Extracellular signal-regulated kinase 1/2 activation is involved in intermedin1-53 attenuating myocardial oxidative stress injury induced by ischemia/reperfusion.
Intermedin (IMD)(1-53) is a novel member of the calcitonin gene-related peptide superfamily and has potent cardioprotective effects against myocardial injury induced by ischemia-reperfusion (I/R). To explore the mechanism of the IMD(1-53) cardioprotective effect, we studied the anti-oxidant effects of IMD(1-53) on myocardial injury induced by I/R in vivo in rat and H(2)O(2) treatment in vitro in rat cardiomyocytes. Compared with sham treatment, I/R treatment induced severe lipid peroxidation injury in rat myocardium: plasma malondialdehyde (MDA) content and myocardial LDH activity was increased by 34% and 85% (all P<0.01); Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) activity was reduced 80% and 86% (all P<0.01), respectively, and the protein levels of the NADPH oxidase complex subunits gp91(phox) and p47(phox) were markedly increased, by 86% (P<0.05) and 95% (P<0.01), respectively; IMD(1-53) treatment ameliorated lipid peroxidation injury: plasma MDA content and myocardial LDH activity was decreased by 30% (P<0.05) and 36% (P<0.01); Mn-SOD and CAT activity was elevated 1.0- and 4.3-fold (all P<0.01), respectively; and the protein levels of gp91(phox) and p47(phox) were reduced, by 28% and 36% (both P<0.05), respectively. Concurrently, IMD(1-53) treatment markedly promoted cell viability and inhibited apoptosis in cardiomyocytes as compared with H(2)O(2) treatment alone. Furthermore, IMD(1-53) increased the ratio of p-ERK to ERK by 66% (P<0.05) as compared with I/R alone, and the protective effect of IMD(1-53) on H(2)O(2)-induced apoptosis was abolished by preincubation with PD98059, a MEK inhibitor. IMD(1-53) may improve the oxidative stress injury induced by I/R via inhibiting the production of reactive oxygen species and enhancing ERK phosphorylation.


The impact of routine frozen section analysis during nephroureterectomy or segmental ureterectomy for urothelial carcinoma on final surgical margin status and long-term oncologic outcome.
The utility of intraoperative frozen section analysis (FSA) at the surgical margins (SMs) in patients with upper urinary tract cancer has not been established. We herein assessed the clinical significance of routine FSA of ureteral SMs during nephroureterectomy (NU) or segmental ureterectomy (SU). A retrospective review of our Surgical Pathology database identified consecutive patients undergoing NU (n=246) or SU (n=42) for urothelial carcinoma from 2004 to 2018. FSA (n=54) was correlated with the diagnosis of frozen section controls, the status of final SMs, and the prognosis of patients. During NU, FSA was performed in 19 (7.7%) patients and was significantly more often requested in cases with ureteral tumor (13.1%) than in those with renal pelvis/calyx tumor (3.5%). Final SMs at the distal ureter/bladder cuff were positive only in non-FSA cases in the entire NU cohort (8.4%; P=0.375) or those with tumor at the lower ureter (57.6%; P=0.046), but not in any of FSA patients (0%). During SU, FSA was performed in 35 (83.3%) cases, including 19 at either proximal or distal SM and 16 at both SMs (SU-FSA2). Final positive SMs were significantly more often detected in non-FSA patients (42.9%) than in all FSA (8.6%; P=0.048) or SU-FSA2 (0%; P=0.020) patients. Overall, FSAs were reported as positive or high-grade carcinoma (n=7), atypical or dysplasia (n=13), and negative (n=34), and all these diagnoses were confirmed accurate on the frozen section controls, except one with a revision from atypical to carcinoma in situ. Meanwhile, 16 (80.0%) of 20 cases with initial positive/atypical FSA achieved negative conversion by excision of additional tissue. Kaplan-Meier analysis revealed that SU-FSA did not significantly reduce the risk of tumor recurrence in the bladder, disease progression, or cancer-specific mortality. Nonetheless, NU-FSA was strongly associated with reduced progression-free (P=0.023) and cancer-specific (P=0.007) survival rates, compared with non-FSA, which may imply a selection bias (e.g., FSA for clinically more aggressive tumors). Performing FSA during NU for lower ureteral tumor, as well as during SU, significantly reduced the risk of positive SMs. However, routine FSA for upper urinary tract cancer failed to considerably improve long-term oncologic outcome.


[Pulmonary hypoplasia: An analysis of cases over a 20-year period].
Pulmonary hypoplasia is the most frequent congenital anomaly associated with perinatal mortality. A retrospective and descriptive review was conducted on cases of patients diagnosed with pulmonary hypoplasia between 1995 and 2014 in a tertiary university hospital. An analysis was made of the prenatal imaging, clinical manifestations, post-natal diagnostic tests, treatment and management, long-term follow up, and survival data. A total of 60 cases were identified, all of them with prenatal imaging. Sixteen patients required foetal surgery. Congenital diaphragmatic hernia was the most frequent diagnosis. Main clinical presentation was respiratory distress with severe hypoxemia and high requirements of mechanical ventilation. Mortality rate was 47% within first 60 days of life, and 75% for the first day of life. Pneumonia and recurrent bronchitis episodes were observed during follow-up. They had a lung function obstructive pattern, and their quality of life and exercise tolerance was good. High neonatal mortality and significant long-term morbidity associated with pulmonary hypoplasia requires an early diagnosis and a specialised multidisciplinary team management.


Spatiotemporal differentiation and the obstacle factors influencing the coupling coordination between economic development and water pollution control capability in the Yangtze River Economic Belt.
The Yangtze River Economic Belt (YREB) is a highly influential economic belt and an innovative demonstration belt for the protection and restoration of ecological and environmental systems. The dynamic coordination between economic development system (EDs) and water pollution control capability system (WPCCs) is a critical issue to be solved for regional sustainable development. However, this topic has not been adequately addressed in previous studies. To bridge this gap, this paper analyzed the spatiotemporal differentiation and obstacle factors influencing the coupling coordination between EDs and WPCCs in the Chinese Five-Year Plan based on coupling coordination degree model and obstacle degree model. The main results suggest that (1) the comprehensive level of the comprehensive level of water pollution control capability presents an upward trend with the increase of economic development. A J-shaped relationship existed between the EDs and WPCCs. (2) The regions with rapid economic growth are mainly distributed in the Shanghai, Zhejiang, Jiangsu, Chongqing, and Sichuan. Moreover, water pollution control capability system shows this pattern, eastern regions > western regions > central regions. (3) The coupling coordination level of each region in the YREB has improved from a moderately unbalanced development level to a superiorly balanced development level from 2006 to 2019. (4) Per capita gross domestic product, gross product of tertiary industry, total volume of waste water treated, and per daily volume treated of sewage treatment facilities are the major indexes influencing the coordinated development of the EDs and WPCCs. These findings are conductive to formulating reasonable strategies for water environment protection and sustainable development and providing a direction for urban planning.


Physical Control of Spider Mites Using Ultraviolet-B With Light Reflection Sheets in Greenhouse Strawberries.
Development of spider mite management technology other than chemical control is desired because of the serious development of acaricide resistance worldwide. Recent studies have evidenced the lethal effects of ultraviolet-B (UVB) radiation on spider mites. To develop the technology on how to use UVB irradiation for spider mite control, we tested whether UVB lamp-light reflection sheet (LRS) combinations suppressed the population size of Tetranychus urticae Koch on strawberry in a greenhouse from December to May (2012-2013, 2013-2014) in Japan. We designed four combinations of UVB lamps and LRSs: 1) neither UVB lamps nor LRSs (UV-LRS-); 2) a UVB lamp without an LRS (UV+LRS-; 2012-2013 only); 3) a UVB lamp and a mulch-type LRS (UV+LRSm); and 4) a UVB lamp and a wing-type LRS (UV+LRSw). The number of adult females peaked at 438.0 and 222.0 per plant in UV-LRS- of 2012-2013 and 2013-2014, respectively, and peaked at 191.6 females in UV+LRS- of 2012-2013. In contrast, the peak abundance was 20.9-98.0 females in UV+LRSm, and fewer than 15 females were noted in UV+LRSw over either experimental period. UVB irradiance on lower leaf surfaces was higher in UV+LRSm and UV+LRSw than UV-LRS- and UV+LRS-, and the mite densities were significantly correlated with UVB irradiance on lower leaf surfaces. Consequently, we conclude that the combinations of UVB lamp-LRS have an excellent capacity to control T. urticae on greenhouse strawberry, and that the LRS was an essential component in this technological approach.


Long-term follow-up of cardiac resynchronization therapy in patients with end-stage heart failure.
Long-term follow-up of cardiac resynchronization therapy. Cardiac resynchronization therapy (CRT) has been introduced to treat patients with end-stage heart failure, and results of this technique are promising. The aim of our study was to assess the sustained benefit of CRT in a large patient cohort with end-stage heart failure at long-term follow-up. In addition, the prognosis of responders and nonresponders was evaluated. 125 patients with end-stage heart failure, NYHA class III or IV, LVEF<35%, QRS duration>120 msec and left bundle branch block morphology received a biventricular device. At baseline and 6 months after implantation the following parameters were evaluated: NYHA class, Minnesota Quality of life score, QRS duration on surface ECG, 6-minute walking distance and LVEF. Follow-up was obtained up to 3 years. After 6 months, patients were divided in clinical responders and nonresponders according to improvement in NYHA class. All clinical parameters improved significantly at 6-month follow-up. Hospitalization for heart failure was 3.8+/-4.9 days/year before and 0.7+/-1.6 days/year after CRT. Survival at 1-, 2-, and 3-year follow-up was 93%, 88%, and 85%, respectively. Responders (78%) showed a significantly better survival than nonresponders at 2- and 3-year follow-up (96% and 93% for responders versus 81% and 73% for nonresponders, P<0.05). The improvement in functional status and symptoms after CRT is maintained at long-term follow-up (up to 3 years). The clinical improvement was associated with a significant reduction in hospitalization rate which was also maintained over the years. Preimplantation selection of responders may result in even better long-term survival.


Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington's disease.
3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17 days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondria isolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animals had impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA + ALCAR for 21 days normalized mitochondrial lipid composition, improved mitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD.


