Infectious optic neuropathies: a clinical update.
Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular findings. Diagnosis is confirmed by serologic testing and polymerase chain reaction in selected cases. Treatment of infectious optic neuropathies involves the use of specific anti-infectious drugs and corticosteroids to suppress the associated inflammatory reaction. The visual prognosis is generally good, but persistent severe vision loss with optic atrophy can occur. This review presents optic neuropathies caused by specific viral, bacterial, parasitic, and fungal diseases.


The symptom burden of chronic critical illness.
To assess self-reported symptom burden of chronic critical illness. Prospective cohort study. Respiratory care unit for treatment of chronically critically ill patients at an academic, tertiary-care, urban medical center. Fifty patients who underwent elective tracheotomy and transfer from an adult intensive care unit to the respiratory care unit for weaning from mechanical ventilation. Assessment of physical and psychological symptoms through patients' self-reports using a modification of the Condensed Form of the Memorial Symptom Assessment Scale. We measured self-reported symptom burden, ventilator outcomes, and vital status and functional status at discharge and 3 and 6 months after discharge. Half of the patients were successfully liberated from mechanical ventilation, but most hospital survivors were discharged to skilled nursing facilities and more than half of the cohort was dead at 3 months after discharge. Seventy-two percent (36 of 50) of patients were able to self-report symptoms during the period of respiratory care unit treatment. Among patients responding to symptom assessment, approximately 90% were symptomatic. Forty-four percent of patients reported pain at the highest levels. More than 60% reported psychological symptoms at these levels, and approximately 90% of patients reported severe distress due to difficulty communicating. Physical and psychological symptom distress is common and severe among patients receiving treatment for chronic critical illness. The majority of these patients die soon after hospital discharge. Given the level of distress in our study patients and the high mortality rate that we and others have observed, greater attention should be given to relief of pain and other distressing symptoms and to assessment of burdens and benefits of treatment for the chronically critically ill.


Gut Microbiota From Sjögren syndrome Patients Causes Decreased T Regulatory Cells in the Lymphoid Organs and Desiccation-Induced Corneal Barrier Disruption in Mice.
Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy (n = 20), dry eye (n = 4) and SS (n = 7) subjects. The observed Operational Taxonomic Units (OTUs) and Shannon alpha diversity were significantly decreased in SS compared to healthy controls, and there was a significant inverse correlation between observed OTUs and ocular severity score. We also identified specific bacterial strains that are differentially modulated in SS vs. healthy subjects. To investigate if the differential composition of intestinal microbiome would have an impact on the immune and eye phenotype, we performed functional studies using germ-free mice colonized with human intestinal microbiota from SS patients and healthy controls. Flow cytometry analysis demonstrated reduced frequency of CD4+ FOXP3+ cells in ocular draining cervical lymph nodes (CLN) in mice colonized with SS patient intestinal microbiota 4 weeks post-colonization. We also found that offspring of SS-humanized mice also have fewer CD4+FOXP3+ cells in the CLN as well as spleen, demonstrating vertical transmission. SS-humanized mice subjected to desiccating stress exhibited greater corneal barrier disruption as compared to healthy control humanized mice under the same conditions. Taken together, these data support the hypothesis that the intestinal microbiota can modulate ocular surface health, possibly by influencing development of CD4+ FOXP3+ regulatory T cells (Tregs) in the ocular draining lymph nodes.


Chronic intermittent hypoxia at high altitude exposure for over 12 years: assessment of hematological, cardiovascular, and renal effects.
The aim of this cross-sectional study was to assess the health status of subjects weekly commuting between sea level and 3550-m altitude for at least 12 yr (average 22.1 +/- 5.8). We studied 50 healthy army men (aged 48.7 +/- 2.0) working 4 days in Putre at 3550-m altitude, with 3 days rest at sea level (SL) at Arica, Chile. Blood pressure, heart rate, Sa(O(2) ), and altitude symptoms (AMS score and sleep status) were measured at altitude (days 1, 2, and 4) and at SL (days 1, 2, and 3). Hematological parameters, lipid profile, renal function, and echocardiography were performed at SL on day 1. The results showed signs of acute exposure to hypoxia (tachycardia, high blood pressure, low Sa(O(2) )), AMS symptoms, and sleep disturbances on day 1, which rapidly decreased on day 2. In addition, echocardiographic findings showed pulmonary hypertension (PAPm > 25 mmHg, RV and RA enlargement) in 2 subjects (4%), a PAPm > 20 mmHg in 14%, and a right ventricle thickness >40 mm in 12%. Hematocrit (45 +/- 2.7) and hemoglobin (15 +/- 1.0) were elevated, but lower than in permanent residents. There was a remarkably high triglyceride level (238 +/- 162) and a mild decrease of glomerular filtration rate (34% under 90 mL/min and 8% under 80 mL/min of creatinine clearance). In conclusion, in these preliminary results, in chronic intermittent hypoxia exposure even over longer periods, most subjects still show symptoms of acute altitude illnesses, but a faster recovery. Findings in triglycerides, in the pulmonary circulation and in renal function, are also a matter of concern.


