Wallerian degeneration in human nerves: serial electrophysiological studies.
After nerve transection, the distal stump undergoes Wallerian degeneration (WD). Little information is available concerning sequential changes in nerve conduction measurements during WD in humans. Five patients with nerve injuries were studied temporally. Motor-evoked amplitudes were reduced by 50% at 3 to 5 days after injury; the response was absent by day 9. Sensory-evoked amplitudes were reduced by 50% at 7 days after injury; the response was absent by day 11. Sensory and motor nerves with shorter distal stumps showed earlier loss of amplitude than did those with longer distal stumps. Denervation potentials were seen 10 to 14 days after injury. Our results suggest that WD occurs earlier if the distal stump is shorter, and that motor-evoked responses are affected earlier than sensory-evoked responses. The time-lag between the loss of the motor-evoked response and the appearance of denervation potentials, the latter coinciding with reduction of sensory evoked responses, suggests that failure of neuromuscular transmission precedes axonal loss during WD.


Cadaveric renal transplantation: surgical results and expectations in the cyclosporine era.
During a 36-month period 100 patients received 104 cadaveric renal transplants with cyclosporine-based immunosuppression. Of the patients 26 required 31 additional operations. Of the 19 secondary operations performed 1 month after transplantation 18 were emergency in nature, whereas beyond this period the majority of the procedures were elective. Both deaths in this series were related to the operation. Only 1 graft loss was directly attributed to a secondary operation. The patient undergoing cadaveric renal transplantation is at significant risk (25 per cent) of requiring at least 1 additional operation. However, despite this high probability of reoperation, graft loss and patient death after such procedures should be rare.


Difficulties Faced by General Surgery Residents. A Qualitative Systematic Review.
General surgery residency training is academically rigorous, taxing and involves complex operative procedures. These trainings are synonymous with alarming burnout rates, high incidence of mistreatment reports and lower job satisfaction. Moreover, the established association between residents' levels of well-being and their capacity for empathy and patient care, emphasises the urgency to mitigate the negative connotations relating to surgical training. This systematic review aims to circumnavigate the multitude of problems faced by general surgical residents in training. Literature searches were conducted on electronic databases Medline, PsycINFO, Embase, CINAHL, and Web of Science Core Collection using specific search criteria. Studies that analyzed the difficulties faced by General Surgery residents were eligible for inclusion Qualitative analysis involved the derivation of analytical themes and grouping data extracted from the papers accordingly. After review of the full study texts, 19 studies met the inclusion criteria. The 3 main analytical themes identified were Problems regarding the Residency Programme, Work Associated Challenges, and Personal Concerns. Problems Regarding Residency Training was associated with residents' lack of experience. Work Associated Challenges highlighted problems with peer interactions, autocratic relationships, and communication with patients. Personal Concerns includes work-life balance, personal well-being and gender biases. This systematic review delves into several prevalent difficulties that general surgical residents face, ranging from work related issues to personal difficulties. The results of this review can be used to provide complementary supportive measures for general surgical residents.


Nephrogenic adenoma arising in a renal cortical cyst.
Nephrogenic adenoma is an unusual lesion of the urinary tract first described by Davis in 1949 as a hamartoma. In 1950, Friedman and Kuhlenbeck subsequently characterized the lesion in more detail and named it nephrogenic adenoma. It appears to be a metaplastic response of the urothelium elicited by trauma and chronic irritation and is considered to be benign. A MEDLINE search of the literature from 1960 to the present revealed no previous documentation of a nephrogenic adenoma arising from a renal cortical cyst. Herein, we present such a case arising in a renal cortical cyst.


Association of B7-1 co-stimulation with the development of graft arterial disease. Studies using mice lacking B7-1, B7-2, or B7-1/B7-2.
To investigate the roles of B7-1 and/or B7-2 co-stimulatory molecule in the development of graft arterial disease (GAD), major histocompatibility complex (MHC) class II-mismatched allograft hearts were transplanted into wild-type, B7-1(-/-), B7-2(-/-), or B7-1/B7-2(-/-) recipient mice. Grafts were explanted at 4 or 8 weeks and used for histological and immunohistochemical analyses, RNase protection assay, and flow cytometry of graft infiltrating cells. Grafts in wild-type recipients showed macrophage, recipient MHC class II, and B7 molecule co-localization by immunohistochemistry to GAD lesions. Flow cytometry revealed that CD11b(+) and MHC class II(+) graft infiltrating cells expressed B7-1 more than B7-2, whereas B7-2 expression was predominant in CD11b(-) cells at 4 and 8 weeks. GAD was significantly attenuated in the allografts in B7-1(-/-) and B7-1/B7-2(-/-) but not in B7-2(-/-) recipients compared to wild-type hosts. Interferon-gamma mRNA levels were comparable in all graft combinations, whereas interleukin-4 mRNA levels decreased in grafts in B7-2 deficient hosts, but did not correlate with GAD attenuation. The findings indicate distinct roles for B7-1 and B7-2 co-stimulatory molecules in the development of GAD, potentially because of differential expression of B7-1 and B7-2 molecules on distinct stimulator and/or effector cell populations.


Modified Mustardé Flap for Lower Eyelid Reconstruction in Basal Cell Carcinoma: Revisited.
Full thickness defects of lower eyelid, following oncological resection, often pose a formidable challenge to the operating surgeon. Although a plethora of reconstructive options have been tried, the Mustardé flap has stood the test of time. Our patient, a 57-year old lady, diagnosed with basal cell carcinoma of the left lower eyelid underwent full-thickness wide local excision and reconstruction using modified Mustardé flap. The anterior part of defect was reconstructed using the flap. The posterior part was reconstructed using septal mucoperichondrial-cartilage composite graft, sutured to remnant palpebral conjunctiva. The patient had an uneventful post-operative period. On serial follow-up, the patient had an acceptable scar. At 6 months follow-up, the facial scar was barely perceptible with normal lower lid disposition. The modified Mustardé flap is a simple and reliable reconstructive option for full-thickness lower eyelid defects following oncological resection in carefully selected cases.


Development of a Graph-Based Database for Ovarian Cancer Symptoms.
Uncontrolled cancer-related symptoms severely affect the quality of life of cancer patients. This study leveraged symptom data written in the online health communities (OHCs) and developed a symptom knowledge database for cancer patients. Further study is needed to apply this pilot study to the larger OHCs data.


Esophageal pyogenic granuloma resected by polypectomy using a detachable snare.
Pyogenic granuloma (PG) is a benign inflammatory vascular lesion rarely seen in the gastrointestinal tract and a possible cause of bleeding. Polypectomy using a detachable snare for esophageal PG with active bleeding is an effective treatment.


Omentin-1 drives cardiomyocyte cell cycle arrest and metabolic maturation by interacting with BMP7.
Mammalian cardiomyocytes (CMs) undergo maturation during postnatal heart development to meet the increased demands of growth. Here, we found that omentin-1, an adipokine, facilitates CM cell cycle arrest and metabolic maturation. Deletion of omentin-1 causes mouse heart enlargement and dysfunction in adulthood and CM maturation retardation in juveniles, including delayed cell cycle arrest and reduced fatty acid oxidation. Through RNA sequencing, molecular docking analysis, and proximity ligation assays, we found that omentin-1 regulates CM maturation by interacting directly with bone morphogenetic protein 7 (BMP7). Omentin-1 prevents BMP7 from binding to activin type II receptor B (ActRIIB), subsequently decreasing the downstream pathways mothers against DPP homolog 1 (SMAD1)/Yes-associated protein (YAP) and p38 mitogen-activated protein kinase (p38 MAPK). In addition, omentin-1 is required and sufficient for the maturation of human embryonic stem cell-derived CMs. Together, our findings reveal that omentin-1 is a pro-maturation factor for CMs that is essential for postnatal heart development and cardiac function maintenance.


Adiponectin activates endothelial nitric oxide synthase through AMPK signaling after subarachnoid hemorrhage.
Adiponectin is produced from fatty tissue and has been reported to be involved with metabolic syndrome. Recently, adiponectin has been demonstrated to play a neuroprotective role against cerebral ischemia. In this study, we explored the time-course serial expression changes of adiponectin in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH) and the effects of adiponectin on cerebral arteries. The concentrations of adiponectin were measured serially until day 14 in CSF of 8 patients with SAH. The CSF samples obtained from 6 patients suffering from an unruptured aneurysm were used as controls. Serum samples were collected from 6 healthy adult volunteers. Rat cerebral arteries were incubated with adiponectin (2μg/ml). Western blot analysis using AMP-activated protein kinase α (AMPKα), phosphorylated (p)-AMPKα at Thr(172), endothelial nitric oxide synthase (eNOS), p-eNOS at Ser(1177) and actin antibodies was then performed. The adiponectin concentrations in serum and control CSF were 17,670±3748ng/ml and 9.2±3.0ng/ml, respectively. After SAH, the concentration of adiponectin in the CSF significantly increased on the first post-SAH day and gradually decreased thereafter. Adiponectin significantly phosphorylated both the AMPKα and eNOS of the cerebral arteries. Our findings suggest that adiponectin is significantly increased in the CSF after SAH, resulting in the activation of AMPKα and eNOS. Adiponectin plays an important role against cerebral vasospasm via the AMPK/eNOS signaling pathway.


High-molecular-weight renin converting enzyme from dog kidney: detection and fractionation.
Renal cortical high-molecular-weight renin (Mw:60,000) of the dog is a complex of renin (low-molecular-weight renin; Mw:40,000) and a renin binding protein. We detected an enzyme-like substance that catalyzes the conversion from high- into low-molecular-weight renin. When the renal cortical extract was added to the high-molecular-weight renin and the preparation incubated at 37 degrees C for 30 min, the high-molecular-weight renin was converted into the low-molecular-weight form. No such conversion occurred in the case of renal medullary extract. This converting substance was fractionated using concanavalin A Sepharose, 70% ammonium sulfate saturation and DEAE-cellulose chromatography. The converting activity was inhibited by potassium tetrathionate, N-ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid). These events suggest that this substance is an enzyme possessing sulfhydryl moieties. However, a cathepsin B inhibitor leupeptin did not affect the activity. Accordingly, the high-molecular-weight renin converting enzyme, which is sensitive to sulfhydryl oxidation, may explain the mechanism of interconversion between high- and low-molecular-weight renin involving the oxidation-reduction of tissue sulfhydryl groups.


