Increased age at diagnosis has a significantly negative effect on outcome in children with Down syndrome and acute myeloid leukemia: a report from the Children's Cancer Group Study 2891.
To determine the outcome of children with Down syndrome (DS) and acute myeloid leukemia (AML) receiving standard timing chemotherapy without bone marrow transplantation (BMT), with determination of prognostic factors. Children with DS and newly diagnosed AML or myelodysplasia were prospectively enrolled on Children's Cancer Group study 2891 (N = 161) and treated uniformly with four standard timing induction courses of dexamethasone, cytarabine arabinoside, 6-thioguanine, etoposide, daunorubicin (DCTER) followed by intensively timed high-dose cytarabine. Children with DS were significantly younger at diagnosis than those without (median age, 1.8 v 7.5 years, respectively; P <.001), with more megakaryocytic leukemia (70% v 6%; P <.001). Higher complete remission rates (91%) were achieved in children with DS than among those without DS (75%; P <.001). Equivalent grade 3 to 4 toxicity (29% v 30%; P =.84) was seen, though children with DS had greater pulmonary toxicity (P <.01) during induction and mucositis during intensification (P =.12). Children with DS had significantly better 8-year event-free survival (EFS; 77% v 21% standard and 40% intensive induction; P <.0001). Multivariate analysis in children with DS revealed that only age at diagnosis of 2 years or older was a risk factor for greater relapse risk (odds ratio, 4.9; P =.006) and worse survival. Children between ages 0 to 2 years (n = 94) had a 6-year EFS of 86%; those from 2 to 4 years (n = 58), 70%; and those older than 4 years (n = 9), 28%. Remission failures were the primary reason for worse 6-year EFSs (1% in those 0 to 2 years v 14% if >2 years; P =.002). Outcome for children with DS and AML is excellent with standard induction therapy, but declines with increasing age.


Can we prevent poststroke cognitive impairment? An umbrella review of risk factors and treatments.
Cognitive impairment poststroke is progressive. We aimed to synthesise the existing evidence evaluating risk factors and the effects of treatments to prevent/improve cognitive function in patients who had a stroke with cognitive impairment. Umbrella review. Medline, PsycINFO, EMBASE, Cochrane and PROSPERO were searched from inception until 11 June 2019. Published systematic review (SR) that incorporated randomised controlled trials to investigate an intervention to improve poststroke cognitive impairment, or SR of longitudinal observational studies that evaluated the risk factors of this condition. No restrictions were applied. From each eligible study, details were recorded by one reviewer in a validated form. Grading of Recommendations, Assessment, Development and Evaluations criteria were used to assess our certainty level of each outcome, and A Measurement Tool to Assess Systematic Reviews 2 to assess quality. Altogether, 3464 abstracts were retrieved, 135 full texts were evaluated and 22 SRs were included in the final analysis. From four SRs of observational studies, we found 19 significant associations with postulated risk factors, and those which we determined to be confident about were: atrial fibrillation (3 SRs, 25 original studies); relative risk 3.01 (1.96-4.61), ORs 2.4 (1.7-3.5) and 2.0 (1.4-2.8), leukoaraiosis, multiple and recurrent strokes, ORs 2.5 (1.9-3.4), 2.5 (1.9-3.1) and 2.3 (1.5-3.5), respectively. From 18 SRs of interventional trials, we found that interventions including physical activity or cognitive rehabilitation were enhancing cognitive function, while the certainty of the other interventions was rated low, due to limited methodological quality. This review represents common risk factors related to poststroke cognitive impairment, in particular atrial fibrillation, and points to different interventions that warrant attention in the development of treatment strategies. Physical activity and cognitive rehabilitation interventions showed evidence of enhancing cognitive function; however, we could not recommend a change in practice yet, due to lack of strong evidence. CRD42018096667.


Characteristics and outcomes of ureteroscopic treatment in 2650 patients with impacted ureteral stones.
To describe stone-free rates and complications of ureteroscopic treatment for impacted compared with non-impacted ureteral stones and evaluate predictive variables for impaction. The Clinical Research Office of the Endourological Society prospectively collected 1 consecutive year of data from 114 centers worldwide. Patients eligible for inclusion were patients treated with ureteroscopy for ureteral stones. Patient characteristics, treatment details, and outcomes were compared with regard to stone impaction. Logistic regression analyses were conducted to explore predictive variables for ureteral stone impaction and to analyse the effect of impaction on outcomes. Of the 8543 treated patients, 2650 (31%) had impacted and 5893 (69%) non-impacted stones. The stone-free rate was 87.1% for impacted stones, which is lower compared with 92.7% for non-impacted stones (p < 0.001). Intra-operative complication rates were higher for impacted stones (7.9 versus 3.0%, p < 0.001). Significantly higher ureteral perforation- and avulsion rates were reported in the impacted stone group compared with the non-impacted stone group. No association between stone impaction and post-operative complications could be shown. Female gender, ASA-score >1, prior stone treatment, positive pre-operative urine culture, and larger stones showed to be predictive variables for stone impaction. Ureteroscopic treatment for impacted stones is associated with lower stone-free rates and higher intra-operative complication rates compared with treatment for non-impacted stones. The predictive variables for the presence of stone impaction may contribute to the identification of stone impaction during the diagnostic process. Moreover, identification of stone impaction may aid the selection of the optimal treatment modality.


Prevalence and correlates of low birth weight in India: findings from national family health survey 5.
Childhood mortality and morbidity has become a major public health issue in low-middle-income countries. However, evidence suggested that Low birth weight(LBW) is one of the most important risk factors for childhood deaths and disability.This study is designed to estimate the prevalence of low birth weight (LBW) in India and to identify maternal correlates associated with LBW. Data has been taken from National Family Health Survey 5 (2019-2021) for analysis. 149,279 women belonging to reproductive age group (15-49) year who had last recent most delivery preceding the NFHS-5 survey. Mother's age, female child, birth interval of less than 24 months, their low educational level, low wealth index, rural residence, lack of insurance coverage, women with low BMI, anaemia, and no ANC visits during pregnancy are predictors that contribute to LBW in India. After adjusting for covariates, smoking and alcohol consupmtion is strongly correlated with LBW. Mother's age, educational attainment and socioeconomic status of living has a highly significant with LBW in India. However, consumption of tobacco and cigarrettes are also associated with LBW.


Moral equivalence theory in neonatology.
This article explores the ethical concept of "the equivalence thesis" (ET), or the idea that withdrawing and withholding life sustaining treatments are morally equivalent practices, within neonatology. We review the historical origins, theory, and clinical rationale behind ET, and provide an analysis of how ET relates to literature that describes neonatal mode of death and healthcare professional and parent attitudes towards end-of-life care. While ET may serve as an ethical tool to optimize resource allocation in theory, its clinical utility is limited given the complexity of end-of-life care decisions.


Lower limb fractures in the chronic spinal cord injured patient.
Experience in managing 33 lower limb fractures in 25 chronic spinal injured patients is described. An increased awareness among patients and medical staff is required to avoid misdiagnosis. Effort should be made to ensure bone union in satisfactory position, recognising the different requirements of ambulant and non-ambulant patients. 'Soft pillow splints' were found to give the best results in all fractures other than those of the femoral neck. Operative treatment with antibiotic prophylaxis is only indicated to correct important deformity.


Survival of outborns with congenital diaphragmatic hernia: the role of protective ventilation, early presentation and transport distance: a retrospective cohort study.
Congenital diaphragmatic hernia (CDH) is a congenital malformation associated with life-threatening pulmonary dysfunction and high neonatal mortality. Outcomes are improved with protective ventilation, less severe pulmonary pathology, and the proximity of the treating center to the site of delivery. The major CDH treatment center in Croatia lacks a maternity ward, thus all CDH patients are transferred from local Zagreb hospitals or remote areas (outborns). In 2000 this center adopted protective ventilation for CDH management. In the present study we assess the roles of protective ventilation, transport distance, and severity of pulmonary pathology on survival of neonates with CDH. The study was divided into Epoch I, (1990-1999, traditional ventilation to achieve normocapnia), and Epoch II, (2000-2014, protective ventilation with permissive hypercapnia). Patients were categorized by transfer distance (local hospital or remote locations) and by acuity of respiratory distress after delivery (early presentation-occurring at birth, or late presentation, ≥ 6 h after delivery). Survival between epochs, types of transfers, and acuity of presentation were assessed. An additional analysis was assessed for the potential association between survival and end-capillary blood CO2 (PcCO2), an indirect measure of pulmonary pathology. There were 83 neonates, 26 in Epoch I, and 57 in Epoch II. In Epoch I 11 patients (42%) survived, and in Epoch II 38 (67%) (P = 0.039). Survival with early presentation (N = 63) was 48 % and with late presentation 95% (P <0.001). Among early presentation, survival was higher in Epoch II vs. Epoch I (57% vs. 26%, P = 0.031). From multiple logistic regression analysis restricted to neonates with early presentation and adjusting for severity of disease, survival was improved in Epoch II (OR 4.8, 95%CI 1.3-18.0, P = 0.019). Survival was unrelated to distance of transfer but improved with lower partial pressure of PcCO2 on admission (OR 1.16, 95%CI 1.01-1.33 per 5 mmHg decrease, P = 0.031). The introduction of protective ventilation was associated with improved survival in neonates with early presentation. Survival did not differ between local and remote transfers, but primarily depended on severity of pulmonary pathology as inferred from admission capillary PcCO2.


Clinical experience with devices for facilitated anastomoses in coronary artery bypass surgery.
Recent developments in minimally invasive coronary artery surgery have been driven by the introduction of new technologies which should facilitate precise surgical maneuvers on the beating heart within confined spaces. Such technologies include coronary stabilizer systems, cardiac positioning vacuum-assisted devices, and telemanipulative systems. Despite these developments, standard suturing techniques using running polypropylene material remains a limiting factor in the surgeon's ability to perform complete revascularization with high quality anastomoses through minimal approaches to the chest cavity. Clinical validation of proximal and distal anastomotic devices has the potential to substantially improve and perhaps revolutionize minimally invasive coronary surgery. Ideal characteristics of such devices would include applicability to all conduit types, all coronary sizes, interchangeable proximal/distal sequencing of the anastomosis, and safe bail out for device malfunction. However there is an urgent need to define the performance objectives of such systems as well as the general criteria for proper and comparable evaluation and validation of different systems in animal models and subsequently in controlled prospective clinical studies. This review summarizes the most interesting systems available in both experimental and clinical settings.