Disease Burden Among Individuals with Severe Mental Illness in a Community Setting.
This study examines the prevalence of comorbid physical health conditions within a community sample of individuals with severe mental illness (SMI), compares them to a matched national sample without SMI, and identifies which comorbidities create the greatest disease burden for those with SMI. Self-reported health status, co-morbid medical conditions and perceived disease burden were collected from 203 adults with SMI. Prevalence of chronic health conditions was compared to a propensity-matched sample without SMI from the National Comorbidity Survey-Replication (NCS-R). Compared to NCS-R sample without SMI, our sample with SMI had a higher prevalence of seven out of nine categories of chronic health conditions. Chronic pain and headaches, as well as the number of chronic conditions, were associated with increased disease burden for individuals with SMI. Further investigation of possible interventions, including effective pain management, is needed to improve the health status of this population.


One thousand initiated cycles of in vitro fertilization in women > or = 40 years of age.
To evaluate the results of IVF in women > or = 40 years of age using their own oocytes. Retrospective study. Wolfson and Royal Masonic in vitro fertilization units, London, United Kingdom. A total of 1,087 IVF cycles were started in women > or = 40 years of age. Medical records of patient outcomes were reviewed. Clinical pregnancy, miscarriage, and delivery rates. Of the 1,087 cycles started in 471 women > or = 40 years of age, 842 reached oocyte retrieval (77.5%) and 702 had embryos transferred (64.6%). The pregnancy rate (PR) was significantly lower in women > or = 40 years of age than in a control group of women <40 years of age (11.3% versus 28.2%). It decreased sharply in women >42 years of age, and no women >45 years of age had a child. Women > or = 40 years of age were more likely to miscarry (27% versus 12.7%). When only one embryo was available for transfer, the PR was 3.3%. When >2 embryos were available for transfer, the PR was similar whether 2 or 3 embryos were replaced. No triplet pregnancy occurred. Women > or = 40 years of age achieved a cumulative PR of 30% after three cycles with a cumulative "take home baby" rate of 21%. In vitro fertilization is a reasonable treatment for women <45 years of age using their own gametes. Those with a "good response" in their first attempt may be encouraged to complete three cycles with an acceptable chance of conception.


Differential effects of superoxide radical on the action potentials in ventricular muscles, Purkinje fibers and atrial muscles in the heart of different aged rats.
The purpose of this study was to determine whether the effects of the superoxide donor menadione on myocardial electrical activity were regional and/or age-dependent. Action potentials were recorded in cardiac muscles that were isolated from 18- and 49-day old rat hearts, using a conventional microelectrode technique. Superoxide dismutase (SOD) activity was determined spectrophotometrically in regional cardiac muscles. Menadione (30 microM) significantly increased the action potential duration at 90% repolarization (APD90) in Purkinje fibers and ventricular muscles from 18-day old rats; and it decreased the APD in ventricular muscles from 49-day old rats. ATP-sensitive K+ (KATP) channel opener pinacidil blocked menadione-induced effects on the APD90 of Purkinje fibers and ventricular muscles from 18-day old rats, but did not block menadione-induced effects on the APD90 of Purkinje fibers and ventricular muscles from 49-day old rats. The cGMP-dependent protein kinase (PKG) activator or inhibitor did not inhibit the menadione-induced effects on APD90 of ventricular muscles and Purkinje fibers from 18- and 49-day old rats. The superoxide dismutase (SOD) activities in ventricular muscles from 4-, 18- and 49-day old rats, were: 1185 +/- 135, 1434 +/- 96, and 1760 +/- 144 U/mg protein, respectively; whereas, the SOD activities in atrial muscles, were: 1135.4 +/- 156.4, 1145.4 +/- 148.8, and 1243.5 +/- 175.2 U/mg protein, respectively. However, the ventricular SOD activities were significantly inhibited under hypoxic conditions. These results indicate that menadione can produce regionally differential effects on cardiac APD, which may be due to differences in the SOD activity, depending on the region and age of the cardiac tissue.


Pinus densiflora extract protects human skin fibroblasts against UVB-induced photoaging by inhibiting the expression of MMPs and increasing type I procollagen expression.
Exposure to ultraviolet (UV) light can cause skin photoaging, which is associated with upregulation of matrix metalloproteinases (MMPs) and downregulation of collagen synthesis. It has been reported that MMPs, especially MMP-1, MMP-3 and MMP-9, decrease the elasticity of the dermis by degrading collagen. In this study, we assessed the effects of Pinus densiflora extract (PDE) on photoaging and investigated its mechanism of action in human skin fibroblast (Hs68) cells after UVB exposure using real-time polymerase chain reaction, Western blot analysis, and enzymatic activity assays. PDE exhibited an antioxidant activity and inhibited elastase activities in vitro. We also found that PDE inhibited UVB-induced cytotoxicity, MMP-1 production and expression of MMP-1, -3 and -9 mRNA in Hs68 cells. In addition, PDE decreased UVB-induced MMP-2 activity and MMP-2 mRNA expression. Moreover, PDE prevented the decrease of type I procollagen mediated by exposure to UVB irradiation, an effect that is linked to the upregulation and downregulation of Smad3 and Smad7, respectively. Another effect of UV irradiation is to stimulate activator protein 1 (AP-1) activity via overexpression of c-Jun/c-Fos, which, in turn, upregulates MMP-1, -3, and -9. In this study, we found that PDE suppressed UV-induced c-Jun and c-Fos mRNA expression. Taken together, these results demonstrate that PDE regulates UVB-induced expression of MMPs and type I procollagen synthesis by inhibiting AP-1 activity and restoring impaired Smad signaling, suggesting that PDE may be useful as an effective anti-photoaging agent.


Efficacy and safety of acarbose add-on therapy in the treatment of overweight patients with Type 2 diabetes inadequately controlled with metformin: a double-blind, placebo-controlled study.
This 6-month, double-blind, placebo-controlled, randomised, parallel-group study investigated the potential of acarbose add-on therapy for improving the glycaemic control of overweight patients with Type 2 diabetes and was inadequately controlled with metformin monotherapy. Patients were randomised to receive acarbose titrated up to 100 mg three times daily (n=74) or placebo (n=78). All patients were receiving metformin 850 mg twice or thrice daily before the study and continued to receive this dose throughout the study. The mean difference in glycated haemoglobin (HbA(1c)) (+/-S.D.) from baseline to endpoint was -0.7+/-1.2% U in the acarbose intention-to-treat (ITT) group, compared with +0.2+/-1.3% in the placebo ITT group (P=0.0001). Significantly, more patients in the acarbose group were classified as 'responders', with an HbA(1c) at the end of treatment of less than 7.0% or a decrease by at least 15% relative to baseline (acarbose vs. placebo; 42 vs. 17%; P=0.002). The difference in fasting blood glucose level from baseline to endpoint was -1.0+/-2.8 (S.D.) mmol/l in the acarbose ITT group, compared with +1.3+/-2.8 mmol/l in the placebo ITT group (P=0.0001), and for 2-h postprandial blood glucose level -1.4+/-3.8 vs. +1.1+/-3.5 mmol/l (P=0.0001). In all, 60% of patients in the acarbose group and 33% in the placebo group had an adverse event considered to be possibly or probably related to drug therapy, leading to withdrawal by 15 and 3%, respectively. The results indicate that acarbose has potential clinical utility for improving glycaemic control in overweight patients with Type 2 diabetes inadequately controlled with metformin.


A portable scanner for magnetic resonance imaging of the brain.
Access to scanners for magnetic resonance imaging (MRI) is typically limited by cost and by infrastructure requirements. Here, we report the design and testing of a portable prototype scanner for brain MRI that uses a compact and lightweight permanent rare-earth magnet with a built-in readout field gradient. The 122-kg low-field (80 mT) magnet has a Halbach cylinder design that results in a minimal stray field and requires neither cryogenics nor external power. The built-in magnetic field gradient reduces the reliance on high-power gradient drivers, lowering the overall requirements for power and cooling, and reducing acoustic noise. Imperfections in the encoding fields are mitigated with a generalized iterative image reconstruction technique that leverages previous characterization of the field patterns. In healthy adult volunteers, the scanner can generate T1-weighted, T2-weighted and proton density-weighted brain images with a spatial resolution of 2.2 × 1.3 × 6.8 mm3. Future versions of the scanner could improve the accessibility of brain MRI at the point of care, particularly for critically ill patients.


First ecotoxicological assessment assay in a hydroelectric reservoir: the Lake Taabo (Côte d'Ivoire).
Organochlorine pesticides (OCPs) contamination was assessed in marketable species, two fishes (tilapia and catfish) and a prawn from the Lake Taabo (Côte d'Ivoire). Lindane and endosulfan were the main contaminants, suggesting their current use. DDT, endrin, heptachlor plus traces of chlordane, aldrin and fipronil were also detected. In fishes and in prawns, enzymatic biomarkers exhibited significant correlations with OCPs levels, showing the feasibility of a biomonitoring. The transfer of OCPs along the aquatic food web and their immunosuppressive effects in human are discussed. This preliminary study highlights that the pesticide contamination was concomitant with the increase in infectious diseases in the bordering population of this African lake.


Observation of the curative effect of Guizhi-Shaoyao-Zhimu decoction combined with methotrexate in the treatment of early rheumatoid arthritis based on ultrasonic evaluation: study protocol of a randomized, double-blind, controlled clinical trial.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with the primary clinical symptoms of joint swelling and pain. Early detection of erosion and synovial inflammation at an active stage resulting from RA can prevent damage to the joints and activity restriction. However, there are still many patients who do not respond to these treatments; the development of newer, safer drugs is urgently needed. Compared to Western medicine, Guizhi-Shaoyao-Zhimu decoction has equal or higher efficacy and safety for RA patients. With the widespread use of musculoskeletal ultrasound (MSUS), this technology holds great value for the degree of joint damage in RA patients, guiding the clinical selection of treatments, and assessing of prognosis. Therefore, we designed a double-blinded randomized controlled clinical trial to measure the safety and efficacy of Guizhi-Shaoyao-Zhimu decoction in treating early-stage RA using MSUS. This study is a randomized, double-blinded, parallel group, placebo-controlled trial. A total of 152 adult participants with early RA will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be Guizhi-Shaoyao-Zhimu decoction plus the conventional medicine methotrexate and the control intervention will be placebo plus the conventional drug methotrexate for 3 months. In addition, both groups will receive folic acid during treatment to prevent side effects from methotrexate. The primary outcomes are the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hepatic and renal function, visual analog scale, disease activity score in 28 joints, measurement scale for TCM symptoms, and 7-joint ultrasound score. We designed this double-blinded randomized controlled clinical trial to evaluate the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in RA patients using MSUS. The results of this trial may provide insights into how to improve the clinical symptoms of RA patients and delay further joint destruction. We hope that this trial may provide preliminary evidence of the efficacy of Guizhi-Shaoyao-Zhimu decoction in treating RA patients and that these results aid researchers, practitioners, and patients alike. The main aim of the study is to clarify the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in patients with early RA. Chinese Clinical Trials Register ChiCTR2000036141 . Registered on 21 August 2020 (retroactively registered).