Network reconstruction for trans acting genetic loci using multi-omics data and prior information.
Molecular measurements of the genome, the transcriptome, and the epigenome, often termed multi-omics data, provide an in-depth view on biological systems and their integration is crucial for gaining insights in complex regulatory processes. These data can be used to explain disease related genetic variants by linking them to intermediate molecular traits (quantitative trait loci, QTL). Molecular networks regulating cellular processes leave footprints in QTL results as so-called trans-QTL hotspots. Reconstructing these networks is a complex endeavor and use of biological prior information can improve network inference. However, previous efforts were limited in the types of priors used or have only been applied to model systems. In this study, we reconstruct the regulatory networks underlying trans-QTL hotspots using human cohort data and data-driven prior information. We devised a new strategy to integrate QTL with human population scale multi-omics data. State-of-the art network inference methods including BDgraph and glasso were applied to these data. Comprehensive prior information to guide network inference was manually curated from large-scale biological databases. The inference approach was extensively benchmarked using simulated data and cross-cohort replication analyses. Best performing methods were subsequently applied to real-world human cohort data. Our benchmarks showed that prior-based strategies outperform methods without prior information in simulated data and show better replication across datasets. Application of our approach to human cohort data highlighted two novel regulatory networks related to schizophrenia and lean body mass for which we generated novel functional hypotheses. We demonstrate that existing biological knowledge can improve the integrative analysis of networks underlying trans associations and generate novel hypotheses about regulatory mechanisms.


Immunoregulatory T cells in autoimmunity.
The aim of this work was to discuss the current knowledge concerning regulatory T cells in the pathogenesis of autoimmune diseases. CD4(+) T cells that constitutively express CD25 exhibit powerful suppressive properties. Such cells have been denominated regulatory T cells (T(R)). Alterations in T(R) cells are known to cause organ-specific autoimmune disease in animal models. These cells are anergic when stimulated via their TCR but proliferate when co-stimulated with IL-2. A particular characteristic is that CD4(+)CD25(+) T cells inhibit the proliferative responses of CD4(+)CD25(-) T cells by suppressing the capacity of the responders to transcribe IL-2. The survival and/or expansion of this regulatory subset in the periphery appears to need the availability of IL-2, the components of the IL-2R, as well as cell surface costimulatory molecules. Cytokine participation has been shown in many of the in vivo models of autoimmunity where regulatory cells participate, providing evidence in favour of a role for IL-10, transforming growth factor-beta and IL-4. The behavior and possible participation of regulatory T cells in human disease is still a poorly explored topic but their pathogenic role is warranted.


Conditioned taste aversions induced by 1-5-hydroxytryptophan are mediated by the area postrema.
Previous studies have shown that injections of 5-HTP can induce conditioned taste aversions when paired with a novel taste. Adult male albino rats received either lesions of the area postrema or were subjected to a sham lesion procedure. All rats were adjusted to a 23 1/2 hr/day water deprivation schedule and on the conditioning day were given a 0.15% saccharin solution for 1/2 hr. After drinking the saccharin fluid 9 area postrema lesioned and 10 sham lesioned rats were injected i.p. with 25 mg/kg 1-5-hydroxytryptophan. Similarly 10 area postrema lesioned and 6 sham lesioned rats were injected with the vehicle solution. A two-bottle choice test between the saccharin solution and water was given to all animals on the third and fourth days after the conditioning day. The sham lesioned rats injected with the 1-5-hydroxytryptophan exhibited a strong aversion to the saccharin taste whereas the vehicle injected sham lesioned rats showed an equal preference for the two fluids. The difference in group mean saccharin preference ratio was significant (p less than .01). Both area postrema lesioned groups exhibited saccharin preference ratios that were comparable to and not significantly different from the sham lesioned animals injected with the vehicle solution. These results show that an intact area postrema is necessary for induction of conditioned taste aversions with 1-5-hydroxytryptophan.


The PRESTO technique for fMRI.
In the early days of BOLD fMRI, the acquisition of T(2)(*) weighted data was greatly facilitated by rapid scan techniques such as EPI. The latter, however, was only available on a few MRI systems that were equipped with specialized hardware that allowed rapid switching of the imaging gradients. For this reason, soon after the invention of fMRI, the scan technique PRESTO was developed to make rapid T(2)(*) weighted scanning available on standard clinical scanners. This method combined echo shifting, which allows for echo times longer than the sequence repetition time, with acquisition of multiple k-space lines per excitation. These two concepts were combined in order to achieve a method fast enough for fMRI, while maintaining a sufficiently long echo time for optimal contrast. PRESTO has been primarily used for 3D scanning, which minimized the contribution of large vessels due to inflow effects. Although PRESTO is still being used today, its appeal has lessened somewhat due to increased gradient performance of modern MRI scanners. Compared to 2D EPI, PRESTO may have somewhat reduced temporal stability, which is a disadvantage for fMRI that may not outweigh the advantage of reduced inflow effects provided by 3D scanning. In this overview, the history of the development of the PRESTO is presented, followed by a qualitative comparison with EPI.


Oxygen Vacancy Management for High-Temperature Mesoporous SnO2 Electron Transport Layers in Printable Perovskite Solar Cells.
The planar SnO2 electron transport layer (ETL) has contributed to the reported power conversion efficiency (PCE) record of perovskite solar cells (PSCs), while the high-temperature mesoporous SnO2 ETL (mp-SnO2 ) brings poor device performance. Herein, we report the application of mp-SnO2 for efficient printable PSCs via oxygen vacancy (OV) management by introducing magnesium (Mg) into the paste. We find that high-temperature annealing suppresses self-doping of SnO2 by reducing OVs. The introduced Mg occupies both the Sn site and interstitial site of SnO2 and promotes the formation of OVs. Lattice Mg tends to induce neutral OVs and interstitial Mg could promote the ionization of neutral OVs for self-doping. The synergy effect on OVs increases the carrier density and upshifts the Fermi level energy of mp-SnO2 , ensuring its capability as the well-performed ETL with trap-less charge transport and suppressed surface recombination for dramatic improved device PCE from 6.62 % to 17.25 %.


The activation of autophagy protects neurons and astrocytes against bilirubin-induced cytotoxicity.
Unconjugated bilirubin (UCB) neurotoxicity involves oxidative stress, calcium signaling and ER-stress. The same insults can also induce autophagy, a process of "self-eating", with both a pro-survival or a pro-apoptotic role. Our aim was to study the outcome of autophagy activation by UCB in the highly sensitive neuronal SH-SY5Y cells and in the resistant astrocytoma U87 cells. Upon treatment with a toxic dose of UCB, the conversion of LC3-I to LC3-II was detected in both cell lines. Inhibition of autophagy by E64d before UCB treatment increased SH-SY5Y cell mortality and made U87 cells sensitive to UCB. In SH-SY5Y autophagy related genes ATG8 (5 folds), ATG18 (5 folds), p62 (3 folds) and FAM 129A (4.5 folds) were induced 8h after UCB treatment while DDIT4 upregulation (13 folds) started at 4h. mTORC1 inactivation by UCB was confirmed by phosphorylation of 4EBP1. UCB induced LC3-II conversion was completely prevented by pretreating cells with the calcium chelator BAPTA and reduced by 65% using the ER-stress inhibitor 4-PBA. Pretreatment with the PKC inhibitor reduced LC3 mRNA by 70% as compared to cells exposed to UCB alone. Finally, autophagy induction by Trifluoroperazine (TFP) increased the cell viability of rat hippocampal primary neurons upon UCB treatment from 60% to 80%. In SH-SY5Y cells, TFP pretreatment blocked the UCB-induced cleaved caspase-3 protein expression, decreased LDH release from 50% to 23%, reduced the UCB-induction of HO1, CHOP and IL-8 mRNAs by 85%, 70% and 97%. Collectively these data indicate that the activation of autophagy protects neuronal cells from UCB cytotoxicity. The mechanisms of autophagy activation by UCB involves mTOR/ER-stress/PKC/calcium signaling.


Ongoing Professional Practice Evaluation for Emergency Medicine Physicians in a Large Health Care System.
Ongoing professional practice evaluation (OPPE) is designed to identify professional practice trends that affect quality and safety of practicing physicians. Focused professional practice evaluation (FPPE) is employed when physician nonconformance is identified. The goal of this novel OPPE initiative was threefold: (1) meet The Joint Commission's accreditation standards, (2) assess documentation for compliance and risk, and (3) maintain procedural competency to provide optimal patient care. A quality assurance project with OPPE program development was initiated in 18 emergency departments across a large health care system. First, a monthly comprehensive peer review meeting assessed cases across the system for medicolegal risk. Physicians with reasonable practice concerns were identified and referred to FPPE. Second, a standardized OPPE chart review was performed biannually by a quality assurance committee assessing all physician charts for clinical care, medicolegal risk, and quality. Last, completion of a procedure lab every three years was required to maintain competency. For systemwide peer review in 2019, 47 cases were referred and 12.8% had quality concerns. For standardized OPPE chart review, 221 physicians were reviewed on 1,219 charts on the following metrics: insufficient medical decision making, diagnoses not medical/legally supported, and charts with red flags. Nine physicians (4.1%) and 17 charts (1.4%) were deficient in all three measures, and 8 physicians (3.6%) had deficiencies in ≥ 50% of their charts. For procedure lab competency, 19.0% of physicians completed the lab in 2019 with no quality concerns. A structured OPPE algorithm can aid large health care systems in identifying deviations from practice standards for which additional FPPE can be beneficial.


Depth of Hepatic Infiltration and Lymph Node Swelling as Factors for Considering Surgery for T2-4 Gallbladder Carcinoma Patients.
The aim of the present study was to clarify if the degree of hepatic infiltration and lymph node swelling of gallbladder carcinoma (GBC) should be held as deciding factors for T2-4 GBC patients to undergo surgery. Fifty consecutive patients with T2-4 GBC who underwent surgery were reviewed retrospectively. We investigated the preoperative information and imaging factors as predictors of survival. The estimated overall survival in all patients was lower in patients with hepatic infiltration ≥5 mm (n=12) than in those with <5 mm (n=38) (p=0.003). Multivariate analyses demonstrated that liver infiltration ≥5 mm (OR=2.251; 95%CI=0.906-5.596, p=0.081) and lymph node swelling (OR=2.462; 95%CI=1.034-5.859, p=0.042) were risk factors of poor survival. Our results suggested that ≥5 mm liver infiltration and lymph node swelling may serve as deciding factors for surgery consideration in GBC patients.