Learning programmes and teaching techniques to enhance oral health literacy or patient-centred communication for healthcare providers: A systematic review.
To investigate the learning programmes and teaching techniques used in interventions to enhance oral health literacy (OHL) or patient-centred communication (PCC) for healthcare providers. A systematic review of OHL and PCC were obtained from four electronic databases (PubMed, ScienceDirect, ProQuest and Scopus) was undertaken. These searches covered the period from January 2008 to December 2017. The quality assessment tool was the Joanna Briggs Institute Critical Appraisal tool for systematic reviews of effectiveness. The final review included nine studies amongst a total of 1475 studies. They showed three learning programmes (workshops, training and community-based rotation) and 17 related teaching techniques to promote OHL and PCC. The most commonly used learning programmes to enhance OHL and PCC for healthcare providers were workshops, and the teaching techniques included feedback and reflection. The intervention periods of the programmes took 20 minutes to half a day. The three studies did not have a follow-up, whilst the rest showed a follow-up range of 2 months to 3 years. Interestingly, there was one study, which applied double follow-ups to show the effectiveness of the programme. Either workshops or training programmes with a combination of teaching techniques were effective in terms of enhancing their OHL or PCC. The more frequent follow-up might increase the long-term effectiveness of the learning programme.


A multifunctional diet improves cardiometabolic-related biomarkers independently of weight changes: an 8-week randomized controlled intervention in healthy overweight and obese subjects.
A multifunctional diet (MFD) was previously shown to reduce blood lipids, CRP and blood pressure in a 4-week intervention under weight-maintenance conditions. Here, MFD effects were evaluated in an 8-week intervention with no restriction for weight changes. Healthy subjects consumed MFD (23 subjects) or a control diet (CD) devoid of the functional components (24 subjects) in a "free-living" randomized controlled experiment. MFD included several functional concepts: low-glycemic-impact meals, antioxidant-rich foods, oily fish, viscous dietary fibers, soybean and whole barley kernel products, almonds and plant stanols. Measured outcomes were fasting blood values of lipids, glucose, insulin, GGT, CRP, HbA1c, PAI-1, GLP-1, GLP-2, body weight, blood pressure and breath hydrogen. At baseline, participants were 51-72 years old, with BMI between 25 and 34 and fasting glycemia ≤ 6.1 mmol/L. Consumption of both diets resulted in similar weight loss after 8 weeks (-4 %; P < 0.001). Compared to baseline, consumption of MFD reduced total serum cholesterol (-26 %; P < 0.0001), LDL cholesterol (-35 %; P < 0.0001), triglycerides (-16 %; P < 0.05), LDL/HDL (-27 %; P < 0.0001) and ApoB/ApoA1 (-15 %; P < 0.0001). There were important net differences between diets, which remained significant after adjustment for body weight. Reduced systolic blood pressure, circulating GGT, HbA1c and insulin concentrations were observed with both MFD and CD with no difference between diets. The Reynolds cardiovascular risk score was decreased by 36 % (P < 0.0001) with MFD. MFD increased breath hydrogen levels (120 %; P < 0.05). Consumption of MFD decreased blood lipids and improved several other aspects of the cardiometabolic risk profile. This effect was not dependent on weight loss.


Genetic Manipulations of Oral Spirochete Treponema denticola.
There have been more than 60 different oral Treponema species identified in the oral cavity; however, only few species can be cultivated in vitro reliably. Among those cultivable species, due to its medical importance and genetic tractability, Treponema denticola, one of the keystone pathogens associated with human periodontitis, has emerged as a paradigm model organism to understanding the genetics, etiology, and pathophysiology of oral Treponema species. During the last two decades, several genetic tools have been developed, which have played an instrumental role in the study of T. denticola. This chapter describes the experimental design and procedure of genetic manipulations of T. denticola.


Deep Penetrating and Sensitive Targeted Magnetic Particle Imaging and Photothermal Therapy of Early-Stage Glioblastoma Based on a Biomimetic Nanoplatform.
Early diagnosis can effectively improve the survival of glioblastoma multiforme (GBM). A specific imaging technique that is simultaneously deep penetrating and sensitive to small tissue changes is desired to identify GBM. Due to its excellent features in signal contrast, detection sensitivity, and none or little attenuation in tissue, magnetic particle imaging (MPI) possesses great potential in cancer diagnosis, especially when the imaging modality is equipped with specifically targeted nanoprobes. However, when gliomas are small, the blood-brain barrier (BBB) is complete and prevents nanoprobes from entering the brain, which negates the theranostic effect. This study proposes a biomimetic nanoplatform that assist the MPI tracers in breaking through the BBB and then demonstrate a targeted and sensitive diagnosis of GBM. Afterward, the photothermal therapy and immune regulation show an excellent therapeutic effect on the GBM. It is experimentally confirmed that the MPI signal does not decay with tissue depth and shows excellent sensitivity for thousands-cells. Only small animals are conducted in this study due to the limitations of the current commercial MPI scanner, however, this research theoretically enables large animal and human studies, which encourages a promising pathway toward the noninvasive diagnosis of early-stage GBM in clinics.


Probably benign lesions at screening breast US in a population with elevated risk: prevalence and rate of malignancy in the ACRIN 6666 trial.
To prospectively validate predefined breast ultrasonographic (US) Breast Imaging Reporting and Data System (BI-RADS) category 3 criteria in a multicenter setting in an elevated-risk population. The American College of Radiology Imaging Network 6666 database was reviewed for prospectively defined BI-RADS category 3 lesions. Patient characteristics, lesion US features at initial detection, and work-up recommendations were analyzed with descriptive statistics. Exact 95% confidence intervals (CIs) were given, where appropriate. Lesion reference standard was biopsy or a minimum of 1-year follow-up. In addition, malignancy rate for lesions that had at least 2 years of follow-up data or that had biopsy data was calculated. Of 2662 participants, 519 (19.5%) had 745 BI-RADS category 3 lesions (25.5% of 2916 US lesions other than simple cysts), with a median size of 7 mm (range, 2-135 mm). The number of new BI-RADS category 3 lesions decreased with year 2-3 screening, but the percentage of new BI-RADS category 3 lesions was stable at 26.4% (506 of 1920 lesions), 23.6% (142 of 601 lesions), and 24.6% (97 of 395 lesions), respectively. Of 745 BI-RADS category 3 lesions, 124 (16.6%) were ultimately sampled for biopsy. Six malignancies (0.8% of BI-RADS category 3 lesions; 95% confidence interval [CI]: 0.3%, 1.7%) occurred in five (1.0%) of 519 participants: Five malignancies were invasive (median size, 10 mm; size range, 2-18 mm), and one was node positive. When the analysis is limited to lesions with at least 2-year follow-up or biopsy, the malignancy rate among BI-RADS category 3 lesions is 0.9% (95% CI: 0.3%, 2.0%). Three malignant BI-RADS category 3 lesions were sampled for biopsy because of a suspicious change at follow-up (two N0 lesions, one each at 6- and 12-month follow-up; one N1 lesion at 24-month follow-up), one was sampled for biopsy because of an upgrade after additional mammography (NX), one was found at mastectomy for another cancer (N0), and one was found at prophylactic contralateral mastectomy in the same patient (NX). As BI-RADS category 3 lesions have a low malignancy rate (0.8%; 95% CI: 0.3%, 1.7%) and only 0.1% of the cancers had suspicious changes at 6-month follow-up and only one (17%; 95% CI: 0.4%, 64%) of six malignancies were node positive at detection (24-month follow-up), a recommendation of 1-year diagnostic follow-up may be appropriate for BI-RADS category 3 lesions detected at screening US. Online supplemental material is available for this article.


Treatment with bevacizumab and irinotecan for recurrent high-grade glial tumors.
Response rates to second-line chemotherapy in recurrent high-grade glial tumors are low and new effective treatments are needed. The objective of this study was to evaluate response rates and tolerability of chemotherapy with bevacizumab and irinotecan in recurrent high-grade gliomas. Twenty patients with recurrent gliomas were treated with bevacizumab 5 mg/kg and irinotecan 125 mg/m(2) every 2 weeks. The response was evaluated by gadolinium-enhanced magnetic resonance imaging performed every 4 cycles of treatment. The patients received 1 to 22 cycles of treatment. Nine of 19 patients available for response evaluation (47.3%) showed an objective radiologic response: 2 patients (10.5%) a complete response (CR), and 7 patients (36.8%) a partial response (PR). Two additional patients showed stable disease (SD) for 2 and 6 months, respectively. Eight patients developed rapid progression after 1 to 4 cycles of treatment. Median time to progression on treatment was 4.7 months. The 6-month progression-free survival (PFS) and overall survival (OS) were 25% and 55%, respectively. The adverse effects were mild and in all but 2 cases were no more than grade 2. There were no thrombotic complications or significant bleeding other than epistaxis. The preliminary data show a promising high response rate of recurrent high-grade gliomas to chemotherapy with bevacizumab and irinotecan. The regimen is associated with minimal toxicity.


Ultrastructural changes in the lateral reticular nucleus of the medulla oblongata in prepubertal rats under the effect of long-term stress exposure.
Ultrastructural changes in the lateral reticular nuclei of the medulla oblongata of rat pups developing under the effect of chronic mental and pain stress indicate impaired histogenesis of structures of the medulla oblongata reticular formation and appearance of pronounced morphofunctional differences between the neurons.


Comparison of Impressions of COVID-19 Vaccination and Influenza Vaccination in Japan by Analyzing Social Media Using Text Mining.
The aim of this study was to compare impressions of COVID-19 vaccination and influenza vaccination in Japan by analyzing social media (Twitter®) using a text-mining method. We obtained 10,000 tweets using the keywords "corona vaccine" and "influenza vaccine" on 15 December 2022 and 19 February 2023. We then counted the number of times the words were used and listed frequency of these words by a text-mining method called KH Coder. We also investigated concepts in the data using groups of words that often appeared together or groups of documents that contained the same words using multi-dimensional scaling (MDS). "Death" in relation to corona vaccine and "severe disease" for influenza vaccine were frequently used on 15 December 2022. The number of times the word "death" was used decreased, "after effect" was newly recognized for corona vaccine, and "severe disease" was not used in relation to influenza vaccine. Through this comprehensive analysis of social media data, we observed distinct variations in public perceptions of corona vaccination and influenza vaccination in Japan. These findings provide valuable insights for public health authorities and policymakers to better understand public sentiment and tailor their communication strategies accordingly.


