Tricuspid regurgitation in patients with acquired, chronic, pure mitral regurgitation. I. Prevalence, diagnosis, and comparison of preoperative clinical and hemodynamic features in patients with and without tricuspid regurgitation.
Most reports of clinical experiences with palliation of acquired tricuspid regurgitation have failed to address the issue of coexisting disease of the mitral or aortic valve, or both. To accurately determine the natural history and the effect of operative interventions, we studied patients with chronic, pure mitral regurgitation who had surgical treatment at the National Heart, Lung, and Blood Institute from 1968 to 1984. Forty-seven patients fulfilled the criteria of a documented history of mitral regurgitation for more than 1.5 years, minimal mitral diastolic gradient, severe mitral regurgitation by angiography, and no prior mitral or tricuspid operative procedure. Twenty-five of the 47 patients (53%) had evidence of tricuspid regurgitation. No statistical differences in age, sex, mean duration of symptoms of congestive heart failure, or functional class were found between those patients with and those without tricuspid regurgitation. However, patients with symptoms of congestive heart failure for more than 6 years were more likely to have tricuspid regurgitation. This increased prevalence also correlated with higher elevations of left ventricular end-diastolic, systolic pulmonary artery, and mean right atrial pressures. The severity of tricuspid regurgitation estimated preoperatively did not correlate statistically with that determined by digital palpation, although the presence of tricuspid regurgitation was reliably confirmed. These data demonstrate that tricuspid regurgitation is frequently present in patients with chronic, pure mitral regurgitation and is associated with prolonged symptoms of congestive heart failure and significant alterations in right heart dynamics.


Hippocampal-amygdalo-ventricular atrophy score: Alzheimer disease detection using normative and pathological lifespan models.
In this article, we present an innovative MRI-based method for Alzheimer disease (AD) detection and mild cognitive impairment (MCI) prognostic, using lifespan trajectories of brain structures. After a full screening of the most discriminant structures between AD and normal aging based on MRI volumetric analysis of 3,032 subjects, we propose a novel Hippocampal-Amygdalo-Ventricular Atrophy score (HAVAs) based on normative lifespan models and AD lifespan models. During a validation on three external datasets on 1,039 subjects, our approach showed very accurate detection (AUC ≥ 94%) of patients with AD compared to control subjects and accurate discrimination (AUC = 78%) between progressive MCI and stable MCI (during a 3-year follow-up). Compared to normative modeling, classical machine learning methods and recent state-of-the-art deep learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.


Adaptation of Plasmodium falciparum to glucose 6-phosphate dehydrogenase-deficient host red cells by production of parasite-encoded enzyme.
There is impressive evidence from geographical data, studies in the field and in vitro culture work that genetically determined deficiency of glucose 6-phosphate dehydrogenase (G6PD) confers relative protection against the human malaria parasite, Plasmodium falciparum. G6PD is encoded by an X-chromosome-linked gene, and protection phenomenon is manifested in heterozygous females who are genetic mosaics but, surprisingly, not in hemizygous males with complete deficiency. We have shown previously that the parasite, when passaged serially through G6PD-deficient red cells, undergoes adaptive changes that gradually improve its ability to multiply in these deficient cells. To explain the above paradox, we now show that this adaptive process is associated with, and may consist in, the induction of synthesis of a novel G6PD coded by Plasmodium falciparum.


Learning curve for endoscopic submucosal dissection of early gastric cancer based on trainee experience.
There have been few previous reports on endoscopic submucosal dissection (ESD) learning curve for early gastric cancer (EGC) so we retrospectively assessed this subject based on experience of our trainees. Trainees in our center start performing ESDs for lesions in lower third of stomach with hands-on support by experts during first 10 cases and then perform ESDs by themselves primarily with verbal guidance from experts. They are gradually assigned to perform ESDs in middle and upper thirds of stomach. From January 1999 to December 2008, 464 EGC patients, who underwent ESD performed by 13 trainees, were assessed by dividing ESD cases into five training periods (A, 1-10; B, 11-20; C, 21-30; D, 31-40; and E, 41-50). We compared data from B to C, D and E. Lesions in lower third were A/59%, B/57%, C/55%, D/36% and E/40% with B significantly higher than D (p<0.01) and E (p<0.05). Mean tumor sizes were A/13.9 ± 7.5mm, B/18.3 ± 11.4mm, C/19.0 ± 12.5mm, D/19.3 ± 11.7 mm and E/16.8 ± 10.3mm. En-bloc resection rate was 100% in every period. Delayed bleeding / perforation rates were A/0%/1.8%, B/2.8%/1.9%, C/1.9%/2.9%, D/1.1%/0% and E/2.1%/2.1%, respectively. Lower third procedure times were A/76 ± 39, B/90 ± 61, C/70 ± 48, D/60 ± 50 and E/55 ± 26 minutes with B significantly longer than D and E (p<0.05). Middle and upper third procedure times were A/104 ± 80, B/115 ± 68, C/106 ± 67, D/134 ± 86 and E/96 ± 55 minutes. Step-by-step training was highly effective with 100% en-bloc resection rate and few complications. Learning curve point for our trainees to acquire performing ESD in lower third of stomach was 30 cases.


Anterior stromal puncture for the treatment of Brown-McLean syndrome.
The Brown-McLean syndrome is defined by peripheral corneal edema sparing the central cornea. We report a patient with bullous annular keratopathy following phacoemulsification and implantation of posterior chamber intraocular lens. The uncorrected and best corrected visual acuity was 20/30. The patient required the use of a bandage contact lens for almost 5 years to relieve the ocular discomfort. Anterior stromal puncture was performed using a cystotome. Two weeks after the procedure the ocular discomfort disappeared and the use of bandage contact lens was no longer required. Anterior stromal puncture is a simple procedure that is performed under the slit lamp, and can alleviate the symptoms in patients with Brown-McLean syndrome.


Aseptic meningitis and hydrocephalus after posterior fossa surgery.
In an attempt to define the tissue of origin of substances causing aseptic meningitis and secondary hydrocephalus after posterior fossa surgery, analysis of several marker substances from blood, brain, tumour and muscle in the CSF was performed early in seven postoperative patients. No clear pattern emerged which could relate the substances, CSF reaction, and meningeal scarring. The effects of various factors such as contrast studies, drainage, and steroids were also not clear. Review of the literature reveals that all four tissues can cause inflammation. Certain facts about the anatomy of the basilar cisterns and arachnoid villi probably make them logical sites for problems in CFS circulation. Children, for several reasons, are most susceptible to this complication. The complexity of factors in human cases suggests that the problem should be studied in an animal model.


In vitro B-lymphocyte switch disturbance from IgM into IgG in IgM mesangial nephropathy.
In vitro immunoglobulin (Ig) synthesis using a co-culture technique after activation of lymphocytes with pokeweed mitogen, T-cell subsets and interleukin-2 (IL-2) production was studied in 10 children who suffered from IgM mesangial nephropathy (IgMN), 10 children who suffered from minimal change nephrotic syndrome (MCNS) with hypercellularity and 6 children who suffered from MCNS with normal cellularity during the acute nephrotic phase. Reduced in vitro IgG production was found in the presence of OKT8 cells from all groups of patients. However, in vitro IgM production was increased only in OKT8 cells from IgMN and MCNS patients with hypercellularity. In vitro Tac expression on the OKT8 cells, IL-2 production, T-cell subsets including Leu2a+15+ (suppressor T-cells), Leu2a+DR+ (activated suppressor T-cells) and Leu3a+8+ (suppressor T-cell inducer) were all increased in IgMN and MCNS patients with hypercellularity. There was a significant correlation between in vitro IgM production by co-culture technique and IL-2 production. These results strongly suggest the hyperfunction of isotype-specific suppressor T-cells which may affect the switch of IgM B-cells to IgG B-cells in IgMN and MCNS patients with hypercellularity and may be used to explain in part the clinical findings of lower serum IgG and increased IgM in those patients.


Measuring microchannel electroosmotic mobility and zeta potential by the current monitoring method.
Electroosmotic flow (EOF) is an electrokinetic flow control technique widely used in microfluidic systems for applications including direct electrokinetic pumping, hydrodynamic pressure generation, and counterflow for microfluidic separations. During EOF, an electric field is applied along the length of a microchannel containing an electrolyte, with mobile ions near the charged microchannel walls experiencing a Coulomb force due to electrostatic interactions with the applied electric field that leads to bulk solution movement. The goal of this laboratory is to experimentally determine the fixed channel surface charge (zeta potential) and electroosmotic mobility associated with a given microchannel substrate material and buffer solution, using a simple current monitoring method to measure the average flow velocity within the microchannel. It is a straightforward experiment designed to help students understand EOF physics while gaining hands-on experience with basic world-to-chip interfacing. It is well suited to a 90-min laboratory session for up to 12 students with minimal infrastructure requirements.


Arthroscopic evaluation of preserved ligament remnant after selective anteromedial or posterolateral bundle anterior cruciate ligament reconstruction.
The purpose of this study was to evaluate the clinical results and morphology of the preserved bundle remnants by second-look arthroscopy postoperatively 1 year after selective anteromedial (AM) or posterolateral (PL) bundle ACL reconstruction. Between July 2004 and September 2009, 1,000 patients underwent arthroscopic anterior cruciate ligament (ACL) reconstruction at our hospital. Among them, 20 (2%) underwent selective AM bundle (group A) or PL bundle (group P) ACL reconstruction surgery with hamstring tendon autografts. At 1 year after surgery, 19 patients (7 male and 12 female patients; age range, 15 to 57 years) underwent second-look arthroscopic evaluations. The follow-up mean was 40.2 months (range, 24 to 70 months). We evaluated the results of manual knee laxity, anterior knee laxity measured by a Telos device (Telos, Marburg, Germany) at 130 N, Lysholm scores, and International Knee Documentation Committee evaluation form and performed evaluations of morphology by second-look arthroscopy. The side-to-side difference in anterior translation by use of the Telos device at 130 N was improved to 2 ± 2 mm (postoperatively) from 6 ± 2.3 mm (preoperatively) in group A and to 1.02 ± 1.26 mm from 4.93 ± 1.73 mm in group P. By second-look arthroscopy, the graft and preserved remnant of each case was considered to have acceptable synovial coverage and to be taut. The preserved ACL remnants possess acceptable morphology and the functions of anterior-posterior and rotational stability after surgery. Our procedure can be recommended for surgery on partial ACL tears. Level IV, therapeutic case series.