Tumor uptake of hollow gold nanospheres after intravenous and intra-arterial injection: PET/CT study in a rabbit VX2 liver cancer model.
This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. Fifteen VX2 tumor-bearing rabbits were randomized into five groups (n = 3 in each group) that received either IV (64)Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA (64)Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated (64)Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated (64)Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA (64)Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 h after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 h after injection, and tissues were evaluated for radioactivity. At 1 h after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 h after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 h, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 vs. 0.099 %ID/g; P < 0.001). Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection.


Non-urgent emergency department attendances in children: a retrospective observational analysis.
A significant proportion of ED attendances in children may be non-urgent attendances (NUAs), which could be better managed elsewhere. This study aimed to quantify NUAs and urgent attendances (UAs) in children to ED and determine which children present in this way and when. Dataset extracted from the CUREd research database containing linked data on the provision of care in Yorkshire and Humber. Analysis focused on children's ED attendances (April 2014-March 2017). Summary statistics and odds ratios (OR) comparing NUAs and UAs were examined by: age, mode and time of arrival and deprivation alongside comparing summary statistics for waiting, treatment and total department times. NUAs were more likely in younger children: OR for NUA in children aged 1-4 years, 0.82 (95% CI: 0.80 to 0.83), age 15 years, 0.39 (95% CI: 0.38 to 0.40), when compared with those under 1 year. NUAs were more likely to arrive out of hours (OOHs) compared with in hours: OR 1.19 (95% CI 1.18 to 1.20), and OOHs arrivals were less common in older children compared with those under 1 year: age 1-4 years, 0.87 (95% CI: 0.84 to 0.89) age 15 years, 0.66 (95% CI: 0.63 to 0.69). NUAs also spent less total time in the ED, with a median (IQR) of 98 min (60-147) compared with 127 min (80-185) for UAs. A substantial proportion of ED attendances in children are NUAs. Our data suggest there are particular groups of children for whom targeted interventions would be most beneficial. Children under 5 years would be such a group, particularly in providing accessible, timely care outside of usual community care opening hours.


Concanavalin A-stimulated murine splenocytes produce a factor with prolactin-like bioactivity and immunoreactivity.
Culture supernatants from concanavalin A activated murine splenic mononuclear cells (splenocytes) were assayed for prolactin-like molecules using the Nb2 node lymphoma bioassay and immunostaining procedures. Con A stimulated splenocytes produced a factor with prolactin-like immunoreactivity that was mitogenic for Nb2 lymphoma cells. This factor first appeared in culture supernatants with the onset of lymphocyte mitogenesis and its activity was proportional to the number of cells cultured. In addition, splenocyte proliferation was inhibited by antiserum to rat prolactin, and this inhibition was partially reversed by added hormone. These findings show that murine splenocytes produce a substance with prolactin-like activity and suggest that this factor is essential for lymphocyte proliferation.


The 5' untranslated regions (UTRs) of CCN1, CCN2, and CCN4 exhibit cryptic promoter activity.
CCNs are structurally related matricellular proteins that are highly expressed in many embryonic and adult tissues, including the skeletal system and tumors, where canonical cap-dependent translation is suppressed under hypoxic environments. CCNs are encoded by mRNAs containing long G/C rich 5'-untranslated regions (5'-UTRs). Given that they are expressed under conditions of cellular stress, it has been suggested that the long G/C-rich regions contain internal ribosomal entry sites (IRES) that allow these mRNAS to be translated under conditions where cap-dependent translation is suppressed. Previously published work supported this possibility. However, recent studies have shown that a number of previously reported cellular IRES elements do not in fact possess IRES activity. Here we aimed to reveal whether the 5'UTRs of CCNs harbor IRES activities. The 5'UTRs of CCN1, 2, and 4 were tested in this study. Our results showed that the 5'UTRs of these genes do not contain IRES elements, but instead appear to contain cryptic promoters. Both promoterless and hairpin-containing dicistronic tests showed that transcription was initiated by cryptic promoter elements in 5'UTRs of CCN1, 2, and 4. When dicistronic mRNAs were translated in vitro or in vivo, no IRES activities were detected in the 5'UTRs of CCN1, 2, and 4. Furthermore, these cryptic promoter activities from 5'UTRs of CCN1, 2, and 4 could be detected in various cell types, including chondrocytes, osteoblasts, and endothelial cells, where the cryptic promoter permitted varying degrees of activation. In addition, the core promoter element of the CCN2 5'UTR was identified. CCNs are expressed under conditions of cellular stress, and it has been suggested that some CCN family members utilize IRES-mediated translation initiation to facilitate this expression. We found no evidence for IRES activity, but rather found that the unusually long 5'UTRs of CCNs 1, 2, and 4 harbor cryptic promoters that showed varying degrees of activity in different cell types. These results suggest that these promoters may contribute to the regulation of CCN genes in vivo.


[Effect of curcumin on IL-17-induced nitric oxide production and expression of iNOS in human keratinocytes].
To investigate the effect of curcumin on IL-17-induced NO production, mRNA and protein expression of iNOS in human keratinocyte cell lines(HaCaT cells). HaCaT cells were stimulated with IL-17 and incubated with three doses of curcumin for 24h in vitro. After collections of supernatant, total RNA and protein, NO levels in supernatant were detected and fluorescence quantitative PCR and Western blot were performed to determine the effect of curcumin on NO levels and iNOS. IL-17 increased NO levels, and expression of iNOS in HaCaT cells(P<0.01). Curcumin decreased IL-17 induced NO production and the iNOS expression at mRNA (P<0.01) and protein (P<0.01) levels significantly. Curcumin down-regulates IL-17-induced NO secretions and iNOS expression in HaCaT cells, thus provides a theoretical basis for the treatment of inflammatory diseases of skin related to keratinocytes.


IL-15 inhibits pre-B cell proliferation by selectively expanding Mac-1+B220+ NK cells.
Natural killer (NK) cells are the cells critical for inhibition of repopulation of allogenic bone marrow cells. However, it is not well known if NK cells affect autologous lymphopoiesis. Here, we observed that NK cells could inhibit pre-B cell proliferation in vitro driven by interleukin (IL)-7 in a manner dependent on IL-15. Interestingly, the great majority of expanding NK cells were Mac-1(+)B220(+), a recently identified potent interferon (IFN)-gamma producer. Indeed, IFN-gamma was produced in those cultures, and pre-B cells lacking IFN-gamma receptors, but not those lacking type I IFN receptors, were resistant to such an inhibition. Furthermore, even NK cells from mice lacking beta2-microglobulin, which were known to be functionally dampened, inhibited pre-B cell proliferation as well. Thus, activated NK cells, which were expanded selectively by IL-15, could potentially regulate B lymphopoiesis through IFN-gamma beyond the selection imposed upon self-recognition.


A systematic review and meta-analysis on adverse childhood experiences: Prevalence in youth offenders and their effects on youth recidivism.
Adverse childhood experiences (ACEs) have been found to be more prevalent among youth involved with the criminal justice system compared to their counterparts in the general population. The present study aims to systematically review the existing empirical studies to provide a comprehensive understanding of the prevalence of ACEs among youth offenders aged between 10 and 19 years, and the effects of both cumulative ACEs and individual ACE items on youth recidivism. A systematic review approach was employed. Narrative synthesis and meta-analysis were performed to synthesise the data in 31 included studies. The pooled prevalence of cumulative ACEs was 39.4 %. The pooled prevalence of individual ACEs ranged between 13.7 % to 51.4 %. Cumulative ACEs and neglect were positively associated with youth recidivism, with OR = 1.966, 95%CI [1.582, 2.444] and OR = 1.328, 95%CI [1.078, 1.637], respectively. Physical and sexual abuse were not significantly associated with youth recidivism. Regarding the mechanisms underlying the relationship between ACEs and recidivism; moderators included gender, positive childhood experiences, strong social bonds, and empathy. Mediators included child welfare placement, emotional and behavioural problems, drug use, mental health problems, and negative emotionality. Developing programs to youth offenders aiming to address the impact of cumulative and individual ACE exposure, strengthen the protective factors and weaken the risk factors would be useful to reduce youth recidivism.


Down-regulation of 5S rRNA by miR-150 and miR-383 enhances c-Myc-rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells.
5S rRNA plays an important part in ribosome biology and is over-expression in multiple cancers. In this study, we found that 5S rRNA is a direct target of miR-150 and miR-383 in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-150 and miR-383 inhibited ESCC cell proliferation in vitro and in vivo. Moreover, 5S rRNA silencing by miR-150 and miR-383 might intensify rpL11-c-Myc interaction, which attenuated role of c-Myc as an oncogenic transcriptional factor and dysregulation of multiple c-Myc target genes. Taken together, our results highlight the involvement of miRNAs in ribosomal regulation during tumorigenesis.


Metronomic breathing shows altered parasympathetic baroreflex function in untreated Fabry patients and baroreflex improvement after enzyme replacement therapy.
In untreated Fabry patients without overt autonomic dysfunction and normal baroreflex sensitivity (BRS) at rest, BRS is impaired during orthostatic, sympathetic challenge but normalizes after enzyme-replacement therapy (ERT) (Hilz et al., J Hypertens 2010; 28:1438-1448). This study evaluated BRS during parasympathetic challenge with six cycles per minute metronomic deep breathing (MDB) in Fabry patients before and after ERT. In 22 Fabry patients (28 ± 8 years), we monitored RR-intervals (RRIs), SBP, and respiratory frequency during spontaneous breathing (spont_breath) and MDB, before and after 18 (11 patients) or 23 months (11 patients) of biweekly ERT (1.0 mg/kg agalsidase beta). We determined spectral powers of mainly sympathetic low-frequency (0.04-0.15 Hz) RRI fluctuations, parasympathetic high-frequency (0.15-0.5 Hz) RRI fluctuations, sympathetically mediated low-frequency powers of SBP and high-frequency powers of SBP. We calculated BRS (ms/mmHg) during spont_breath and MDB as low-frequency-high-frequency alpha index (coherence >0.5). We compared parameters during spont_breath and MDB within and between patients before and after ERT and 15 age-matched (27 ± 5 years) healthy men (RANOVA and posthoc analysis; significance: P < 0.05). During spont_breath and MDB, parameters were similar between groups. Within the three groups, RRIs were lower, whereas RRI low-frequency powers and SBP low-frequency powers were higher during MDB than during spont_breath. BRS was similar during MBD and spont_breath in untreated patients (P > 0.05), but increased significantly with MDB in patients after ERT (P = 0.048) and in controls (P = 0.035). In untreated Fabry patients, MDB uncovers impaired BRS. After 18 or 23 months of ERT, MDB-induced BRS increase is similar in Fabry patients and controls, demonstrating that ERT not only restores sympathetic but also parasympathetic baroreflex activation.