Virology analysis of chronic hepatitis B virus-infected patients treated for 28 days with JNJ-56136379 monotherapy.
Four weeks of once-daily oral JNJ-56136379 (JNJ-6379; 25, 75, 150 or 250 mg), a class-N capsid assembly modulator (CAM-N), was well tolerated with potent antiviral activity in treatment-naïve, chronic hepatitis B e antigen-positive and hepatitis B e antigen-negative patients (NCT02662712). Hepatitis B virus (HBV) genome sequence analysis, using HBV DNA next-generation sequence technology, was performed, and impact of substitutions on efficacy was assessed. Analyses focused on HBV core protein amino acid positions associated with JNJ-6379 and/or other CAMs in vitro resistance, and those within the CAM-binding pocket. 31/57 patients had ≥ 1 polymorphism at any of the core amino acid positions of interest, most frequently at positions 38 (32%), 105 (23%) and 109 (14%). None of these polymorphisms are known to reduce JNJ-6379 in vitro activity (fold change [FC] in 50% effective concentration <3.0). Two JNJ-6379-treated patients carried a Y118F baseline core polymorphism known to reduce JNJ-6379 activity in vitro (FC = 6.6) and had HBV DNA declines of 2.77 (75 mg) and 2.19 log10 IU/mL (150 mg) at the end of treatment. One 75 mg JNJ-6379-treated patient had an emerging T109S substitution (FC = 1.8; HBV DNA decline 3.18 log10 IU/mL). A 25 mg JNJ-6379-treated patient had on-treatment enrichment of Y118F variant (HBV DNA decline 2.13 log10 IU/mL). In conclusion, baseline polymorphisms and enrichment of substitutions reducing JNJ-6379 in vitro activity were rare, with no consistent impact on virological response during a 4-week phase 1b study. Emergence of resistance to longer treatments of JNJ-6379 will be evaluated in phase 2 studies.


Rapid and accurate determination of total lung capacity (TLC) from routine chest radiograms using a programmable hand-held calculator.
Since its appearance in 1960, the method of Barnhard and associates for the determination of total lung capacity (TLC) from routine chest radiograms has been widely studied in normal and diseased subjects. The method appears to be as accurate as the current definitive procedure, total body plethysmography. The method is in routine use in major medical institutions where the procedure has been automated, but the method does not seem to have gained the wide use it deserves. This is likely due to the tedium of the technique when performed manually--a single determination can require 30 min. We present here an implementation of the Barnhard method for the HP41-C hand-held programmable calculator. In conjunction with the use of a transparent reticle used for obtaining the required measurements, the program allows a single measurement to be made in under 12 minutes. We hope this technique will make radiographic TLC measurements more broadly accessible to the medical profession.


Preparation of S-2-halophenyl-2,1-benzothiazines.
Derivatives of 2,1-benzothiazines are useful synthetic intermediates for a variety of applications. We became interested in developing a one-pot procedure to S-2-halophenyl-2,1-benzothiazines as potential precursors to P,N type ligands for metals. Accordingly, we reacted S-2-halophenyl-S-methylsulfoximines with 2-bromobenzaldehydes using the Buchwald-Hartwig reaction under conditions previously developed in our laboratory. We found that 2-halophenylmethyl sulfoximines show lower reactivity in process than methylphenyl sulfoximine. Among the 2-(S)-2-halophenyl-(S)-methylsulfoximines tested, S-2-fluorophenyl-S-methyl sulfoximine was found to afford higher yields of benzothiazines than the bromine- or chlorine-substituted congeners. In the coupling of S-2-halophenyl-S-methylsulfoximines to 2-bromobenzaldehyde, using Ruphos as a ligand gave the best yields.


Right ventricle-to-pulmonary artery conduit longevity: is it related to allograft size?
Cryopreserved valved allografts are routinely oversized to account for somatic growth in children requiring right ventricle-to-pulmonary artery (RV-PA) continuity. The objective of this study is to determine the effect of oversizing on conduit longevity. We reviewed the records of all patients undergoing RV-PA cryopreserved valved allograft placement from 1988 to 2006 for diagnosis, age, allograft type, time to valved conduit explant, and indication for surgery. Conduit size at the time of insertion was compared with pulmonary valve size normalized for body surface area (z score). Multivariate Cox regression models with cluster analysis were constructed to assess risk of allograft oversizing for conduit failure. Kaplan-Meier analysis was used to obtain median freedom from explantation time. A total of 140 cryopreserved valved allografts (z score, 1.8 +/- 1.3; range, -1.5 to 4.9) were implanted in 99 patients (median age, 5.6 years). Reoperation was required in 66 (67%) of 99 patients during the study period. Modeling z scores as a dichotomous variable revealed that risk of allograft explantation increases 113% when allografts with z scores of 2.7 or higher are used compared with those with z scores of less than 2.7 (p < 0.01). Median adjusted freedom from explantation for this same grouping was 4.9 years versus 9.4 years. The presence of branch pulmonary artery stenosis shortens the conduit life (p < 0.001), whereas insertion of a pulmonary allograft may extend the conduit life (p = 0.13). Cryopreserved valved allograft oversizing (z score > or = 2.7) in the pulmonary position results in decreased longevity in children. Presence of branch pulmonary artery stenosis is also associated with earlier conduit explantation.


Safety and comparative costs of preoperative assessments for cataract surgery: traditional mandatory assessment versus a novel graded assessment system.
We conducted this study to evaluate the safety and costs of traditional mandatory preoperative assessment for cataract surgery patients compared with a novel graded preoperative assessment system. Patients were recruited at a high-volume surgical centre from May to November 2013. Patients completed a health-related questionnaire which allowed for a graded preoperative assessment of all participants. Based on responses to the questionnaire, patients were classified preoperatively into a) low-risk patients not requiring a preoperative assessment and b) high-risk patients requiring this assessment. Anesthesiologists still assessed all patients immediately before surgery but with staff blinded to preoperative assessment information for low-risk patients. Observed complication rates and costs were compared with those expected in the mandatory assessment system. We examined 3,347 cataract surgeries on 2,766 patients and categorized 59.9% of patients as low risk. In the graded system cohort, there were no major complications and a low rate of minor complications occurred. Wherever a complication occurred in a low-risk patient, the anesthesiologist doubted that the preoperative assessment information would have prevented the complication. If implemented, the graded system would save approximately 4,414 preoperative assessments per year in our region, with an associated cost of approximately $40.00 per surgery, or $359,000 in total. The cost to prevent a single minor complication with the mandatory system was approximately $8,976, with a number needed to treat of 223. The graded system resulted in no major complications and a low rate of minor complications. The information obtained from the mandatory assessment is unlikely to prevent complications. Additionally, the cost effectiveness of the mandatory system was poor. This novel graded preoperative assessment system for cataract surgery patients can save time and resources by eliminating unnecessary patient visits.


Regulation of the malic enzyme gene malE by the transcriptional regulator MalR in Corynebacterium glutamicum.
Corynebacterium glutamicum is a Gram-positive nonpathogenic bacterium that is used for the biotechnological production of amino acids. Here, we investigated the transcriptional control of the malE gene encoding malic enzyme (MalE) in C. glutamicum ATCC 13032, which is known to involve the nitrogen regulator AmtR. Gel shift experiments using purified regulators RamA and RamB revealed binding of these regulators to the malE promoter. In DNA-affinity purification experiments a hitherto uncharacterized transcriptional regulator belonging to the MarR family was found to bind to malE promoter DNA and was designated as MalR. C. glutamicum cells overexpressing malR showed reduced MalE activities in LB medium or in minimal media with acetate, glucose, pyruvate or citrate. Deletion of malR positively affected MalE activities during growth in LB medium and minimal media with pyruvate, glucose or the TCA cycle dicarboxylates l-malate, succinate and fumarate. Transcriptional fusion analysis revealed elevated malE promoter activity in the malR deletion mutant during growth in pyruvate minimal medium suggesting that MalR acts as a repressor of malE. Purified MalR bound malE promoter DNA in gel shift experiments. Two MalR binding sites were identified in the malE promoter by mutational analysis. Thus, MalR contributes to the complex transcriptional control of malE which also involves RamA, RamB and AmtR.


Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.
A new approach to the measurement of intestinal permeability in man has been developed, using low molecular weight polyethylene glycol (PEG 400) as probe molecules. PEG 400 (range of molecular weight 232 to 594) is a mixture of water-soluble molecules of different sizes which can be extracted readily from biological fluids and analyzed by gas-liquid chromatography. PEG 400 is nontoxic, not degraded by intestinal bacteria, not metabolized after absorption, and rapidly excreted in urine. The different-sized molecular components cross the intestinal epithelium at different rates, allowing characterization of the passive permeability properties of the mucosa.


Eating problems and personality traits. An Italian pilot study among 992 high school students.
To evaluate the prevalence of eating problems and to investigate personality traits associated with disturbed eating behaviours among Italian high school students. Cross-sectional study involving 992 students from six high schools in Turin, Italy. Students completed the Eating Attitudes Test-40 (EAT-40), the Temperament and Character Inventory (TCI) and a Food Frequency Questionnaire (FFQ); their weight and height were measured. 5.5% of the whole sample and 7.4% of girls scored above the EAT-40 cutoff value. A higher Body Mass Index (BMI) correlates with higher EAT scores. Low scores on Self-Directedness and Reward Dependence together with high Persistence emerged in subjects with eating problems. Dieting and higher BMI are confirmed as correlates of eating problems. Personality traits measured with the TCI emerge for the first time as correlates of eating problems. Longitudinal studies should clear whether these are risk factors or not.


Effects of Sputtering Parameters on AlN Film Growth on Flexible Hastelloy Tapes by Two-Step Deposition Technique.
AlN thin films were deposited on flexible Hastelloy tapes and Si (100) substrate by middle-frequency magnetron sputtering. A layer of Y₂O₃ films was used as a buffer layer for the Hastelloy tapes. A two-step deposition technique was used to prepare the AlN films. The effects of deposition parameters such as sputtering power, N₂/Ar flow rate and sputtering pressure on the microstructure of the AlN thin films were systematically investigated. The results show that the dependency of the full width at half maximum (FWHM) of AlN/Y₂O₃/Hastelloy on the sputtering parameters is similar to that of AlN/Si (100). The FWHM of the AlN (002) peak of the prepared AlN films decreases with increasing sputtering power. The FWHM decreases with the increase of the N₂/Ar flow rate or sputtering pressure, and increases with the further increase of the N₂/Ar flow rate or sputtering pressure. The FWHM of the AlN/Y₂O₃/Hastelloy prepared under optimized parameters is only 3.7° and its root mean square (RMS) roughness is 5.46 nm. Based on the experimental results, the growth mechanism of AlN thin films prepared by the two-step deposition process was explored. This work would assist us in understanding the AlN film's growth mechanism of the two-step deposition process, preparing highly c-axis-oriented AlN films on flexible metal tapes and developing flexible surface acoustic wave (SAW) sensors from an application perspective.