Analysis of gene expression with cDNA microarrays in rat brain after 7 and 42 days of oral lithium administration.
The gene expression profile in rat brain was examined using microarrays in rats fed lithium chloride for 7 days (subacute) or 42 days (chronic). Brain lithium concentrations were 0.39 mM and 0.79 mM (therapeutically relevant), at 7 and 42 days, respectively. Of the 4132 genes represented in the microarrays, 25 genes were downregulated by at least twofold and none was upregulated after 7 days of treatment. Expression of 50 genes was downregulated by at least two-fold at 42 days, without any being upregulated. Lithium treatment for 7 days did not affect at a measurable extent expression of 37 of the 50 genes that were downregulated at 42 days. Genes whose expression was changed at 42 days coded for a number of receptors, protein kinases, transcription and translation factors, markers of energy metabolism, and signal transduction. Thus, chronic lithium at a therapeutically relevant concentration reduced expression of a large number of genes involved in multiple signaling and other pathways, without increasing expression at a comparable extent.


Steering Toward Normative Wide-Dynamic-Range Neuron Activity in Nerve-Injured Rats With Closed-Loop Peripheral Nerve Stimulation.
Chronic pain is primarily treated with pharmaceuticals, but the effects remain unsatisfactory. A promising alternative therapy is peripheral nerve stimulation (PNS), but it has been associated with suboptimal efficacy because its modulation mechanisms are not clear and the current therapies are primarily open loop (ie, manually adjusting the stimulation parameters). In this study, we developed a proof-of-concept computational modeling as the first step toward implementing closed-loop PNS in future biological studies. When developing new pain therapies, a useful pain biomarker is the wide-dynamic-range (WDR) neuron activity in the dorsal horn. In healthy animals, the WDR neuron activity occurs in a stereotyped manner; however, this response profile can vary widely after nerve injury to create a chronic pain condition. We hypothesized that if injury-induced changes of neuronal response can be normalized to resemble those of a healthy condition, the pathological aspects of pain may be treated while maintaining protective physiological nociception. Using an in vivo electrophysiology data set of WDR neuron recordings obtained in nerve-injured rats and naïve rats, we constructed sets of linear phenomenologic models of WDR firing rate during windup stimulation for both conditions. Then, we applied robust control systems techniques to identify a closed-loop PNS controller, which can drive the dynamics of WDR neuron response in neuropathic pain model into ranges associated with normal physiological pain. The sets of identified linear models can accurately predict, in silico, nonlinear neural responses to electrical stimulation of the peripheral nerve. In addition, we showed that continuous closed-loop control of PNS can be used to normalize WDR neuron firing responses in three injured cases. In this proof-of-concept study, we show how tractable, linear mathematical models of pain-related neurotransmission can be used to inform the development of closed-loop PNS. This new application of robust control to neurotechnology may also be expanded and applied across other neuromodulation applications.


[Submillimeter 3D coronary MR angiography with real-time navigator correction in 107 patients with suspected coronary artery disease].
To evaluate the clinical value of high-resolution coronary MR angiography (coronary MRA) in a large group of patients with suspected coronary artery disease. 107 patients with suspected coronary artery disease underwent free-breathing coronary MRA (Intera, 1.5 T, Philips Medical Systems). To compensate for artefacts due to respiratory motion, a right hemidiaphragmatic navigator with real time-time slice correction was used. An ECG-gated, fat-suppressed, 3D segmented-k-space gradient echo sequence (in plane resolution 0.70 x 0.79 mm(2)) was used. Cardiac catheterization with selective coronary angiography was performed in all patients. Visualization of the coronary arteries (CA) was qualitatively assessed using a four-point grading scale. Image quality of grade 1 was achieved in 24 %, grade 2 in 48 %, grade 3 in 24 % and grade in in 4 % of patients. Based on an evaluation of the coronary MRAs of all patients (n = 107) sensitivity and specificity for the detection of stenoses > 60 % in the proximal and middle main coronary arteries were 74 % and 63 %, respectively. In coronary MRAs with good quality [grade 1 and 2, n = 77/107 (72 %)] sensitivity and specificity for the detection of coronary stenoses were 88 % and 91 %, respectively. Submillimeter 3D coronary MRA with real-time navigator correction allows high quality imaging of the proximal and middle main coronary arteries with good sensitivity and specificity for detection of stenoses > 50 % in selected patients. However, in about 28 % of patients image quality is severely impaired.


[Pediatric imported malaria. Experience of the hospital center of Versailles (1997-2001)].
Few data are available about pediatric imported malaria, whereas the number of cases seems in constant increase. all pediatric malaria cases diagnosed by a positive thin or thick blood film at the Versailles Hospital, from January 1997 to December 2001, were studied retrospectively. sixty cases of pediatric imported malaria were studied. They were 58 cases of uncomplicated malaria and 2 cases of severe malaria; 85% of the children had travelled to sub-Saharan Africa and 15% to Oceania; 90% of the children were of African origin. Plasmodium falciparum was found alone in 84% of the cases. The anti-malarial chemoprophylaxis was inappropriate in 92% of the cases. No child had profited from preventive measures against mosquitos. Fever > 37,5 degrees C was observed in 100% of the cases. The other clinical signs were present in less than 50% of the cases. The median of haemoglobin and platelet was 10.5 g/dL and 141,000/mm(3), respectively. After treatment, the evolution was good in all the cases, without relapse or any consequences. our study, in agreement with the national data, confirms the increase in the number of case of pediatric imported malaria, and underlines the mediocrity of the prevention, in particular in term of anti-malarial chemo-prophylaxis. These data, in a context of regular increase of international travels to endemic areas, suggest the necessity to improve the information of the general public, and the urgency of a better staff training of health care workers concerning malaria, in order to improve the prevention and the treatment of this potentially fatal disease.


Bidirectional association between psoriasis and depression: Two longitudinal follow-up studies using a national sample cohort.
Few studies have investigated the bidirectional association between psoriasis and depression. The aim of our study was to identify the association between psoriasis and depression. Data collected by the Korean Health Insurance Review and Assessment from 2002 to 2013 were used. In study I, psoriasis patients (n = 10,932) were matched 1:4 with control I group participants. In study II, depression patients (n = 60,383) were matched 1:4 with control II group participants. Matching was performed for age, sex, income, and region of residence. The stratified Cox-proportional hazard model was used to calculate the hazard ratio (HR) with crude and adjusted models. In study I, the adjusted HR for depression was 1.13 (95% confidence interval (CI) = 1.03-1.24) in the psoriasis group compared to the control I group. In study II, the adjusted HR for depression was 1.11 (95% CI = 1.00-1.22) in the depression group compared to the control II group. In the subgroup analyses, the adjusted HRs for depression were 1.24 (95% CI = 1.00 - 1.53) in females aged < 40 years and 1.31 (95% CI = 1.04 - 1.66) in males aged ≥ 60 years. In the subgroup analyses from study II, the adjusted HRs for psoriasis were 1.56 (95% CI = 1.15 - 2.12) in males aged < 40 years and 1.35 (95% CI = 1.04 - 1.75) in males aged ≥ 60 years. We suggest that psoriasis and depression might have a bidirectional association.


Binding sites for calcitonin gene-related peptide in distinct areas of rat brain.
Calcitonin gene-related peptide (CGRP) binding sites were localized in rat brain and spinal cord by an in vitro labeling light microscopic technique using [125I]rCGRP as radioligand. Specific rCGRP binding with a dissociation constant (Kd) of 0.53 nM to membrane preparations from rat brain cortex was characterized. The presence and the selective distribution of specific high affinity CGRP binding sites in the central nervous system suggest a role for this recently predicted peptide as a neurotransmitter.


Post-transcriptional control of gene expression: a genome-wide perspective.
Gene expression is regulated at multiple levels, and cells need to integrate and coordinate different layers of control to implement the information in the genome. Post-transcriptional levels of regulation such as transcript turnover and translational control are an integral part of gene expression and might rival the sophistication and importance of transcriptional control. Microarray-based methods are increasingly used to study not only transcription but also global patterns of transcript decay and translation rates in addition to comprehensively identify targets of RNA-binding proteins. Such large-scale analyses have recently provided supplementary and unique insights into gene expression programs. Integration of several different datasets will ultimately lead to a system-wide understanding of the varied and complex mechanisms for gene expression control.


The Role of Robotic Surgery in Sinonasal and Ventral Skull Base Malignancy.
Over the past decade, robotic surgery has gained wide popularity, making a significant impact on multiple surgical specialties. In the head and neck arena, transoral robotic surgery has proven to be safe and associated with acceptable oncological and superior functional outcomes for surgery of the oropharynx, hypopharynx, supraglottis, and glottis; thus, changing the paradigm for the management of tumors in these anatomic locations. Robotic surgery of the ventral skull base is at an early stage of development. In this article reviews the literature discussing the role of robotic surgery in managing sinonasal and ventral skull base malignant lesions.


A 9-year-old boy with atypical retroauricular pain: a case report.
Idiopathic causes of retroauricular pain are rarely seen in clinical practice. We present a 9-year-old child who suffered from atypical retroauricular pain resistant to conventional treatment. After excluding any other cause of retroauricular pain, a nerve block was performed with a 0.3 ml lidocaine 1% injection into the trigger point. We believe that this case report is important because in the literature there are no similar cases described in children.


Intelligence level of patients with the Duchenne type of progressive muscular dystrophy (pmd-d).
The I.Q. of 129 patients with PMD-D and 27 patients suffering from Werdnig-Hoffmann disease were estimated. Among the patients with PMD-D there was one group without any complicating factors and 3 other groups with additional factors that might influence the intelligence level. Comparing mean values and distribution of I.Q. for all these groups, one can conclude that, besides additional unfavourable pathological and environmental factors in all cases, PMD-D itself causes a small decrease of the I.Q. by about 1 SD. The frequent changes of the EEG record in these patients could reflect involvement of the CNS by the pathological process.


Differential turnover of phospholipid acyl groups in mouse peritoneal macrophages.
Phospholipid acyl turnover was assessed in mouse peritoneal exudate cells which consisted primarily of macrophages. The cells were incubated for up to 5 h in media containing 40% H218O, and uptake of 18O into ester carbonyls of phospholipids was determined by gas chromatography-mass spectrometry of hydrogenated methyl esters. The uptake was highest in choline phospholipids and phosphatidylinositol, less in ethanolamine phospholipids, and much less in phosphatidylserine. Acyl groups at the sn-1 and sn-2 positions of diacyl glycerophospholipids, including arachidonic and other long-chain polyunsaturated fatty acids, acquired 18O at about the same rate. Acyl groups of alkylacyl glycerophosphocholine exhibited lower rates of 18O uptake, and acyl groups of ethanolamine plasmalogens (alkenylacyl glycerophosphoethanolamines) acquired only minimal amounts of 18O within 5 h, indicating a low average acyl turnover via free fatty acids. Pulse experiments with exogenous 3H-labeled arachidonic acid supported the concept that acylation of alkenyl glycerophosphoethanolamine occurs by acyl transfer from other phospholipids rather than via free fatty acids and acyl-CoA. The 18O content of intracellular free fatty acids increased gradually over a 5-h period, whereas in extracellular free fatty acids it reached maximal 18O levels within the first hour. Arachidonate and other long-chain polyunsaturated fatty acids were found to participate readily in deacylation-reacylation reactions but were present only in trace amounts in the free fatty acid pools inside and outside the cells. We conclude that acyl turnover of macrophage phospholipids through hydrolysis and reacylation is rapid but tightly controlled so that appreciable concentrations of free arachidonic acid do not occur.