Is there a relationship between executive functions and resilience in youth elite soccer players?
While the relationship between cognitive performance and sport performance in youth elite soccer players has proponents as well as opponents, many aspects of this relationship remain unclear. Therefore, this quasi-experimental study wants to contribute to this relationship including the psychological aspect of resilience when investigating youth elite soccer players during an assessment selection for a representative team. Questionnaires as well as computer-based tests were conducted. Results of this study showed no relationship between resilience and executive function in youth elite soccer players. Furthermore, no differences in executive functions or in resilience were found between those players who are selected for a representative team and those who were not selected. The results indicate that further research needs to be conducted to clarify possible relationships in more detail.


Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity.
Effects of ammonia on astrocytes play a major role in hepatic encephalopathy, acute liver failure and other diseases caused by increased arterial ammonia concentrations (e.g., inborn errors of metabolism, drug or mushroom poisoning). There is a direct correlation between arterial ammonia concentration, brain ammonia level and disease severity. However, the pathophysiology of hyperammonemic diseases is disputed. One long recognized factor is that increased brain ammonia triggers its own detoxification by glutamine formation from glutamate. This is an astrocytic process due to the selective expression of the glutamine synthetase in astrocytes. A possible deleterious effect of the resulting increase in glutamine concentration has repeatedly been discussed and is supported by improvement of some pathologic effects by GS inhibition. However, this procedure also inhibits a large part of astrocytic energy metabolism and may prevent astrocytes from responding to pathogenic factors. A decrease of the already low glutamate concentration in astrocytes due to increased synthesis of glutamine inhibits the malate-aspartate shuttle and energy metabolism. A more recently described pathogenic factor is the resemblance between NH4+ and K+ in their effects on the Na+,K+-ATPase and the Na+,K+, 2 Cl- and water transporter NKCC1. Stimulation of the Na+,K+-ATPase driven NKCC1 in both astrocytes and endothelial cells is essential for the development of brain edema. Na+,K+-ATPase stimulation also activates production of endogenous ouabains. This leads to oxidative and nitrosative damage and sensitizes NKCC1. Administration of ouabain antagonists may accordingly have therapeutic potential in hyperammonemic diseases.


New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors.
A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2f inhibits TXA2 synthase with an IC50 value of 0.64 microM and the aggregation of human platelets with an IC50 value of 0.063 microM and shows a long duration of action in different species after oral administration.


Changes in the blood redox balance during a simulated duathlon race and its relationship with athletic performance.
The duathlon is an endurance multisport event that consists of sequential running, cycling, and further running. Imbalance in the redox homeostasis is associated with fatigued status and underperformance in various sports; however, there are no corresponding reports regarding the duathlon. The purpose of this study was to examine the changes in the blood redox balance during a simulated duathlon race and to determine the relationship between performance and the redox balance. Eight male triathletes participated in a simulated race, consisting of a 5-km run, 30 km cycling, and a further 5-km run, with 5 min rest between two parts to collect the blood samples. The serum levels of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured and BAP/d-ROMs ratio and oxidative stress index (OSI) were calculated. The d-ROMs levels after the first Run were significantly increased compared with the levels observed before the race. Moreover, BAP levels increased significantly over the race. The BAP/d-ROMs ratio also gradually increased through the race, while the OSI was gradually decreased. In addition, a significant relationship was observed only between d-ROMs levels after the first Run and the first Run performance. These results suggest that the redox balance shifts toward reduction (antioxidation) during the duathlon race and increased oxidant potential levels are negatively correlated with performance in the early stages of the race.


Evolution of the CBL and CIPK gene families in Medicago: genome-wide characterization, pervasive duplication, and expression pattern under salt and drought stress.
Calcineurin B-like proteins (CBLs) are ubiquitous Ca2+ sensors that mediate plant responses to various stress and developmental processes by interacting with CBL-interacting protein kinases (CIPKs). CBLs and CIPKs play essential roles in acclimatization of crop plants. However, evolution of these two gene families in the genus Medicago is poorly understood. A total of 68 CBL and 135 CIPK genes have been identified in five genomes from Medicago. Among these genomes, the gene number of CBLs and CIPKs shows no significant difference at the haploid genome level. Phylogenetic and comprehensive characteristic analyses reveal that CBLs and CIPKs are classified into four clades respectively, which is validated by distribution of conserved motifs. The synteny analysis indicates that the whole genome duplication events (WGDs) have contributed to the expansion of both families. Expression analysis demonstrates that two MsCBLs and three MsCIPKs are specifically expressed in roots, mature leaves, developing flowers and nitrogen fixing nodules of Medicago sativa spp. sativa, the widely grown tetraploid species. In particular, the expression of these five genes was highly up-regulated in roots when exposed to salt and drought stress, indicating crucial roles in stress responses. Our study leads to a comprehensive understanding of evolution of CBL and CIPK gene families in Medicago, but also provides a rich resource to further address the functions of CBL-CIPK complexes in cultivated species and their closely related wild relatives.


Central processing of sensory information in electric fish.
Comparative studies of neural mechanisms underlying the perception of natural stimulus patterns and the control of adaptive behavioral responses have revealed organizational principles that are shared by a wide spectrum of animals. Mechanisms of perception and motor control are commonly executed in a distributed network of neurons that lack 'pontifical' elements. Individual neurons even at an organizational level as high as the optic tectum may still have very general response characteristics, and the recruitment of individual neurons reveals little about the nature of the stimulus situation outside. Only the joint evaluation of messages from large populations of such neurons yields unambiguous pictures of the outside world. Stimulus variables are commonly mapped continuously within a stratum of neurons so that their variation over time can be monitored by mechanisms similar to motion detection in a retina. The ordered representation of a stimulus variable within an array of broadly tuned elements allows for a degree of stimulus resolution that by far exceeds that of individual elements in the array. Neural systems are burdened by their evolutionary history and suffer from imperfections that are overcome by a patchwork of compensations. The existence of multiple neuronal representations of sensory information and multiple circuits for the control of behavioral responses should provide the necessary freedom for evolutionary tinkering and the invention of new designs.


Erythrocyte populations in pyruvate kinase deficiency anaemia following splenectomy. I. Cell morphology.
Light and scanning electron microscopic examination of fresh erythrocytes from the blood of four patients splenectomized for severe pyruvate kinase (PK) deficiency haemolytic anaemia has revealed three morphologically different cell populations. Most striking in these patients was the presence of crenated red cells (30-50% of total) which fit current criteria for definition as echinocytes, but also with unusual surface retraction compatible with the existence of intracellular shrinkage, a phenomenon known to occur after incubation of PK deficient red cells in vitro. Additional cell types include immature reticulocytes (7-8% of total) and thin macrocytic discocytes (45-65% of total) none of which are considered specific for the disease. These morphological findings are in sharp contrast with the paucity of red cell shape abnormalities usually described in PK deficient patients before splenectomy and may provide insight into the mechanisms leading to accelerated erythrocyte destruction in this disease.


Calcium chloride effects on salinity-induced oxidative stress, proline metabolism and indole alkaloid accumulation in Catharanthus roseus.
Catharanthus roseus (L.) G. Don. plants were grown with NaCl and CaCl2 in order to study the effect of CaCl2 on NaCl-induced oxidative stress in terms of lipid peroxidation (TBARS content), H2O2 content, osmolyte concentration, proline (PRO)-metabolizing enzymes, antioxidant enzyme activities, and indole alkaloid accumulation. The plants were treated with solutions of 80 mM NaCl, 80 mM NaCl with 5 mM CaCl2 and 5 mM CaCl2 alone. Groundwater was used for irrigation of control plants. Plants were uprooted randomly on 90 days after sowing (DAS). NaCl-stressed plants showed increased TBARS, H2O2, glycine betaine (GB) and PRO contents, decreased proline oxidase (PROX) activity, and increased gamma-glutamyl kinase (gamma-GK) activity when compared to control. Addition of CaCl2 to NaCl-stressed plants lowered the PRO concentration by increasing the level of PROX and decreasing the gamma-GK activities. Calcium ions increased the GB contents. CaCl2 appears to confer greater osmoprotection by the additive role with NaCl in GB accumulation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT) were increased under salinity and further enhanced due to CaCl2 treatment. The NaCl-with-CaCl2-treated C. roseus plants showed an increase in total indole alkaloid content in shoots and roots when compared to NaCl-treated and untreated plants.


How vegans and vegetarians negotiate eating-related social norm conflicts in their social networks.
This qualitative study, framed by social identity theory, examines how self-identified vegans and vegetarians negotiate diet-related social norm conflicts within their social networks. Twenty-one semi-structured interviews with 18- to 58-year-old vegans and vegetarians who represented five nationalities were analysed inductively through thematic analysis. According to the results, social norm conflicts occurred in contexts where tense family relations or boundaries between in-group and out-group were salient. The results also show that in order to manage norm conflict situations, the interviewees used strategies towards the dominant social norms, such as adapting, challenging, and weakening. In particular, adapting to the dominant social norms was used in relationships that were not close, whereas challenging and weakening were used within close relationships. The interviewees had developed practical solutions to resolve social norm conflicts, such as eating what was served, actively providing information, or acting as an example to others. The results enhance understanding of the challenges entailed by practising vegan or vegetarian diet in an omnivorous society.


