autosomally translocated Y-chromosome of the Indian mongoose, Herpestes auropunctatus (Hodgson).
The multiple sex chromosome system, X1X2Y male/X1X1X2X2 female, in the small Indian mongoose, Herpestes auropunctatus, results from a translocation of a part of Y chromosome to an autosome. It is not possible to distinguish the autosome which harbours the Y chromosome element in the somatic complement. By employing the surface-spreading technique to prophase I meiocytes we have identified the region to which the Y chromosome has been translocated as the short arm of chromosome 9 which is a subtelocentric chromosome. This Y chromosome component lacks heterochromatin and no sex vesicle is organised during meiotic prophase. This suggests to us that Y heterochromatin in mammals may be required for the production of a sex vesicle.


Laryngoscopic findings of age-related vocal fold atrophy are reliable but not specific.
We aimed to evaluate the reliability of laryngoscopic features of vocal fold atrophy as assessed by novice otolaryngology trainees and expert laryngologists. Two expert fellowship-trained laryngologists and three non-expert otolaryngology resident trainees were recruited to view 50 anonymised laryngo-stroboscopic examinations of patients presenting with dysphonia and non-voice, laryngeal complaints. Reviewers were asked to stratify the patient's age, provide an opinion about the presence of age-related vocal fold atrophy and specify which laryngoscopy features were present to make the diagnosis. Tertiary care laryngology practice. Two fellowship-trained laryngologists and three trainee otolaryngologists. Accuracy of age categorisation was determined and Kappa analysis was performed to assess inter-rater agreement. The mean age of patients was 54.9 years old with near equal male to female distribution. The overall accuracy of age category determination by raters was only 30.8%. Kappa analysis demonstrated fair agreement regarding the presence of vocal fold atrophy in non-expert reviewers, and moderate agreement amongst expert reviewers. Features of glottic gap, muscular atrophy of vocal folds and prominent vocal processes were all identified with high agreement (>80.0%). Our study illustrates that while raters can agree on the presence of age-related vocal fold atrophy, the findings may be non-specific and do not necessarily correlate with age.


Rapid and efficient oxidative decarboxylation of carboxylic acids with sodium periodate catalyzed by manganese (III) Schiff base complexes.
Rapid and efficient oxidative decarboxylatoin of alpha-aryl carboxylic acids was observed. In the chemical system containing Mn(III)-salophen complex as catalyst, carboxylic acids are converted efficiently to the corresponding carbonyl derivatives with sodium periodate. The ability of various Schiff base complexes in the oxidative decarboxylation of carboxylic acids was also investigated.


Versatility of Ilizarov technique in difficult cases of ankle arthrodesis and review of literature.
Ankle arthrodesis is a well-established procedure that has been successfully used for treatment of end stage arthritis of the ankle for well over a century. Internal fixation for ankle arthrodesis is adequate in most of the cases. However, surgeons and patients are occasionally confronted with cases in need for ankle arthrodesis but do not lend itself well to the ideal position and/or internal fixation. These cases may even contraindicate internal fixation. The aim of this study is to assess the results of ankle arthrodesis using different modalities of Ilizarov techniques and demonstrating its high versatility in treating such difficult cases. This is a prospective study. Thirty cases of ankle fusion for end stage arthritis or instability were performed in the period between January 2002 and December 2007 at the Health Insurance Reference Hospitals, Alexandria, Egypt. Tibiotalar fusion was done in 22 cases and tibiocalcaneal fusion in 8 cases using different modalities of Ilizarov technique. The mean follow up period was 5.5 years (range 4-8, SD 1.9). Sound and painless fusion was achieved in all the cases except one (97%). The difference between the mean preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) was found to be statistically highly significant (t=10.1, p=0.001). Many minor complications were encountered during the course of treatment in the form of: pin tract infections, wound dehiscence, cellulitis that was managed effectively with local wound care, oral antibiotics. The versatility of the combinations of assemblies afforded by Ilizarov fixator was found to be endless. This makes the Ilizarov fixator to be an effective and versatile mean of treating difficult cases of ankle arthrodesis.


Impact of smartphone overuse on 1-year severe depressive symptoms and momentary negative affect: Longitudinal and experience sampling findings from a representative epidemiological youth sample in Hong Kong.
Smartphone overuse can have detrimental impacts on youth mental health. How it may be longitudinally associated with depressive symptoms and functioning, and with daily momentary affect, remains to be investigated. A total of 3,033 young people were consecutively recruited from a large-scale epidemiological youth mental health study in Hong Kong. A subsample (n = 936) was followed-up after 1 year, with experience sampling data collected from 177 participants. Separate multivariable logistic regression models were applied to examine the prospective associations between smartphone overuse and depressive symptoms, with multilevel models fitted to examine its associations with momentary affect. The prevalence of smartphone overuse in the Hong Kong youth population was 29.3%. Smartphone overuse was significantly associated with more depressive symptoms and functional impairments both cross-sectionally and longitudinally. The associations between smartphone overuse and 1-year depressive symptoms were significant, even when accounting for baseline symptoms, social media use, and other risk and protective factors. Baseline depressive symptoms, in contrast, were not associated with 1-year smartphone overuse after adjusting for baseline smartphone overuse. Smartphone overuse was also significantly associated with higher levels of momentary negative affect, even when accounting for depressive symptoms. Strategies to mitigate the impact of smartphone overuse can have important long-term implications.