Water hydration in cutinized cell walls: a physico-chemical analysis.
Water sorption by plant cuticular membrane isolates, mainly identified as polysaccharides, after selective extraction of the lipid components waxes and cutin was measured over the whole range of water activity. From water sorption isotherm, the strengths of water binding and water clustering were estimated. Data obtained by differential scanning calorimetry and Fourier-transform and near infrared spectroscopy confirmed the existence of water molecules in different macromolecular environments.


[Evaluation of toluene toxicity using Sidman avoidance behavior by lever pressing in rats (author's transl)].
Effects of single exposure to toluene on the operant behavior in rats were studied. The animals, in which the behavioral base line had been established, were exposed to 0, 1,000 and 3,000 ppm of toluene vapor for four hours, and the effects on the behavioral pattern of lever pressing were investigated for one hour after the end of exposure using Sidman avoidance test. 1) Exposure to 0 or 1,000 ppm of toluene did not affect the established operant behavior of the rats. 2) Exposure to 3,000 ppm produced increased responses, shortening of the inter-response-time, and no change in shock counts at the early stage of Sidman avoidance test when compared with those before exposure. 3) The behavioral change indicated here appears to be caused by a temporary breakdown of the established timing of lever pressing. 4) The effect of toluene on the operant behavior was strongest immediately after the aviodance test begun and the behavior recovered in about an hour. From the results of our experiment it can be said that the experimental methods used in this study is useful to evaluate the toxicity of toluene to the central nervous system of the animals.


Vanadium compounds and ferrocyanide as ionic redox agents in photosynthesis.
The effect of such ionic redox agents as ferrocyanide and several vanadium compounds was determined on photosynthetic reactions of spinach chloroplasts. It was found that: 1. Vanadyl sulfate like ferrocyanide in moderately high concentrations (0.03 M) donates electrons to Photosystem II. 2. Decavanadate in the presence of 2,5-dibromothymoquinone accepts electrons in Photosystem II. 3. In the absence of a block between the two photosystems, decavanadate accepts electrons in Photosystem I in the vicinity of plastocyanin or beyond. 4. Vanadite and ferrocyanide in high concentrations (0.32 M) donate electrons to Photosystem I. 5. On the basis of chelator inhibition and polyoxyethylene sorbitan monolaureate treatment, the vanadite oxidation site is located near plastocyanin while the ferrocyanide site is between plastocyanin and P-700.


Trends in assessment of IT-based solutions in healthcare and recommendations for the future.
State-of-the-art assessments of IT-based solutions in Healthcare is discussed in this paper. Special emphasis is placed on the human and organisation-centred perspective at the development of IT-based solutions. Based on this and basic conditions for system analysis and design reported in the literature, requirements for a methodology for user-driven, constructive assessment during the entire life-cycle of the IT-based system are synthesised. Finally, the outcome is discussed in the light of the presentations on technology assessment during the MIE 97 Congress and other related literature.


Atherosclerotic occlusive disease of the vertebrobasilar system in young adults and its surgical consideration.
A young diabetic man with recurrent attacks of headache, dizziness, and blurred vision who was originally thought to have episodes of hypoglycaemia, underwent investigation for the possibility of an occlusive cerebrovascular disease; and eventually was operated upon for vertebrobasilar insufficiency. The young age, the degree of occlusive disease, the clinical picture, and the surgical results in this patient on the one hand, and the scanty literature on the other prompted this report.


Photodynamic therapy with verteporfin in mallatia leventinese.
To describe a case of a patient with documented genetic mallatia leventinese who developed a classic choroidal neovascular membrane and underwent photodynamic therapy (PDT) with verteporfin (Visudyne; CIBA Vision Corp., Duluth, GA). Interventional case report. The patient underwent a complete ophthalmologic evaluation and fluorescein angiography. Photodynamic therapy with verteporfin was performed. Clinical and angiographic records were analyzed for evidence of changes in visual acuity, clinically evident subretinal fluid and the extent of fluorescein leakage from choroidal neovascularization (CNV). Three weeks after treatment, a fluorescein angiogram showed closure of the neovascular membrane, no evident subretinal fluid was seen, and visual acuity had improved from 20/60- to 20/40. Nine weeks after the application, fluorescein angiography demonstrated a microscopic hyperfluorescent spot at the site of the previously active CNV at which a small area of shallow subretinal fluid was observed, and visual acuity was 20/50. Thirty-four weeks after PDT, visual acuity was 20/60, subretinal fluid resolved, and fluorescein angiography did not show any further changes. Photodynamic therapy with verteporfin may be considered as a possible treatment in patients with mallatia leventinese who develop classic CNV.


Water mobility and structure in poly[2-hydroxyethylmethacrylate] hydrogels by means of the pulsed field gradient NMR technique.
The translational mobility of water in poly[2-hydroxyethylmethacrylate] (pHEMA) hydrogels, cross-linked with ethyleneglycoldimethacrylate, was studied by means of the pulsed field gradient (PFG) nuclear magnetic resonance (NMR) technique, which offers the opportunity to study the molecular displacements directly under well-defined equilibrium conditions, resulting in a determination of the self-diffusion coefficient. It is possible to check whether coexisting water phases with different mobilities (on a timescale of ca. 10 ms) are present. The dependence of the diffusion coefficient of water on the degree of hydration and the cross-linker concentration was measured. Magnetic interaction is found to cause cross-relaxation between the protons of water and those of the polymer matrix. This affects the data, rendering the evaluation by the standard equation invalid. An equation taking cross-relaxation into account has been derived. Amplitude measurements have shown that all the water in the gels contributes to the NMR signal. The PFG measurements have shown that the total water phase in a gel diffuses as one homogeneous phase, which can be characterized by a diffusion coefficient. The self-diffusion coefficient is strongly dependent on the degree of hydration of the gel; the cross-linker concentration has no measurable effect. The strong dependence of the diffusion of water on its concentration in the gel has consequences for the modelling of the swelling and drug-release dynamics of pHEMA and necessitates a revision of the present models describing these processes.


Total extract of Anemarrhenae Rhizoma attenuates bleomycin-induced pulmonary fibrosis in rats.
Pulmonary fibrosis is a progressive interstitial lung disease with poor prognosis. Anemarrhenae Rhizoma is a traditional Chinese herbal medicine and has been applied in clinical practice for a long history. Recently, components of Anemarrhenae Rhizoma were reported to possess anti-inflammatory and immunomodulatory features; however, the effect of them on pulmonary fibrosis remains unknown. In this study, we explored the therapeutic effect of total extract of Anemarrhenae Rhizoma (TEAR) on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis rat model was established by a single intratracheal instillation of bleomycin, three doses of TEAR were intragastrically administered for consecutive 28 days. Subsequent to sacrificing of rats, pulmonary fibrosis was observed in rats treated with bleomycin, but administration of TEAR attenuated lung fibrosis, as evidenced by the improved lung histopathological damage and decreased weight loss and lung index. Moreover, TEAR treatment inhibited the inflammatory response in lung fibrosis, which was shown by the reduced nitrogen oxide level and myeloperoxidase activity. Furthermore, TEAR modulated the redox balance in lung tissue by alleviated lipid peroxidation and enhanced enzymatic antioxidants activity. Meanwhile, TEAR protected the rats from fibrosis in a dose-dependent manner, and the anti-fibrotic activity of TEAR may be related to the modulation of TGF-β1/Smad signaling pathway. Collectively, TEAR alleviates bleomycin-induced pulmonary fibrosis, indicating perspectives for development of a potential agent for lung fibrosis therapy.


Frequency, characteristics, and predictors of headache attributed to acute ischemic stroke.
Although headache is a common symptom in acute ischemic stroke, the clinical and radiological factors associated with its occurrence are controversial. This work aimed to determine the frequency, characteristics, and predictors of headache occurrence among patients with acute ischemic stroke. This cross-sectional study was conducted on 303 patients with acute ischemic stroke. The patients were submitted to detailed history taking, clinical and radiological assessment. A detailed analysis of headache was performed for the patients who experienced headache temporally related to stroke onset. Diagnosis of headache attributed to the ischemic stroke was established in 129 (42.6%) patients; sentinel headache in 17.2% of patients, and headache at stroke onset in 25.4% of patients. The headache group had a significantly younger age (P=0.017), lower NIHSS score (P=0.042), higher frequency of pre-existing headache disorders (P=0.001), substance use disorder (P=0.021), and fever (P=0.036), and lower frequency of chronic hypertension (P=0.013) and small vessel disease (P=0.004) than non-headache group. Infarction involving posterior circulation was more frequent in headache than in non-headache groups (P=0.003). The presence of migraine, tension-type headache, other types of headache, fever and posterior circulation stroke increased the odds of headache by 27.4 (95%CI=8.0-94.4), 7.6 (95%CI=3.93-14.6), 26.2 (95%CI=8.0-85.8), 3.75 (95%CI=1.22-11.6) and 3.15 (95%CI=1.65-6.0) times, respectively, whereas, the presence of small vessel disease decreased the odds of headache by 0.51 (95%CI=0.279-0.95) times. Pre-existing headache disorder, fever, and posterior circulation stroke were associated with headache occurrence in acute ischemic stroke patients.


The effect of illumination on the pigment composition of the zeta-carotenic mutant, PG1, of Scenedesmus obliquus.
Dark grown Scenedesmus obliquus strain PG1 accumulated zeta-carotene and phytoene as its major carotenoids. On illumination of dark-grown cultures in air/CO2, cyclic carotenes and xanthophylls were formed, apparently at the expense of the accumulated phytoene and zeta-carotene. This interconversion of carotenoids was accompanied by chlorophyll synthesis. In an atmosphere of nitrogen/CO2 the light-induced changes occurred more slowly and in nitrogen alone the changes were incomplete. No massive production of cyclic carotenes from the accumulated zeta-carotene was observed in cultures illuminated under anaerobic conditions.