Inhibition of biliary phospholipid and cholesterol secretion by cefoperazone.
The effect of cefoperazone, a third-generation cephalosporin, on biliary lipid secretion in rats was examined. Rats were anesthetized with ether and the mid-lumbar vein and common bile duct cannulated. Bile acid secretion was maintained by intravenous taurocholic acid infusion (28 mumol/hr). A 1-hr control period was followed by intravenous cefoperazone infusion at either submaximal (20 mumol/hr), or supramaximal (60 mumol/hr) concentrations. At the cefoperazone infusion rate of 20 mumol/hr (biliary secretion of 7.1 +/- 1.6 mumol/hr) phospholipid secretion fell 19% and cholesterol secretion fell 31%; at a cefoperazone infusion rate of 60 mumol/hr (biliary secretion rate of 27.1 +/- 5.1 mumol/hr) phospholipid and cholesterol secretion were further reduced 40% and 56%, respectively, of controls. All changes were significant (P less than 0.01). Inhibition of both cholesterol and phospholipid secretion paralleled each other, was dose-dependent, and reversible. Cefoperazone's inhibitory action was abolished at a bile acid infusion rate of 108 mumol/hr. Cefoperazone was not found to be associated with bile acid micelles or mixed micelles as determined by ultracentrifugation and gel filtration. Thus, the effect of cefoperazone on biliary lipid secretion is not due to the impairment of mixed micelle formation in the canalicular lumen but rather its inhibitory effect appears to be due to a presecretory event.


Dynamic lipid turnover in photoreceptors and retinal pigment epithelium throughout life.
The retinal pigment epithelium-photoreceptor interphase is renewed each day in a stunning display of cellular interdependence. While photoreceptors use photosensitive pigments to convert light into electrical signals, the RPE supports photoreceptors in their function by phagocytizing shed photoreceptor tips, regulating the blood retina barrier, and modulating inflammatory responses, as well as regenerating the 11-cis-retinal chromophore via the classical visual cycle. These processes involve multiple protein complexes, tightly regulated ligand-receptors interactions, and a plethora of lipids and protein-lipids interactions. The role of lipids in maintaining a healthy interplay between the RPE and photoreceptors has not been fully delineated. In recent years, novel technologies have resulted in major advancements in understanding several facets of this interplay, including the involvement of lipids in phagocytosis and phagolysosome function, nutrient recycling, and the metabolic dependence between the two cell types. In this review, we aim to integrate the complex role of lipids in photoreceptor and RPE function, emphasizing the dynamic exchange between the cells as well as discuss how these processes are affected in aging and retinal diseases.


[Application of monoclonal antibodies to cancer therapy: idiotype mapping of monoclonal antibodies to tumor-associated antigens].
Polyclonal and monoclonal anti-idiotypic antibodies were prepared against several monoclonal antibodies which reacted with high molecular-weight melanoma-associated antigens. Idiotype mapping was proposed from the serological data obtained from these anti-idiotypic antibodies. This mapping will be of use for applying the anti-idiotypic monoclonal antibodies for cancer therapy.


[Laser-tyndallometry in eyes with acute retinal necrosis syndrome. Erlanger Laser-tyndallometry study group].
Acute retinal necrosis syndrome (ARN) is a rapidly progressive viral necrotic retinitis. We used noninvasive measurement of aqueous flare to quantify blood-ocular barrier breakdown in eyes with ARN und to follow the inflammatory activity and treatment effects. We report on seven patients (5 males und 2 females, age: 16 to 57 years) with ARN that were treated in our institution between 1991 to 1996. Aqueous flare was quantified regularly during treatment using the laser flare-cell meter (Kowa, FC-1000) following pupillary dilation. Aqueous flare was highly significantly increased in eyes with ARN (145.5 +/- 139.7, range 30 to 367 photon counts/ms). Contralateral, unaffected eyes showed normal flare values (3.6 +/- 0.8 photon counts/ms, p < 0.0001; normals: 4.1 +/- 1.1 photon counts/ms). Flare values correlated with inflammatory activity before and during antiviral treatment. In two patients with ARN caused by herpes simplex-virus aqueous flare values were extremely increased (367 and 316 photon counts/ms), and retinal necrosis was rapidly progressive despite antiviral therapy. One patient developed early ARN in his contralateral eye with flare values increasing from 3.5 to 22.0 photon counts/ms, which quickly normalized following antiviral treatment. Measurement with the laser flare-cell meter allows quantification of blood-ocular barrier breakdown in eyes with ARN und may be useful for monitoring inflammatory activity during treatment.


The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Nutrition.
Data show that starved head-injured patients lose sufficient nitrogen to reduce weight by 15% per week. Class II data show that 100-140% replacement of resting metabolism expenditure with 15-20% nitrogen calories reduces nitrogen loss. Data in non-head injured patients show that a 30% weight loss increased mortality rate. Class I data suggests that nonfeeding of head-injured patients by the first week increases mortality rate. The data strongly support feeding at least by the end of the first week. It has not been established that any method of feeding is better than another or that early feeding prior to 7 days improves outcome. Based on the level of nitrogen wasting documented in head-injured patients and the nitrogen sparing effect of feeding, it is a guideline that full nutritional replacement be instituted by day 7.


[Biometry 2000. Fetal growth charts by the French College of fetal ultrasonography and the Inserm U 155].
The aim of Biometry 2000 was to establish reliable sonographic fetal auxology reference charts for biparietal diameter, head circumference, abdominal diameter, abdominal circumference and femur length. A prospective multicentric longitudinal and transversal study was carried out. The data of this study were obtained from 35,456 scans recorded in 10,043 women for a period of one year. Sonographic measurements were performed using a single method for each parameter. Twins and unknown gestational ages were not included. No exclusions were made for small-for-age, congenital malformations or any event during pregnancy. Assuming measurements have a normal distribution, centiles were calculated after polynomial regression models from mean and standard deviation according to gestational age in exact weeks from last menstrual period. A total of 32,584 fetal biparietal diameters, 20,400 direct cephalic circumferences, 31,790 transverse abdominal diameters, 21,562 direct abdominal circumferences and 30,960 femur lengths were obtained. Fetal growth charts with means, standard deviations and centiles are presented. The multicentric study, Biometry 2000, has established sonographic fetal charts derived from a large sample of scans and unselected pregnant women assuming a normal distribution.


Flow Mediated Skin Fluorescence technique reveals remarkable effect of age on microcirculation and metabolic regulation in type 1 diabetes.
Flow Mediated Skin Fluorescence (FMSF) is a novel technique for non-invasive evaluation of the microcirculation and metabolic regulation. This study describes the diagnostic potential of FMSF for type 1 diabetes (DM1). All study participants, in both the control (n = 31) and DM1 (n = 40) groups, were between the ages of 30-49 y. The patients in the DM1 group had all been suffering from diabetes for at least 10 y. The parameters HRindex, HRmax and MR inversely correlate with age and BMI. An unidentified compensatory effect was observed among the younger members of the DM1 group. The majority of DM1 patients with HRindex < 8% showed signs of dysfunctional metabolic regulation. FMSF appears to be an extremely useful technique for monitoring diabetic patients over time, enabling early diagnosis of potentially dysfunctional microcirculation and metabolic regulation.


Selective inhibitors of monoamine oxidase type B and the "cheese effect".
Potentiation of the cardiovascular and other effects of dietary tyramine by monoamine oxidase (MAO) inhibitors (cheese effect) has been a major limitation to clinical use of these drugs. The discovery that MAO exists in two distinct isoforms, MAO-A and MAO-B, together with the development of selective inhibitors of each isoform, enabled the understanding that selective inhibition of MAO-A, or inhibition of both isoforms, will cause cheese effect, but selective inhibition of MAO-B can be elicited without dangerous pressor reaction. This development has permitted the introduction of selective MAO-B inhibitors to clinical medicine for treatment of Parkinson's disease. This review describes the basic mechanisms involved in cheese effect, as well as providing information on tyramine levels in a variety of foodstuff, and surveys clinical information from tyramine pressor testing with the selective MAO-B inhibitors, selegiline and rasagiline.


Alleviating neuropathic pain mechanical allodynia by increasing Cdh1 in the anterior cingulate cortex.
Plastic changes in the anterior cingulate cortex (ACC) are critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Cdh1, a co-activator subunit of anaphase-promoting complex/cyclosome (APC/C) regulates synaptic differentiation and transmission. Based on this, we hypothesised that the APC/C-Cdh1 played an important role in long-term plastic changes induced by neuropathic pain in ACC. We employed spared nerve injury (SNI) model in rat and found Cdh1 protein level in the ACC was down-regulated 3, 7 and 14 days after SNI surgery. We detected increase in c-Fos expression, numerical increase of organelles, swollen myelinated fibre and axon collapse of neuronal cells in the ACC of SNI rat. Additionally, AMPA receptor GluR1 subunit protein level was up-regulated on the membrane through a pathway that involves EphA4 mediated by APC/C-Cdh1, 3 and 7 days after SNI surgery. To confirm the effect of Cdh1 in neuropathic pain, Cdh1-expressing lentivirus was injected into the ACC of SNI rat. Intra-ACC treatment with Cdh1-expressing lentivirus vectors elevated Cdh1 levels, erased synaptic strengthening, as well as alleviating established mechanical allodynia in SNI rats. We also found Cdh1-expressing lentivirus normalised SNI-induced redistribution of AMPA receptor GluR1 subunit in ACC by regulating AMPA receptor trafficking. These results provide evidence that Cdh1 in ACC synapses may offer a novel therapeutic strategy for treating chronic neuropathic pain.