[A case of mucinous tubular and spindle cell carcinoma of the kidney].
We report a case of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. A 68-years old female consulted a primary hospital with a chief complaint of back pain. Computed tomography revealed the tumor of the left kidney, so she was referred to our department. The tumor, 45 x 42 mm in length, was slightly enhanced, and that had well-defined margins. We performed radical nephrectomy. Pathological findings suggested MTSCC. MTSCC is a rare type of renal cell carcinoma composed of a combination of low-grade tubular cuboidal cells and spindle cells in a mucinous stroma. The immunohistochemistry is effective in its diagnosis.


Pregnancy outcomes in HIV-infected and uninfected women in rural and urban South Africa.
To describe pregnancy outcomes among clade C HIV-infected and uninfected women in South Africa. A longitudinal cohort study. Pregnant women attending 9 rural/urban antenatal clinics were prospectively recruited and followed up. Women were seen at the clinic or at home after delivery on 4 occasions after enrollment: 2 times within the first 2 weeks of the newborn's life at home, and every 2 weeks thereafter until their first health clinic visit when the infant was 6 weeks old. A total of 3465 women were enrolled; 615 withdrew after delivery, moved away, or had a missing or indeterminate HIV status, leaving 2850 women (1449 HIV-infected women). Six women died after delivery and there were 17 spontaneous abortions and 104 stillbirths. An adverse pregnancy outcome was independently associated with HIV infection (adjusted odds ratio [AOR] = 1.63; P = 0.015), urban enrollment (AOR = 0.39; P = 0.020), and nonhospital delivery (AOR = 13.63; P < 0.001) as well as with a CD4 count <200 cells/mL among HIV-infected women (AOR = 1.86; P = 0.127). Among 2529 singleton liveborn babies, birth weight was inversely associated with maternal HIV (AOR = 1.45; P = 0.02) and maternal middle upper arm circumference (AOR = 0.93; P < 0.001). Early infant mortality was not significantly associated with maternal HIV (hazard ratio [HR] = 1.18; P = 0.52) but was with urban sites (HR = 0.34; P = 0.045). Low birth weight substantially increased mortality (AOR = 8.3; P < 0.001). HIV status of infants by 8 weeks of age (14.6%, 95% confidence interval: 12.5% to 17.0%) was inversely associated with maternal CD4 cell count and birth weight. HIV-infected women are at a significantly increased risk of adverse pregnancy outcomes. Low-birth-weight infants of HIV-infected and uninfected women are at substantially increased risk of dying.


Acute massive myelofibrosis with acute lymphoblastic leukemia.
Acute myelofibrosis is characterized by pancytopenia of sudden onset, megakaryocytic hyperplasia, extensive bone marrow fibrosis, and the absence of organomegaly. Acute myelofibrosis in patients with acute lymphoblastic leukemia is extremely rare. We report a 4-year-old boy who was diagnosed as having acute massive myelofibrosis and acute lymphoblastic leukemia. Performing bone marrow aspiration in this patient was difficult (a "dry tap"), and the diagnosis was established by means of a bone marrow biopsy and immunohistopathologic analysis. The prognostic significance of acute myelofibrosis in patients with acute lymphoblastic leukemia is not clear.


Measured maximal oxygen uptake in a multi-stage shuttle test and treadmill-run test in trained athletes.
The aims of the study were: i) to compare the measured maximal oxygen uptake (MVO2max) during the 20 m multi-stage shuttle test (MST) with MVO2max during an incremental treadmill-run test (TRT), and ii) to establish the reliability of MVO2max during MST, in trained athletes. 8 well-trained endurance-athletes (END) and 8 athletes involved in team games (GAM) performed the MST twice (i.e. MST1 and MST2) and the TRT once, in 3 separate sessions. MVO2maxx attained in the MST and TRT was measured using a portable respiratory analyser (model K4 RQ, Cosmed). MVO2max attained in the MST and TRT were significantly different for the END athletes (4.1+/-0.28 vs 4.45+/-0.31 Lxmin-1, P<0.05) but not for GAM athletes (4.01+/-0.51 vs 4.1+/-0.59 Lxmin-1, P>0.05). The 95% limits of agreement for MVO2max in the MST in Lxmin-1 were -0.67 to 0.27. MVO2max in MST1 and MST2 were not significantly different for END athletes (4.18+/-0.39 vs 4.1+/-0.28 Lxmin-1, P>0.05) and GAM athletes (4.01+/-0.55 vs 4.01+/-0.51 Lxmin-1, P>0.05). Reliability indicators for MVO2max in Lxmin-1 for MST test-retest were: typical error (TE)=0.14, coefficient of variation (CV)=3.5 and intra-class correlation (ICC)=0.90. MVO2max in the MST was lower than that measured in the TRT for the END athletes but not for the GAM athletes. Sport-specificity was an important consideration, especially when testing END athletes for VO2max. MVO2max in the MST showed acceptable levels of reproducibility.