Camelina (Camelina sativa (L.) Crantz) as Feedstuffs in Meat Type Poultry Diet: A Source of Protein and n-3 Fatty Acids.
Camelina seed or seed processing derivatives, i.e., cake, are cheap alternative protein feed ingredients for meat type poultry. Camelina is an oilseed crop containing 36.8% oil in seeds, while in the cake the oil content accounts for 6.4-22.7%. If compared with other Brassicaceae family plants, camelina is distinguished by a unique fatty acid composition, because the content of α-linolenic fatty acid (C18:3n-3; ALA) varies from 25.9 to 36.7% of total fatty acids. The total tocopherol content in camelina oil and cake are, respectively, 751-900 and 687 mg/kg. Addition of camelina to poultry nutrition increases the amount of n-3 polyunsaturated fatty acids (PUFA) in poultry meat and liver. The content of ALA in chicken muscles increases by 1.3-4.4, 2.4-2.9 and 2.3-7.2 times after supplementing chicken diets with, respectively, camelina cake (8-24%), seed (10%), and oil (2.5-6.9%) in comparison with the control group. Camelina cake (5-25%), seed (10%) and oil (2.5-4%) inclusion in chicken diets results in 1.5-3.9 times higher total n-3 PUFA content in muscles and liver. Meanwhile, supplementation of chicken diets with camelina oil (4-6.9%), seed (5-10%) and cake (5-25%) results in, respectively, a 1.8-8.4, 1.6-1.9 and 1.3-2.9 times lower n-6/n-3 PUFA ratio in muscles, and 3.29 times lower n-6/n-3 PUFA ratio in the liver. After inclusion of different amounts of camelina cake in chicken diets, a healthy for human nutrition n-6/n-3 PUFA ratio from 1.6 to 2.9 was found in chicken muscles.


Stage specific kinetoplast DNA-binding proteins in Trypanosoma cruzi.
Knowledge regarding kinetoplast DNA organization in all members of the Trypanosomatid family is incomplete. Recently, the presence of kinetoplast-associated proteins in condensing kDNA networks in Crithidia fasciculata has been described and a role for these proteins in the maintenance of these complex structures was suggested. To investigate the presence of protein components in Trypanosoma cruzi kinetoplast, we previously described seven epimastigote kinetoplast-associated proteins. We report here the existence of kinetoplast binding proteins in amastigote and trypomastigote stages of T. cruzi, which could bind both mini and maxicircles components with a stage specific elements for every infective form of the parasite. We propose three major classes of kinetoplast-associated proteins related to the basic processes of this intricate disc structure and suggest a possible function of these binding proteins in the T. cruzi mitochondrial DNA organization.


Increased apoptosis in the adult rat liver after a single dose of adriamycin administration.
The purpose of this study was the evaluation of hepatocytes in the adult rat's liver after adriamycin administration in a single dose. The presented above morphological changes, on tissue, cell and ultrastructural level are the evidence of persistent and irreversible damage of liver tissue via adriamycin. Cells damaged in that way waste away. In the present study cell death touched mainly single cells and necrosis was not observed. It is the evidence of apoptosis--the natural death of cells.


Functional and quality-of-life outcomes following salvage surgery for recurrent squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.
Recurrent head and neck squamous cell carcinomas (HNSCC) are frequently managed with salvage surgery, but the impact these operations have on function and quality-of-life (QoL) is understudied. This review aimed to provide a quantitative and qualitative assessment of the functional and QoL effects of salvage surgical procedures. Systematic review and meta-analysis were conducted of studies reporting QoL and function following salvage HNSCC resections. The search identified 415 articles and 34 were selected for inclusion. Pooled random effects analysis revealed long-term feeding and tracheostomy tube rates of 18% and 7%. Pooled long-term feeding tube rates in open oral and oropharyngeal, transoral robotic, total and partial laryngectomy surgeries were 41%, 25%, 11% and 4%. Eight studies used validated QoL questionnaires. Functional and QoL outcomes from salvage surgery are acceptable, but appear to be worse following open procedures. Prospective studies measuring changes over time are needed to assess these procedures impact on patient well-being.


In Vitro Reconstitution of Pseudouridylation Catalyzed by Human Box H/ACA Ribonucleoprotein Particles.
Pseudouridine (Ψ) is the most common chemical modification in RNA. In eukaryotes and archaea, pseudouridine synthases, mainly guided by box H/ACA snoRNAs, convert uridine to Ψ. Ψ stabilizes RNA structure and alters RNA-RNA and RNA-protein interactions, conferring important roles in gene expression. Notably, several Ψ-linked human diseases have been identified over the years. In addition, Ψ has also been extensively used in developing mRNA vaccines. Furthermore, it has been shown that pseudouridylation can be site-specifically directed to modify specific nonsense codons, leading to nonsense suppression. All of these, together with a need to better understand the specific functions of Ψs, have motivated the development of in vitro pseudouridylation assays using purified and reconstituted box H/ACA RNPs. Here, we describe an in vitro system for box H/ACA RNA-guided RNA pseudouridylation using human cell extracts. We show that a half guide RNA (only one hairpin) is just as functionally competent as the full-length guide RNA (two hairpins) in guiding site-specific pseudouridylation in the human cell extracts. This discovery offers the opportunity for direct delivery of a short guide RNA to human cells to promote site-specific nonsense suppression and therefore has potential clinical applications.


A high plasma prostaglandin to thromboxane ratio protects against renal ischemia.
Pretreatment with the thromboxane synthase inhibitor OKY-046 but not the cyclo-oxygenase inhibitor ibuprofen protects against ischemia-induced acute tubular necrosis. However, ibuprofen together with the vasodilating agent prostaglandin E1 is protective. This suggests that a high prostaglandin to thromboxane ratio is the major factor operative in preventing tubular necrosis, the subject of this study. Rats that had unilateral nephrectomy (n = 60) with the exception of rats that had sham operations (n = 8) underwent 45 minutes of left renal pedicle clamping. Thirty minutes before the operation, the rats received either a saline solution or a thromboxane synthase inhibitor that was given intravenously. The inhibitors OKY-046 (2 milligrams per kilogram, n = 10), UK38485 (1 milligram per kilogram, n = 9) and U63357A (10 milligrams per kilogram, n = 10) were given as a single bolus while the inhibitor CGS13080 (0.1 milligram per kilogram, n = 9, and 1.0 milligram per kilogram, n = 7) was given by constant infusion and continued for 60 minutes after reperfusion. With saline solution therapy, five minutes after reperfusion, thromboxane B2 increased from 154 to 2,537 picograms per milliliter (p less than 0.00001) and 6-keto-prostaglandin F1 alpha increased from 51 to 266 picograms per milliliter (p less than 0.004). At 24 hours, the creatinine level increased from 0.5 to 2.8 milligrams per deciliter (p less than 0.00001). Only OKY-046 yielded a creatinine level at 24 hours of 1.2 milligrams per deciliter, a value lower than that for those in the saline solution control group (p less than 0.002). Furthermore, OKY-046 led to the highest prostaglandin to thromboxane ratio (p less than 0.035). The five other ratios which occurred after drug therapy were inversely related to the decrease in the creatinine value (r = -0.93, p less than 0.02). Histologically, OKY-046 was the only thromboxane synthase inhibitor to prevent acute tubular necrosis (p less than 0.05). Results show that a high prostaglandin to thromboxane ratio protects against acute tubular necrosis.


Impact of GAN-based lesion-focused medical image super-resolution on the robustness of radiomic features.
Robust machine learning models based on radiomic features might allow for accurate diagnosis, prognosis, and medical decision-making. Unfortunately, the lack of standardized radiomic feature extraction has hampered their clinical use. Since the radiomic features tend to be affected by low voxel statistics in regions of interest, increasing the sample size would improve their robustness in clinical studies. Therefore, we propose a Generative Adversarial Network (GAN)-based lesion-focused framework for Computed Tomography (CT) image Super-Resolution (SR); for the lesion (i.e., cancer) patch-focused training, we incorporate Spatial Pyramid Pooling (SPP) into GAN-Constrained by the Identical, Residual, and Cycle Learning Ensemble (GAN-CIRCLE). At [Formula: see text] SR, the proposed model achieved better perceptual quality with less blurring than the other considered state-of-the-art SR methods, while producing comparable results at [Formula: see text] SR. We also evaluated the robustness of our model's radiomic feature in terms of quantization on a different lung cancer CT dataset using Principal Component Analysis (PCA). Intriguingly, the most important radiomic features in our PCA-based analysis were the most robust features extracted on the GAN-super-resolved images. These achievements pave the way for the application of GAN-based image Super-Resolution techniques for studies of radiomics for robust biomarker discovery.


A new transvenous lead for both atrial and ventricular pacing.
A new transvenous tined unipolar lead (Medtronic SP 342) has been implanted in 56 patients; 35 leads were positioned in the atrium and 34 in the ventricle. The lead comprises a trifilar DBS-conductor within an insulation of polyurethane, four symetrically placed polyurethane tines furnished with scallops and a platinum-iridium ring-tipped electrode. The scallops in the tines ensure flexibility and a small effective diameter of the lead which makes the choice of vein less critical than with most previous tined leads. It allows use of the same normally sized vein for a second lead for dual-chamber sensing pacing. Mean atrial and ventricular electrogram amplitudes (+/-SD) were 4.6 +/- 1.2 mV and 8.8 +/- 4.4 mV; mean atrial and ventricular stimulation thresholds were 0.8 +/- 0.3 V and 0.4 +/- 0.2 V; and mean atrial and ventricular lead impendances were 415 +/- 114 ohms and 456 +/- 105 ohms, respectively. The results of this study show that the SP 342 lead is useful especially in dual chamber systems.


Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine.
The intestinal epithelial cells (IECs) constitute the primary barrier between host cells and numerous foreign antigens; it is unclear how IECs induce the protective immunity against pathogens while maintaining the immune tolerance to food. Here, we found IECs accumulate a less recognized 13-kD N-terminal fragment of GSDMD that is cleaved by caspase-3/7 in response to dietary antigens. Unlike the 30-kD GSDMD cleavage fragment that executes pyroptosis, the IEC-accumulated GSDMD cleavage fragment translocates to the nucleus and induces the transcription of CIITA and MHCII molecules, which in turn induces the Tr1 cells in upper small intestine. Mice treated with a caspase-3/7 inhibitor, mice with GSDMD mutation resistant to caspase-3/7 cleavage, mice with MHCII deficiency in IECs, and mice with Tr1 deficiency all displayed a disrupted food tolerance phenotype. Our study supports that differential cleavage of GSDMD can be understood as a regulatory hub controlling immunity versus tolerance in the small intestine.