Overexpression of miR-27a predicts poor prognosis and promotes the progression in cholangiocarcinoma.
The function of microRNA-27a (miR-27a) expression in cholangiocarcinoma (CCA) remains largely unclear; therefore, this study aimed to investigate the clinical significance and functional role of miR-27a in CCA. This study included 117 paired CCA tissues and adjacent normal tissues from CCA patients who received surgical resection. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression levels of miR-27a in CCA tissues and cell lines. A Kaplan-Meier curve and Cox regression analysis were used to determine overall prognostic performance. The effects of miR-27a on cell proliferation, migration, and invasion were measured by CCK-8 and Transwell assays. The expression levels of miR-27a in patients with CCA and cell lines were higher than those in adjacent normal tissues and normal cells, respectively. Additionally, miR-27a levels were found to be associated with lymph node metastasis and TNM stages. The overall survival time of CCA patients with high miR-27a expression was poorer than that of those with low miR-27a expression. Furthermore, miR-27a overexpression promoted CCA cell proliferation, migration, and invasion, whereas knockdown of miR-27a suppressed cell proliferation, migration, and invasion. Taken together, these results suggest the potential usefulness of miR-27a in the prognosis and progression of CCA.


Advancing description and explanation in clinical linguistics: a legacy of Martin J. Ball.
This article asserts the importance of explication of order and disorder in language as a privileged objective of clinical linguistics and service delivery and reviews the contributions of Martin Ball in advancing this agenda.


A Randomized Trial of Fixed-Dose Combination Brinzolamide 1%/Brimonidine 0.2% as Adjunctive Therapy to Travoprost 0.004.
To evaluate the safety and efficacy of adding fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) as adjunctive therapy to travoprost 0.004% (TRAV) in patients with open-angle glaucoma or ocular hypertension. Multicenter, randomized, double-masked, parallel-group phase 4 clinical trial. setting: Multicenter; 32 sites in the United States. Total of 233 patients with open-angle glaucoma or ocular hypertension and with mean intraocular pressure (IOP) ≥21 mm Hg and <32 mm Hg while receiving once-daily TRAV monotherapy. Masked BBFC or vehicle (3 times daily) adjunctive to TRAV for 6 weeks. Mean diurnal IOP averaged over 8 AM, 10 AM, 3 PM, and 5 PM time points at week 6. Superiority of BBFC+TRAV over vehicle+TRAV was based on statistical significance of a treatment difference favoring BBFC+TRAV. Mean diurnal IOP at week 6 (least squares mean ± standard error) was 17.6 ± 0.4 mm Hg and 20.7 ± 0.4 mm Hg in the BBFC+TRAV and vehicle+TRAV groups, respectively (between-group difference, -3.2 ± 0.5 mm Hg; P < .0001). Superiority of BBFC+TRAV over vehicle+TRAV was established. Mean and percent diurnal IOP change from baseline were significantly greater with BBFC+TRAV compared with vehicle+TRAV (P < .0001 for both). Conjunctival hyperemia was the most common treatment-related adverse event in either group (BBFC+TRAV, 12.8%; vehicle+TRAV, 6.0%). Adjunctive treatment with BBFC added to TRAV resulted in lower mean diurnal IOP after 6 weeks of treatment compared with vehicle added to TRAV; this difference was both statistically and clinically significant.


On-Demand Chemomagnetic Modulation of Striatal Neurons Facilitated by Hybrid Magnetic Nanoparticles.
Minimally invasive manipulation of cell signaling is critical in basic neuroscience research and in developing therapies for neurological disorders. Here, we describe a wireless chemomagnetic neuromodulation platform for the on-demand control of primary striatal neurons that relies on nanoscale heating events. Iron oxide magnetic nanoparticles (MNPs) are functionally coated with thermoresponsive poly (oligo (ethylene glycol) methyl ether methacrylate) (POEGMA) brushes loaded with dopamine. Dopamine loaded MNPs-POEGMA are co-cultured with primary striatal neurons. When alternating magnetinec fields (AMF) are applied, MNPs undergo hysteresis power loss and dissipate heat. The local heat produced by MNPs initiates a thermodynamic phase transition on POEGMA brushes resulting in polymer collapse and dopamine release. AMF-triggered dopamine release enhances the response of dopamine ion channels expressed on the cell membranes enhancing the activity of ~50% of striatal neurons subjected to the treatment. Chemomagnetic actuation on dopamine receptors is confirmed by blocking D1 and D2 receptors. The reversible thermodynamic phase transition of POEGMA brushes allow the on-demand release of dopamine in multiple microdoses. AMF-triggered dopamine release from MNPs-POEGMA causes no cell cytotoxicity nor promotes cell ROS production. This research represents a fundamental step forward for the chemomagnetic control of neural activity using hybrid magnetic nanomaterials with tailored physical properties.


Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso.
Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2-7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR) = 1.61, 95% confidence interval (CI): 1.4-1.8). High-risk HPV types (71 vs 40%, PR = 1.79, 95% CI: 1.5-2.2), in particular HPV-16+18 (22 vs 9%, PR = 2.35, 95% CI: 1.4-4.0), and multiple HPV infections (56 vs 23%, PR = 2.45, 95% CI: 1.8-3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio = 17.0; 95% CI 2.2-134.1, P = 0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine.


Fathers of children with cancer: involvement, coping, and adjustment.
This study examined the role of fathers caring for children with cancer. Psychological adjustment, coping, and work patterns of mothers and fathers were described. Twenty fathers of children with cancer were compared with 20 mothers of children with cancer and 20 control fathers of healthy children. Questionnaire data were collected regarding coping, parental adjustment, child adjustment, and family involvement. Fathers did not differ from mothers or control fathers in terms of psychological adjustment or coping. However, fathers of children with cancer spent more hours at work and more hours caring for children than did control fathers. Paternal adjustment was significantly related to child adjustment only when the child had cancer. Coping was related to work outside the home for fathers and adjustment for mothers. Models of family adaptation may be different for fathers and mothers. Treatment teams must attend to the unique needs of fathers.


Trend of blood donors entering the coronavirus pandemic era and challenges: Age-period-cohort analysis using 75.5 million all blood donations data during 2006-2020 in Japan.
In Japan, "Blood Donation Promotion 2025," a blood donation target, was established based on a predicted blood donation rate of 5.7% in 2025, which was calculated by the Blood Donation Promotion Study Group (BD research group) of the Ministry of Health, Labor and Welfare using nationwide blood donation data through 2018. However, COVID-19 since 2020 may affect the blood donation rate in Japan. Data from 75.5 million blood donations from 2006 to 2020 was used. The age-period-cohort model (APC model) was applied to estimate age, period, and birth cohort factors on blood donation rate and to predict the age-specific blood donation rates from 2021 to 2035. The APC model was highly reproducible for blood donation rates (modified R2 = 0.99). The blood donation rate in 2020 was 6.0% (5.04 million), an increase compared to 2019. Comparing this study with the BD research group, the predicted blood donation rates in 2025 for those 16-19 years old and in 20s are lower (4.8% vs. 5.2% and 5.3% vs. 5.5%) but those among 50s and 60s are higher (7.9% vs. 7.5% and 4.2% vs. 3.9%, respectively). The number of blood donations in 2020 increased despite COVID-19 and it proved that the blood donation promotion was effective. The different age-specific blood donation rates between our study and the report of BD research group infers the effect of COVID-19 on blood donation were differed by age and suggested the need for different approaches to blood donation promotion by generation.


Human health risk assessments for three neuropharmaceutical compounds in surface waters.
Enhanced sensitivity of analytical chemistry methods has enabled the detection of low-levels of pharmaceuticals in the environment, resulting in questions about the safety of surface waters used for drinking supplies. Human health risk assessments were performed to evaluate the risks from residues of atomoxetine, duloxetine, and olanzapine, which might be found in surface waters. Preclinical safety studies and human clinical data were used to determine an acceptable daily intake (ADI) for each compound: atomoxetine, 1.4 microg/kg/day; duloxetine, 1.8 microg/kg/day; and olanzapine, 1.4 microg/kg/day. The calculated predicted no-effect concentrations (PNECs) for children were 25.7, 19.1, and 35.9 microg/L for atomoxetine, duloxetine, and olanzapine, respectively. Estimated exposure concentrations determined using United States Food and Drug Administration guidelines and predicted exposure concentrations from the PhATE model were compared with each PNEC to determine margins of safety, which ranged from 147 to 642. Based on currently available data used in this assessment, no appreciable human health risks exist from exposure to the highest 99th percentile of predicted residue levels of atomoxetine, duloxetine or olanzapine in surface waters under low-flow conditions.


Post-treatment late complications of nasopharyngeal carcinoma.
Radiotherapy (RT) or concurrent chemoradiation therapy (CCRT) is not only effective at patients' survival rates, but also produces undesirable late complications. The purpose of this study is to investigate the post-treatment late complications in nasopharyngeal carcinoma (NPC) patients, and to analyze the individual impact factors. We enrolled 188 newly diagnosed NPC patients who had received complete treatments and at least 3 years' follow-up between March 1984 and March 2010. Late complications were modified from the Toxicity Criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer. Of 188 patients, 132 were male and 56 were female. Eighty-eight patients received CCRT and the other 100 patients received RT alone. The median follow-up duration was 7.34 years (range 3.30-26.54). Only 5.3% of patients reported no complication during post-treatment follow-up. The most common major and minor complications were osteoradionecrosis (10.1%) and xerostomia (56.4%), respectively. There was no impact factor for age, underlying disease, and cancer staging. However, there was a negative impact factor for xerostomia and limb numbness in the CCRT group compared with the RT group. Besides, re-radiation for recurrent patients could increase the risk of major complications. Fortunately, these major complications were reduced after the introduction of intensity-modulated radiotherapy in 2003. The improvement of treatment modality decreased the risk of major complications. Physicians should pay more attentions and improve patients' quality of life during follow-up.


Hepatitis B in the Female Population.
Chronic hepatitis B infection in the female population has implications not just for the individual but for her children as well. This article discusses the natural history of hepatitis B and how it plays an important role in hepatitis B virus (HBV) transmission, the current strategies and new strategies to control HBV and reduce transmission, and the updated guidelines for the management of HBV.