The degree of increment in plasma catecholamines in patients with mitral stenosis by mild exercise.
Although sympathetic excitation during mild exercise may readily occur in patients with mitral stenosis (MS), the degree of increment in plasma catecholamines has not been fully investigated. We imposed mild ergometric exercise (50 watts, 300 kg/min for 5 minutes) on five patients with mild MS (mitral valve area greater than or equal to 1.0 cm2) and eight with severe MS (mitral valve area less than 1.0 cm2) while they were undergoing cardiac catheterization. In patients with severe MS, total plasma catecholamine levels during exercise were remarkably higher (2821 +/- 783 [SEM] pg/ml) than in those with mild MS (957 +/- 113 pg/ml, p less than 0.05) and in seven control subjects (612 +/- 75 pg/ml, p less than 0.05). This marked increment could not be predicted by heart rate response, which did not differ between severe and mild MS (166 +/- 5 vs 153 +/- 10 bpm). In contrast with catecholamine change, the cardiac index in severe MS showed a very small increment. Results suggest that mild daily exercise can remarkably increase plasma catecholamine levels in severe MS, and this may accelerate various complications of this disorder.


Grasping through dynamic weaving with entangled closed loops.
Pick-and-place is essential in diverse robotic applications for industries including manufacturing, and assembly. Soft grippers offer a cost-effective, and low-maintenance alternative for secure object grasping without complex sensing and control systems. However, their inherent softness normally limits payload capabilities and robustness to external disturbances, constraining their applications and hindering reliable performance. In this study, we propose a weaving-inspired grasping mechanism that substantially increases payload capacity while maintaining the use of soft and flexible materials. Drawing from weaving principles, we designed a flexible continuum structure featuring multiple closed-loop strips and employing a kirigami-inspired approach to enable the instantaneous and reversible creation of a woven configuration. The mechanical stability of the woven configuration offers exceptional loading capacity, while the softness of the gripper material ensures safe and adaptive interactions with objects. Experimental results show that the 130 g·f gripper can support up to 100 kg·f. Outperforming competitors in similar weight and softness domains, this breakthrough, enabled by the weaving principle, will broaden the scope of gripper applications to previously inaccessible or barely accessible fields, such as agriculture and logistics.


Retracted: Painting Classification in Art Teaching under Machine Learning from the Perspective of Emotional Semantic Analysis.
[This retracts the article DOI: 10.1155/2022/9592050.].


A novel vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection.
To develop a vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection, the genes of porcine IL-18, capsid protein (Cap) of PCV2 and M-like protein (SzP) of SEZ were inserted into the swinepox virus (SPV) genome by homologous recombination. The recombinant swinepox virus rSPV-ICS was verified by PCR and indirect immunofluorescence assays. To evaluate the immunogenicity of rSPV-ICS, 28 PCV2 and SEZ seronegative Bama minipigs were immunized with rSPV-ICS (n=8), commercial PCV2 vaccine and SEZ vaccine (n=8) or wild type SPV (n=8). The results showed that SzP-specific antibody and PCV2 neutralizing antibody of the rSPV-ICS immunized group increased significantly compared to the wild type SPV treated group after vaccination and increased continuously over time. The levels of IL-4 and IFN-γ in the rSPV-ICS immunized group were significantly higher than the other three groups, respectively. After been co-challenged with PCV2 and SEZ, 87.5% piglets in rSPV-ICS immunized group were survived. Significant reductions in gross lung lesion score, histopathological lung lesion score, and lymph node lesion score were noticed in the rSPV-ICS immunized group compared with the wtSPV treated group. The results suggested that the recombinant rSPV-ICS provided piglets with significant protection against PCV2-SEZ co-infection; thus, it offers proof-of-principle for the development of a vaccine for the prevention of these swine diseases.


Graves' disease and HLA: clinical and epidemiologic associations.
Correlation between clinical and epidemiological features of Graves' disease and HLA were sought in 175 patients, eighty-three of whom were typed for HLA DR antigens. The relative risks (x) conferred by HLA-B8 and DR3 were 3.1 and 5.7 respectively (P less than 0.0005 uncorrected). The disease occurred at an earlier age in HLA-DR3 positive patients compared to negative patients (P less than 0.005 in females greater than and less than 30-years-old). Eighty-four out of ninety-two patients could specify the season of onset of hyperthyroidism; an excess of HLA-B8 positive patients in the summer and a lack of these in the spring and autumn was found. No association between B8 and exophthalmos and/or soft tissue eye changes were observed. However, significant associations between exophthalmos and either exophthalmos and/or soft tissue changes were found with DR3 (x = 3.6 and 3.8 respectively). HLA-DR3 positive patients were found to be more resistant to radioiodine therapy than patients negative for these antigens. No heterogeneity in the distribution of HLA antigens was found when the following indices were examined: sex, goitre size, severity of disease, pretibial myxoedema, antecedent psychological disorder, consumption of oral contraceptives, family history of Graves' disease or thyroid antibody titre. HLA does not appear to distinguish subvariants of Graves' disease, rather it influences the susceptibility to disease and its persistence once it becomes clinically manifest.


Transient expression of insulin-like growth factor I immunoreactivity in skeletal muscle cells during postnatal development in the rat.
The immunohistochemical expression of insulin-like growth factor I (IGF-I; somatomedin C) was investigated in hindlimb skeletal muscle of rats during postnatal development. IGF-I immunoreactivity could be demonstrated in satellite fibres and myotubes 1, 2 and 3 days after birth, while no IGF-I immunoreactivity could be demonstrated in the more mature primary fibres. Five days after birth only scattered cells showed IGF-I immunoreactivity and 10 days after birth no specific IGF-I immunoreactivity could be demonstrated in muscle cells, i.e. the adult pattern was established. It is concluded that IGF-I immunoreactivity is expressed during a limited period of postnatal skeletal muscle maturation in rats. IGF-I is probably synthesized by IGF-I immunoreactive muscle cells and contributes to the differentiation/maturation process by autocrine and/or paracrine mechanisms.


What do they need to know: achieving consensus on paediatric musculoskeletal content for medical students.
Children present commonly with musculoskeletal (MSK) problems, due to a spectrum of causes including potentially life threatening disease, to doctors in varied health care settings. However, doctors involved in the care of children report a lack of confidence in their paediatric musculoskeletal (pMSK) clinical skills and many have little exposure to pMSK teaching. There is no current guidance on the pMSK clinical skills and knowledge required for medical students. The objective of this study was to achieve consensus amongst experts on the learning outcomes for a pMSK curriculum for medical students. This was a two-phase study. In Phase one, pMSK educational topics and categories were identified from UK medical students and experts (recruited from pMSK medicine, child health, education and primary care) utilising focus groups and interviews. These themes and concepts informed the structure of learning outcomes that were presented to a Delphi panel in Phase two, with the aim of achieving consensus on the final content of the curriculum. In Phase 1 participants identified pMSK skills, knowledge and attitudes relevant for medical students. This content was translated into learning outcomes. In Phase 2, the proposed outcomes were submitted to scrutiny by a two-iteration Delphi process with experts in the field. The agreed learning outcomes (n = 45) were either generic to child health or specific to pMSK medicine, and related to history taking and examination, knowledge about normal development, key clinical presentation and conditions, approaches to investigation and referral pathways. This study has identified evidence and consensu based content for a pMSK curriculum for medical students, derived from key stakeholders and to be integrated into medical student pMSK teaching. It is envisaged that implementation of this content will equip graduating doctors with relevant and important skills and knowledge to assess children with MSK presentations, and facilitate early diagnosis and referral to specialist care.


PICK1 attenuates high glucose-induced pancreatic β-cell death through the PI3K/Akt pathway and is negatively regulated by miR-139-5p.
Diabetes mellitus is a metabolic disease characterized by an increase in blood glucose levels due to lack of insulin secretion. Previous studies have confirmed that PICK1 is critical for both β-cell function and glucose homeostasis. The aim of this study was to investigate the role of PICK1 in response to high glucose-induced β-cell dysfunction and the molecular mechanism of regulation of PICK1. We found that overexpression of PICK1 in db/db diabetic mice significantly improved glucose tolerance and increased insulin release. High glucose treatment of Min6 cells inhibited PICK1 expression, and overexpression of PICK1 protected against high glucose-induced pancreatic cell dysfunction. Activation of the PI3K/Akt pathway by PICK1 in Min6 cells resulted in increased GLUT2 expression and this increase was abolished by treatment with a PI3K-specific inhibitor. Further, we showed that expression of PICK1 is negatively regulated by miR-139-5p through directly targeting its 3'UTR. These data suggested that PICK1 may participate in the functional protection of pancreatic β-cells through PI3K/Akt signaling, promote insulin secretion, and delay the progression of diabetes, and is negatively regulated by miR-139-5p, further clarifying the regulation of pancreatic β-cell function.


Management of undescended testis.
The term cryptorchidism indicates a testis, which has failed to descend to the scrotum and is located at any point along the normal path of descent or at an ectopic site. Hormones play a pivotal role in testicular descent except during the migration to the level of internal inguinal ring. Cryptorchidism is present in about 4.5% of newborns with a higher incidence in preterms. The incidence decreases to 1.2% by the first year. It is classified as palpable and impalpable. The most common site of an ectopic testis is superficial inguinal pouch. Retractile testis is often bilateral and most common in boys between 5 and 6 years of age. Hypospadias and inguinal hernias are the most common associated anomalies seen with undescended testis. A thorough clinical examination helps in arriving at the etiology. A short hCG stimulation test helps to exclude anorchia. Different imaging techniques are of little help in diagnosis and require the help of an experienced radiologist. Laparoscopy has an important role in the diagnosis and management of undescended testis. The common complications include torsion and atrophy of testis. Infertility is seen in about 40% of unilateral and 70% of bilateral cryptorchidism. Undescended testis is 20 to 40 times more likely to undergo malignant transformation than normal testis. Both hCG and GnRH have been used with limited success in these children. All boys with cryptorchidism should be referred to a pediatric surgeon before 2 years of age. These children should be followed up every year after surgery to identify testicular tumors.