Acceptability of the Kangaroo Mother Care at the University Hospital of Treichville in Côte d'Ivoire.
Kangaroo Mother Care (KMC) is a low-tech, highimpact intervention for preterm and low-birth-weight newborns. In 2019, Côte d'Ivoire opened its first KMC unit. We wanted to determine KMC's acceptability in Côte d'Ivoire after a year. This qualitative study used semi-structured interviews in September 2020 at the Teaching Hospital of Treichville's first KMC unit. Mothers of preterm and low birth weight babies who received KMC were studied. Deductive (TFA-driven) framework analysis was performed. Coded using Nvivo 12. KMC was acceptable overall. Mothers knew KMC's goal and benefits, including self-confidence and breastfeeding benefits. Most women reported that the method was easy to implement and were confident in implementing KMC at the unit or in the household, even though some of them found KMC not aligned with their cultural values. Some mothers, especially housewives and self-employed, highlighted the benefits of KMC, but they must have given up. Our study highlighted the need to increase KMC awareness, advocacy, education, and training for pregnant women and the community to reduce preterm and low birth weight infant mortality and morbidity.


Long-term variation (1960-2003) and causal factors of non-point-source nitrogen and phosphorus in the upper reach of the Yangtze River.
The knowledge of long-term variation and causal factors of non-point source (NPS) pollution in large-scale watersheds is helpful in the development of water quality control programs. In this study, the Improved Export Coefficient Model and the Revised Universal Soil Loss Equation were combined to estimate the temporal and spatial variations (1960-2003) of NPS pollution in the upper reach of the Yangtze River (URYR). Two change points for NPS pollution were successfully detected. In the URYR, the dissolved nitrogen (DN) and dissolved phosphorus (DP) increased before 2000 and decreased after 2000, whereas the inflection points from increase to decline were around 1980 for the adsorbed N (AN) and adsorbed P (AP). The results also indicated that the dissolved pollutants were mainly contributed by the anthropogenic factors, while the adsorbed pollutants were primarily exported by the natural factors. By comparing the load intensities from each source, it revealed that for the dissolved pollutants, the major source of the high load intensity transferred from urban land to dry land after 1980. Simultaneously, the high load intensity areas of the adsorbed pollutants transferred from forest to orchard around 1980, which was mainly attributed to the increasing fertilizer application. These results may be useful for planning and management of the URYR and other large-scale watersheds.


A photometric method for the dosage of factor XIII applied to the study of chronic hepatopathies.
The photometric method of Fickenscher et al. for the determination of factor XIII (FXIII) activity has been used in the study of 35 patients with severe chronic hepatopathy, in comparison with 25 normal subjects. The FXIII proteic fractions a and b were determined by quantitative immuno-electrophoresis after Laurell. The plasmatic FXIII activity, as well as the proteic fractions a and b, were significantly reduced in hepatopatic patients, in comparison to controls, and proportional to the prolongation of prothrombin times. Ratios between functional and immunological levels of FXIII in hepatopatics were similar to those observed in controls. These results confirm the involvement of fibrin stabilization deficiency in the coagulation defect of severe chronic hepatopathies. The correlations between functional and antigenic values are in agreement with the hepatic origin of FXIII. The method of Fickenscher has been proved to be rapid and simple, and it may be useful in the routine study of hepatopathies, for a better knowledge of the role of FXIII deficiency in the complex coagulopathy of liver diseases, as well as of other acquired FXIII deficiencies.


Lactose malabsorption in Bangladeshi village children: relation with age, history of recent diarrhea, nutritional status, and breast feeding.
The prevalence of lactose malabsorption (LM) among Bangladeshi village children has been determined using the recent developed breath hydrogen test. Initial hospital-based comparison studies showed general agreement between the breath hydrogen test and a modified lactose tolerance test. Two hundred thirty-four children, stratified by age, nutritional status, and history of recent diarrhea then participated in the field study. LM was diagnosed in more than 80% of children over 36 months of age but in none of the children under 6 months. Rates of LM were significantly increased in children with a history of recent diarrhea and a greater proportion of children in some age groups evidenced malabsorption in association with acute undernutrition. In the weanling age group children who were still breast feeding had a lower rate of LM than fully weaned subjects.


NOD2 mRNA expression and NFkappaB activation in dogs with lymphocytic plasmacytic colitis.
Nucleotide Oligomerization Domain Two (NOD2) is suggested to be an intracellular pathogen-associated molecular pattern recognition molecule. NOD2, plays a key role against bacteria by triggering a host defense response through activation of the transcription factor NFkappaB and subsequent proinflammatory cytokine production. NOD2 recently was reported to be overproduced in inflamed colonic mucosa in Crohn's disease, and to be accompanied by a significant increase in NFkappaB activity. However, few studies to date have investigated intercellular signaling molecules in dogs with lymphocytic plasmacytic colitis (LPC). NOD2 mRNA expression and NFkappaB activation are increased in mucosal biopsies of LPC dogs as compared with control dogs. Five healthy dogs and 19 dogs with LPC. Descending colon biopsies were obtained endoscopically. Expression of NOD2 mRNA was evaluated by semiquantitative RT-PCR in the colonic mucosa. NFkappaB binding activity was assessed by electrophoretic mobility shift assay. NOD2 mRNA expression was approximately 63% greater in LPC dogs than in healthy controls (P = .019). NFkappaB binding activity was approximately 45% higher in the inflamed colonic mucosa of the LPC dogs, as compared with healthy controls (P = .011). No correlations were observed among NOD2 mRNA expression levels, NFkappaB binding activity, and CIBDAI in LPC dogs. NOD2 mRNA and NFkappaB activity were significantly higher in the inflamed colon of dogs with LPC, as compared with healthy controls. Our data suggest that NOD2 and NFkappaB play an important role in the pathogenesis of LPC.


Planning ultrasound for percutaneous radiofrequency ablation to treat small (≤ 3 cm) hepatocellular carcinomas detected on computed tomography or magnetic resonance imaging: a multicenter prospective study to assess factors affecting ultrasound visibility.
To assess factors affecting tumor visibility on planning ultrasound (US) for percutaneous radiofrequency (RF) ablation to treat small hepatocellular carcinomas (HCCs) primarily detected on computed tomography (CT) or magnetic resonance (MR) imaging. Patients referred for planning US for percutaneous RF ablation between September 2008 and June 2009 were prospectively enrolled from nine institutions in Korea. The first small (≤ 3 cm) single HCC or new single HCC after treatment was included. The study enrolled 898 patients (684 men and 214 women, age range 32-86 years). HCCs that were invisible on planning US were compared with visible HCCs with respect to tumor size, distance between the tumor and the diaphragm, subcapsular location, etiology of liver disease, liver cirrhosis, macronodular cirrhosis on US, ascites, Child-Pugh class, serum alpha fetoprotein (AFP) level, body mass index (BMI), previous treatments for HCC, previous chemoembolization treatments for HCC, institutions, and experience of radiologists. Among 898 HCCs, 671 (74.7%) were visible on the planning US. In multivariate analysis, tumor size, distance between the tumor and the diaphragm, liver cirrhosis, and macronodular cirrhosis were statistically significant factors affecting US detection (each P < .05). Smaller tumors, subphrenic location of the tumor, liver cirrhosis, and macronodular cirrhosis were independent predictors of invisible tumors on planning US.


Chemoprevention with aromatase inhibitors--trial strategies.
Estrogen and its catechol metabolites from both the circulation and synthesized within the breast are important in the pathogenesis of breast cancer. Blocking estrogen's effects on the breast with selective estrogen receptor modulators (SERMS) is an ongoing strategy. Thus, tamoxifen and raloxifene reduce risk as monotherapy. Aromatase (estrogen synthetase) inhibitors are a logical alternative to SERMS. To date, SERMS have demonstrated reduction only in estrogen-progesterone receptor positive cancers without reduction in receptor negative tumors. By inhibiting the parent estrogens and their catechol metabolites, true prevention of cancer initiation might occur and reduction not only in the receptor positive but also negative tumors might result. Ongoing adjuvant breast cancer trials are exploring aromatase inhibitors as alternatives to tamoxifen, or in sequence or in combination with tamoxifen. Relative efficacies including reduction in contralateral breast cancer, toxicities and end-organ effects and impact on quality of life, are being explored. Data from these trials will help to guide future chemoprevention strategies. Proof of principal trials in 'high risk' cohorts such as premalignant breast lesions, dense screening mammograms, high plasma estradiol levels or increased bone density are already ongoing. Issues such as dose, schedule, therapeutic index and mono versus combination therapy are important to define.


A Randomized Controlled Pilot Study Assessing Feasibility and Impact of Yoga Practice on Quality of Life, Mood, and Perceived Stress in Women With Newly Diagnosed Breast Cancer.
A breast cancer diagnosis can entail numerous physical and psychosocial challenges. Yoga practice (YP) may contribute to improved well-being for these patients. Investigate feasibility and impact of YP on quality of life (QoL), mood, fatigue, and perceived stress immediately after breast cancer diagnosis. Thirty women were randomly assigned to a yoga group (YG) or control group (CG) immediately after cancer diagnosis. Pilot study conducted at an academic medical center breast clinic. Females (N = 30) who received a biopsy-proven breast cancer diagnosis without metastatic disease. One individual YP session at baseline, then 2 individual and 8 weekly group sessions followed by weekly gentle yoga at home (DVD). Questionnaires and saliva samples (ie, cortisol) completed at baseline and 12 weeks postdiagnosis. Both groups reported significant improvements in QoL postintervention but with no significant difference between groups. Emotional well-being, mood-related tension-anxiety, depression-dejection, and confusion-bewilderment scores improved for both groups, and cortisol and cortisone levels decreased. Lumpectomies were prevalent with YG (67%) and CG (47%). YP was rated as "very effective," providing relaxation (85%), stress relief (69%), and reduced muscle tension/general feeling of wellness (each 62%). Feasibility of YP immediately after breast cancer diagnosis was good. Improvement in emotional well-being, anxiety, depression, and levels of confusion was found in both groups. To our knowledge, this is the first study examining the impact of YP immediately after breast cancer diagnosis. Further research in this area is warranted.