Influence of internal structures of hair fiber on hair appearance. III. Generation of light-scattering factors in hair cuticles and the influence on hair shine.
The effects of thermal treatments on hair fiber induced by blow-drying have been investigated. It was found that the hair shows whitish and powdery appearance after heat drying, especially when dark hair is rapidly dried from a wet condition. For all kinds of hair, the appearance of numerous glittering speckles was confirmed on the cuticle surface by optical microscopic observations. SEM images of hair transverse and longitudinal sections with glittering speckles revealed that the splitting of cuticle layers generated by blow-drying occurred not only at the outermost parts of cuticle cells but also at the inner parts of the cellular interfaces. The release and uptake of moisture through fiber surfaces induces deformation of cuticle cells, probably because of anisotropic swelling or drying of the cells. The cuticles with glittering speckles are found to be fragile and are easily damaged in combination with other mechanical stresses such as combing force. Furthermore, the authors have found an efficient system for both improving hair shine and preventing cuticle damage caused by the blow-drying/combing process.


Collagen abundance controls melanoma phenotypes through lineage-specific microenvironment sensing.
Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree of pigmentation, indicative for a differentiated phenotype. Indeed, studies in mice and fish show that melanoma cells switch to a differentiated phenotype at secondary sites, possibly because in melanoma differentiation is closely linked to proliferation through the lineage-specific transcriptional master regulator MITF. Importantly, while a lot of effort has gone into identifying factors that induce the de-differentiated/invasive phenotype, it is not well understood how the switch to the differentiated/proliferative phenotype is controlled. We identify collagen as a contributor to this switch. We demonstrate that collagen stiffness induces melanoma differentiation through a YAP/PAX3/MITF axis and show that in melanoma patients increased collagen abundance correlates with nuclear YAP localization. However, the interrogation of large patient datasets revealed that in the context of the tumour microenvironment, YAP function is more complex. In the absence of fibroblasts, YAP/PAX3-mediated transcription prevails, but in the presence of fibroblasts tumour growth factor-β suppresses YAP/PAX3-mediated MITF expression and induces YAP/TEAD/SMAD-driven transcription and a de-differentiated phenotype. Intriguingly, while high collagen expression is correlated with poorer patient survival, the worst prognosis is seen in patients with high collagen expression, who also express MITF target genes such as the differentiation markers TRPM1, TYR and TYRP1, as well as CDK4. In summary, we reveal a distinct lineage-specific route of YAP signalling that contributes to the regulation of melanoma pigmentation and uncovers a set of potential biomarkers predictive for poor survival.


The relationship between beta-adrenoceptor regulation and beta-adrenergic responsiveness in hepatocytes. Studies on acquisition, desensitization and resensitization of isoproterenol-sensitive adenylate cyclase in primary culture.
The role of beta-adrenoceptor regulation in the mechanisms controlling beta-adrenergic responsiveness in hepatocytes was explored, using primary monolayer cultures. When plated in vitro, these cells gradually acquire a strong catecholamine-sensitive adenylate cyclase activity and an enhanced ability to bind the beta-adrenoceptor ligand [125I]iodocyanopindolol (125ICYP). Examination of the time course showed that the increase in the number of 125ICYP binding sites was detectable within 1-2 h of culturing and slightly preceded the elevation of isoproterenol-responsive activity. Then the responsiveness rose steeply and between about 5-24 h it closely followed the increase in beta-receptor binding. Addition of isoproterenol (10 microM) to cells after 20 h of culturing caused a rapid homologous desensitization of the adenylate cyclase (50% after about 5 min). This was paralleled by a down-regulation of beta-adrenoceptors measured both in membrane particles and in total cell lysates. Removal of isoproterenol led to a resensitization of the adenylate cyclase, which was rapid and protein-synthesis-independent after a brief (10-min) desensitization, or slow and cycloheximide-sensitive after prolonged (4-h) exposure to the agonist. In both cases an up-regulation of the 125ICYP binding paralleled the recovery from refractoriness. In contrast, no concurring changes in 125ICYP binding were measured when the beta-adrenoceptor-linked adenylate cyclase activity was enhanced by pretreatment with pertussin toxin (islet-activating protein, IAP) or was desensitized by exposure of the cells to glucagon or 8-bromo-cAMP; however, these modulations of the adenylate cyclase were nonselective, since the pretreatments with IAP, glucagon or 8-bromo-cAMP affected both isoproterenol-sensitive and glucagon-sensitive activities. The results suggest that, in hepatocytes, regulation at the beta-adrenoceptor level is a major determinant for both short-term and long-term selective changes of the beta-adrenergic responsiveness.