Impact of endotoxins on bioengineered tissues and models.
Endotoxins are commonly present in both naturally derived and synthetic biomaterials. This Forum highlights the consequences of endotoxin contamination in biomaterials on different engineered tissues, such as bone, skin, or cartilage, and discusses the potential effects on novel 3D immunocompetent pathophysiological models.


HLA-peptide binding prediction using structural and modeling principles.
Short peptides binding to specific human leukocyte antigen (HLA) alleles elicit immune response. These candidate peptides have potential utility in peptide vaccine design and development. The binding of peptides to allele-specific HLA molecule is estimated using competitive binding assay and biochemical binding constants. Application of this method for proteome-wide screening in parasites, viruses, and virulent bacterial strains is laborious and expensive. However, short listing of candidate peptides using prediction approaches have been realized lately. Prediction of peptide binding to HLA alleles using structural and modeling principles has gained momentum in recent years. Here, we discuss the current status of such prediction.


Inhibition of phosphorylated tyrosine hydroxylase attenuates ethanol-induced hyperactivity in adult zebrafish (Danio rerio).
Zebrafish have been successfully employed in the study of the behavioural and biological effects of ethanol. Like in mammals, low to moderate doses of ethanol induce motor hyperactivity in zebrafish, an effect that has been attributed to the activation of the dopaminergic system. Acute ethanol exposure increases dopamine (DA) in the zebrafish brain, and it has been suggested that tyrosine hydroxylase, the rate-limiting enzyme of DA synthesis, may be activated in response to ethanol via phosphorylation. The current study employed tetrahydropapaveroline (THP), a selective inhibitor of phosphorylated tyrosine hydroxylase, for the first time, in zebrafish. We treated zebrafish with a THP dose that did not alter baseline motor responses to examine whether it can attenuate or abolish the effects of acute exposure to alcohol (ethanol) on motor activity, on levels of DA, and on levels of dopamine's metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). We found that 60-minute exposure to 1% alcohol induced motor hyperactivity and an increase in brain DA. Both of these effects were attenuated by pre-treatment with THP. However, no differences in DOPAC levels were found among the treatment groups. These findings suggest that tyrosine hydroxylase is activated via phosphorylation to increase DA synthesis during alcohol exposure in zebrafish, and this partially mediates alcohol's locomotor stimulant effects. Future studies will investigate other potential candidates in the molecular pathway to further decipher the neurobiological mechanism that underlies the stimulatory properties of this popular psychoactive drug.


Gemcitabine as prolonged infusion and vinorelbine in anthracycline and/or taxane pretreated metastatic breast cancer: a phase II study.
Gemcitabine and vinorelbine are active agents for the treatment of metastatic breast cancer. Prolonged infusion of gemcitabine can result in higher levels of active metabolites compared to shorter administration. This phase II trial was initiated to evaluate the efficacy and tolerability of gemcitabine as prolonged infusion in combination with vinorelbine in anthracycline and/or taxane pretreated patients with metastatic breast cancer. Patients who had received one prior line of chemotherapy for metastatic disease were treated with gemcitabine (350 mg/m2 as 4 h infusion) and vinorelbine (25 mg/m2 on days 1 and 8. Treatment was repeated every 3 weeks for a maximum of six cycles. Of 26 patients enrolled, 84% had received prior anthracycline treatment and 50% prior taxane therapy. In total, one complete and six partial responses were achieved, accounting for an overall response rate of 30.4%. The clinical benefit rate was 47.8%. Median duration of response and median time to progression were 7.3 months and 4.6 months, respectively. Median overall survival was 14.5 months. Although the predominant toxicity was myelosuppression with grade 3/4 neutropenia in 42% of patients, few neutropenic complications resulted. Non-hematological toxicity was generally moderate. Most common non-hematologic toxicities were nausea, vomiting, alopecia, peripheral neuropathy and elevation of liver enzymes. Gemcitabine as prolonged infusion and vinorelbine are a safe and effective combination treatment in anthracycline and/or taxane pretreated patients. Approximately 47.8% of patients derived clinical benefit from treatment. This regimen represents a therapeutic option for patients receiving second-line therapy for metastatic breast cancer.


Modification of voltage-dependent Na+ current by triphenyltin, an environmental pollutant, in isolated mammalian brain neurons.
In order to reveal the profile of neurotoxicity of triphenyltin on the mammalian central nervous system (CNS) through the modification of a voltage-dependent Na+ channel, the effects of triphenyltin on the kinetics of voltage-dependent Na+ current (INa) were examined in acutely dissociated pyramidal neurons of rat hippocampus. Triphenyltin at the concentration of 1.10(-6) M decreased both the time to peak and the half-decay time of the INa without affecting the current-voltage relationship. Triphenyltin moved the steady-state inactivation curve to a depolarizing direction. In the presence of triphenyltin, the reactivation of Na+ channel inactivated during the depolarization occurred quicker than that of the control at the pulse intervals of less than 10 ms. It can be suggested that triphenyltin potentially increases the cell excitability in mammalian CNS through the modification of the INa.


Checkpoint blockade meets gene therapy: Opportunities to improve response and reduce toxicity.
Immune checkpoint inhibitors (ICIs) based on monoclonal antibodies represent a breakthrough for the treatment of cancer. However, their efficacy varies among tumor types and patients, and they can lead to adverse effects due to on-target/off-tumor activity, since they are administered systemically at high doses. An alternative and attractive approach for the delivery of ICIs is the use of gene therapy vectors able to express them in vivo. This review focuses on the most recent studies using viral vectors able to express ICIs locally or systemically in preclinical models of cancer. These vectors include non-replicating viruses, oncolytic viruses able to propagate specifically in tumor cells and destroy them, and self-amplifying RNA vectors, armed with different formats of antibodies against immune checkpoints. Non-replicating vectors usually lead to long-term ICI expression, potentially eliminating the need for repeated administration. Vectors with replication capacity, although they have a shorter window of expression, can induce inflammation which enhances the antitumor effect. Finally, these engineered vectors can be used in combination with other immunostimulatory molecules or with CAR-T cells, further boosting the antitumor immune responses.


Changes in longevity inequality by education among OECD countries before the COVID-19 pandemic.
Disparities in life expectancy between socioeconomic groups are one of the main challenges for health policy, and their reduction over time is an important policy objective. Observational study using routinely registered data on mortality around 2011 and 2016 by sex, age, educational attainment level, and cause of death in 13 member countries of the Organization for Economic Cooperation and Development (OECD). The main outcome measures are life expectancy by education at the ages of 25 and 65 in 2011 and 2016. Between 2011 and 2016, the life expectancy gap has increased by 0·2 years among men and 0·3 years among women from 13 available countries. The United States recorded one the largest increases in the absolute life expectancy gap, 1·3 years for women and 1·1 years for men respectively. Inequality in longevity has increased in over half of the countries surveyed and starkly so in the United States in a context of deteriorating health. Not applicable.


Formation of gut-like structures in vitro from mouse embryonic stem cells.
Embryonic stem (ES) cells have the potential to differentiate into all cell types originating from the three germ layers; however, there are still few reports about the formation of functional organs from embryonic stem cells. Recently, we reported that by hanging drops of mouse ES cells, embryoid bodies (EBs) formed gut-like structures in vitro composed of three layers corresponding to the epithelium, lamina propria, and musculature. The morphological features and the process of formation are similar to gut and its organogenesis in vivo. Thus, this is a good model for development of the gut and a useful tool for analysis of the factors required for gut organogenesis. The protocol basically involves a method of hanging drops to make EBs, which are then plated on coated dishes for outgrowth. EBs develop to form gut-like structures when induced to spontaneously enter a program of differentiation in vitro without addition of any extrinsic factors.


Thoracic and Thoracoabdominal Aneurysms: Etiology, Epidemiology, and Natural History.
Thoracic aortic aneurysms and thoracoabdominal aneurysms are often found incidentally. Complications include dissection or rupture. Most of the thoracic aortic aneurysms and thoracoabdominal aneurysms develop in patients with risk factors for atherosclerosis. Younger patients without significant cardiovascular risk factors may have a genetic basis and include syndromes such as Marfan, Ehlers-Danlos, and Loeys-Dietz and bicuspid aortic valve. Most thoracic aneurysms grow slowly over time and factors that accelerate growth rate include dissection, aneurysm size, bicuspid valve disease, and Marfan syndrome. Size cutoffs where complications occur determine when surgery or intervention should be considered.


Surgical outcomes for low-volume vs high-volume surgeons in gynecology surgery: a systematic review and meta-analysis.
The aim of this study was to determine the impact of gynecological surgeon volumes on patient outcomes. Eligible studies were selected through an electronic literature search from database inception up until September 2015 and references in published studies. Search terms included surgical volume, surgeon volume, low-volume or high-volume, and gynecology or hysterectomy or sling or pelvic floor repair or continence procedure. The literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We defined a low-volume surgeon (LVS) as one performing the procedure once a month or less, and studies were excluded if their definition of LVS was > ±33% of our definition. Primary outcomes were total complications, intraoperative complications, and postoperative complications. All outcome data for individual studies were entered into systematic review software. When 2 or more studies evaluated a designated outcome, a meta-analysis of the entered data was undertaken as per the Cochrane database methodology. Data analysis was entered into a software product, which generated a summary of findings table that included structured and qualified grading (very low to high) of the quality for the evidence of the individual outcomes and provided a measure of effect. Fourteen peer-reviewed studies with 741,760 patients were included in the systematic review. For gynecology the LVS group had an increased rate of total complications (odds ratio [OR], 1.3, 95% confidence interval [CI], 1.2-1.5), intraoperative complications (OR, 1.6, 95% CI, 1.2-2.1), and postoperative complications (OR, 1.4 95% CI, 1.3-1.4). In gynecological oncology, the LVS group had higher mortality (OR, 1.9, 95% CI, 1.3-2.6). In the urogynecology group, a single study reported that the LVS group had a higher rate of any complication (risk ratio [RR], 1.4, 95% CI, -1.2-1.6). Another single study found that LVS had higher rates of reoperation for mesh complications after midurethral sling procedures (RR, 1.4, 95% CI, 1.2-1.5). The evidence is of moderate to very low quality. Gynecologists performing procedures approximately once a month or less were found to have higher rates of adverse outcomes in gynecology, gynecological oncology, and urogynecology, with higher mortality in gynecological oncology.