Post-infectious inflammatory response syndrome in an HIV-negative patient after Cryptococcus gattii meningoencephalitis: a case report and review of the literature.
Cryptococcal meningitis (CM) is an inflammatory mycosis of the central nervous system caused by meninge infection or brain parenchyma with Cryptococcus species. It is associated with high morbidity and mortality, and patients with acquired immune deficiency syndrome are particularly susceptible. There have been increasing reports of CM in HIV-negative patients in China over the last few years. A 31-year-old healthy Chinese male presented with fever and gradually developed headache, projectile vomiting, and other manifestations that were later confirmed as Cryptococcus gattii meningoencephalitis. However, multiple disease changes occurred during the course of treatment, and the regimen was accordingly modified after the diagnosis of post-infectious inflammatory response syndrome (PIIRS). The patient eventually recovered. There has been a growing trend in the incidence of C. gattii meningoencephalitis in HIV-negative patients. It shows rapid onset and severe prognosis. This case report can provide a reference to treat PIIRS following CM in HIV-negative patients.


Metal-free melem/g-C3N4 hybrid photocatalysts for water treatment.
In this study, graphitic carbon nitride was engineered to produce metal-free melem/g-C3N4 hybrid photocatalysts through a hydrothermal technique. It was revealed that the hydrothermal treatment of g-C3N4 could produce a hybrid structure of "thorn ball" liked melem on g-C3N4 layer at a high temperature, and was able to modify the photoelectronic properties of g-C3N4. The spectroscopic measurements implied that a melem/g-C3N4 hybrid has better light absorption and lower electron/hole recombination than pristine g-C3N4. Therefore, the melem/g-C3N4 photocatalysts can decompose methylene blue solution under artificial sunlight with a higher rate and also present good stability.


Ureteroscopy: results and complications.
The results and complications of 100 consecutive ureteroscopy studies are reported. Introduction through the orifice or the intramural ureter failed in 11 per cent of the patients and in 14 per cent the ureteroscope could not be advanced up to the level of the lesion. Ureteroscopy was successful in 75 per cent of the patients and stone extraction was successful in 69 per cent. Complications occurred in 9 patients: 4 had an uncomplicated urinary tract infection, 4 had a ureteral perforation and 1 presented with ureteral stenosis at the site of the extracted stone a few weeks later. At followup 1 to 3 months after ureteroscopy clinical examination, excretory urography and/or renography revealed no further late sequelae.


Prevention of diabetes development in those with the metabolic syndrome.
Metabolic syndrome is characterized by abnormal glucose levels, central obesity, hypertension, elevated triglycerides, and low HDL cholesterol. This article reviews available data regarding the impact of lifestyle modification and drug therapies on the progression to diabetes in high risk individuals, such as those with hypertension, dyslipidemia, obesity, and prediabetes. Lifestyle and pharmacological interventions may alter metabolic parameters and impact progression to diabetes. However, the cost-effectiveness of these interventions are unclear.


Electromagnetic analysis of an RF rectangular resonant cavity applicator for hyperthermic treatment using whole-body voxel human model of Japanese adult male.
The numerical whole-body voxel human model (numerical model) developed by National Institute of Information and Communications Technology (NICT) was assumed and hyperthemic treatment using radio-frequency wave was investigated. We assumed 51 different human tissues and organs with 2-mm spatial resolution in the numerical model, inserted it into the resonant cavity applicator, and Maxwell's equations were solved by FDTD method with variable mesh. We obtained the realistic energy patterns for a deep-seated tumor as compared to those obtained in our previous studies.


In-hospital outcomes after carotid endarterectomy for stroke stratified by modified Rankin scale score and time of intervention.
Although the benefits of carotid endarterectomy (CEA) for treating symptomatic carotid stenosis are well known, the optimal timing of intervention after acute stroke and whether the optimal timing will vary with preoperative stroke severity has remained unclear. Therefore, we assessed the effect of stroke severity and timing of the intervention on the postoperative outcomes for patients who had undergone CEA for stroke. We identified all patients in the Vascular Quality Initiative who had undergone CEA from 2012 to 2020 for prior stroke. The patients were stratified using the preoperative modified Rankin scale score (mRS score, 0-5) and time to CEA after stroke onset (≤2 days, 3-14 days, 15-90 days, 91-180 days). After univariate comparisons, the patients were stratified into the following mRS cohorts for further analysis: 0 to 1, 2, 3 to 4, and 5. The primary outcome was in-hospital stroke/death. We identified 15,601 patients, of whom 30% had had an mRS score of 0, 34% an mRS score of 1, 17% an mRS score of 2, 11% an mRS score of 3, 8% an mRS score of 4, and 1% an mRS score of 5. Overall, 9.3% of the patients had undergone CEA within ≤2 days, 46% within 3 to 14 days, 36% in 15 to 90 days, and 8.4% within 90 to 180 days. A decreasing mRS score and an increasing time to CEA were associated with lower rates of perioperative stroke/death (Ptrend < .01). After risk adjustment, with CEA at 3 to 14 days as the comparator group, the mRS score 0 to 1 group had had a higher incidence of stroke/death after CEA within ≤2 days (3.6% vs 2.0%; odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.7). The mRS score 2 group had had a similar incidence of stroke/death after CEA within ≤2 days (4.4% vs 3.9%; OR, 1.2; 95% CI, 0.6-2.3) but a lower incidence after CEA at 15 to 90 days (2.1% vs 3.9%; OR 0.5; 95% CI, 0.3-0.96). The mRS score 3 to 4 group had had a higher incidence of stroke/death after CEA within ≤2 days (8.0% vs 3.8%; OR, 2.4; 95% CI, 1.5-3.9) but a similar incidence of stroke/death after CEA at 15 to 90 days (3.0% vs 3.8%; OR, 0.8; 95% CI, 0.5-1.3). For the mRS score 5 group, the stroke/death rates were ≥6.5% across all the time to CEA groups. However, the low sample size limited meaningful comparisons. Patients with minimal disability after stroke (mRS score, 0-1) seemed to benefit from CEA within 3 to 14 days. However, those with severe disability (mRS score 5) have a very high risk from CEA at any time point given the poor outcomes. In contrast to the current guidelines, patients with mild disability (mRS score 2) could benefit from delaying CEA to 15 to 90 days, and those with moderate disability (mRS score 3-4) might benefit from CEA within 3 to 90 days given the acceptable in-hospital outcomes. These data should be considered within the context of the clinical situation in the weeks after index event to determine the net benefit of delayed CEA.


Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers.
The purpose of this study was to determine whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) suppresses coronary spasm. Coronary spasm is associated with endothelial dysfunction. Statins have been shown to improve endothelial function. This was a prospective, randomized, open-label, end point study. Sixty-four patients who had no significant organic coronary stenosis and in whom coronary spasm was induced by intracoronary injection of acetylcholine (ACh) were randomly assigned to fluvastatin 30 mg/day plus the conventional calcium-channel blocker (CCB) therapy (31 patients, statin group) or the conventional CCB therapy (33 patients, nonstatin group). After 6 months of treatment, the intracoronary injection of ACh was repeated and the coronary spasm was assessed. Coronary spasm was suppressed in 16 of the 31 patients (51.5%, p < 0.0001) of the statin group and in 7 of the 33 patients (21.2%, p = 0.0110) of the nonstatin group after 6 months of treatment. Thus, the number of patients with ACh-induced coronary spasm was significantly reduced in the statin group as compared with the nonstatin group (51.6% vs. 21.2%, p = 0.0231) after 6 months of treatment. The addition of fluvastatin 30 mg/day to the conventional CCB therapy for 6 months significantly reduced the number of patients with ACh-induced coronary spasm as compared with the conventional CCB therapy. Thus, a statin (fluvastatin) may possibly be a novel therapeutic drug for coronary spasm.


Neurologic Complications of Influenza B Virus Infection in Adults, Romania.
We characterized influenza B virus-related neurologic manifestations in an unusually high number of hospitalized adults at a tertiary care facility in Romania during the 2014-15 influenza epidemic season. Of 32 patients with a confirmed laboratory diagnosis of influenza B virus infection, neurologic complications developed in 7 adults (median age 31 years). These complications were clinically diagnosed as confirmed encephalitis (4 patients), possible encephalitis (2 patients), and cerebellar ataxia (1 patient). Two of the patients died. Virus sequencing identified influenza virus B (Yam)-lineage clade 3, which is representative of the B/Phuket/3073/2013 strain, in 4 patients. None of the patients had been vaccinated against influenza. These results suggest that influenza B virus can cause a severe clinical course and should be considered as an etiologic factor for encephalitis.


How contemporary human reproductive behaviors influence the role of fertility-related genes: the example of the p53 gene.
Studies on human fertility genes have identified numerous risk/protective alleles involved in the occurrence of reproductive system diseases causing infertility or subfertility. Investigations we carried out in populations at natural fertility seem to suggest that the clinical relevance that some fertility genes are now acquiring depends on their interaction with contemporary reproductive behaviors (birth control, delayed childbearing, and spacing birth order, among others). In recent years, a new physiological role in human fertility regulation has emerged for the tumor- suppressor p53 gene (P53), and the P53 Arg72Pro polymorphism has been associated with recurrent implantation failure in humans. To lend support to our previous observations, we examined the impact of Arg72Pro polymorphism on fertility in two samples of Italian women not selected for impaired fertility but collected from populations with different (premodern and modern) reproductive behaviors. Among the women at near-natural fertility (n = 98), the P53 genotypes were not associated with different reproductive efficiency, whereas among those with modern reproductive behaviors (n = 68), the P53 genotypes were associated with different mean numbers of children [Pro/Pro = 0.75<Pro/Arg = 1.7<Arg/Arg = 2, (p = 0.056)] and a significant negative relationship between the number of children and P53 Pro allele frequencies (p = 0.028) was observed. These results are consistent with those of clinical studies reporting an association between the P53 Pro allele and recurrent implantation failure. By combining these findings with previous ones, we suggest here that some common variants of fertility genes may have become "detrimental" following exposure to modern reproductive patterns and might therefore be associated with reduced reproductive success. Set within an evolutionary framework, this change could lead to the selection of a set of gene variants fitter to current reproductive behaviors as the shift to later child-bearing age in developed countries.