Autoimmune thyroid disease in children with diabetes and adolescents: A single center study from south Punjab.
To evaluate the prevalence of autoimmune thyroid disease in children with diabetes. The descriptive cross-sectional study was conducted from January to December 2019 at the Children Hospital and the Institute of Child Health, Multan, Pakistan, and comprised paediatric type 1 diabetes mellitus patients of both genders. Blood samples were obtained for detailed testing of thyroid functions tests. Data was analysed using SPSS 20. Of the 161 paediatric subjects, 83(51.6%) were boys. The overall mean age was 9.7±4.3 years. Thyroid peroxidase antibody was positive in 34(21.1%) patients and thyroglobulin antibody in 27(16.7%). Both antibodies were positive in 17(10.5%) patients. Six (3.7%) patients had evidence of subclinical hypothyroidism, 8(4.9%) had overt hypothyroidism and 1(0.62%) had hyperthyroidism. The prevalence of autoimmune thyroid disease among children and adolescents with type 1 diabetes mellitus was 21%, with hypothyroidism being more prevalent compared to hyperthyroidism.


The presence of dental disease can be a risk factor for recurrent Helicobacter pylori infection after eradication therapy: a 3-year follow-up.
We investigated whether dental disease might be associated with a higher recurrence of Helicobacter pylori infection after successful eradication by triple therapy. Consecutive patients with successful H. pylori eradication, defined by negative results for both histology and (13)C-urea breath test (UBT) performed 6 weeks after triple therapy, were enrolled in the study. Each patient was scheduled for serial UBT and dental assessments at the end of the first, second, and third years. Patients were categorized into a "dental disease" group or "no dental disease" group at the first-year follow-up. Patients in the dental disease group whose dental disease had been cured during the second- and third-year follow-up periods, were transferred to a "dental treatment" group. The first-year H. pylori recurrence rate was higher in the 159 patients with dental disease than in those 200 patients without dental disease (13.2 % vs. 3.5 %, P < 0.001; relative risk [95 %CI], 4.2 [1.7 - 10.1]). At both the second-year and the third-year follow-up, the annual H. pylori recurrence rates were higher in the dental disease group than in the no dental disease group or dental treatment group (second year, 18.4 % vs. 2.8 % or vs. 5.7 %, P < 0.001; third year, 20 % vs. 3.8 % or vs. 6.3 %, P < 0.001). The presence of dental disease could predispose to recurrent H. pylori infection after successful eradication. Dental surveillance and care after H. pylori eradication is a rational step for preventing recurrence of H. pylori, especially in those with dental diseases.


Validation of QuEChERS Method for Estimation of Imidacloprid and its Metabolites in Cotton Flower, Pollen, Nectariferous Tissue, and Honey.
Exposure of Apis mellifera to neonicotinoid insecticides is one of the factors attributed to the recent decline in A. mellifera populations resulting in economic and ecological losses due to loss of pollination services. Honeybees can get exposed to neonicotinoids like imidacloprid directly in the field at the time of application as well as during consumption of pollen and nectar from treated plants. In addition, some metabolites of imidacloprid are more toxic than the parent compound. So, the fate of imidacloprid and its metabolites in commodities to which honeybees get exposed needs to be overhauled. To validate QuEChERS method for estimation of imidacloprid and its metabolites in cotton flower, pollen, nectariferous tissue, and honey using HPLC. The QuEChERS method was validated in terms of selectivity, linearity, LOD, LOQ, matrix match, accuracy, and precision. The estimation of residues was done by HPLC. Recoveries of imidacloprid and its metabolites for cotton flowers, nectariferous tissue, pollen and honey samples were in the range of 80.42-99. 83%. LOQ for imidacloprid and its metabolites was 0.01 µg/g. Acceptable precision (RSD < 20%) was obtained. The method allows simple and fast extraction of imidacloprid and its metabolites from cotton flower, pollen, nectariferous tissue, and honey. An accurate, simple, and sensitive analytical method was validated for imidacloprid and its metabolites. The method was validated according to the SANTE/12682/2019 guidelines.


Lessons on Data Collection and Curation From the NFL Injury Surveillance Program.
"Research-ready" evidence platforms that link sports data with anonymized electronic health records (EHRs) or other data are important tools for evaluating injury occurrence in response to changes in games, training, rules, and other factors. While there is agreement that high-quality data are essential, there is little evidence to guide data curation. We hypothesized that an EHR used in the course of clinical care and curated for research readiness can provide a robust evidence platform. Our purpose was to describe the data curation used for active injury surveillance by the National Football League (NFL). Dynamic cohort study. Level 2. Players provide informed consent for research activities through the collective bargaining process. A league-wide EHR is used to record injuries that come to the attention of the teams' athletic trainers and physicians, NFL medical spotters, or unaffiliated neurotrauma consultants. Information about football activities and injuries are linkable by player, setting, and event to other sports-related data, including game statistics and game-day stadium quality measures, using a unique player identification designed to protect player privacy. Ongoing data curation is used to review data completeness and accuracy and is adjusted over time in response to findings. The core data curation activities include monthly injury summaries to team staff, queries to resolve incomplete reporting, and periodic external checks. Experiences derived from producing more than 100 reports per year on diverse topics are used to update coding training and related guidance documents in response to missing data or inconsistent coding that is observed. Roughly 20% more injuries were recorded for the same "reportable" injuries after switching from targeted reporting to an EHR. Research-ready databases need systematic curation for quality and completeness, along with related action plans. More injuries were reported through EHR than through targeted reporting. Evidence-driven decision-making thrives on reliable data fine-tuned through systematic use, review, and ongoing adjustments to the curation process.