Sarcomatoid Urothelial Carcinoma Is Associated With Limited Response to Neoadjuvant Chemotherapy and Poor Oncologic Outcomes After Radical Cystectomy.
To examine oncologic outcomes and response to neoadjuvant chemotherapy (NAC) in patients with sarcomatoid urothelial carcinoma (SUC) treated with radical cystectomy (RC). We retrospectively queried our institutional database (2003-18) and Surveillance, Epidemiology, and End Results (SEER)-Medicare (2004-2015) for patients with cT2-4, N0-2, M0 SUC and conventional UC (CUC) treated with RC. Clinicopathologic characteristics were described using descriptive statistics (t test, χ2-test and log-rank-test for group comparison). Overall (OS) and recurrence-free-survival (RFS) after RC were estimated with the Kaplan Meier method and associations with OS were evaluated with Cox proportional hazards models. We identified 38 patients with SUC and 287 patients with CUC in our database, and 190 patients with SUC in SEER-Medicare. In the institutional cohort, patients with SUC versus CUC had higher rates of pT3/4 stage (66% vs. 35%, P < 0.001), lower rates of ypT0N0 (6% vs. 35%, P = .02), and worse median OS (17.5 vs. 120 months, P < .001). Further, patients with SUC in the institutional versus SEER-Medicare cohort had similar median OS (17.5 vs. 21 months). In both cohorts, OS was comparable between patients with SUC undergoing NAC+RC vs. RC alone (17.5 vs. 18.4 months, P = .98, institutional cohort; 24 vs. 20 months, P = .56, SEER cohort). In Cox proportional hazards models for the institutional RC cohort, SUC was independently associated with worse OS (HR 2.3, CI 1.4-3.8, P = .001). SUC demonstrates poor pathologic response to NAC and worse OS compared with CUC, with no OS benefit associated with NAC. A unique pattern of rapid abdominopelvic cystic recurrence was identified.


Parotid gland swelling in primary Sjögren's syndrome: activity and other sialadenosis causes.
To assess the prevalence of parotid gland swelling (PGS) and its association with features of SS and other causes of sialadenosis in a Latin-American cohort of primary SS. We included 668 patients from Argentina, Brazil, Mexico and Paraguay. We retrospectively registered demographics, disease duration, oral/ocular symptoms, serology and scored the basal ESSDAI. We defined PGS as a recurrent or persistent increase of volume of any parotid glands during adulthood (self-reported and/or physical examination). We registered the presence of diabetes mellitus, dyslipidaemia, body mass index and alcohol consumption. We used logistic regression analysis reporting odds ratio (OR) and 95% CI. PGS was present in 242 patients (36.2%): 78 previous to SS diagnosis, 86 concomitantly, 73 during follow-up and five unknown. At the multivariate analysis, PGS was associated with RF (OR 2.47, 95% CI: 1.1, 6.5, P = 0.0001), basal articular ESSDAI domain (OR 1.63, 95% CI: 1.01, 2.6, P = 0.04) and alcohol consumption (OR 2.42, 95% CI: 1.41, 4-15). Patients with PGS during the follow-up had a higher prevalence of alcohol consumption (45.3%) compared with the remaining PGS cases (26.8%; OR 2.41 95% CI: 1.2, 4.7), or patients without parotid gland swelling (15.6%; OR 3.8 95% CI: 1.7, 8.2) in all the adjusted models. PGS generally precedes or presents concomitantly with SS diagnosis, and is related to RF and articular activity. Alcohol consumption is an additional factor in PGS, especially during follow-up. The meaning of this last finding as well as its prognostic implications remains to be elucidated and deserves further evaluation in prospective studies.


Periodontal disease increases the host susceptibility to COVID-19 and its severity: a Mendelian randomization study.
Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity. Summary statistics of COVID-19 susceptibility and severity were retrieved from the COVID-19 Host Genetics Initiative and used as outcomes. Single nucleotide polymorphisms associated with PD in Genome-wide association study were included as exposure. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy, including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations. The MR estimates showed that PD was significantly associated with significantly higher susceptibility to COVID-19 using IVW (OR = 1.024, P = 0.017, 95% CI 1.004-1.045) and weighted median method (OR = 1.029, P = 0.024, 95% CI 1.003-1.055). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW, OR = 1.025, P = 0.039, 95% CI 1.001-1.049; weighted median, OR = 1.030, P = 0.027, 95% CI 1.003-1.058). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19. We provide evidence on the possible causality of PD accounting for the susceptibility and severity of COVID-19, highlighting the importance of oral/periodontal healthcare for general wellbeing during the pandemic and beyond.


Metabolic markers in blood can separate prostate cancer from benign prostatic hyperplasia.
An individualised risk-stratified screening for prostate cancer (PCa) would select the patients who will benefit from further investigations as well as therapy. Current detection methods suffer from low sensitivity and specificity, especially for separating PCa from benign prostatic conditions. We have investigated the use of metabolomics analyses of blood samples for separating PCa patients and controls with benign prostatic hyperplasia (BPH). Blood plasma and serum samples from 29 PCa patient and 21 controls with BPH were analysed by metabolomics analysis using magnetic resonance spectroscopy, mass spectrometry and gas chromatography. Differences in blood metabolic patterns were examined by multivariate and univariate statistics. By combining results from different methodological platforms, PCa patients and controls were separated with a sensitivity and specificity of 81.5% and 75.2%, respectively. The combined analysis of serum and plasma samples by different metabolomics measurement techniques gave successful discrimination of PCa and controls, and provided metabolic markers and insight into the processes characteristic of PCa. Our results suggest changes in fatty acid (acylcarnitines), choline (glycerophospholipids) and amino acid metabolism (arginine) as markers for PCa compared with BPH.


A new major projection from locus coeruleus: the main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord.
Almost all catecholamine (CA)-containing nerve terminals in the ventral column, intermediate grey and ventral half of the dorsal column disappeared after bilateral stereotaxic lesions of nucleus locus coeruleus, as revealed by fluorescence histochemistry. Some of the CA nerve terminals in the dorsal half of the column seemed to be unaffected by the lesions, as well as the CA terminals innervating the thoracic sympathetic lateral column and the band of nerve terminals crossing the midline and innervating the central grey. This coeruleo-spinal pathway in the rat is located in the anterior funiculus and the ventral parts of the lateral funiculus. A schematic map of the different CA projections to the spinal cord is presented. It was concluded that locus coeruleus innervates almost all parts of the central nervous system.


SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice.
Nicotinamide phosphoribosyltransferase (NAMPT), the key NAD(+) biosynthetic enzyme, has two different forms, intra- and extracellular (iNAMPT and eNAMPT), in mammals. However, the significance of eNAMPT secretion remains unclear. Here we demonstrate that deacetylation of iNAMPT by the mammalian NAD(+)-dependent deacetylase SIRT1 predisposes the protein to secretion in adipocytes. NAMPT mutants reveal that SIRT1 deacetylates lysine 53 (K53) and enhances eNAMPT activity and secretion. Adipose tissue-specific Nampt knockout and knockin (ANKO and ANKI) mice show reciprocal changes in circulating eNAMPT, affecting hypothalamic NAD(+)/SIRT1 signaling and physical activity accordingly. The defect in physical activity observed in ANKO mice is ameliorated by nicotinamide mononucleotide (NMN). Furthermore, administration of a NAMPT-neutralizing antibody decreases hypothalamic NAD(+) production, and treating ex vivo hypothalamic explants with purified eNAMPT enhances NAD(+), SIRT1 activity, and neural activation. Thus, our findings indicate a critical role of adipose tissue as a modulator for the regulation of NAD(+) biosynthesis at a systemic level.


Neither simple nor sequential arm movements are bradykinetic in parkinsonian patients with peak-dose dyskinesias.
To find out whether parkinsonian patients with levodopa-induced peak-dose dyskinesias are bradykinetic. The performance of a sequential internally determined arm movement and a simple externally triggered arm movement was studied in a group of dyskinetic parkinsonian patients during their best clinical condition and when they were OFF treatment. Patients' performance was compared with that of an age-matched control group. Movements in the three-dimensional space were recorded by the ELITE motion analysis system. Kinematic variables analysed for the sequential motor task were total movement duration and total pause duration; for the simple motor task, movement duration and reaction time; and for both tasks, movement inaccuracy. When patients were OFF therapy they performed sequential and simple movement tasks slower than healthy subjects whereas when they were dyskinetic they did not. During the sequential task, when the patients were dyskinetic total pause duration shortened and movement inaccuracy increased. Our kinematic finding indicates that parkinsonian patients' with peak-dose dyskinesias are not bradykinetic. Parkinsonian patients with peak-dose dyskinesias are not bradykinetic, probably because dopamine at peak doses functionally normalizes the mechanisms controlling movement speed.


Dysfunction of Caveolae-Mediated Endocytic TβRI Degradation Results in Hypersensitivity of TGF-β/Smad Signaling in Osteogenesis Imperfecta.
Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen-related genes, and excessive transforming growth factor-beta (TGF-β) signaling is a common mechanism. TGF-β/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF-β receptors (TβRI and TβRII). During internalization, clathrin-mediated endocytosis enhances TGF-β/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae-mediated endocytosis turns off TGF-β/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2oim , osteogenesis imperfecta murine [oim]/oim mouse), we found that osteoblastic cells of oim/oim mice were more sensitive to the inhibitory effects of TGF-β on osteoblast differentiation and maturation and had much higher cell membrane protein levels of TGF-β receptors than those of wild-type (wt)/wt mice. Further results showed that clathrin-mediated endocytosis of TβRI was enhanced, whereas caveolae-mediated TβRI endocytic degradation was reduced in oim/oim mice, combined with reduced caveolin-1 (Cav-1) phosphorylation. In addition, type I collagen downregulated TβRI via focal adhesion kinase (FAK) and Src activation-dependent Cav-1 phosphorylation. To further examine this mechanism, 4-week-old oim/oim and wt/wt mice were treated with either TβRI kinase inhibitor (SD-208) or vehicle for 8 weeks. SD-208 treatment significantly reduced the fracture incidence in oim/oim mice. Micro-computed tomography and biomechanical testing showed that femoral bone mass and strength were significantly improved with SD-208 treatment in both genotypes. Additionally, SD-208 significantly promoted osteoblast differentiation and bone formation and inhibited bone resorption. In conclusion, dysfunction of caveolae-mediated endocytic TβRI degradation is a possible mechanism for the enhanced TGF-β/Smad signaling in OI. Targeting this mechanism using a TβRI kinase inhibitor effectively reduced fractures and improved bone mass and strength in OI model and, thus, may offer a new strategy for the treatment of OI. © 2022 American Society for Bone and Mineral Research (ASBMR).