Pregnane steroid alphaxalone attenuates anxiogenic behavioral effects of corticotropin releasing factor and stress.
The 3 alpha-hydroxy A-ring-reduced steroid alphaxalone was examined for its ability to block stress-induced behavioral effects. Alphaxalone (3 and 6 mg/kg, IP) significantly antagonized the response-suppressing effects of corticotropin releasing factor (CRF) (0.5 micrograms, ICV) on punished responding in a conflict paradigm. In the plus maze, alphaxalone (3 and 6 mg/kg, IP) blocked the anxiogenic behavioral effects produced by a prior ambient-temperature swim stress. These doses of alphaxalone produced no intrinsic effects on plasma ACTH levels, nor did they attenuate CRF-induced increases in plasma ACTH. These findings support the hypothesis that some pregnane steroids may be involved in the modulation of an animal's behavioral response to stress and suggest that these effects may occur independently of the hypothalamic-pituitary-adrenocortical axis.


Hipersensitivity Reactions to Corticosteroids.
Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce immediate and delayed hypersensitivity reactions. Allergic contact dermatitis is the most frequent presentation of corticosteroid allergy and it should be studied by patch testing in specific units. The corticosteroids included in the Spanish standard battery are good markers but not ideal. Therefore, if those makers are positive, it is useful to apply a specific battery of corticosteroids and the drugs provided by patients. Immediate reactions are relatively rare but potentially severe, and it is important to confirm the sensitization profile and to guide the use of alternative corticosteroids, because they are often necessary in several diseases. In this article we review the main concepts regarding these two types of hypersensitivity reactions in corticosteroid allergy, as well as their approach in the clinical practice.


Aerobic and oxygen-limited enrichment of BTEX-degrading biofilm bacteria: dominance of Malikia versus Acidovorax species.
Due to their high resistance against environmental challenges, bacterial biofilms are ubiquitous and are frequently associated with undesired phenomena in environmental industry (e. g. biofouling). However, because of the high phylogenetic and functional diversity, bacterial biofilms are important sources of biotechnologically relevant microorganisms, e.g. those showing bioremediation potential. In our previous work, the high phylogenetic and metabolic diversity of a clogging biofilm, developed in a simple aromatic hydrocarbon (BTEX)-contaminated groundwater well was uncovered. The determination of relationships between different groups of biofilm bacteria and certain metabolic traits has been omitted so far. Therefore, by setting up new biofilm-based enrichment microcosms, the research goal of the present study was to identify the aerobic/hypoxic BTEX-degrading and/or prolific biofilm-forming bacteria. The initial bacterial community composition as well as temporal dynamics due to the selective enrichment has been determined. The obtained results indicated that the concentration of dissolved oxygen may be a strong selective force on the evolution and final structure of microbial communities, developed in hydrocarbon-contaminated environments. Accordingly, members of the genus Malikia proved to be the most dominant community members of the aerobic BTEX-degrading enrichments. Acidovorax spp. dominated the oxygen-limited/hypoxic setup. During the study, a strain collection of 23 different bacterial species was obtained. Non-pathogenic members of this strain collection, with outstanding biodegradation (e.g. Pseudomonas, Variovorax isolates) and biofilm-forming potential (e.g. Rhizobium), may potentially be applied in the development of biofilm-based semipermeable reactive biobarriers.


Characterisation of Ca2+ transport activity by white adipose tissue mitochondria.
Ca2+ transport in mitochondria isolated from rat white adipocytes has been examined and many of the properties found to be similar to those reported for mitochondria isolated from rat liver. Ca2+ transport is ruthenium red-sensitive (Ki approximately 5 pmol . mg protein-1), the affinity for free Ca2+ is high (Km approximately 3.3 microM) and the Vmax is 135 nmol Ca2+ . min-1 . mg protein-1 at 4 degrees C with 0.2 mM Pi present. Ca2+ transport is stimulated by increasing the medium [Pi], and is inhibited when ATP or Mg2+ is added to the incubation system and in contrast to brown adipocyte mitochondria, Ca2+ efflux is not promoted by Na+. White adipocyte mitochondria may play a rôle in the regulation of total cell calcium in this tissue.


Is formal scoring better than just looking? A comparison of subjective and objective scoring methods of the Rey Complex Figure Test for lateralizing temporal lobe epilepsy.
ObjectiveNeuropsychologists labor over scoring the Rey Complex Figure Test (RCFT), a measure of visuospatial functioning and nonverbal memory. Compelling arguments suggest that pathognomonic signs of the RCFT are observable to the "naked eye." Standard scoring systems are insensitive to lateralizing temporal lobe epilepsy (TLE) and alternative "qualitative" scoring systems are ineffective and time-consuming. Method: We examined accuracy of TLE lateralization using subjective classifications and standard scoring. Participants were 84 TLE patients (53 female; mean age=36yrs) and 46 controls (27 female; mean age = 27.5). The former were classified as right (n = 41) or left (n = 43) TLE by neurologists using EEG and MRI studies. RCFT were scored using standard scoring with cut-offs of z ≤ -2 classified as impaired and were rated as "characteristic" of RTLE (Ugly) or LTLE (Not Ugly) performance by neuropsychologists. Accuracy of seizure lateralization for both methods was examined. Results: Neuropsychologists' ratings accuracy were at or below chance. Standard scoring criteria showed chance or slightly better lateralization prediction. Standard scoring predicted RTLE laterality more accurately than subjective ratings for copy trials; standard scoring was no better at lateralizing RTLE with delays. Subjective ratings were better at distinguishing TLE patients from controls. Conclusion: Findings highlight concerns regarding the usefulness of the RCFT in TLE lateralization, regardless of scoring approach.


Limits to the temporal fidelity of cortical spike rate signals.
The cerebral cortex processes information primarily through changes in the spike rates of neurons within local ensembles. To evaluate how reliably the average spike rate of a group of cortical neurons can represent a time-varying signal, we simulated an ensemble with realistic spike discharge behavior. We found that weak interneuronal correlation, or synchrony, allows the variability in spike rates of individual neurons to compromise the ensemble representation of time-varying signals. Brief cycles of sinusoidal modulation at frequencies above 115 Hz could not be represented by an ensemble of hundreds of neurons whose interneuronal correlation mimics that of the visual cortex. The spike variability and correlation assumed in our simulations are likely to apply to many areas of cortex and therefore may constrain the fidelity of neural computations underlying higher brain function.


A root acyl carrier protein-II from spinach is also expressed in leaves and seeds.
During the synthesis of fatty acids and their utilization in plastids, fatty acyl moieties are linked to acyl carrier protein (ACP). In contrast to previously cloned organ-specific ACP isoforms, we have now isolated a cDNA clone for a potentially constitutive ACP isoform from a spinach root library. Identity between the amino acid sequence encoded by this cDNA and N-terminal sequence data for ACP-II protein from spinach leaf indicates that the root cDNA encodes ACP-II. The deduced amino acid sequence for ACP-II shows 62% identity with spinach leaf ACP-I. Southern analysis suggests that multiple ACP genes or pseudogenes occur in the spinach genome. High-stringency northern blot analysis and RNase protection studies confirm that, within the region encoding the mature ACP-II, the cloned ACP sequence is expressed in leaves and seeds as well as in roots. Quantitative RNase protection data indicate that the ratio of ACP-I and ACP-II mRNA sequences in leaf is similar to the ratio of the two proteins.


Emergence of NMDAR-independent long-term potentiation at hippocampal CA1 synapses following early adolescent exposure to chronic intermittent ethanol: role for sigma-receptors.
Adolescent humans who abuse alcohol are more vulnerable than adults to the development of memory impairments. Memory impairments often involve modifications in the ability of hippocampal neurons to establish long-term potentiation (LTP) of excitatory neurotransmission; however, few studies have examined how chronic ethanol exposure during adolescence affects LTP mechanisms in hippocampus. We investigated changes in LTP mechanisms in hippocamal slices from rats exposed to intoxicating concentrations of chronic intermittent ethanol (CIE) vapors in their period of early-adolescent (i.e., prepubescent) or late-adolescent (i.e., postpubescent) development. LTP was evaluated at excitatory CA1 synapses in hippocampal slices at 24 h after the cessation of air (control) or CIE vapor treatments. CA1 synapses in control slices showed steady LTP following induction by high-frequency stimulation, which was fully dependent on NMDAR function. By contrast, slices from early-adolescent CIE exposed animals showed a compound form of LTP consisting of an NMDAR-dependent component and a slow-developing component independent of NMDARs. These components summated to yield LTP of robust magnitude above LTP levels in age-matched control slices. Bath-application of the sigma-receptor antagonist BD1047 and the neuroactive steroid pregnenolone sulfate, but not acute ethanol application, blocked NMDAR-independent LTP, while leaving NMDAR-dependent LTP intact. Analysis of presynaptic function during NMDAR-independent LTP induction demonstrated increased presynaptic function via a sigma-receptor-dependent mechanism in slices from early-adolescent CIE-exposed animals. By contrast, CIE exposure after puberty onset in late-adolescent animals produced decrements in LTP levels. The identification of a role for sigma-receptors and neuroactive steroids in the development of NMDAR-independent LTP suggests an important pathway by which hippocampal synaptic plasticity, and perhaps memory, may be uniquely altered by chronic ethanol exposure during the prepubescent phase of adolescent development.


Childhood cataract in sub-Saharan Africa.
Investment by organizations and agencies has led to a growing body of evidence and information to assist ophthalmologists and others to meet the needs of children with cataract in Africa. The geographic distribution of research, training, and programme development across Africa has been uneven; investment has been greatest in eastern and southern Africa. Population based surveys (using key informants) suggest that 15-35% of childhood blindness is due to congenital or developmental cataract. There may be up to 82,000 children with non-traumatic cataract in Africa, with approximately 19,000 new cases each year. Effective strategies to find and refer children are those that engage the community in case detection. Identification and referral does not automatically mean surgical intervention with distance to the surgical facility being the most common reason for failure to seek care. Surgical management has become more specialized and a team based approach has been adopted by many paediatric ophthalmologists and their programmes. Although many children still present late for surgery, outcomes of surgery are much improved from previous experiences. Research suggests that post-operative follow up, still a challenge, can be improved through adoption of specific strategies. There has been limited success in ensuring that children are placed in appropriate educational settings. While eye care professionals may feel their responsibility ends with clinical care, it is important for the paediatric eye care team to be engaged with educational and rehabilitation services.