Atomically Dispersed Fe/N4 and Ni/N4 Sites on Separate-Sides of Porous Carbon Nanosheets with Janus Structure for Selective Oxygen Electrocatalysis.
Dual single atoms catalysts have promising application in bifunctional electrocatalysis due to their synergistic effect. However, how to balance the competition between rate-limiting steps (RDSs) of reversible oxygen reduction and oxygen evolution reaction (OER) and fully expose the active centers by reasonable structure design remain enormous challenges. Herein, Fe/N4 and Ni/N4 sites separated on different sides of the carbon nanosheets with Janus structure (FeNijns /NC) is synthesized by layer-by-layer assembly method. Experiments and calculations reveal that the side of Fe/N4 is beneficial to oxygen reduction reaction (ORR) and the Ni/N4 side is preferred to OER. Such Janus structure can take full advantage of two separate-sides of carbon nanosheets and balance the competition of RDSs during ORR and OER. FeNijns /NC possesses superior ORR and OER activity with ORR half-wave potential of 0.92 V and OER overpotential of 440 mV at J = 10 mA cm-2 . Benefiting from the excellent bifunctional activities, FeNijns /NC assembled aqueous Zn-air battery (ZAB) demonstrates better maximum power density, and long-term stability (140 h) than Pt/C+RuO2 catalyst. It also reveals superior flexibility and stability in solid-state ZAB. This work brings a novel perspective for rational design and understanding of the catalytic mechanisms of dual single atom catalysts.


Comparative Evaluation of Sealing Ability of Moisture-tolerant Sealant and Glass Ionomer Sealant Using Stereomicroscope: An In Vitro Study.
The preventive benefits of pit and fissure sealants rely on their retention and sealing ability. The drawback of the conventional pit and fissure sealant is its poor retention due to the presence of moisture. Among the numerous pit and fissure sealants available, newer hydrophilic sealants are ideal for children. This study evaluates and compares the sealing ability of hydrophilic sealant Embrace WetBond with conventionally used glass ionomer sealant under a stereomicroscope. A total of 48 extracted human premolars were randomly divided into two groups (N = 24) and sealed with Embrace WetBond and GC Fuji VII as per manufacturers' instructions. Following thermocycling, the sectioned samples were evaluated for sealant penetration, unfilled space, and total length of fissure under a stereomicroscope at magnifications 2.5×, 4×, and 5×. The values were measured in microns and in various fissure types using the "ImageJ app" to measure the sealant penetrability and sealing ability. The data recorded were statistically evaluated. The penetrability of moisture-tolerant sealant was better (87.8 ± 10.7) compared to that of glass ionomer sealant (73.8 ± 15.5) (p = 0.002). Among the samples, U-type fissure patterns displayed greater penetrability (94.2 ± 6.2), whereas IK-type fissures revealed the lowest degree of penetrability (67.5 ± 7.3). Embrace WetBond is better than glass ionomer sealant with respect to penetrability and sealing ability under stereomicroscope hence recommended as a better sealant for pediatric clinical practice. Priscilla S, Shivashankarappa PG, Mohandoss S, et al. Comparative Evaluation of Sealing Ability of Moisture-tolerant Sealant and Glass Ionomer Sealant Using Stereomicroscope: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(S-1):S67-S71.


Myogenesis in thymic transplants in the severe combined immunodeficient mouse model of myasthenia gravis. Differentiation of thymic myoid cells into striated muscle cells.
Thymic myoid cells (TMCs) bearing acetylcholine receptors (AchR) on their surface have a central role in the concept of intrathymic autosensitization in the pathogenesis of myasthenia gravis. In a SCID mouse model of myasthenia gravis, solid pieces of thymuses with lymphofollicular hyperplasia were transplanted into SCID mice. The chimeric mice displayed long-term secretion of anti-AchR antibodies. Here, we traced the fate of TMCs contained in transplanted myasthenia gravis thymuses. Unexpectedly, the number of thymic TMCs in transplanted tissue was slightly higher than in untransplanted thymus. More strikingly, the transplanted TMCs were more highly differentiated than their nontransplanted counterparts. This was demonstrated by a more than 10-fold increase of AchR-main immunogenic region epitopes recognized by monoclonal antibody 198. Some TMCs had even differentiated into striated muscle cells. The abundance of AchRs in human thymic transplants in the SCID mouse model of myasthenia gravis may help to study the mechanisms of autosensitization against the AchR in vivo.


EC-IC bypass for adult patients with moyamoya disease.
We have performed 10 bypass operations on 7 adult patients with moyamoya disease over the past 6 years. Four had haemorrhagic episodes and three had ischemic episodes. Three patients underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass on both sides and the other four had the procedure on one side. Six of 7 patients showed angiographical improvement after the bypass operation while one patient did not. This patient underwent the second severe stroke and became vegetative during the course of follow-up. Another patient died of myocardial infarction during the follow-up time. Five patients are capable of carrying out their original work. Considerations regarding the cause, operative methods and disease course in the patients are discussed.