Combined application of H2S and a plant growth promoting strain JIL321 regulates photosynthetic efficacy, soil enzyme activity and growth-promotion in rice under salt stress.
Salinity stress is one of the most harmful abiotic stresses that inhibit crop growth and grain yield. In this study, a salt-tolerant bacterium was isolated from the soil of the rice rhizosphere and named Myroides sp. JIL321, based on the results of the phylogenetic tree analysis. The strain JIL321 tolerated up to 1, 283.37 mM of NaCl and exhibited positive plant growth-promoting traits, such as the production of indole acetic acid (IAA) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase. Therefore, the effects of JIL321 on rice (Oryza sativa L.) under salinity stress were determined. The inoculation of strain JIL321 significantly increased the chlorophyll content and the accumulation of osmotic adjustment substances, such as proline and soluble sugars, in rice expose to salt stress. Additionally, strain JIL321 inoculation significantly enhanced the activities of some enzymes commonly found in soil, such as urease, invertase and catalase. Moreover, the production of hydrogen sulfide (H2S), a pivotal signaling molecule, was also induced in rice by salt stress. Treatment with sodium hydrogen sulfide (NaHS, H2S donor) improved salt stress tolerance of the rice, while treatment with hypotaurine (HT, H2S scavenger) significantly suppressed it. Interestingly, NaHS treatment also improved the production of IAA and ACC deaminase in strain JIL321 under 0 mM and 150 mM salt concentrations. The combined treatment of JIL321 and NaHS could further improve the growth of salt-stressed rice seedlings, most likely due to the interaction effect between H2S and strain JIL321. To our knowledge, this study is the first to demonstrate that the combined use of H2S and plant growth-promoting bacteria could alleviate the adverse effects of salt stress on rice plants, and further verifies the novel role of H2S as a signaling molecule that enhance the tolerance of plant to abiotic stresses.


Urgotul: alternative to conventional non-adherence dressings.
This article describes a novel dressing product that was developed from existing technology: hydrocolloid. The main benefits of Urgotul relate to the fact that it does not adhere to the wound surface, so both wound trauma on removal and the build up of moisture under the dressing are avoided.


Rapid assessment of sound-evoked olivocochlear feedback: suppression of compound action potentials by contralateral sound.
The compound action potential (CAP) measured at the round window of anesthetized cats in response to low-level tone pips can be significantly suppressed by addition of tones or noise to the opposite ear. This contralateral-sound suppression disappears upon transection of the olivocochlear bundle. The frequency and level dependence of the suppression phenomenon are well explained by known sound-evoked discharge properties of single olivocochlear neurons. Thus, the contralateral-sound suppression of cochlear CAP should prove useful as a rapid measure of the magnitude of the sound-evoked efferent feedback to the cochlea.


Serological and clinical remission in systemic lupus erythematosus.
The frequency of a combined clinical and serological remission in patients with systemic lupus erythematosus (SLE) was examined. Thirteen (4%) of 305 patients had both a seroconversion from a positive to a negative ANA and became asymptomatic in respect to their SLE. These remissions lasted from 6 months to 13 years. It is not clear what role, if any, therapy played in these remissions. Nevertheless, these remissions provided hope for the patients and their physicians.


Diagnostic and Therapeutic Considerations for Extramedullary Leukemia.
The purpose of this review is to summarize the current literature on the presentation, diagnosis, and treatment options available for extramedullary (EM) manifestations of leukemia including myeloid sarcoma (MS) and leukemia cutis (LC). Advanced imaging using 18FDG-PET/CT is an effective screening tool for EM manifestations of leukemia. The role of radiation therapy has been more clearly delineated in the treatment of both MS and LC. FDA-approved targeted agents have improved outcomes in patients with AML but have not demonstrated improvements specifically for EM; however, a checkpoint inhibitor, Ipilimumab, holds promise in impacting local control for the treatment of AML-related EM. EM manifestations of leukemia pose significant therapeutic challenges. Treatment of EM is predicated on multiple factors including the presence of concomitant bone marrow involvement, AML-risk classification, and timing of presentation at initial diagnosis or relapse following systemic therapy.


Recent advances in quantitative neuroproteomics.
The field of proteomics is undergoing rapid development in a number of different areas including improvements in mass spectrometric platforms, peptide identification algorithms and bioinformatics. In particular, new and/or improved approaches have established robust methods that not only allow for in-depth and accurate peptide and protein identification and modification, but also allow for sensitive measurement of relative or absolute quantitation. These methods are beginning to be applied to the area of neuroproteomics, but the central nervous system poses many specific challenges in terms of quantitative proteomics, given the large number of different neuronal cell types that are intermixed and that exhibit distinct patterns of gene and protein expression. This review highlights the recent advances that have been made in quantitative neuroproteomics, with a focus on work published over the last five years that applies emerging methods to normal brain function as well as to various neuropsychiatric disorders including schizophrenia and drug addiction as well as of neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. While older methods such as two-dimensional polyacrylamide electrophoresis continued to be used, a variety of more in-depth MS-based approaches including both label (ICAT, iTRAQ, TMT, SILAC, SILAM), label-free (label-free, MRM, SWATH) and absolute quantification methods, are rapidly being applied to neurobiological investigations of normal and diseased brain tissue as well as of cerebrospinal fluid (CSF). While the biological implications of many of these studies remain to be clearly established, that there is a clear need for standardization of experimental design and data analysis, and that the analysis of protein changes in specific neuronal cell types in the central nervous system remains a serious challenge, it appears that the quality and depth of the more recent quantitative proteomics studies is beginning to shed light on a number of aspects of neuroscience that relates to normal brain function as well as of the changes in protein expression and regulation that occurs in neuropsychiatric and neurodegenerative disorders.


Filiform polyposis presenting with rapid growth and severe anemia case report.
Giant inflammatory polyposis (GIP) is a rare manifestation of inflammatory bowel disease (IBD), and it is described as a worm-like projection of 1.5 cm or more in diameter with unclear pathogenesis. GIP may be related to the severity of IBD. GIP presents with a wide range of symptoms, including crampy abdominal pain, anemia, and intestinal obstruction. The histopathology of GIP is a polyp lined by normal colonic mucosa with superficial ulceration that may show mild crypt distortion. Our case reports a patient with ulcerative colitis diagnosed via colonoscopy and histopathology 10 months before presenting with severe anemia due to lower gastrointestinal bleeding. Colonoscopy showed GIP obstructing the descending and sigmoid colon, and total colectomy showed the entire colon full of worm-like polyps up to 14 cm the longest polyp. Giant inflammatory polyposis which is seen in 17 % of UC with active colitis, as seen in our patient, the histopathology component was acute in addition to chronic, which formed within 6 months. According to the data in the literature, the average duration reported for formation since diagnosis with UC is approximately 3 to 276 months. With a length up to 16 cm, the sigmoid colon is the most common site. Surgical intervention is indicated for filiform polyposis (FP) if it is complicated, such as bleeding or obstruction, which is reported in a few cases. However, there are no clear guidelines for surgical intervention for complicated FP, but the safest method is to tailor the management according to the guidelines for each underlying disease.


Disorders of balance and gait in essential tremor are associated with midline tremor and age.
Disorders of balance and gait have been observed in patients with essential tremor (ET), but their association with tremor severity remains unclear. This study aimed to evaluate postural instability and gait changes in ET patients and to investigate their relationship to tremor characteristics with regard to cerebellar dysfunction as a possible common pathogenetic mechanism in ET. Thirty ET patients (8F, mean (SD) age 55.8 (17.8), range 19-81 years) and 25 normal controls (7F, 53.0 (17.7), 19-81) were tested with the scales of Activities-specific Balance Confidence (ABC), Fullerton Advanced Balance (FAB), and International Cooperative Ataxia Rating Scale (ICARS). Posturography and gait were assessed using a Footscan® system. Tremor was evaluated by the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and accelerometry in five upper limb positions. A mean (SD) TRS sum score of 27.0 (13.2) corresponded to mild to moderate tremor severity in most patients. In comparison with controls, ET subjects exhibited lower tandem gait velocity (0.21 vs. 0.26 m/s, P = 0.028), more missteps (0.57 vs. 0.12, P = 0.039), and increased postural sway in tandem stance (sway area 301.1 vs. 202.9 mm(2), P = 0.045). In normal gait, step width increased with the midline tremor subscore of TRS (Pearson r = 0.60, P = 0.046). Moreover, significant correlations were found between age and quantitative measures of normal and tandem gait in ET patients but not in controls. ABC, FAB, and ICARS scores did not significantly differ between patients and controls. In conclusion, gait and balance alterations in ET patients occur even without subjective complaints. Their relationship with midline tremor and dependence on age suggest a connection with cerebellar dysfunction.


The multiple facets of flow analysis. A tutorial.
The amazing development of flow analysis has led to a loss of conceptual uniformity and to the proposals of a number of modalities, each assigned to an acronym, and this aspect may hinder further developments in the field. As any sample handling step of a flow-based analytical procedure can be accomplished in different ways, there are multiple facets associated to it. This tutorial is focused on the critical evaluation of these facets and the proposal of a novel way to present the flow analyzers, disregarding or even avoiding the need for specifying flow modalities and acronyms.