Interrelationship between ATP-binding cassette transporters and oxysterols.
ATP-binding cassette (ABC) transporters constitute a ubiquitous superfamily of membrane proteins responsible for the translocation of several substances across membranes using the chemical energy provided by ATP hydrolysis. ABC transporters participate in many physiological and pathophysiological processes, including cholesterol and lipid transportation and multidrug resistance. Oxysterols are the products of cholesterol oxidation, formed by both enzymatic and non-enzymatic mechanisms. The role of oxysterols in cholesterol metabolism and several diseases has been widely investigated, but many questions remain to be answered. Several lines of evidence link ABC transporter functions with cholesterol and oxysterol metabolism. This review discusses ABC transporters, oxysterols, and how they interact with each other.


Prospective study of post-traumatic stress disorder in children involved in road traffic accidents.
To determine the prevalence of severe psychological trauma --that is, post-traumatic stress disorder--in children involved in everyday road traffic accidents. 12 month prospective study. Accident and emergency department, Royal United Hospital, Bath. 119 children aged 5-18 years involved in road traffic accidents and 66 children who sustained sports injuries. Presence of appreciable psychological distress; fulfillment of diagnostic criteria for post-traumatic stress disorder. Post-traumatic stress disorder was found in 41 (34.5%) children involved in road traffic accidents but only two (3.0%) who sustained sports injuries. The presence of post-traumatic stress disorder was not related to the type of accident, age of the child, or the nature of injuries but was significantly associated with sex, previous experience of trauma, and subjective appraisal of threat to life. None of the children had received any psychological help at the time of assessment. One in three children involved in road traffic accidents was found to suffer from post-traumatic stress disorder when they were assessed 6 weeks after their accident. The psychological needs of such children after such accidents remain largely unrecognised.


Blast phase of chronic myeloid leukemia with concurrent BCR::ABL1 and SET::NUP214: A report of two cases.
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm defined by the presence of t(9;22)(q34;q11.2)/BCR::ABL1. Additional chromosomal abnormalities play an important role in the progression to CML. However, the additional fusion gene was rarely reported such as CBFB::MYH11. In this report, we described two cases of the co-occurrence of BCR::ABL1 and SET::NUP214 in CML-BP for the first time, which is associated with poor outcomes during tyrosine kinase inhibitor (TKI) treatment. Meanwhile, we retrospectively analyzed SET::NUP214 fusion transcript of the two cases at initial diagnosis of the CML chronic phase by quantitative RT-PCR, and detected at a ratio of 1.63% and 1.50%, respectively. SET::NUP214 may promote disease progression during the transformation of CML. This study highlights the importance of extended molecular testing at the initial diagnosis of CML-CP at TKI resistance and/or disease transformation.


Malnutrition according to the Global Leadership Initiative on Malnutrition criteria is associated with in-hospital mortality and prolonged length of stay in patients with cirrhosis.
Malnutrition is prevalent and negatively affects patients with cirrhosis, but a generally accepted consensus pertaining to its diagnosis is lacking. Recently, a framework called the Global Leadership Initiative on Malnutrition (GLIM) has been proposed to diagnose malnutrition, but there is scant evidence regarding its validity. We aimed to investigate associations of malnutrition according to the GLIM criteria, as well as its individual indicator with in-hospital adverse outcomes. This was a prospective, observational study of consecutively hospitalized patients with cirrhosis. The malnutrition diagnosis was built on a stepwise GLIM process with initial screening, followed by fulfillment of at least one phenotypic and one etiologic criterion. Patients were followed up for a combined endpoint of in-hospital mortality and prolonged length of stay (LOS). Covariates compromise malnutrition according to the GLIM criteria and its indicators in separation. Logistic regression analyses were implemented to determine predictive validity. A total of 387 cirrhotic patients were assessed. Malnutrition was diagnosed in 28.7% of patients according to the GLIM criteria, and increased the risk of in-hospital mortality and prolonged LOS by 2.166 and 1.767 times, respectively, adjusting for age, sex, biochemical parameters, and clinical scores of disease severity. When analyzing separate criteria, all constituents were independently associated with in-hospital adverse outcomes, adjusting for model for end-stage liver disease sodium score. Malnutrition according to the GLIM criteria was considerably prevalent among hospitalized patients with cirrhosis, and associated with approximately two times greater probability of in-hospital mortality and prolonged LOS. These diagnostic criteria may be implemented and disseminated during daily practice considering their predictive validity.


Open fractures of the lower limb in Nigeria.
During an 18-month period we studied prospectively 63 consecutive patients (42 males, 21 females) with an open fracture of the lower limb. Their mean age was 32 years (range: 4-78 years) and 58 patients with 59 fractures were available until the conclusion of the study. Forty-seven had tibial fractures, 12 had femoral fractures and the majority of the patients were either students or traders. According to Gustilo and Anderson's grading, 21 fractures were of type II and 16 of type IIIA. On arrival all the wounds were irrigated and debrided and the patients also received tetanus prophylaxis and intravenous antibiotics. Of the 47 tibial fractures 39 were managed with an above-knee plaster of Paris cast which was windowed so as to allow wound care. Of the 12 femoral fractures ten were treated with skeletal traction on a Bohler frame. The time taken for soft tissue healing was not significantly different between the tibial and femoral fractures. There were, however, significant differences with respect to (1) the time interval between injury and debridement, (2) the incidence of wound infection, (3) the occurrence of osteomyelitis, (4) fracture union time, and (5) time spent in hospital. The most common complications were wound infections (27 cases) and delayed union (26 cases). The time interval between injury and wound debridement was a major prognostic factor.


Bridging Anticoagulation with Mechanical Heart Valves: Current Guidelines and Clinical Decisions.
The management of patients with mechanical heart valves who require surgery or invasive procedures is a common clinical scenario in contemporary practice. The risk of thromboembolism versus the risk of bleeding is the foundation of optimal patient care. Randomized, controlled trials are not available; yet, there is a wealth of experience to guide best practice. Current guidelines represent a compilation of data from trials of atrial fibrillation and expert opinion. Results from the PERI-OP trial of patients with either a mechanical heart valve, atrial fibrillation, or atrial flutter requiring interruption of oral anticoagulant therapy for surgery will inform clinical practice. Patient-specific factors and valve-specific factors are paramount when deciding whether a period of anticoagulant therapy interruption is safe. Similarly, the safety and efficacy of bridging anticoagulant therapy and the optimal time after surgery for restarting oral anticoagulants is vital to optimal patient care.


Fecal blood loss during isoxicam and piroxicam administration for 28 days.
After an 11-day baseline period, groups of eight healthy men received isoxicam, 200 mg once a day, or piroxicam, 20 mg once a day, for 28 days. Fecal blood loss (FBL) was quantitated by the 51Cr-labeled erythrocyte method. FBLs for both isoxicam and piroxicam were only slightly higher than baseline for the first 3 drug dosing days, confirming the results of a previously published 4-day study of piroxicam, but FBL subsequently steadily increased, with maxima occurring for most subjects receiving isoxicam in 2 or 3 weeks and for most subjects receiving piroxicam in 3 or 4 weeks. This implies that dosing for 7 days or less, as is frequent in FBL studies of nonsteroidal anti-inflammatory drugs, may be insufficient to detect the peak drug-induced FBL. In week 4, FBL for both drugs was elevated approximately 0.6 ml/day over baseline. FBLs in week 4 were comparable to those reported for naproxen and less than those reported for indomethacin and acetylsalicylic acid. Statistical analyses of weekly plasma drug minimum concentrations suggest steady state was reached at week 2 for isoxicam and week 3 for piroxicam. There were large between-subject variations in steady-state plasma drug concentrations for both drugs. One subject in each drug group indulged in excessive alcohol consumption during the medication period, with a concomitant significant increase in FBL, which suggests exacerbation of the drug effect.


The EPAS1 gene influences the aerobic-anaerobic contribution in elite endurance athletes.
EPAS1 is a gene involved in complex oxygen sensing. It is expressed in microvascular endothelial cells, lung epithelial cells, cardiac myocytes and the brain. An association study was undertaken comparing elite endurance athletes classified into two groups according to a power-time model of performance intensity: power-time-maximum (PT-MAX; N=242, event duration 50 s to 10 min) and power-time-steady state (PT-SS; N=151, event duration ~2-10 h), with normal controls (N=444) using 12 SNPs across EPAS1. Ordinal regression analysis of allele frequencies revealed significant differences at SNPs 2 and 3 (P=0.01). Haplotype analysis revealed the presence of haplotypes involving SNPs 2-5 that significantly differentiated (P<0.05) the groups based on an ordinal ranking using the power-time classification. These same haplotypes differentiated the PT-MAX group in which a significant decrease in a haplotype (F: G-C-C-G; OR=0.57, P=0.02, 95% CI 0.36-0.92) and increase in a second haplotype (G: A-T-G-G; OR=1.75, P=0.03, 95% CI 1.05-2.91) was observed compared to controls. The PT-SS group was differentiated from the PT-MAX group by a third haplotype (H: A-T-G-A; OR=0.46, P=0.04, 95% CI 0.22-0.96). Since EPAS1 has a role as a sensor capable of integrating cardiovascular function, energetic demand, muscle activity and oxygen availability into physiological adaptation, we propose that DNA variants in EPAS1 influence the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration.


Skin sensitization to fragrance hydroperoxides: interplay between dendritic cells, keratinocytes and free radicals.
Skin sensitization to hydroperoxides (R-OOHs) of the commonly used fragrance terpenes limonene, linalool and citronellol is frequently reported. R-OOHs are believed to initiate the process leading to sensitization and allergic contact dermatitis through mechanisms involving radical intermediates. Thus, radical intermediates, keratinocytes and dendritic cells (DCs) may act in concert to initiate the process. To evaluate individual DC activation profiles by R-OOHs in the context of keratinocytes with regard to frequency, specificity and magnitude of upregulation. We used 2D and 3D cocultures with keratinocytes/reconstructed human epidermis (RHE) and DCs to evaluate cell surface levels of the costimulatory molecules CD86, CD80 and the adhesion molecule CD54 on cocultured DCs. Analysis of radical formation from limonene hydroperoxides in RHE was performed using electron paramagnetic resonance combined with the spin trapping technique. R-OOHs induce donor-dependent DC activation. Major differences were found between the limonene-OOHs. Limonene-1-OOH was stronger with respect to both frequency and magnitude of response. Using a 3D coculture model, no DC activation was detected after topical application of 0·2% limonene-OOHs (20 µg cm-2 ), while 1·2% limonene-1-OOH or 2% limonene-2-OOH induced DC activation. Furthermore, we demonstrated differences in the carbon and oxygen radicals formed from the limonene-OOHs using RHE, mimicking what may happen in vivo. We report clear individual differences in DC maturation induced by the most important hydroperoxides. Response rates and magnitude of response both indicate that very small structural alterations in the hydroperoxides are translated into specific DC responses. In addition, we provide more insight into the amounts of hydroperoxides that can activate DCs and induce sensitization.