[Bioluminescent method for determination of concentration metabolic substrates and NAD+ in the lymphocytes].
We have developed a new bioluminescent method for determination of concentrations of pyruvate, lactate, malate, glutamate and NAD+ in the periferal blood lymphocytes from mice with Ehrlich ascites carcinoma. There were blood samples of intact mice for control. We found that variations of these substrates, depend on stage of malignant growth.


Optical anisotropy of alcian blue-stained acid glycosaminoglycans.
Optical anisotropy as dispersion of birefringence (DB) (birefringence studied for light of different wavelengths) and linear dichroism (LD) (selective absorption of polarized light) in stained substrates reflects their macromolecular orientation states. Birefringence interference colors of alcian blue (AB)-stained glycosaminoglycans (GAG) and glycoconjugates observed with polarization microscopy have been found to vary, although their staining characteristics under unpolarized light are practically the same. We investigated the optical anisotropy of GAG-AB and some glycoconjugate-AB complexes used as standards, to provide a basis for interpreting results for AB-stained materials in situ. Filamentous preparations of hyaluronic acid (HA), chondroitinsulfates, proteoglycans, and a mucus sulfoglycoconjugate were studied. Anomalous DB (birefringence sign changing with the wavelength of the incident light) was generally observed, but LD was seen only in the AB-HA complex. LD simultaneous to anomalous DB characteristics on the AB-HA complex were assumed to be caused by a maximally oriented helical conformation of the HA. For the other AB-GAG studied, the optical anisotropic characteristics were suggestive of some degree of folding of their chains into a tertiary structure. The profiles of the anomalous DB curves for the AB-stained sulfoglycoconjugate differed from those of the other materials, probably due to different organization of its dye-binding sites.


Neuropsychiatric Manifestations of Scrub Typhus.
Scrub typhus is caused by Orientia tsutsugamushi characterized by focal or disseminated vasculitis and perivasculitis which may involve the lungs, heart, liver, spleen and central nervous system. It was thought to have been eradicated from India. Recently it is being reported from many areas of India. The clinical picture and severity of the symptoms varies widely. The neurological manifestations of scrub typhus are not uncommon but are diverse. Meningoencephalitis is classical manifestation of scrub typhus but cerebellitis, cranial nerve palsies, plexopathy, transverse myelitis, neuroleptic malignant syndrome and Guillan-Barré syndrome are other manifestations reported in literature. The availability of literature on the neurological manifestations of scrub typhus is limited to case reports mainly. This article reviews various neurological manifestations of scrub typhus reported in literature.


Quantitative mapping reveals age and sex differences in vasopressin, but not oxytocin, immunoreactivity in the rat social behavior neural network.
The neuropeptides vasopressin (AVP) and oxytocin (OT) have been implicated in the regulation of numerous social behaviors in adult and juvenile animals. AVP and OT signaling predominantly occur within a circuit of interconnected brain regions known collectively as the "social behavior neural network" (SBNN). Importantly, AVP and OT signaling within the SBNN has been shown to differentially regulate diverse social behaviors, depending on the age and/or sex of the animal. We hypothesized that variation in the display of these behaviors is due in part to age and sex differences in AVP and OT synthesis within the SBNN. However, a thorough characterization of AVP and OT-immunoreactive (ir) fibers and cell bodies across age and sex within the SBNN has been lacking in rats. We therefore quantified AVP- and OT-ir fibers and cell bodies in 22 subregions of the forebrain SBNN in juvenile and adult, male and female rats. We found numerous age (16 subregions) and sex (10 subregions) differences in AVP-ir fiber fractional areas, and AVP-ir cell body numbers, which were mainly observed in the medial amygdala/bed nucleus of the stria terminalis to lateral septum circuit. In contrast to AVP, we observed no age or sex differences in OT-ir fiber fractional areas or cell bodies in any of the 22 subregions of the forebrain SBNN. Thus, unlike the static pattern observed for OT, AVP innervation of the forebrain SBNN appears to undergo developmental changes, and is highly sexually dimorphic, which likely has significant functional consequences for the regulation of social behavior.


lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis.
Diabetic nephropathy (DN) is the most common microvascular complication of diabetes and has become the second leading cause of end-stage renal disease in the world. This study aims to clarify the regulatory mechanism of the lncRNA MSC-AS1/miR-325/cyclin G1 (CCNG1) axis in DN. The regulatory mechanism of lncRNA MSC-AS1/miR-325/CCNG1 was evaluated by RT-qPCR, CCK-8 assay, flow cytometry assay, RNA pull-down assay, ELISA, and western blot assay. Upregulation of lncRNA MSC-AS1 was detected in DN patients and HRMC cells treated with high glucose (HG). Knockdown of lncRNA MSC-AS1 reduced the proliferation, fibrosis, and inflammation of HRMC cells induced by HG. In addition, lncRNA MSC-AS1 acts as a miR-325 sponge in the DN. CCNG1 is the direct target of miR-325, which can be positively regulated by lncRNA MSC-AS1 in DN. More importantly, downregulation of miR-325 and upregulation of CCNG1 can attenuate the protective effect of lncRNA MSC-AS1 knockdown on DN. lncRNA MSC-AS1 aggravates DN by downregulating miR-325 and upregulating CCNG1.