Effect of hydrogen bonding interaction on the photophysics of α-amino-orcein.
This paper reports for the first time a detailed spectroscopic investigation into the ground- and excited-state properties of α-amino-orcein (α-AO), one of the main components of the orcein dye, in solvents of different proticity and water at different pHs. In order to gain insight into the nature of the involved transitions and excited state deactivation pathways, the study was carried out by means of UV-Visible steady state and ultrafast spectroscopic techniques with the support of quantum mechanical calculations (DFT and TDDFT). The results highlight that the photophysical and photodynamic behaviour of α-AO are highly sensitive to the solvent proticity and pH. In particular, protic environment induces a red shift (55 nm) of the absorption spectrum together with a relevant decrease of the fluorescence quantum yield (from 0.19 in acetonitrile to 6.6 × 10-3 in methanol) and radiative rate constant (two orders of magnitude). A notable red shift is also caused by increasing the pH leading the molecule from monocationic to neutral and then monoanionic form through two deprotonation steps (pKa = 3.539 ± 0.006 and 11.180 ± 0.006). Following deprotonation, the molecule assumes spectral and photophysical properties very similar to those retrieved in protic media. The observed behaviour has been rationalized through the occurrence of hydrogen bonding, likely involving to a greater extent the carbonyl oxygen of α-AO and the protic solvent, that favours the charge delocalization on the whole chromophore as well as fast non-radiative excited state deactivation. The ultrafast spectroscopic investigation revealed in fact the presence, in protic solvent, of a short living component (tens of picoseconds), assignable to solvent complexed S1 state, alongside the long living component (few nanoseconds) observed in aprotic media and attributed to the solvent free S1 state. The results achieved in this study for α-AO provides an important contribution to the interpretation of absorption and fluorescence features of orcein dye mixture in more complex systems (protein based substrates within the many aspects of the cultural heritage and biomedical field) where hydrogen bonds are expected to play a crucial role in mediating the interaction with the environment.


Hemispheric asymmetry of visual evoked potentials in patients with well-defined occipital lesions.
Visual evoked potentials were examined in 3 patients who had well defined unilateral occipital lobectomy. In an attempt to resolve discrepancies in the interpretation of hemispheric asymmetries in evoked potentials, recordings were obtained from a wide array of electrodes with multiple montages during full-field and hemi-field stimulation with checkerboard pattern reversal and during full-field flash stimulation. The discrepancies appear to be due primarily to differences in electrode montages used in recording. The use of a midfrontal reference electrode reliably produces a paradoxical EP lateralization: abnormal EPs are recorded over the intact occipital lobe and normal EPs are recorded over the ablated occipital lobe. These findings are fully consistent with the interpretation of Barrett et al. (1976) that the generator of the P100 has an equivalent dipole located in the calcarine cortex on the posteromedial surface of the contralateral hemisphere. Our findings support the use of the Queen Square montage (Halliday et al. 1977). The use of electrodes at O1 and O2 referred to the ipsilateral earlobe yields inconsistent lateralization and should be discouraged. The lateralization of EP abnormalities did not differ for flash and pattern reversal, although the asymmetries were sometimes more prominent with pattern reversal.


Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes.
Basic calcium phosphate (BCP) crystals, including hydroxyapatite, octacalcium phosphate (OCP) and carbonate-apatite, have been associated with severe osteoarthritis and several degenerative arthropathies. Most studies have considered the chondrocyte to be a bystander in the pathogenesis of calcium crystal deposition disease, assuming that synovial cell cytokines were the only triggers of chondrocyte activation. In the present study we identified direct activation of articular chondrocytes by OCP crystals, which are the BCP crystals with the greatest potential for inducing inflammation. OCP crystals induced nitric oxide (NO) production and inducible nitric oxide synthase (NOS) mRNA expression by isolated articular chondrocytes and cartilage fragments, in a dose-dependent manner and with variations over time. OCP crystals also induced IL-1beta mRNA expression. Using pharmacological and cytokine inhibitors, we observed that OCP crystals induced NO production and inducible NOS mRNA activation were regulated at both the transcriptional and the translational levels; were independent from IL-1beta gene activation; and involved p38 and c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, as further confirmed by OCP crystal-induced p38 and JNK MAPK phosphorylation. Taken together, our data suggest that the transcriptional inducible NOS response to OCP crystals involved both the p38 and the JNK MAPK pathways, probably under the control of activator protein-1. NO, a major mediator of cartilage degradation, can be directly produced by BCP crystals in chondrocytes. Together with synovial activation, this direct mechanism may be important in the pathogenesis of destructive arthropathies triggered by microcrystals.


Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus.
In the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetrahydrocurcumin in streptozotocin-induced diabetic rats by synthesizing tetrahydrocurcumin-loaded solid lipid nanoparticles. Box Behnken Design was employed for the optimization of tetrahydrocurcumin-loaded solid lipid nanoparticles (THC-SLNs). The optimal formulation was determined by doing an ANOVA to examine the relationship between the independent variables (drug-to-lipid ratio, surfactant concentration, and co-surfactant concentration) and the dependent variables (particle size, percent entrapment efficiency, and PDI). Particle size, PDI, and entrapment efficiency all showed statistical significance based on F-values and p-values. The optimized batch was prepared using a drug-to-lipid ratio (1:4.16), 1.21% concentration of surfactant, and 0.4775% co-surfactant (observed with a particle size of 147.1 nm, 83.58 ± 0.838 % entrapment efficiency, and 0.265 PDI, and the values were found very close with the predicted ones. As the THC peak vanishes from the DSC thermogram of the improved formulation, this indicates that the drug has been transformed from its crystalline form into its amorphous state. TEM analysis of optimized formulation demonstrated mono-dispersed particles with an average particle size of 145 nm which are closely related to zetasizer's results. In-vitro release study of optimized formulation demonstrated burst release followed by sustained release up to 71.04% throughout 24 hrs. Increased bioavailability of the adjusted THC-SLN was found in an in vivo pharmacokinetics research with 9.47 folds higher AUC(0-t) compared to plain THC-suspension. Additionally, pharmacodynamic experiments of optimized formulation demonstrated a marked decrease in blood glucose level to 63.7% and increased body weight from 195.8 ± 7.223 to 231.2 ± 7.653 on the 28th day of the study and showed a better anti-diabetic effect than plain drug suspension. Results of stability studies revealed that formulation can be stored for longer periods at room temperature. Tetrahydrocurcumin can be effectively administered by SLN for the treatment of diabetes.


Comparison of cytokine effects on mouse pancreatic alpha-cell and beta-cell lines. Viability, secretory function, and MHC antigen expression.
Cytokine effects on permanent cell lines of transformed mouse pancreatic alpha- and beta-cells were compared. The beta-tumor cell 1 (beta TC1) line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat insulin II promoter) produced insulin predominantly, although small quantities of intracellular glucagon (100:1 insulin to glucagon) were detectable by radioimmunoassay. The alpha TC1 line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat preproglucagon promoter) produced not only glucagon but also considerable quantities of insulin (4:1 glucagon to insulin) and preproinsulin mRNA. We therefore cloned alpha TC1 cells and obtained 12 glucagon-producing clonal cell lines that did not produce levels of insulin detectable by radioimmunoassay. Analysis by Northern blotting of total RNA from two lines, alpha TC1 clones 6 and 9, confirmed the absence of preproinsulin mRNA. No somatostatin or pancreatic polypeptide was detected by immunohistochemical staining in alpha TC1 clones 6 or 9 or beta TC1 cells. Rat recombinant gamma-interferon (IFN-gamma; 5-250 U/ml) or mouse recombinant interleukin 1 (IL-1; 1-25 U/ml) individually inhibited DNA synthesis in beta TC1 cells after 3 days of treatment. The two cytokines in combination acted synergistically to further depress DNA synthesis and increase cytotoxicity. In contrast, alpha TC1 clone 9 cells were not sensitive to inhibition of DNA synthesis by each cytokine individually, although glucagon synthesis was inhibited. The combination of these cytokines caused marked inhibition of DNA and glucagon syntheses in alpha TC1 clone 9 cells. alpha TC1 clone 9 cells were somewhat more resistant to the cytotoxic action of the combined cytokines than were beta TC1 cells. Incubation with 50 U/ml IFN-gamma induced class II MHC molecules (I-Ab, I-Ad, and I-Ed) and enhanced the constitutive expression of class I molecules (H-2Kb and H-2Kd) on the cell surfaces of beta TC1, uncloned alpha TC1, and alpha TC1 clones 6 and 9. Thus, these cell lines are heterozygous for MHC alleles derived from both parental strains used in the construction of the transgenic mice [C57BL/6J (H-2b) and DBA/2J (H-2d)]. Class II gene transcription induced by IFN-gamma was confirmed in beta TC1 and alpha TC1 clone 9 cells by Northern blot analysis with A alpha-, A beta-, E alpha, and E beta-DNA probes.(ABSTRACT TRUNCATED AT 400 WORDS)


Metal ion levels in total hip arthroplasty versus hip resurfacing.
Recent studies suggest that the tapered interface between stem and femoral head may be a substantial source of cobalt and chromium ion release after metal-on-metal (MOM) total hip arthroplasty (THA). This study compared patient ion levels after MOM hip resurfacing (HR) and MOM THA performed with identical acetabular components. 110 HRs were compared with 22 THAs. All had well-oriented components, unilateral implants, and serum ion studies beyond one year post-operatively. The HR group's median cobalt value was 1.11 μg/L vs. 2.86 μg/L for the THA patients. The HR group's median chromium value was 1.49 μg/L vs. 2.94 μg/L for THA. Significantly higher THA ion levels suggest a source of ions other than the MOM bearing itself.


Effects of cations on protein and peptide charging in electrospray ionization from aqueous solutions.
The effects of eight different cations with ionic radii between 69 and 337 pm on the charging of peptides and proteins with electrospray ionization from aqueous acetate salt solutions are reported. Significant adduction occurs for all cations except NH4(+), and the average protein charge is lower when formed from solutions containing salts compared with solutions without salts added. Circular dichroism and ion mobility results show the protein conformations are different in pure water compared with salt solutions, which likely affects the extent of charging. The average charge of protein and peptide ions formed from solutions with Li(+) and Cs(+), which have Gibbs solvation free energies (GSFEs) that differ by 225 kJ/mol, is similar. Lower charge states are typically formed from solutions with tetramethylammonium and tetraethylammonium that have lower GSFE values. Loss of the larger cations that have the lowest GSFEs is facile when adducted protein ions are collisionally activated, resulting in the formation of lower analyte charge states. This reaction pathway provides a route to produce abundant singly protonated protein ions under native mass spectrometry conditions. The average protein and peptide charge with NH4(+) is nearly the same as that with Rb(+) and K(+), cations with similar GSFE and ionic radii. This indicates that proton transfer from NH4(+) to proteins plays an insignificant role in the extent of protein charging in native mass spectrometry.