Factors associated with chest wall toxicity after accelerated partial breast irradiation using high-dose-rate brachytherapy.
The purpose of this analysis was to evaluate dose-volume relationships associated with a higher probability for developing chest wall toxicity (pain) after accelerated partial breast irradiation (APBI) by using both single-lumen and multilumen brachytherapy. Rib dose data were available for 89 patients treated with APBI and were correlated with the development of chest wall/rib pain at any point after treatment. Ribs were contoured on computed tomography planning scans, and rib dose-volume histograms (DVH) along with histograms for other structures were constructed. Rib DVH data for all patients were sampled at all volumes ≥0.008 cubic centimeter (cc) (for maximum dose related to pain) and at volumes of 0.5, 1, 2, and 3 cc for analysis. Rib pain was evaluated at each follow-up visit. Patient responses were marked as yes or no. No attempt was made to grade responses. Eighty-nine responses were available for this analysis. Nineteen patients (21.3%) complained of transient chest wall/rib pain at any point in follow-up. Analysis showed a direct correlation between total dose received and volume of rib irradiated with the probability of developing rib/chest wall pain at any point after follow-up. The median maximum dose at volumes ≥0.008 cc of rib in patients who experienced chest wall pain was 132% of the prescribed dose versus 95% of the prescribed dose in those patients who did not experience pain (p = 0.0035). Although the incidence of chest wall/rib pain is quite low with APBI brachytherapy, attempts should be made to keep the volume of rib irradiated at a minimum and the maximum dose received by the chest wall as low as reasonably achievable.


Prevalence and associated factors of common mental disorders among residents of Illu Ababore zone, southwest Ethiopia: a cross-sectional study.
A common mental disorder is characterized by anxiety, depression, and unexplained somatic symptoms that usually encountered in community and primary care settings. Both short and long term bio psychosocial disabilities are inevitable if common mental disorder is not treated. Despite its impact, the prevalence of common mental disorder in the Illu Ababore zone is not well known. Therefore, this study aimed to assess the prevalence and associated factors of common mental disorder among Ilu Ababore zone residents, Southwest Ethiopia. A community based cross-sectional study was conducted from July 1 to August 30, 2018. A multi-stage sampling technique was applied to recruit participants. Self-Reporting Questionnaire (SRQ-20) was used to assess the presence of common mental disorder. The data were entered into Epidata version 3.1 and analyzed by using SPSS version 23 software. Bivariate and multivariate binary logistic regressions were computed to identify the associated factors. Statistical significance was considered at P value < 0.05. A total of 690 participants were enrolled in this study with a response rate of 91.39%. The prevalence of common mental disorder was 27.2% (95% CI, 23.9, 31.0%). Being female (AOR = 1.76, 95% CI = 1.15, 2.69), unable to read and write (AOR = 3.06, 95% CI = 1.37, 6.82), living in the rural area (AOR = 3.53, 95% CI = 2.01, 6.18), having a family member with mental illness (AOR = 2.68, 95% CI = 1.6, 4.5), having a chronic physical illness (AOR = 3.48, 95% CI = 2.26, 5.34) and lifetime alcohol use (AOR = 4.55, 95% CI = 2.93, 7.0) had a significant association with common mental disorder. The current study showed that the proportion of the common mental disorder was high. Females showed a higher prevalence of the common mental disorder. Having a chronic physical illness, resides in the rural areas and history of lifetime alcohol use were also significantly associated with CMD. Psychological and social interventions with greater emphasis on females who have low educational status and residing in the rural area are recommended. Strategies that focus on the proper treatment of chronic physical illness can be also helpful to minimize the occurrence of common mental disorder.


Mulberry leaf polysaccharides ameliorate obesity through activation of brown adipose tissue and modulation of the gut microbiota in high-fat diet fed mice.
Improving energy homeostasis and the gut microbiota is a promising strategy to improve obesity and related metabolic disorders. Mulberry leaf is one of the traditional Chinese medicines and functional diets. In this work, a mouse model induced by high-fat diet (HFD) was used to reveal the role of mulberry leaf polysaccharides (MLP). It was found that MLP had a significant effect in limiting body weight gain (reduced by 19.95%, 35.47% and 52.46%, respectively), ameliorating hepatic steatosis and regulating lipid metabolism in HFD induced obese mice (P < 0.05). RT-PCR and western blot analysis suggested that these metabolic improvements were mediated by inducing the development of brown-like adipocytes in inguinal white adipose tissue and enhancing brown adipose tissue activity. Besides, 16S rRNA sequencing results led to the inference that MLP could mitigate the composition and function of the gut microbiota. Together, these findings indicated that MLP possess great potential as a diet supplement or medication for obesity.


Feasibility of laparoscopy and factors associated with conversion to open in minimally invasive emergency major abdominal surgery: population database analysis.
There is limited evidence regarding the overall feasibility and success rates of the laparoscopic approach in major emergency surgery, despite its potential to improve outcomes. This study aims to investigate the association between patient, procedural, and surgical factors and likelihood of successful laparoscopic completion in emergency major surgery and derive a predictive model to aid clinical decision-making. All patients recorded in the NELA emergency laparotomy database 1 December 2013-31 November 2018 who underwent laparoscopically attempted surgery were included. A retrospective cohort multivariable regression analysis was conducted for the outcome of conversion to open surgery. A predictive model was developed and internally validated. Of 118,355 patients, 17,040 (7.7%) underwent attempted laparoscopic surgery, of which 7.915 (46.4%) were converted to open surgery. Procedure type was the strongest predictor of conversion (compared to washout as reference, small bowel resection OR 25.93 (95% CI 20.42-32.94), right colectomy OR 6.92 (5.5-8.71)). Diagnostic [free pus, blood, or blood OR 3.67 (3.29-4.1)] and surgeon [subspecialist surgeon OR 0.56 (0.52-0.61)] factors were also significant, whereas age, gender, and pre-operative mortality risk were not. A derived predictive model had high internal validity, C-index 0.758 (95% CI 0.748-0.768), and is available for free-use online. Surgical, patient, and diagnostic variables can be used to predict likelihood of laparoscopic success with a high degree of accuracy. This information can be used to inform peri-operative decision-making and patient selection.


The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial.
To assess the impact of luteal phase support on the expression of estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH). A prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B. One-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value. The administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR.


Interface cisplatin-crosslinked doxorubicin-loaded triblock copolymer micelles for synergistic cancer therapy.
Combination chemotherapy is an effective way to improve the therapeutic efficiency in anticancer treatment. Herein, we synthesized a novel amphiphilic triblock copolymer via a two-step ring-opening polymerization (ROP) followed by post-modification. Doxorubicin (DOX) was encapsulated into the copolymeric micelles through hydrophobic interactions, cisplatin (CDDP) was employed to in situ crosslink the interface of DOX-loaded micelles through Pt-carboxyl coordination interaction. The CDDP-mediated crosslinking improved the stability of the micelles and also reduced the release of DOX at physiological pH. After being taken up into the endosome/lysosome, the low environmental pH weakened the Pt-carboxyl coordination interactions, resulting in the destruction of the micelles and the release of CDDP and DOX. Moreover, these micelles loaded with dual drugs enabled a synergistic anticancer effect, showing promise as a potential drug delivery platform for cancer therapy.


The outcomes of midline versus medio-lateral episiotomy.
Episiotomy is the surgical enlargement of the vaginal orifice by an incision of the perineum during the second stage of labor or just before delivery of the baby. During the 1970s, it was common to perform an episiotomy for almost all women having their first delivery, ostensibly for prevention of severe perineum tears and easier subsequent repair. However, there are no data available to indicate if an episiotomy should be midline or medio-lateral. We compared midline versus medio-lateral episiotomy for complication such as extended perineal tears, pain scores, wound infection rates and other complications. We conducted a prospective cohort including 1,302 women, who gave birth vaginally between April 2005 and February 2006 at Srinagarind Hospital - a tertiary care center in Northeast Thailand. All women included had low risk pregnancies and delivered at term. The outcome measures included deep perineal tears (including perineal tears with anal sphincter and/or rectum tears), other complications, and women's satisfaction at 48 hours and 6-weeks postpartum. In women with midline episiotomy, deep perineal tears occurred in 14.8%, which is statistically significantly higher compared to 7% in women who underwent a medio-lateral episiotomy (p-value < 0.05). There was no difference between the groups for other outcomes (such as blood loss, vaginal hematoma, infection, pain, dyspareunia, and women's satisfaction with the method). The risk factors for deep perineal tears were: midline episiotomy, primiparity, maternal height < 145 cm, fetal birth weight > 3,500 g and forceps extraction. Midline compared to medio-lateral episiotomy resulted in more deep perineal tears. It is more likely deep perineal tears would occur in cases with additional risk factors.


Association of Proton Pump Inhibitors Usage with Risk of Pneumonia in Dementia Patients.
To determine the association between usages of proton pump inhibitors (PPIs) and subsequent risk of pneumonia in dementia patients. Retrospective cohort study. Taiwanese National Health Insurance Research Database. The study cohort consisted of 786 dementia patients with new PPI usage and 786 matched dementia patients without PPI usage. The study endpoint was defined as the occurrence of pneumonia. The Cox proportional hazard model was used to estimate the pneumonia risk. Defined daily dose methodology was applied to evaluate the cumulative and dose-response relationships of PPI. Incidence of pneumonia was higher among patients with PPI usage (adjusted hazard ratio (HR) = 1.89; 95% CI = 1.51-2.37). Cox model analysis also demonstrated that age (adjusted HR = 1.05; 95% CI = 1.03-1.06), male gender (adjusted HR = 1.57; 95% CI = 1.25-1.98), underlying cerebrovascular disease (adjusted HR = 1.30; 95% CI = 1.04-1.62), chronic pulmonary disease (adjusted HR = 1.39; 95% CI = 1.09-1.76), congestive heart failure (adjusted HR = 1.54; 95% CI = 1.11-2.13), diabetes mellitus (adjusted HR = 1.54; 95% CI = 1.22-1.95), and usage of antipsychotics (adjusted HR = 1.29; 95% CI = 1.03-1.61) were independent risk factors for pneumonia. However, usage of cholinesterase inhibitors and histamine receptor-2 antagonists were shown to decrease pneumonia risk. PPI usage in dementia patients is associated with an 89% increased risk of pneumonia.