Preventing sciatic nerve injury from intramuscular injections: literature review.
Injury to the sciatic nerve (SN) is a serious complication of intramuscular injection. The purpose of this paper was to identify factors associated with such iatrogenic injury in adults and measures that nurses may take to prevent it. A review of the English language literature was undertaken to identify applicable research studies and determine the information that currently is being disseminated on relevant injection procedure. Legal databases were also searched for pertinent court decisions. The evidence is that injury to the SN is associated with use of the dorsogluteal (DG) site for injection. The choice of site for injection must be based on good clinical judgment, using the best evidence available and individualized assessment of the client. There is wide agreement in the literature that the ventrogluteal site is preferable. If the DG site is chosen, the nurse must have a full appreciation of the anatomy of the site and proximate anatomic structures, be able to accurately identify anatomic landmarks and site boundaries, and administer the injection with meticulous technique. Not only may SN injury resulting from erroneous injection cause client discomfort, morbidity and lasting disability, but it also provides the basis for nursing negligence suits. The research base for intramuscular injection is limited. Studies on various aspects of the procedure need to be carried out to provide support for clinical guidelines.


Prevalence of factor XII (Hageman factor) deficiency among 426 patients with coronary heart disease awaiting cardiac surgery.
Several case reports of myocardial infarction in patients with factor XII deficiency have been published. In the present study we investigated the prevalence of this condition. Factor XII activity (one-stage clotting assay), fibrinogen (derived method), and lipoprotein (a) (enzyme-linked immunosorbent assay) were measured in the plasma of 426 consecutive patients with coronary heart disease awaiting cardiac surgery. Among the 426 patients, 44 (10.3%) were found to be moderately deficient in factor XII (factor XII activity 17-50%, antigen 15-57%). The prevalence of factor XII deficiency was significantly higher (P < 0.0001) among patients with coronary heart disease than among 300 healthy blood donors (2.3%). Among coronary heart disease patients with this deficiency, elevated levels of fibrinogen, lipoprotein (a), and blood pressure were no more prevalent than in those without the deficiency; nor were cigarette smoking or a positive family history of thromboembolism more prevalent. Coronary heart disease patients showed a 10% prevalence of factor XII deficiency. However, the pattern of atherosclerotic risk factors did not differ between patients with or without the deficiency.


Reporting breast implant complications.
The Food and Drug Administration (FDA) defines a complaint (or complication) as "any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distribution." The FDA, the medical device manufacturers, and the health care providers using these devices share the responsibility for complaint reporting, investigation and follow-up. Each has unique yet interrelated roles and responsibilities in this process.


Cadmium uptake and metabolism in cultured cells.
Cultured cells have been made resistant to otherwise lethal concentrations of the toxic Cd ion, probably by induction of metallothionein (MT) synthesis and binding of Cd to the MT. One human epithelial cell line (HE) and two enzyme-deficient mutants of mouse fibroblasts (L-cells) (Cl 1D and A9) and their Cd-resistant substrains with a high content of MT, have been used to study cellular Cd uptake and metabolism. For cell survival of "wild type" cells, the critical level of intracellular Cd is determined to be around 6 nmole Cd/mg cell protein. Resistant cells can tolerate Cd levels several times above this concentration, if the major part of Cd is bound to MT. The technique of perturbed angular correlation spectroscopy (PAC) has been applied to living Cd-resistant cells. It was shown that greater than 66% of Cd in the resistant strains was bound to MT, and that MT is apparently freely suspended in the cell cytoplasm. Chelating agents differ in toxicity and Cd-releasing effect on the cells, but apparently remove the non-MT-bound Cd pool. After various periods of Cd omission, either in vitro or in vivo, growing the cells as tumors in athymic nude mice, the stability of Cd resistance in these cells seems to be dependent on the capacity of cells for de novo synthesis of MT shortly after re-exposure to the metal.


Fervidobacterium changbaicum sp. nov., a novel thermophilic anaerobic bacterium isolated from a hot spring of the Changbai Mountains, China.
A thermophilic, obligately anaerobic, rod-shaped bacterium (strain CBS-1(T)) was isolated from a hot spring mixture of water and mud of the Changbai Mountains, China. Strain CBS-1(T) was found to be non-sporulating, Gram-negative, with optimal growth at 75-80 degrees C. It grew on a wide range of carbon sources, including glucose, lactose, maltose, starch, sorbitol and pyruvate amongst others. The DNA G+C content of strain CBS-1(T) was 31.9 mol%. The 16S rRNA gene sequence analysis indicated that the strain was a member of the genus Fervidobacterium. The high concentration of C(16 : 0) (52.2 %) in the fatty acid profile of the cell envelope supported its inclusion as a member of the genus Fervidobacterium. On the basis of the low values of DNA-DNA hybridization (25.8 and 20.5 %) and phenotypic features, strain CBS-1(T) represents a novel species of the genus Fervidobacterium, for which the name Fervidobacterium changbaicum sp. nov. is proposed. The type strain is CBS-1(T) (=DSM 17883(T)=JCM 13353(T)).