Targeting 14-3-3ζ by a small-molecule compound AI-34 maintains epithelial barrier integrity and alleviates colitis in mice via stabilizing β-catenin.
Aberrant intestinal epithelial barrier function is the primary pathology of Ulcerative colitis (UC), making it a desirable drug target. In this study, our small-molecule compound AI-34 exerted a significant protective effect in an LPS-induced epithelial barrier injury model. In vitro, AI-34 treatment significantly decreased cell permeability, increased transmembrane resistance, and maintained the junctional protein (ZO-1 and E-cadherin) levels in monolayer cells. Using the LiP-small molecule mapping approach (LiP-SMap), we demonstrated that AI-34 binds to 14-3-3ζ. AI-34 promoted the interaction between 14-3-3ζ and β-catenin, decreasing the ubiquitination of β-catenin and thus maintaining intestinal epithelial barrier function. Finally, AI-34 triggered the stabilization of β-catenin mediated by 14-3-3ζ, provoking a significant improvement in the DSS-induced colitis model. Our findings suggest that AI-34 may be a promising candidate for UC treatment.


Spontaneous pneumothorax in Norfolk.
A Chest Unit's experience of spontaneous pneumothorax over a 14-year period has been analysed: 236 patients, the majority of whom were young males and were smokers, had a total of 315 episodes of spontaneous pneumothorax during this time. Ninety-five per cent were successfully treated at first attendance by observation alone or by intercostal tube drainage. The choice of treatment did not influence the recurrence rate. The remaining 5% were treated surgically. Altogether 37 pleural abrasions or pleurectomies were performed, half because the lung failed to expand with intercostal tube drainage and the remainder because of one or more further episodes. There were no recurrences following this procedure. When definitive surgery was not performed after a recurrence there was a 40% incidence of third episodes. There was no mortality. The results of this study confirm that the vast majority of cases can be treated successfully under medical supervision with a recurrence rate around 20%. Surgical intervention should be considered in those who have a second episode or when pneumothorax occurs on the other side.


Accuracy assessment of a novel semiautomatic method evaluating bone grafts around the dental implant: an in vitro and ex vivo study.
The present study aimed to evaluate the accuracy and repeatability of morphological contour interpolation (MCI)-based semiautomatic segmentation method for volumetric measurements of bone grafts around dental implants. Three in vitro (one with a cylinder and two with a geometrically complex form) and four ex vivo models (peri-implant cylinder-shaped bone defect) were created for imitating implant placement with simultaneous guided bone regeneration (GBR) procedure. Cone beam computerized tomography (CBCT) scans of all models were obtained with the same parameters. For volumetric measurements, the actual volumes of bone grafts in models were assessed by computer-aided calculation and both manual and MCI-based methods were utilized as test methods. The accuracy of the methods was evaluated by comparing the measured value and the actual volume. The repeatability was assessed by calculating the coefficients of variation of repeated measurements. For the accuracy of three dimensional (3D) reconstructions, the computer-designed corresponding models were set as the reference and the morphological deviation of 3D surface renderings created by two methods were evaluated by comparing with reference. Besides, measurement time was recorded and a comparison between the two methods was performed. High accuracy of the MCI-based segmentation method was found with a discrepancy between the measured value and actual value never exceeding - 7.5%. The excellent repeatability was shown with coefficients of variation never exceeding 1.2%. The MCI-based method showed less measurement time than the manual method and its 3D surface rendering showed a lower deviation from the reference.


Plasma levels of soluble adhesion molecules sPECAM-1, sP-selectin and sE-selectin are associated with relapsing-remitting disease course of multiple sclerosis.
Adhesion molecule mediated leukocyte migration into the central nervous system is considered to be a critical step in the pathogenesis of multiple sclerosis (MS). We measured plasma levels of the soluble adhesion molecules sPECAM-1, sP-selectin and sE-selectin in 166 MS patients and in 36 healthy blood donors with ELISA. sPECAM-1, sP-selectin and sE-selectin plasma concentrations showed a significant increase in the relapsing-remitting disease course of MS and were elevated during relapse. These findings indicate that sPECAM-1, sP-selectin and sE-selectin might be implemented as paraclinical markers of disease activity in MS with restriction to the clinical course of the disease.


Explosive nucleosynthesis in stars.
Recent calculations provide convincing evidence that the naturally occurring nuclei were produced in explosions. The required temperature, density and expansion rate strongly suggest that before the explosion the objects were ordinary evolved massive stars. We review these new developments and present a new table indicating our hypothesis concerning the origin of the nuclei in the mass range 20 < or = A < or = 62.


A new steroidal saponin from Agave attenuata.
A new steroidal saponin was isolated from the leaves of Agave attenuata. Its structure was established as (3beta,beta,25S)-spirostan-3-yl O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 2)-O-[beta-D-glucopyranosyl-(1 --> 3)]-beta-D-glucopyranosyl-(1 --> 4)-beta-D-galactopyranoside. The structural identification was performed using detailed analyses of 1H- and 13C-NMR spectra including 2D NMR spectroscopic techniques (COSY, HETCOR, and COLOC) and chemical conversions. The hemolytic activity of the steroidal saponin was evaluated using an in vitro assay.


Nitrogen and energy balance in depleted patients undergoing major gastrointestinal surgery: response to TPN.
We studied energy and nitrogen balance during pre- and post-operative parental nutrition in 16 malnourished patients undergoing major abdominal surgery due to suspected gastrointestinal malignancy. The response to amino-acids alone (1.5g/kg; group AA) and energy alone (energy intake equal to pre-nutrition energy expenditure; group REE) was studied during the first day of pre- and post-operative nutrition. On the second day of parental nutrition both groups received amino-acids (1.5g/kg) and non-protein energy equal to pre-nutrition energy expenditure. Energy expenditure (EE) was increased both pre- and post-operatively (EE 112 +/- 15 and 121 +/- 14% of predicted, respectively). Nitrogen balance in group REE was more positive than in group AA on pre-operative day 2 (81.1 +/- 35.8 vs. 17.8 +/- 60.5 mg/kg; p < 0.05). N balance was better pre- than post-operatively on day 2 in both groups (17.8 +/- 60.5 vs. -49.6 +/- 49.2 mg/kg; group AA and 81.1 +/- 35.8 vs. 7.8 +/- 82.6 mg/kg; group REE; p < 0.05). Pre-operatively, administration of energy alone reduced EE (1489 +/- 301 vs. 1403 +/- 312 kcal/day; p < 0.05). We conclude that: 1) The patients were hypermetabolic both pre- and post-operatively. 2) Surgical trauma had a minor effect on EE. 3) Good nitrogen retention could be obtained both pre- and post-operatively at close to zero energy balance. 4) EE increased during the infusion of amino-acids more post-operatively than pre-operatively; non-protein energy at EE had no thermogenic effect. 5) Priming with energy improved nitrogen balance on the following day.


U12 intron positions are more strongly conserved between animals and plants than U2 intron positions.
We report that the positions of minor, U12 introns are conserved in orthologous genes from human and Arabidopsis to an even greater extent than the positions of the major, U2 introns. The U12 introns, especially, conserved ones are concentrated in 5'-portions of plant and animal genes, where the U12 to U2 conversions occurs preferentially in the 3'-portions of genes. These results are compatible with the hypothesis that the high level of conservation of U12 intron positions and their persistence in genomes despite the unidirectional U12 to U2 conversion are explained by the role of the slowly excised U12 introns in down-regulation of gene expression.


Newly designed six-membered azasugar nucleotide-containing phosphorothioate oligonucleotides as potent human immunodeficiency virus type 1 inhibitors.
A series of modified oligonucleotides (ONs), characterized by a phosphorothioate (P S) backbone and a six-membered azasugar (6-AZS) as a sugar substitute in a nucleotide, were newly synthesized and assessed for their ability to inhibit human immunodeficiency virus type 1 (HIV-1) via simple treatment of HIV-1-infected cultures, without any transfection process. While unmodified P S ONs exhibited only minor anti-HIV-1 activity, the six-membered azasugar nucleotide (6-AZN)-containing P S oligonucleotides (AZPSONs) exhibited remarkable antiviral activity against HIV-1/simian-human immunodeficiency virus (SHIV) replication and syncytium formation (50% effective concentration = 0.02 to 0.2 microM). The AZPSONs exhibited little cytotoxicity at concentrations of up to 100 microM. DBM 2198, one of the most effective AZPSONs, exhibited antiviral activity against a broad spectrum of HIV-1, including T-cell-tropic, monotropic, and even drug-resistant HIV-1 variants. The anti-HIV-1 activities of DBM 2198 were similarly maintained in HIV-1-infected cultures of peripheral blood mononuclear cells. When we treated severely infected cultures with DBM 2198, syncytia disappeared completely within 2 days. Taken together, our results indicate that DBM 2198 and other AZPSONs may prove useful in the further development of safe and effective AIDS-therapeutic drugs against a broad spectrum of HIV-1 variants.


Saxagliptin mitigates airway inflammation in a mouse model of acute asthma via modulation of NF-kB and TLR4.
Saxagliptin (Saxa), a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, is widely used for the treatment of type 2 diabetes mellitus. It has been documented to have immunomodulatory and anti-inflammatory actions. Our objective was to delineate the protective effect and the underlying mechanism of Saxa-in comparison with Dexamethasone (Dexa) - in airway inflammation induced by ovalbumin (OVA) in mice. Mice were OVA-sensitized and challenged for the induction of acute asthma. Mice were orally administrated Saxa or Dexa. Total and differential cell counts, lactate dehydrogenase (LDH) and total protein concentrations were assessed in bronchoalveolar lavage fluid (BALF). The toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-kB), reduced glutathione (GSH), and total nitrate/nitrite products (NOx) levels as well as myeloperoxidase (MPO) activity in lung tissues were measured. Histopathological examination of the lung specimens was carried out using the hematoxylin and eosin (H & E) staining. Histopathological examination revealed that both Saxa and Dexa ameliorated OVA-induced inflammatory changes and significantly reduced total and differential leukocyte counts, LDH and total protein level in BALF upon comparison with OVA group. In addition, both treatments significantly mitigated OVA-induced oxidative stress as evidenced by diminished lung NOx level and MPO activity and elevated GSH level. The elevation of TLR4 and NF-kB levels in lung tissue were ameliorated by Saxa and Dexa administration. Saxa had marked antiasthmatic effect in OVA-induced allergic asthma through modulation of TLR4 and NF-κB signaling. Also, Saxa may represent a promising therapeutic agent for acute allergic asthma.