Relationship between dihedral angles of N1 and C9 substituents in 1,4-benzodiazepines and dual cholecystokinin-A and -B antagonistic activities.
Introduction of a methyl moiety to the C9 position of a 1,4-benzodiazepine ring system afforded dual CCK-A and -B antagonistic activity. Novel derivatives having ethyl, isopropyl and chloro substituents at C9 were prepared in order to obtain more potent antagonistic activities. AM1(MOPAC93) calculations of the dihedral angles between the N1 and C9 substituents indicated that dihedral angles for dual antagonistic activities were between 50 degrees and 60 degrees. A methyl moiety was selected as the most suitable C9 substituent in this series for potent dual CCK-A and -B receptor antagonistic properties.


[Is chirality a key to stereoselective drug action?].
The aim of this paper is to analyse examples of stereoselective binding of drugs to receptor sites. Selected examples are also given for the binding of drugs to serum albumin and for stereochemical aspects of drug metabolism.


Sepsis risk factors associated with HIV-1 patients undergoing surgery.
Recent developments in the treatment of HIV-1 have improved the disease prognosis from a terminal disease to a chronic disease. The number of HIV-1-infected patients who require surgery has become more common. The main threat to HIV-1-infected patients following surgery is the development of sepsis. In this study, we collected a large number of clinical recordings of HIV-1-infected patients from two hospitals in China, specializing in HIV-1 treatment in order to summarize the risk indicators of sepsis in HIV-1-infected patients. We compared the significant risk indicators between the sepsis and non-sepsis groups. Using logistic regression based on the indicators of four separate surgery-based diseases, we generally found that low CD4 and hypoalbuminemia counts prior to surgery were the significant risk factors for developing sepsis. The morbidity of sepsis in trauma patients was approximately 10 times higher than the dysfunction group, whereas the tumor and the infection groups were approximately 1.5 and 2 times higher, respectively. Based on the comparison between the sepsis and non-sepsis groups for each surgery-based disease, we found that the severity of trauma is a critical risk factor for trauma patients; therefore, limiting the size of the wound during surgery is crucial. HIV-1-infected patients often develop postoperative sepsis due to immunodeficiency and complications due to the surgery. We hope that this study can help to reduce the risk of developing sepsis due to surgery and improve the survival rate of HIV-1-infected patients.


Stressors and chemical imbalances: Beliefs about the causes of depression in an acute psychiatric treatment sample.
Public perceptions of mental illness are increasingly construed in neurobiological and genetic terms. Accumulating evidence suggests there are some unintended consequences of these explanations, including reduced optimism for recovery among individuals with depression. However, little is known about how these beliefs relate to treatment process and outcomes in a psychiatric treatment setting, a gap this study aimed to fill. We examined etiological beliefs about depression in a sample of patients (N = 279) seeking acute treatment in a behaviorally-based therapy program at a psychiatric hospital and examined relations with treatment expectations and outcomes. We found that although psychosocial explanations of depression were most popular, biogenetic beliefs, particularly the belief that depression is caused by a chemical imbalance, were prevalent in this sample. Further, the chemical imbalance belief related to poorer treatment expectations. This relationship was moderated by symptoms of depression, with more depressed individuals showing a stronger relationship between chemical imbalance beliefs and lower treatment expectations. Finally, the chemical imbalance belief predicted more depressive symptoms after the treatment program ended for a 2-week measure of depression (but not for a 24-hour measure of depression), controlling for psychiatric symptoms at admission, inpatient hospitalizations, and treatment expectations. The sample was homogenous in terms of race and ethnicity and we did not assess how patients came to their beliefs. Together, the results illustrate the correlates and possible impacts of etiological beliefs in a real-world clinical setting and invite a critical discussion about predominant messages about the etiology of depression.


Upregulation of CD40 ligand and enhanced monocyte-platelet aggregate formation are associated with worse clinical outcome after ischaemic stroke.
The white blood cell count and mean platelet volume determined shortly after the symptom onset are known as independent predictors for clinical outcome after stroke. In the present study we sought to evaluate the prognostic value of platelet-derived inflammatory biomarkers measured prospectively after an ischaemic event. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P and subpopulations of leukocyte-platelet aggregates were assessed in 93 stroke patients on the first (V(0)), 10th (V(1)) and 90th (V(2)) day after stroke, and once in 65 disease controls. The clinical outcome was evaluated using the Scandinavian Stroke Scale (SSS) and modified Rankin Scale (mRS) at the same time points as blood sampling and 24 months after the event. Patients with either CD40L surface expression or the percentage of monocyte-platelet aggregates (M-plt) in the third tertile (T3) at V0 had a significantly lower score on the SSS at V(1). Patients with the percentage M-plt at V(0) higher than the median value of M-plt in controls were at increased risk of SSS < 40 at V(1) (odds ratio: 2.6; 95% confidence interval [CI]: 1.4 - 8.7; p=0.006). Patients with the percentage of M-plt in T3 at V(0) showed progressive decline in survival (hazard ratio [HR]: 1.6; 95% CI: 1.1-1.9; p=0.02) and a significantly higher number of recurrent vascular events (HR: 2.64; 95% CI: 1.3-3.2; p=0.02) when compared to the first tertile. In conclusion, increased levels of M-plt could be a predictive marker for both early outcome and long-term prognosis while increased CD40L was correlated with worse clinical outcome.


Toxic Site Identification Program in Azerbaijan.
The need to protect communities from hazardous waste is an important agenda for any nation. Although pollutant management and policy development are attempted in many developing countries, it is not always successful due to limited funds, project resources, and access to trained experts to conduct toxic site identification projects. For this reason, Pure Earth created the Toxic Site Identification Program (TSIP). The goal of the TSIP program is to provide reliable information and data that identifies location of toxic sites and the level of toxic severity. TSIP is significant because it provides developing countries a database of ranked toxic sites identified as hazardous risk to human health. For example, Azerbaijan is one of the most polluted post-Soviet nations, but has limited resources to address and manage its polluted sites. The Azerbaijani TSIP database is the first reliable data source that identifies hazardous pollutants in the country. Our study is significant because it discusses how the TSIP labels and ranks the level of toxic severity to human health. It is also the first data source in Azerbaijan that identifies which Soviet legacy toxic sites are affecting local communities. Although our study is specific to Azerbaijan, the TSIP method can be applied to nations with similar data limitations and the need for a database that identifies country specific environmental and hazardous locations. The data sampling method and results are mapped and accompanied by tables of the collected pollutant types to identify communities at greatest health-risk to legacy toxic sites.


Intravenous versus topical tranexamic acid in primary total hip replacement: A systemic review and meta-analysis.
Total hip arthroplasty (THA) is associated with substantial blood loss. Tranexamic acid (TXA) could reduce perioperative blood loss. The optimal administration routine of TXA remains controversial. The objective of the present systemic review and meta-analysis was to compare the effectiveness and safety of various application methods of tranexamic acid in primary THA. Potential relevant literature was identified from electronic databases including Medline, PubMed, Embase, ScienceDirect, web of science and Cochrane Library. Grey academic studies were also identified from the references of the included literature. There was no language restriction. The pooling of data was carried out by using RevMan 5.1. Three randomized controlled trials (RCTs) and two non-RCTs involving 1614 patients met the inclusion criteria. Current meta-analysis indicated that there were no significant differences in terms of total blood loss (MD = -30.04, 95% CI: -114.67 to 54.59, P = 0.49), postoperative hemoglobin level (MD = -0.29, 95% CI: -0.68 to 0.10, P = 0.14), transfusion rate (RD = -0.02, 95% CI: -0.5 to -0.00, P = 0.09), length of stay ((MD = -0.14, 95% CI: -0.30 to 0.01, P = 0.07) or operation time ((MD = 1.00, 95% CI: -0.31 to 2.31, P = 0.14) between treatment groups. No significant differences were found regarding the incidence of adverse effects such as wound infection (RD = -0.01, 95% CI: -0.06 to 0.04, P = 0.66), myocardial infarction (MI) (RD = -0.01, 95% CI: -0.04 to 0.02, P = 0.61), deep venous thrombosis (DVT) (RD = 0.00, 95% CI: -0.01 to 0.01, P = 0.51) or pulmonary embolism (PE) (RD = RD = 0.00, 95% CI: -0.01 to 0.01, P = 0.63) between groups. The topical administration of TXA in THA carried similar hemostasis effects compared with intravenous use without an increased risk of thrombotic complications. No other adverse effect was identified. Topical TXA application was a simple, safe, effective and cost-effective adjunct for blood management following primary THA. For patients with a high risk of thromboembolic events, there may be benefits with topical administration.


The effects of intramuscular norethisterone oenanthate used as a contraceptive on intravenous glucose tolerance and on blood coagulation factors VII and X.
Intravenous glucose tolerance tests, and estimations of prothrombin time, and plasma coagulation factors VII and X, were made on 12 women receiving 200 mg norethisterone oenanthate intramuscularly as a contraceptive. These estimations were made before, and at 2 and 12 weeks after, a single injection of norehisterone oenanthate. There was no significant effect on the intravenous glucose tolerance, prothrombin time, or on plasma coagulation factors VII and X, further confirming the safety of norehisterone oenanthate when used as a short-term injectable contraceptive.


CdS quantum dots confined in mesoporous TiO2 with exceptional photocatalytic performance for degradation of organic polutants.
In this paper, the mesoporous TiO2 with different concentration of CdS quantum dots (i.e., x% CdS/TiO2) was successfully fabricated by the sol-gel method. The composition, structure and morphology of the nanocomposites were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), UV-vis diffuse reflectance spectroscopy (UV-Vis/DRS) and nitrogen physical adsorption test and so on. The proportion of CdS and TiO2 is very important for the photocatalytic performance. As a result, the photocatalytic degradation performance from the most to the least is in the order of 2% CdS/TiO2, 4% CdS/TiO2, 8% CdS/TiO2, pure TiO2 and 1% CdS/TiO2. The photocatalytic (PC) activity of the 2% CdSTiO2 is characterized by photocatalytic degradation of methyl orange, which can be completely degraded within 45 min better than 60 min TiO2 takes. It is also much better than CdS. Moreover, other four organic pollutants, such as methylthionine chloride, bisphenol A, rhodamine B, malachite green can also be degraded quickly on the condition of 2% CdS/TiO2. What's more, the chemical stability and cycling capability of 2% CdS/TiO2 are reflected by five cyclic degradation of methyl orange.