Prediction of Burkholderia pseudomallei DsbA substrates identifies potential virulence factors and vaccine targets.
Identification of bacterial virulence factors is critical for understanding disease pathogenesis, drug discovery and vaccine development. In this study we used two approaches to predict virulence factors of Burkholderia pseudomallei, the Gram-negative bacterium that causes melioidosis. B. pseudomallei is naturally antibiotic resistant and there are no clinically available melioidosis vaccines. To identify B. pseudomallei protein targets for drug discovery and vaccine development, we chose to search for substrates of the B. pseudomallei periplasmic disulfide bond forming protein A (DsbA). DsbA introduces disulfide bonds into extra-cytoplasmic proteins and is essential for virulence in many Gram-negative organism, including B. pseudomallei. The first approach to identify B. pseudomallei DsbA virulence factor substrates was a large-scale genomic analysis of 511 unique B. pseudomallei disease-associated strains. This yielded 4,496 core gene products, of which we hypothesise 263 are DsbA substrates. Manual curation and database screening of the 263 mature proteins yielded 81 associated with disease pathogenesis or virulence. These were screened for structural homologues to predict potential B-cell epitopes. In the second approach, we searched the B. pseudomallei genome for homologues of the more than 90 known DsbA substrates in other bacteria. Using this approach, we identified 15 putative B. pseudomallei DsbA virulence factor substrates, with two of these previously identified in the genomic approach, bringing the total number of putative DsbA virulence factor substrates to 94. The two putative B. pseudomallei virulence factors identified by both methods are homologues of PenI family β-lactamase and a molecular chaperone. These two proteins could serve as high priority targets for future B. pseudomallei virulence factor characterization.


Prion protein disease and neuropathology of prion disease.
Human prion diseases, in common with other neurodegenerative diseases, may be sporadic or inherited and are characterized by the accumulation of cellular proteins accompanied by neuronal death and synaptic loss. Prion diseases are, however, unique in being transmissible. Central to the pathogenesis of all forms of prion disease is the prion protein. This article provides a brief overview of the biology of human prion diseases followed by a more in-depth discussion of the neuropathology of these diseases, including features of neuroradiologic relevance.


Miliary pulmonary metastases from a clinically occult pleural mesothelioma.
Mesothelioma is a rare neoplasm of the serosal membranes. Signs and symptoms of a pleural effusion typically herald discovery of the tumor. We report a case of miliary metastatic mesothelioma involving both lungs in a 54-year-old man who presented with right-sided chest discomfort, numerous pulmonary nodules detected by computed tomography of the chest, and absent pleural effusion. Immunohistochemical and electron microscopy studies performed on wedge biopsies of parenchymal pulmonary nodules led to the diagnosis of metastatic mesothelioma. Subsequent pleural evaluation and biopsy of pleural thickening noted at a site of prior chest wall trauma identified the primary neoplasm and confirmed the diagnosis as malignant epithelioid mesothelioma. The histologic appearance of discohesive epithelioid cells in a distinctly myxoid background was the clue in this case leading to the consideration of metastatic mesothelioma and a thorough immunohistochemical evaluation of the tumor. This case shows that mesothelioma may metastasize throughout the lungs in a miliary pattern and the metastases may be clinically detected before the primary pleural tumor. Metastatic mesothelioma is a consideration for metastatic pulmonary tumors of unknown origin.


Correction to: A rare presentation of skull-base osteomyelitis with neurovascular sheath extension following external otitis resolved by PET/MRI.
The figure in the original published version of this article was omitted.


The dedifferentiation of metastatic prostate carcinoma.
Two hundred consecutive staging lymphadenectomies with metastatic prostate adenocarcinoma and 100 consecutive autopsies with widely disseminated metastatic prostate adenocarcinoma were identified. The metastases from 41% of the staging lymphadenectomies were entirely differentiated (gland forming) and an additional 43% were predominantly (50% or more) differentiated. In contrast, the metastases from 70% of the autopsies were entirely undifferentiated (non-gland forming) and an additional 18% were predominantly undifferentiated. Further, five patients with completely or predominantly differentiated metastases in staging lymphadenectomies were found to have widespread completely or predominantly undifferentiated metastases at autopsy 4-7 years later. These findings suggest that dedifferentiation occurs within metastases and that dedifferentiation within metastases may be important in understanding the widespread dissemination of metastatic prostate carcinoma.


Tuning the organelle specificity and cytotoxicity of iridium(III) photosensitisers for enhanced phototheranostic applications.
Luminescent cyclometallated iridium(III) complexes with a polyhedral oligomeric silsesquioxane (POSS) unit were designed as efficient theranostic agents that displayed tuneable organelle-targeting properties, minimal dark cytotoxicity and substantial photocytotoxicity even under hypoxic conditions.


Epidural anesthesia for laminectomy lead placement in spinal cord stimulation.
Spinal cord stimulation (SCS) is used to treat chronic pain and requires an awake patient for optimized lead positioning to locate paresthesias. Epidural anesthesia may be a suitable anesthetic but has not been evaluated. We performed an open-label, prospective, observational, single-center study to evaluate the safety and efficacy of laminectomy lead placement under epidural anesthesia for the treatment of neuropathic chronic pain. The results in our study demonstrate that epidural anesthesia is a suitable technique for SCS lead implant. This is the first study using epidural anesthesia for SCS lead implants by laminectomy. The technique seems to be safe and effective.


Use of the Atad catheter for the induction of labour in women who have had a previous Caesarean section--a case series.
Abstract The induction of labour of women with an unfavourable cervix who have had a previous Caesarean section, is challenging. Eight women who had a Caesarean section in a previous pregnancy had labour induced with an Atad catheter. Six out of eight women achieved labour, and two out of these six women had a vaginal delivery. An Atad catheter is an option for women needing induction of labour with an unfavourable cervix who have had a Caesarean section previously and are motivated to have a vaginal delivery.


Liver failure unmasks celiac disease in a child.
Liver involvement in celiac disease (CD) varies from asymptomatic mild non-specific hepatitis to liver failure. Here we report the first child with liver failure due to a sclerosing cholangitis associated with CD. An 11 year old girl presented with fatigability for 1 year and jaundice and abdominal distension for 3 weeks. On examination, the growth parameters were below 3rd percentile; she had splenomegaly and severe ascites. Liver function tests revealed elevated liver enzymes (ALT 84 U/L, total bilirubin 98.7 μmol/L, and direct 58.3 μmol/L, gamma-glutamyltransferase 111 U/L, INR 2.7, and albumin 16 g/L). Extensive investigations excluded infectious, metabolic, structural, and endocrine causes of chronic liver disease. Because of the short stature and anemia, CD was suspected, and serological evaluation revealed increased IgA antibodies to tissue transglutaminase (385 units; normal, 0-20 units). Histopathological examination of small intestinal biopsies showed total villous atrophy consistent with celiac disease. Liver biopsy showed bridging fibrosis, portal tract expansion by lymphocytes, plasma cells, and neutrophils, bile ductular proliferation, and periductular fibrosis. Magnetic resonance cholangiography revealed beading and narrowing appearance of intra- and extrahepatic bile ducts. The histopathological and imaging findings are diagnostic of sclerosing cholangitis. The child was initiated on ursodeoxycholic acid, gluten free diet for life, and steroid that was tapered over 3 months. At 3 month follow up, liver function tests completely normalized. CD is a potentially treatable cause of liver failure. All patients with severe unexplained liver disease should undergo serological screening for CD.


Coherent magnetic and electronic structure symmetry broken in frustrated bilayer Kagome ferromagnet Fe3Sn2.
In this letter, by measuring resistivity and magnetization with magnetic fieldHrotated inabplane and currentIalongcaxis, we studied the magnetic and electronic structure symmetry of frustrated topological bilayer Kagome ferromagnet Fe3Sn2. We observed that the curves of the resistivity and magnetization both showed broken two-fold symmetry from 5 K to 380 K. The further analysis indicates that there is a close causality between the spin arrangement and the electronic states in Fe3Sn2even above room temperature. These phenomena are closely related to the change in spin-orbit coupling (SOC) under the magnetic field. Our experimental results suggest that Fe3Sn2is an ideal platform to study the influence of spin arrangement on electronic state in topological materials and can also be used to design next generation magnetic devices by modulating SOC at external magnetic field.


Caution in using a unique technique of banded revision gastric bypass: Successful endosopic and surgical management of a rare complication.
Revision surgery is increasingly performed as result of the increase in primary bariatric procedures. We describe a new technique of revision Roux-en-Y gastric bypass (RYGB) acombining stapled gastroenterostomy with fixed band placement. We report two cases of unique complications and its successful endoscopic and surgical management. Two out of twenty patients undergoing this revision RYGB procedure presented with gastric outlet obstruction due to band erosion within 10 weeks. Endoscopic band retrieval was successful in the first patient but the second patient required surgical removal. We report the new complication of band erosion in 10% patients using a unique revision RYGB technique combining restriction of the gastric outlet and band placement. We advise using one or the other technique but not both in combination. Surgeons need to be aware of this as erosion which occurs early due to close proximity of band with fresh staple line. We report successful endoscopic and surgical management. Revision surgery using this technique predisposes to bande erosion, presenting as gastric outlet obstruction. Endoscopic management should be attempted prior to surgical removal.


Two cases where bedside ultrasound was able to distinguish pulmonary bleb from pneumothorax.
Distinguishing large pulmonary bullae from an acute pneumothorax can present a diagnostic challenge in the emergency setting. Plain film radiography of the chest may be inadequate to make the diagnosis. As the management of these two entities varies significantly, a clinical adjunct to aid diagnosis would prove useful. Using emergency department bedside ultrasound, we identified the typical "comet tailing" phenomenon of the movement of the lung tissue against the pleura during respiration, present in bullous disease but absent if the lung has collapsed. We present two patients, one with bullous emphysema and another with pneumothorax, in whom bedside ultrasound aided in making the diagnosis.


Ultrasound-guided supraclavicular central venous catheterization in patients with malignant hematologic diseases.
We present two cases of central venous catheterization (CVC) in which an ultrasound-guided in-plane approach was used. Case 1 was a 60-year-old man with acute myelogenous leukemia in whom a right supraclavicular CVC was performed. He had pancytopenia (leukocytes 2,000/μL; erythrocytes 350 × 10(4)/μL; platelets 5.6 × 10(4)/μL), and abnormal coagulability (prothrombin time-international normalized ratio 1.35). A linear array transducer was positioned cephalad to the right clavicle and rotated 30° clockwise. The 21-gauge needle was manipulated from outside of the transducer. A CV catheter (CV legaforce EX(®); Terumo Co., Japan) was placed and stitched near the right clavicle. The patient felt no discomfort caused by the catheter. Case 2 was a 64-year-old women with malignant lymphoma whose right internal jugular vein was surrounded by abnormally enlarged lymph nodes. CVC was performed by the in-plane supraclavicular approach, avoiding puncture of the lymph node. This novel CVC technique is useful to minimize the risk of complications and patient discomfort by indwelling catheter.