[Significance of glomerular filtration rate in evaluating renal function of comparative study of methods thereof].
To evaluate the applicability of the Cockcroft-Gault equation and the abbreviated Modification of diet in Renal Disease (MDRD) study equation to estimate the renal function of diabetic patients. Glomerular filtration rates measured by these two equations were compared with the value of GFR measured by 99Tc(m)-DTPA dynamic renal Imaging (considered as gold standard), to determine which equation is more appropriate in the subjects with diabetes. Both of the results of the two equations deviated from the GFR measured by 99Tc(m)-DTPA dynamic renal Imaging: the GFRCG result was lower and the GFR(MDRD) result was higher than the real GFR value. However, the correlation analysis, coherence testing, and accuracy by receiver operating characteristic curve analysis showed that the coefficient of correlation, coherence rate, and accuracy of the GFR(MDRD) formula with the gold standard were all higher than those of the GFR(CG) formula. The abbreviated style of MDRD equation is more appropriate than Cockcroft-Gault equation for the estimating of renal function in diabetic patients.


Absence of VIII AHF response to adrenalin in hemophilia A.
Proportionate twofold or greater increases in both Factor VIII procoagulant activity (VIII AHF) and Factor VIII-like antigen (VIII AGN) have been observed to follow the administration of adrenalin in normal individuals. Levels of factor VIII procoagulant or clot-promoting activity (VIII AHF) and VIII AGN were measured immediately before and one hour after the subcutaneous injection of adrenalin (0.35 ml) in ten adults with hemophilia A documented by low VIII AHF levels (ranging from 0.01-0.25 units/ml, normal VIII AGN levels, and normal VIII VWF levels as measured by the washed-platelet ristocetin assay). Eighteen normal adults served as controls. Results were analyzed by the paired test. It was shown that VIII AGN increased significantly, while VIII AHF did not change, in hemophiliacs after adrenalin stimulation, regardless of the base line level. This fixed rate of VII AHF production, release, or activation may help to explain the constancy of VII AHF levels in individual hemophiliacs and their affected family members.


An ATP-binding cassette transporter G2 (CgABCG2) regulates the haemocyte proliferation by modulating the G1/S phase transition of cell cycle in oyster Crassostrea gigas.
ATP-binding cassette transporter G2 (ABCG2) is a half-transporter of the G subfamily in ATP-binding cassette transporters (ABC transporter), which is involved in the regulation of multidrug-resistant, cell cycle, and cell proliferation. In the present study, a homologue of ABCG2 (named as CgABCG2) with the conserved AAA domain and ABC2 membrane domain was identified from the Pacific oyster Crassostrea gigas. The open reading frame (ORF) of CgABCG2 was of 1956 bp encoding a predicted polypeptide of 652 amino acids, which shared 56.7%-65.7% sequence similarities with previously identified ABCG2s from other animals. The mRNA transcripts of CgABCG2 were detected in all the tested tissues with higher expression levels in gonad and haemocytes (19.31-fold and 11.23-fold of that in adductor muscle respectively, p < 0.05). CgABCG2 was mainly distributed on the cell membrane of the haemocytes with a partial distribution in the cytoplasm and nucleus. After Vibrio splendidus stimulation, the mRNA expression level of CgABCG2 in haemocytes was significantly up-regulated at 3 h and 6 h, which was 5.22-fold and 8.60-fold (p < 0.05) of that in control, respectively. After the expression of CgABCG2 was interfered by RNAi, the number of cells with EdU positive signals was reduced in both haemocytes and the potential hematopoietic sites. And the mRNA expression level of CgPCNA, CgGATA3, CgRunx, CgSCL and CgC-kit decreased significantly (p < 0.05), which were about 0.66-, 0.37-, 0.32-, 0.50-, and 0.50-fold of that in the negative control group, respectively. While the mRNA expression level of CgCDK2 increased significantly (1.84-fold to that in control, p < 0.05) and that of stem cell-related factor CgSOX2 did not change significantly in the si-CgABCG2 oysters. Moreover, the cell cycle of haemocytes was detected by flow cytometry, which was arrested at G0/G1 phase in the si-CgABCG2 oysters. All the results collectively suggested that CgABCG2 might involve the proliferation of haemocytes by regulating the expression of haematopoiesis related transcription factors and the G1/S phase transition of the cell cycle in oyster C. gigas.


High performance recycled CFRP composites based on reused carbon fabrics through sustainable mild solvolysis route.
A novel environmentally friendly recycling method is developed for large carbon-fibers reinforced-polymers composite panels whose efficiency is demonstrated through a proof-of-concept fabrication of a new composite part based on recycled fibers. The recycling process relies on formic acid as separation reagent at room temperature and atmospheric pressure with efficient recycling potential of the separating agent. Electron microscopy and thermal analysis indicate that the recycled fibers are covered by a thin layer of about 10wt.% of residual resin, alternating with few small particles, as compared to the smooth virgin fibers. The recycled composites show promising shear strength and compression after impact strength, with up to 93% retention of performance depending on the property as compared to the reference. The recycled carbon fibers can thus be reused for structural applications requiring moderate to high performances. The loss of properties is attributed to a lower adhesion between fresh epoxy resin and recycled carbon fibers due to the absence of sizing, partly compensated by a good interface between fresh and residual cured epoxy thanks to mechanical anchoring as well as chemical reactions. The room temperature and atmospheric pressure operating conditions combined to the recyclability of the forming acid contribute to the sustainability of the entire approach.


Total Wrist Arthroplasty: A Single-Center Study of 219 Cases With 5-Year Follow-up.
To assess implant survival and radiographic loosening after total wrist arthroplasty (TWA) operated at a single tertiary referral center in Sweden. In a prospective cohort study, we evaluated 189 consecutive patients with a TWA (219 wrists). The wrists were implanted between 2002 and 2013. The primary end point was revision for any reason. The mean follow-up period was 7 years (range, 2-13 years). In addition, radiological examination was done for evidence of prosthetic loosening 5 years postoperatively. Implant survival was estimated using the Kaplan-Meier method. Secondary outcome measures included range of motion, visual analog scale pain scores, hand grip strength, and patient-related outcome measures. Cumulative implant survival after 8 years was 81% for Biax, 94% for Remotion, and 95% for Maestro implants. Radiographic loosening was present in 26% of wrists with the Biax design, 18% of those with Remotion, and 2% of those with Maestro. Visual analog scale pain scores and patient-related outcome scores improved significantly for all TWAs. Improved hand grip strength was noted for all TWAs except for the Universal 2. Range of motion improved somewhat, especially for the Biax and Maestro TWAs. Good midterm to long-term results were achieved in patients undergoing TWA. Radiographic loosening did not necessarily correlate with implant survival rates, but rather to severe arthritic destruction of the wrist preoperatively. All TWA implants studied offered a high level of patient satisfaction. Therapeutic III.


1,4-benzoquinone-induced STAT-3 hypomethylation in AHH-1 cells: Role of oxidative stress.
Benzene, a known occupational and environmental contaminant, is associated with increased risk of leukemia. The objectives of this study were to elucidate the regulatory mechanism of the hypomethylated STAT3 involved in benzene toxicity in vitro. As 1,4-benzoquinone (1,4-BQ) is one of benzene's major toxic metabolites, AHH-1 cells were treated by 1,4-BQ for 24 h with or without pretreatment of the antioxidant a-LA or the methyltransferase inhibitor, 5-aza-2' deoxycytidine (5-aza). The cell viability was investigated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ROS was determined via 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) flow cytometric assays. The level of oxidative stress marker 8-OHdG was measured by enzyme-linked immunosorbent assay. Methylation-specific PCR was used to detect the methylation status of STAT3. Results indicated the significantly increasing expression of ROS and 8-OHdG which accompanied with STAT3 hypomethylation in 1,4-BQ-treated AHH-1 cells. α-LA suppressed the expression of both ROS and 8-OHdG, simultaneously reversed 1,4-BQ-induced STAT3 hypomethylation. However, although the methylation inhibitor, 5-aza reduced the expression level of ROS and 8-OHdG, but had no obvious inhibiting effect on STAT3 methylation level. Taken together, oxidative stress are involved 1,4-BQ-induced STAT3 methylation expression.


Anaesthetic choice in the colposcopy clinic: a retrospective analysis of routinely collected data.
Current guidelines recommend that less than 20% of treatments in colposcopy clinics should be under general anaesthetic. The objective of this study was to increase the evidence base for guidelines by establishing the proportion of women receiving general anaesthesia for treatment, determining the predictors of and reasons recorded for general anaesthetic use. Retrospective analysis of routinely collected data. NHS Trust in the West Midlands. Colposcopy patients; January 2003 to March 2005. Logistic regression of factors associated with general anaesthetic choice. Proportion of women treated under general anaesthesia, factors associated with anaesthetic choice and reasons recorded for general anaesthetic use. About 5.4% (204/3777) of new appointments for colposcopy received treatment under general anaesthetic. Of women requiring treatment, 20% (204/1003) received general anaesthetic. General anaesthetic was more likely to be used when the woman required loop excision (OR = 3.63, 95% CI 2.11-6.24) and less likely when directed biopsy was performed (OR = 0.11, 95% CI 0.01-0.80), when the patient appointment date was after introduction of new guidelines (OR = 0.37, 95% CI 0.24-0.56) or when the assessment visit was with a nonconsultant status doctor rather than nurse or consultant (OR = 0.70, 95% CI 0.50-0.97). General anaesthetic use varied between colposcopists ranging from 0 to 16.5% of new patients seen. Woman's choice was the most commonly specified reason for the use of general anaesthetic. The proportion of colposcopy patients treated under general anaesthetic is 20%, within guideline limits. Substantial variation in general anaesthetic rates between colposcopists was observed, and further investigation is required to discover the reason for this.


Effects of physical, chemical, and biological ageing on the mineralization of pine wood biochar by a Streptomyces isolate.
If biochar is to be used for carbon (C) management, we must understand how weathering or ageing affects biochar C mineralization. Here, we incubated aged and unaged eastern white pine wood biochar produced at 350 and 550°C with a Streptomyces isolate, a putative biochar-decomposing microbe. Ageing was accelerated via three different processes, namely, (a) physical ageing-subjecting biochar to alternating freeze-thaw and wet-dry cycles, (b) chemical ageing-treating biochar with concentrated hydrogen peroxide and (c) biological ageing-incubating biochar in the presence of nutrients and microorganisms. Elemental composition and surface chemistry (Fourier Transform Infrared spectroscopy) of biochar samples were compared before and after ageing. Biochar C mineralization between ageing treatments was significantly different in the case of 350°C biochar (p value = 0.03). Among the 350°C biochars, physical ageing resulted in the greatest increase (by 103%) in biochar C mineralization (p value = 0.05). However, in the case of 550°C biochar, ageing did not result in a significant change in biochar C mineralization (p value = 0.40). Biochar C mineralization was positively correlated with an increase in O/C ratio post-ageing (rs = 0.86, p value = 0.01). In the case of 350°C biochar, surface oxidation during ageing enhanced biochar degradation by the isolate. For 550°C biochar, however, ageing did not significantly increase biochar C mineralization, likely due to high condensed aromatic C content and lower surface oxidation during ageing. The results from our study suggest that low temperature aged biochar is more susceptible to biological degradation by soil microbes. These findings have implications for the use of biochar for long term C storage in soils.