Plasma protein binding of furosemide in the elderly.
The protein binding of furosemide was investigated in plasma from 22 old and 11 young subjects by equilibrium dialysis. The unbound fraction of furosemide was 3.16% in plasma from the elderly and 1.7% in plasma from the young. A significant correlation was found between the unbound fraction of furosemide and the plasma concentration of albumin. The average number of binding sites was 3.8 (elderly) and 2.7 (young) 10(-6) mol/g albumin. The average association constant (K) was 4.3 (elderly) and 4.2 (young) 10(5) M-1. By increasing the concentration of furosemide up to 200 micrograms/ml buffer the unbound fraction of the drug rose to 5.2% (elderly) and 3.5% (young).


The role of sonographic optic nerve sheath diameter measurements in pediatric head trauma.
To determine the accuracy of bedside sonographic measurements of optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse (ETD) diameter ratios to predict space-occupying lesions (SOLs) or elevated intracranial pressure (ICP) in pediatric head trauma. Children who presented to the emergency department with head trauma and underwent cranial computed tomography (CT) were enrolled and examined by ocular ultrasonography (US), and the ONSD was measured at 3 mm posterior to the globe and ETD were measured. Ratios of ONSD at 3 mm/ETD were calculated. All ONSD measurements and ratios were calculated from cranial CT images. Subjects with elevated ICP had increased ONSD measurements and ratios. To predict elevated ICP, the AUC for ONSD at 3 mm was 0.956 (95% CI 0.896-1). At a cut-off level of 5.1 mm, the sensitivity and specificity of ONSD 3 mm values for elevated ICP were 92.9% and 94.0%. For the ONSD 3 mm/ETD ratio, it was 0.980 (95% CI 0.959-1). At a cut-off level of 0.22, the sensitivity and specificity were 100% sensitivity and 88.0%. All sonographic ONSD measurements and ratios were significantly correlated with readings calculated from cranial CT images. Sonographic ONSD measurements and ratios were found to be quite sensitive to detect elevated ICP on cranial CT images. Additionally, there was a significant correlation between measurements calculated by ocular US and cranial CT scans. Bedside ocular US seems to be a promising and useful tool to determine ICP in children with head trauma.


Qualitative and quantitative cellular glycomics of glycosphingolipids based on rhodococcal endoglycosylceramidase-assisted glycan cleavage, glycoblotting-assisted sample preparation, and matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry analysis.
Glycosphingolipids (GSLs) are crucially important components of the cellular membrane, where they comprise microdomains with many critical biological functions. Despite this fact, qualitative and quantitative techniques for the analysis of GSLs still lag behind the needs of researchers. In this study, a reliable procedure for the elucidation of cellular GSL-glycomes was established based on (a) enzymatic glycan cleavage by endoglycosylceramidases derived from Rhodococcus sp. in combination with (b) glycoblotting-assisted sample preparation. The mixture of endoglycosylceramidase I and II was employed to maximize the release of glycan moieties from the major classes of GSLs (i.e. ganglio-, (neo)lacto- and globo-series GSLs). The glycoblotting technique enabled the quantitative detection of GSL-glycans using as few as 2 × 10(5) cells. Thirty-seven different kinds of cellular GSL glycans were successfully observed in 11 kinds of cells, including Chinese hamster ovary cells and their lectin-resistant mutants as well as murine and human embryonic carcinoma cells. Furthermore, in-depth structural clarification in terms of discrimination of isomers was achieved by MALDI-TOF/TOF mass spectrometry analysis and/or linkage-specific glycosidase digestion. These novel analytical techniques were shown to be capable of delineating cell-specific GSL-glycomes. Thus, they are anticipated to have a broad range of applications for the characterization, description, and comparison of various cellular/tissue samples in the fields of drug discovery and regenerative medicine.


Relationship between extent of coronary artery disease and correlative risk factors.
An analysis was made of correlative factors which might be related to the angiographically measured extent of coronary artery disease in 140 patients. All patients presented with clinically important chest pain. Thirty-three had a normal coronary arteriogram. The extent of the atheromatous process was measured precisely at angiography by three different techniques. A coronary score, based on the percentage of luminal narrowing, was found to be best suited for the analysis. The most important contributory factors to the severity of atherosclerosis was duration of clinical history, number of previous myocardial infarctions, and male sex, but more specifically elevation of serum cholesterol and diabetes mellitus. Cigarette smoking, obesity, hypertension, a family history of atherosclerosis, and elevated serum triglycerides had a positive influence but this was not statistically significant.


Plasma apolipoprotein C1 concentration is associated with plasma triglyceride concentration, but not visceral fat, in patients with type 2 diabetes.
Apolipoprotein C1 (apoC1) is likely to play an important role in triglyceride (TG) metabolism. Mice overexpressing human apoC1 present decreased adipose tissue stores. This study aimed to determine whether apoC1 concentration influences fat mass and distribution and liver fat content (LFC) in patients with type 2 diabetes (T2D). ApoC1 concentrations were measured by ELISA in 113 T2D patients and 56 normolipidaemic-normoglycaemic subjects. Visceral and subcutaneous fat areas were determined by single-slice axial T1-weighted magnetic resonance imaging (MRI), while LFC was measured by hydrogen-1 ((1)H) MR spectroscopy. ApoC1 concentrations were higher in T2D patients than in normolipidaemic-normoglycaemic subjects (P<0.0001), and did not correlate with visceral or subcutaneous fat areas, but significantly correlated with TG (P<0.0001) and LFC (P=0.02) in T2D patients. However, the correlation between apoC1 and LFC was lost after adjusting for TG. ApoC1 concentration was also significantly higher in T2D patients with TG<1.5mmol/L than in control subjects (P<0.0001), although both groups had similar TG levels. On multivariate analysis performed in T2D patients with TG<1.5mmol/L and control subjects, apoC1 concentration was independently and positively associated with type 2 diabetes (P<0.0001) and TG levels (P=0.03). This study reports, for the first time, that apoC1 is increased in T2D patients and is significantly correlated with TG, whereas no association was found between apoC1 and adipose tissue. This indicates that, in T2D, apoC1 may play a role in TG metabolism, but is unlikely to modulate fat mass and distribution. This increased apoC1 concentration in T2D patients is not only explained by the increased TG level in T2D patients.


Psychometric properties of an instrument to measure nursing students' quality of life.
It is important for clinical nursing teachers and managers to recognize the importance of nursing students' quality of life (QOL) since they are the source of future nurses. As yet, there is no quality of life evaluation scale (QOLES) specific to them. This study designed a quantitative instrument for evaluating QOL of nursing students. The study design was a descriptive survey with mixed methods including literature review, panel discussion, Delphi method, and statistical analysis. The data were collected from 880 nursing students from four teaching hospitals in Wuhan, China. The reliability and validity of the scale were tested through completion of the QOLES in a cluster sampling method. The total scale included 18 items in three domains: physical, psychological, and social functional. The cumulative contributing rate of the three common factors was 65.23%. Cronbach's alpha coefficient of the scale was 0.82. This scale had good reliability and validity to evaluate nursing students' QOL.


Changes in use of breast-conserving therapy in years 1978-2000.
The treatment of breast cancer patients has changed rapidly in the past decade, but empirical data at local and national level are scarce. Predicting the consequences of screening for primary treatment is consequently difficult. The aim of this analysis of records on admissions to hospital of women with breast cancer and/or for breast surgery (1975-90) together with a survey of all Dutch radiotherapy departments (1986-88) is to show the change in breast-conserving therapy and other primary treatment before the start of breast cancer screening in The Netherlands. There was a modest increase in breast-conserving therapy after 1981, coinciding with the first publication on its trial, followed by a sharp increase between 1985 and 1990, after the second publication. At the end of that 5 year period, 36% of all women with newly diagnosed invasive breast cancer underwent this type of surgery. Breast-conserving surgery is always followed by radiotherapy, but there has been a clear reduction in post-operative radiation after mastectomy. The percentage of breast-conserving therapy is at present higher in The Netherlands than in the USA. Implementing the Dutch screening programme will result in a maximum increase in breast-conserving therapy at national level of 34%, which stabilises at +21%, or a 50% maximum increase at local level. The number of women treated by mastectomy will ultimately decrease by 9%. Given the rapidity of change towards the use of breast-conserving surgery, which is enhanced by screening, recent information will be needed in predicting capacity and assessing whether screen-detected women are treated adequately.


Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome.
The prevalence of myocarditis was retrospectively evaluated in 71 consecutive necropsy patients who died from acquired immunodeficiency syndrome (AIDS) between 1982 and 1986. Myocarditis was found in 37 cases (52%). Biventricular dilation at necropsy was present in seven cases (10%) and was accompanied by myocarditis in each case; fatal congestive heart failure occurred in four of these seven cases. Although viral, protozoan, bacterial, fungal and mycobacterial opportunistic pathogens were present in myocardial sections of 7 of 37 myocarditis cases, the etiology of myocarditis in the majority of these patients with AIDS remained idiopathic. Thus, myocarditis is a frequent finding at necropsy in patients with AIDS and may contribute to the development of biventricular dilation.


FixL-like sensor FlbS of Brucella abortus binds haem and is necessary for survival within eukaryotic cells.
Replication of Brucella inside eukaryotic cells is essential for pathogenesis, and successful infection requires rapid adaptation to the intracellular milieu. Close relatives of Brucella use the two-component system FixLJ to survive inside the host. We aimed to identify a homologous sensor in Brucella abortus. A predicted protein with transmembrane and conserved histidine kinase domains was identified as the Fix-like Brucella sensor, FlbS. Although it lacks the PAS domain, recombinant FlbS binds haem in vitro. An internal in-frame deletion in flbS severely decreased B. abortus survival inside professional and non-professional phagocytes. This phenotype was reverted by genetic complementation. These results indicate the critical role of this haemoprotein in the intracellular lifestyle of Brucella.