Hepatitis B third-generation vaccines: improved response and conventional vaccine non-response--third generation pre-S/S vaccines overcome non-response.
A new triple-S containing recombinant hepatitis B vaccine was evaluated in terms of immunogenicity and reactogenicity in a cohort of healthy healthcare professionals who were persistent non-responders to the currently licensed hepatitis B vaccines. One hundred subjects were allocated randomly to receive two doses of 5, 10, 20 or 40 micrograms of a new hepatitis B vaccine 2 months apart. The overall seroconversion rate was 70% with a single dose of 20 micrograms of the vaccine being as effective as two doses of either 20 micrograms or 40 micrograms of the vaccine formulation in terms of seroconversion, seroprotection and geometric mean titres.


A digital biomarker of diabetes from smartphone-based vascular signals.
The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. Here we developed a deep neural network (DNN) to detect prevalent diabetes using smartphone-based photoplethysmography from an initial cohort of 53,870 individuals (the 'primary cohort'), which we then validated in a separate cohort of 7,806 individuals (the 'contemporary cohort') and a cohort of 181 prospectively enrolled individuals from three clinics (the 'clinic cohort'). The DNN achieved an area under the curve for prevalent diabetes of 0.766 in the primary cohort (95% confidence interval: 0.750-0.782; sensitivity 75%, specificity 65%) and 0.740 in the contemporary cohort (95% confidence interval: 0.723-0.758; sensitivity 81%, specificity 54%). When the output of the DNN, called the DNN score, was included in a regression analysis alongside age, gender, race/ethnicity and body mass index, the area under the curve was 0.830 and the DNN score remained independently predictive of diabetes. The performance of the DNN in the clinic cohort was similar to that in other validation datasets. There was a significant and positive association between the continuous DNN score and hemoglobin A1c (P ≤ 0.001) among those with hemoglobin A1c data. These findings demonstrate that smartphone-based photoplethysmography provides a readily attainable, non-invasive digital biomarker of prevalent diabetes.


Comprehensive (apo)lipoprotein profiling in patients with genetic hypertriglyceridemia using LC-MS and NMR spectroscopy.
Mutations in genes encoding lipoprotein lipase (LPL) or its regulators can cause severe hypertriglyceridemia (HTG). Thus far, the effect of genetic HTG on the lipid profile has been mainly determined via conventional techniques. To show detailed differences in the (apo)lipoprotein profile of patients with genetic HTG by combining LC-MS and NMR techniques. Fasted serum from 7 patients with genetic HTG and 10 normolipidemic controls was used to measure the concentration of a spectrum of apolipoproteins by LC-MS, and to estimate the concentration and size of lipoprotein subclasses and class-specific lipid composition using NMR spectroscopy. Patients with genetic HTG compared to normolipidemic controls had higher levels of apoB48 (fold change [FC] 11.3, P<0.001), apoC-I (FC 1.5, P<0.001), apoC-II (FC 4.3, P=0.007), apoC-III (FC 3.4, P<0.001), and apoE (FC 4.3, P<0.001), without altered apoB100. In addition, patients with genetic HTG had higher concentrations of TG-rich lipoproteins (i.e., chylomicrons and very low-density lipoproteins [VLDL]; FC 3.0, P<0.001), but lower LDL (FC 0.4, P=0.001), of which medium and small-sized LDL particles appeared even absent. While the correlation coefficient between NMR and enzymatic analysis in normolipidemic controls was high, it was considerably reduced in patients with genetic HTG. The lipoprotein profile of patients with genetic HTG is predominated with large lipoproteins (i.e., chylomicrons, VLDL), explaining high levels of apoC-I, apoC-II, apoC-III and apoE, whereas small atherogenic LDL particles are absent. The presence of chylomicrons in patients with HTG weakens the accuracy of the NMR-based model as it was designed for normolipidemic fasted individuals.


[Gastric ruptures caused by diving accidents. Apropos of 2 cases. Review of the literature].
Underwater diving was responsible for gastric rupture in two cases seen personally and five cases of total gastric rupture reported in the literature. The various possible mechanisms for onset of this rupture are envisaged, the diagnosis of this rare accident being established from the existence of a large pneumoperitoneum. Emergency laparotomy allows suture of wound and ensures recovery.


Changes in soil properties and in the growth of Lolium multiflorum in an acid soil amended with a solid waste from wineries.
The agronomic utility of a solid waste, waste perlite (WP), from wine companies was assessed. In this sense, the natural characteristics of the waste were measured, followed by the monitoring of its effects on the chemical properties of acid soils and the growth of Lolium multiflorum. Taking into account that heavy metals associated to the waste (such as Cu, Zn and Mn) could cause problems when used as amendment, the changes in their total levels and in their soil fractionation were also studied, together with their total contents in L. multiflorum. The high content in C (214gkg(-1)), N (25gkg(-1)), P (534mgkg(-1)) and K (106gkg(-1)) of WP turned it into an appropriate amendment to increase soil fertility, solving at the same time its disposal. WP contributed to increase soil pH (in 2 pH units) and cation exchange capacity (CEC increased in 3cmolckg(-1)units), but reduced the potential Cu phytotoxicity due to a change in Cu distribution towards less soluble fractions. The growth of L. multiflorum adequately responds to the treatment with WP at addition rates below 2.5gkg(-1), whereas the imbalance between nutrients can justify the reduction in biomass production at higher WP addition rates. The levels of heavy metals analyzed in L. multiflorum biomass (8-85gkg(-1)) do not seem to cause undesirable effects on its growth.


Green synthesis of carbon dots from pork and application as nanosensors for uric acid detection.
In this work, a green, simple, economical method was developed in the synthesis of fluorescent carbon dots using pork as carbon source. The as-prepared carbon dots exhibit exceptional advantages including high fluorescent quantum yield (17.3%) and satisfactory chemical stability. The fluorescence of carbon dots based nanosensor can be selectively and efficiently quenched by uric acid. This phenomenon was used to develop a fluorescent method for facile detection of uric acid within a linear range of 0.1-100μM and 100-500μM, with a detection limit of 0.05μM (S/N=3). Finally, the proposed method was successfully applied in the determination of uric acid in human serum and urine samples with satisfactory recoveries, which suggested that the new nanosensors have great prospect toward the detection of uric acid in human fluids.


Differential effects of paternal presence on pup survival in two species of dwarf hamster (Phodopus sungorus and Phodopus campbelli).
The effect of the presence or absence of the male, and of decreased ambient temperature (21 degrees C vs. 4 degrees C) on litter survival, pup survival and pup growth was measured from birth through day 18 after birth in Siberian (P. sungorus) and Djungarian (P. campbelli) hamsters. Siberian hamsters were not significantly affected by the experimental manipulations. In contrast, whereas 100% of litters and 95% of pups were successfully raised to weaning at 21 degrees C by paired Djungarian hamsters, survival fell to 47% when the mate was absent and even further, to 32%, when the ambient temperature was lowered. No significant differences in litter size or pup weight at birth were detected between species at the warmer temperature. However, P. sungorus pups gained weight significantly faster through day 12 after birth (while dependence upon the mother for food was absolute) than P. campbelli pups under all experimental conditions. Although the species are closely related, these data show that male Djungarian hamsters are essential to offspring survival under conditions where Siberian hamsters do not require conspecific help. Species differences in metabolism and thermoregulation may account for the differential pup survival.


Malignant lymphoma and extensive viral wart formation in a patient with intestinal lymphangiectasia and lymphocyte depletion.
A patient is described, the subject of a previous report (Ross et al., 1971), who subsequently developed gross peripheral mosaic warts and a malignant small bowel lymphoma in association with marked lymphocyte depletion.


Thiol antioxidant and thiol-reducing agents attenuate 15-deoxy-delta 12,14-prostaglandin J2-induced heme oxygenase-1 expression.
Heme oxygenase-1 (HO-1) is induced as a beneficial and adaptive response in cells and tissues exposed to oxidative stress. Herein we examined how various eicosanoids affect the induction of HO-1, and the possible mechanism underlying 15-deoxy-Delta(12,14)- prostaglandin J(2) (15d-PGJ(2))-induced HO-1 expression. PGH(2), PGD(2) and its metabolites of the PGJ(2) series, and PGA(1) markedly induced the protein expression of HO-1. Arachidonic acid (AA), docosahexaenoic acid (DHA), PGE(2), PGF(2 alpha), and thromboxane B(2) (TXB(2)) were shown to have no effect on the induction of HO-1. 15d-PGJ(2) was the most potent activator achieving significance at 5 microM. Although 15d-PGJ(2) significantly activated the MAPKs of JNK and ERK, the activation of JNK and ERK did not contribute to the induction of HO-1 as determined using transfection of dominant-negative plasmids and MAPKs inhibitors. Additional experiment indicated that 15d-PGJ(2) induced HO-1 expression through peroxisome proliferator-activated receptor (PPAR)-independent pathway. 15d-PGJ(2) significantly decreased the intracellular level of reduced glutathione; and the thiol antioxidant, N-acetyl-L-cysteine (NAC), and the thiol-reducing agent, dithiothreitol (DTT), inhibited the induction of HO-1 by 15d-PGJ(2). Finally, NAC and DTT exhibited significant inhibition of HO-1 mRNA and HO-1 promoter reporter activity induced by 15d-PGJ(2). These results suggest that thiol antioxidant and reducing agents attenuate the expression of HO-1 induced by 15d-PGJ(2), and that the cellular thiol-disulfide redox status may be linked to HO-1 activation.


Activation of the intronic cryptic 5' splice site depends on its distance to the upstream cassette exon.
Splice site selection is a key step that determines the mRNA isoforms generated from a single transcript. The large diversity in splice site sequences emphasizes the plasticity of splice site recognition and selection. In this report, a cell-based reporter system using a SMN1/2 cassette exon was applied to study the roles governing the activation of a cryptic 5'SS from the intron 4 of the CT/CGRP gene. We found that the cryptic site was activated when placed within 124nt downstream the cassette exon, and the level of activation was negatively correlated with its distance from the exon. In addition, activation was not affected by PTB but was eliminated by an insertion extending the exon length. Activated cryptic 5'SSs in intron or exon could override the original alternative 5'SS, obeying the U1 base-pairing rule. These results suggest that the exon length itself could represent a factor in determining the splice site selection.