Visceral pentastomiasis caused by Armillifer armillatus in a captive striped hyena (Hyaena hyaena) in Chiang Mai Night Safari, Thailand.
Visceral pentastomiasis (porocephalosis) caused by Armillifer armillatus larvae was incidentally diagnosed in a female striped hyena (Hyaena hyaena) of unknown age which died unexpectedly in 2013. The hyena had been imported from Tanzania 8years earlier and have been since then in a zoo in Chiang Mai, northern Thailand. Pathological examination revealed visceral nymph migrans of pentastomes throughout the intestine, liver, diaphragm, omentum and mesentery, spleen, kidneys, and urinary bladder. Polymerase chain reaction and sequencing that targeted the pentastomid-specific 18S rRNA gene determined 100% identity with reference sequence for A. armillatus, suggesting that its ova can infect the hyena to serve as an intermediate host for the parasite. Further studies to identify the source of infection, its risk factors, and host range for A. armillatus are important to determine its zoonotic potential and to better prevent and manage the disease to protect animal and human health.


Effects of amrinone in an experimental model of hepatic ischemia-reperfusion injury.
During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischemia-reperfusion (IR) injury. Recent studies suggest that type 3 phosphodiesterase inhibitors may have a beneficial effect on liver IR injury. The aim of this study was to investigate whether amrinone, a type 3 phosphodiesterase inhibitor, could have a protective effect on liver having experimental liver IR injury. Sixty Wistar albino rats were randomly divided into three groups. The IR and amrinone groups were subjected to 1 h total hepatic ischemia, followed by 2 h of reperfusion. The sham group underwent midline laparotomy only. Amrinone 10 microg/kg/min was infused to the amrinone group during the 3 h of the IR period. Histopathological examination, biochemical liver function, and liver adenosine triphosphate concentration after reperfusion and survival rate on the seventh day after the IR insult were recorded. Serum aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase levels, and histological damage scores in the amrinone and IR groups were significantly higher compared with the sham group (P < 0.01). However, all of these values were significantly lower in the amrinone group than in the IR group (P < 0.05). Liver adenosine triphosphate levels and the rat survival rate in the amrinone and IR groups were significantly lower than those in the sham group (P < 0.01). However, these values were significantly higher in the amrinone group compared to those in the IR group (P < 0.01). These results suggest that amrinone plays a significant role in the protection of liver against IR injury and that this treatment may be a novel pharmacological agent for safe and efficient liver surgery.


Novel microbial epoxide hydrolases for biohydrolysis of glycidyl derivatives.
Microbial isolates from biofilters and petroleum-polluted bioremediation sites were screened for the presence of enantioselective epoxide hydrolases active towards tert-butyl glycidyl ether, benzyl glycidyl ether, and allyl glycidyl ether. Out of 270 isolated strains, which comprised bacteria, yeasts, and filamentous fungi, four were selected based on the enantioselectivities of their epoxide hydrolases determined in biotransformation reactions. The enzyme of Aspergillus niger M200 preferentially hydrolyses (S)-tert-butyl glycidyl ether to (S)-3-tert-butoxy-1,2-propanediol with a relatively high enantioselectivity (the enantiomeric ratio E is about 30 at a reaction temperature of 28 degrees C). Epoxide hydrolases of Rhodotorula mucilaginosa M002 and Rhodococcus fascians M022 hydrolyse benzyl glycidyl ether with relatively low enantioselectivities, the former reacting predominantly with the (S)-enantiomer, the latter preferring the (R)-enantiomer. Enzymatic hydrolysis of allyl glycidyl ether by Cryptococcus laurentii M001 proceeds with low enantioselectivity (E=3). (R)-tert-Butyl glycidyl ether with an enantiomeric excess (ee) of over 99%, and (S)-3-tert-butoxy-1,2-propanediol with an ee-value of 86% have been prepared on a gram-scale using whole cells of A. niger M200. An enantiomeric ratio of approximately 100 has been determined under optimised biotransformation conditions with the partially purified epoxide hydrolase from A. niger M200. The regioselectivity of this enzyme was determined to be total for both (S)-tert-butyl glycidyl ether and (R)-tert-butyl glycidyl ether.


Can temperature rise change the impacts induced by e-waste on adults and sperm of Mytilus galloprovincialis?
Nowadays, it is of utmost importance to consider climate change factors, such as ocean warming, since the risk of negative impacts derived from increased surface water temperature is predicted to be high to the biodiversity. The need for renewable energy technologies, to reduce greenhouse gas emissions, has led to the increasing use of rare earth elements (REEs). Dysprosium (Dy) is widely used in magnets, motors, electrical vehicles, and nuclear reactors, being considered a critical REE to technology due to its economic importance and high supply risk. However, the increasing use of this element contributes to the enrichment of anthropogenic REEs in aquatic systems. Nevertheless, the information on the potential toxicity of Dy is limited. Moreover, the effects of pollutants can be amplified when combined with climate change factors. Thus, this study aimed to assess the effects of Dy (10 μg/L) in the species Mytilus galloprovincialis under actual (17 °C) and predicted warming conditions (21 °C). The Dy concentration in contaminated mussels was similar between temperatures, probably due to the detoxification capacity in individuals under these treatments. The combined stressors affected the redox balance, but higher impacts were caused by Dy and warming acting alone. In terms of cellular damage, although Dy acting alone was prejudicial to mussels, warming and both stressors acting together induced higher levels of LPO and PC. The histopathological effects of Dy in the digestive tubules were independent of the temperature tested. Regarding effects on sperm, only warming induced cellular damage, while both stressors, alone and together, impaired sperm movement. Overall, this study highlights that warming might influence the effects induced by Dy, but greater impacts were caused by the element. Eventually, the tested stressors may have consequences on mussels' reproduction capacity as well as their growth, abundance, and survival.


Evidence for basolateral but not apical membrane localization of outwardly rectifying depolarization-induced Cl(-) channel in airway epithelia.
The rat primary cultured-airway monolayer had been an excellent model for deciphering the ion channel after nystatin permeabilization of its basolateral or apical membrane (Hwang et al., 1996). After apical membrane permeabilization of rat primary cultured-airway monolayer, 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS)-sensitive outwardly rectifying depolarization-induced Cl(-) (BORDIC) currents were observed across the basolateral membrane in symmetrical NMG-Cl solution in this study. No significant Cl(-) current induced by the application of voltage clamping was observed across the apical membrane in symmetrical NMG-Cl solution after basolateral membrane permeabilization. The halide permeability sequence for BORDIC current was Br(-) = I(-) > Cl(-). BORDIC current was not affected by basolaterally applied bumetanide (0.5 mm). Basolateral DIDS (0.2 mm) but not apical DIDS inhibited CFTR mediated short-circuit current (I(sc)) in an intact monolayer of rat airway epithelia, a T84 human colonal epithelial cell line, and a Calu-3 human airway epithelial cell line. This is the first report showing that depolarization induced Cl(-) current is present on the basolateral membrane of airway epithelia.


Associations of leisure time physical activity, self-rated physical fitness, and estimated aerobic fitness with serum C-reactive protein among 3,803 adults.
Serum C-reactive protein (CRP), a marker of systemic inflammation, is a risk factor for cardiovascular disease. Obesity and physical activity are associated with CRP, though population studies are sparse. We assessed the cross-sectional relationship of physical activity, self-rated fitness and estimated aerobic fitness with serum CRP among a population-based random sample of 3,803 Finnish adults aged 25-74 years. Conditioning, commuting and non-conditioning physical activity was measured by a recall and self-rated physical fitness by a questionnaire. A non-exercise test was used to estimate aerobic fitness. The combined association of aerobic fitness and waist-to-hip ratio (WHR) on CRP was also assessed. Self-rated fitness and aerobic fitness had inverse associations with CRP (adjusted for age, WHR, smoking, anti-hypertensive drugs, aspirin, diabetes, hypercholesterolemia, hormone replacement therapy and menopausal status) in both sexes (p < 0.001). An inverse age-adjusted association of conditioning and non-conditioning physical activity with CRP was found in both sexes. After further adjustments, associations remained significant in women for conditioning and non-conditioning activity (p < 0.001 and p = 0.010, respectively) and borderline significant in men (p = 0.074 and p = 0.070, respectively). Commuting physical activity was inversely associated with CRP among women only (p = 0.012). Physical activity and fitness may have an anti-inflammatory effect, which is independent of obesity.


Assessing the combined effect of household cooking fuel and urbanicity on acute respiratory symptoms among under-five years in sub-Saharan Africa.
This study sought to investigate the association between urbanicity (rural-urban residency), the use of solid biomass cooking fuels and the risk of Acute Respiratory Infections (ARIs) among children under the age of 5 in sub-Saharan Africa (SSA). Cross-sectional data from the most recent surveys of the Demographic and Health Survey Program conducted in 31 sub-Saharan African countries were pooled for the analysis. The outcome variables, cough and rapid short breath were derived from questions that asked mothers if their children under the age of 5 suffered from cough and short rapid breath in the past two weeks preceding the survey. To examine the associations, multivariable negative log-log regression models were fitted for each outcome variable. Higher odds ratios of cough occurred among children in urban households that use unclean cooking fuel (aOR = 1.05 95% CI = 1.01, 1.08). However, lower odds ratios were observed for rural children in homes that use clean cooking fuel (aOR = 0.93 95% CI = 0.87, 0.99) relative to children in urban homes using clean cooking fuel. We also found higher odds ratios of short rapid breaths among children in rural households that use unclean cooking fuel compared with urban residents using clean cooking fuel (aOR = 1.12 95% CI = 1.08, 1.17). Urbanicity and the use of solid biomass fuel for cooking were associated with an increased risk of symptoms of ARIs among children under five years in SSA. Thus, policymakers and stakeholders need to design and implement strategies that minimize children's exposure to pollutants from solid biomass cooking fuel. Such interventions could reduce the burden of respiratory illnesses in SSA and contribute to the realization of Sustainable Development Goal 3.9, which aims at reducing the number of diseases and deaths attributable to hazardous chemicals and pollution of air, water and soil.