Synthesis and Characterization of N-Doped Porous TiO₂ Hollow Spheres and Their Photocatalytic and Optical Properties.
Three kinds of N-doped mesoporous TiO₂ hollow spheres with different N-doping contents, surface area, and pore size distributions were prepared based on a sol-gel synthesis and combined with a calcination process. Melamine formaldehyde (MF) microspheres have been used as sacrificial template and cetyltrimethyl ammonium bromide (CTAB) or polyvinylpyrrolidone (PVP) was selected as pore-directing agent. Core-shell intermediate spheres of titania-coated MF with diameters of 1.2-1.6 μm were fabricated by varying the volume concentration of TiO₂ precursor from 1 to 3 vol %. By calcining the core-shell composite spheres at 500 °C for 3 h in air, an in situ N-doping process occurred upon the decomposition of the MF template and CTAB or PVP pore-directing surfactant. N-doped mesoporous TiO₂ hollow spheres with sizes in the range of 0.4-1.2 μm and shell thickness from 40 to 110 nm were obtained. The composition and N-doping content, thermal stability, morphology, surface area and pore size distribution, wall thickness, photocatalytic activities, and optical properties of the mesoporous TiO₂ hollow spheres derived from different conditions were investigated and compared based on Fourier-transformation infrared (FTIR), SEM, TEM, thermogravimetric analysis (TGA), nitrogen adsorption-desorption, and UV-vis spectrophotoscopy techniques. The influences of particle size, N-doping, porous, and hollow characteristics of the TiO₂ hollow spheres on their photocatalytic activities and optical properties have been studied and discussed based on the composition analysis, structure characterization, and optical property investigation of these hollow spherical TiO₂ matrices.


Distribution of style and pollen polygalacturonases among distylous and homostylous Turnera and Piriqueta spp. (Turneraceae).
We explore the distribution of a style and pollen polygalacturonase in a number of distylous and homostylous species of Turnera, and two species of Piriqueta (Turneraceae). We show, using immunoblotting with antibodies made against these proteins, that the style polygalacturonase is specific to styles of short-styled plants of all the six distylous species of Turnera we have investigated. Styles of a somatic homostylous mutant derived from a short-styled plant do not possess the style polygalacturonase. Distylous P. caroliniana did not appear to possess this protein. We show that the pollen polygalacturonase, while associated with the short-styled morph in three species, is polymorphic among short-styled plants of T. krapovickasii, and absent from T. joelii, T. grandiflora and P. caroliniana. These data support a role for the style polygalacturonase in distyly, possibly in the incompatibility system, but cast doubt on any role for the pollen polygalacturonase. In concert with the predictions for the mode of origin, and the response of styles of homostylous species to pollen from long- and short-styled plants, we find that none of the homostylous species possess the style polygalacturonase. The pollen polygalacturonase does occur in some homostylous species, but not in others. It is not clear that the pollen polygalacturonase, however, provides a marker for the mode of origin of homostyly.


Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV fusion-active intermediate state.
During viral entry, the fusogenic state of human immunodeficiency virus Type 1 (HIV-1) envelope protein gp41 is a quaternary structure consisting of three gp41 glycoproteins, each with two conserved helical domains (N-HR and C-HR). Thus far, the examination of monomeric gp41 peptides as an immunologically focused approach to vaccine design has not been successful. Here we report an approach using quaternary protein mimetics (called 3alpha mimetics) that are based on the gp41 N-HR and C-HR domains to closely mimic the fusogenic state and overcome the deficiencies of the monomeric peptide approach for synthetic vaccine design. The 3alpha mimetics are conveniently prepared by chemoselective ligation of unprotected monomeric peptides to an interstrand linker, and display enhanced conformational stability compared to the corresponding monomers. The 3alpha mimetics with or without a covalently attached T-helper epitope were immunogenic and elicited antisera that bound both recombinant gp160, which contains gp41, and HIV-1 virions and immunoprecipitated recombinant gp41. Anti-3alpha mimetic antisera neutralized viral infectivity against R5- and X4-tropic strains of HIV-1 at 31.5 degrees C. The results suggest that a quaternary protein approach to mimic conserved and functional domains of viral envelope proteins is desirable for HIV vaccine development as such antigens are more likely to produce immunologically-focused and broadly neutralizing antibody responses.