Intergenerational family support following infant death.
The death of a child is a traumatic, nonnormative family life event. Although parental bereavement has received substantial attention, little research has focused on extended family members affected by a child's death, and still less on how multiple family members perceive and respond to one another following the loss. Guided by a life course perspective, this article examines social support between grandparents and their adult children in the aftermath of infant death. Through structured, open-ended interviews, 21 grandparents and 19 parents from 10 families described how they provided support to and received support from their intergenerational partners. Data were analyzed using a grounded theory approach. Six categories of support were identified: being present, acknowledgment, performing immediate tasks, information, unskilled support, and no support. Most support was provided by grandparents to adult children rather than from adult children to grandparents. All families reported significant support from at least one grandparent and nearly all families described ambivalent relationships that complicated support. Gender, family lineage, and family history were major influences. Multiple family perspectives about a significant life event contribute to our understanding about the intersection between individual and family life.


Neurokinin-1 (NK1) receptors mediate tachykinin-induced depression of GABA current in bullfrog sensory neurons.
Receptors responsible for the tachykinin-induced depression of gamma-aminobutyric acid-A (GABAA) receptors in neurons of bullfrog dorsal root ganglia (DRG) were investigated by using whole-cell voltage-clamp techniques. Substance P (10 nM-1 microM) depressed the inward current produced by GABA (GABA current) in a concentration-dependent manner. Substance P did not change the reversal potential of the GABA current. Neurokinin A also depressed the GABA current with potency similar to those of substance P. [D-Arg1, D-Trp7,9, Leu11]substance P (spantide, 1 microM) shifted the concentration-inhibition curve of substance P to the right. Spantide (1 microM) increased the IC50 from 56 nM to 210 nM. Lineweaver-Burk plot, a reciprocal plot of the concentration-inhibition curve, showed that spantide did not change the maximum response (Vmax) to substance P but increased the apparent dissociation constant (Kd). CP99994 (1 microM), an neurokinin-1 (NK1) receptor antagonist, inhibited the substance P-induced depression of the GABA current. These results suggest that the tachykinin-induced depression of the GABAA receptor sensitivity is mediated by NK1 receptors in neurons of bullfrog DRG.


Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004.
This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153-237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.


Experimental and theoretical studies of the photophysical properties of 2- and 2,7-functionalized pyrene derivatives.
Pyrene derivatives substituted at the 2- and 2,7-positions are shown to display a set of photophysical properties different from those of derivatives substituted at the 1-position. It was found that, in the 2- and 2,7-derivatives, there was little influence on the S(2) ← S(0) excitation, which is described as "pyrene-like", and a strong influence on the S(1) ← S(0) excitation, which is described as "substituent-influenced". In contrast, the 1-substituted derivatives display a strong influence on both the S(1) ← S(0) and the S(2) ← S(0) excitations. These observations are rationalized by considering the nature of the orbitals involved in the transitions. The existence of a nodal plane passing through the 2- and 7-positions, perpendicular to the molecular plane in the HOMO and LUMO of pyrene, largely accounts for the different behavior of derivatives substituted at the 2- and 2,7-positions. Herein, we report the photophysical properties of a series of 2-R-pyrenes {R = C(3)H(6)CO(2)H (1), Bpin (2; pin = OCMe(2)CMe(2)O), OC(3)H(6)CO(2)H (3), O(CH(2))(12)Br (4), C≡CPh (5), C(6)H(4)-4-CO(2)Me (6), C(6)H(4)-4-B(Mes)(2) (7), B(Mes)(2) (8)} and 2,7-R(2)-pyrenes {R = Bpin (9), OH (10), C≡C(TMS) (11), C≡CPh (12), C≡C-C(6)H(4)-4-B(Mes)(2) (13), C≡C-C(6)H(4)-4-NMe(2) (14), C(6)H(4)-4-CO(2)C(8)H(17) (15), N(Ph)-C(6)H(4)-4-OMe (16)} whose syntheses are reported elsewhere. Furthermore, we compare their properties to those of several related 1-R-pyrene derivatives {R = C(3)H(6)CO(2)H (17), Bpin (18), C≡CPh (19), C(6)H(4)-4-B(Mes)(2) (20), B(Mes)(2) (21)}. For all derivatives, modest (0.19) to high (0.93) fluorescence quantum yields were observed. For the 2- and 2,7-derivatives, fluorescence lifetimes exceeding 16 ns were measured, with most being ca. 50-80 ns. The 4-(pyren-2-yl)butyric acid derivative (1) has a long fluorescence lifetime of 622 ns, significantly longer than that of the commercially available 4-(pyren-1-yl)butyric acid (17). In addition to measurements of absorption and emission spectra and fluorescence quantum yields and lifetimes, time-dependent density functional theory calculations using the B3LYP and CAM-B3LYP functionals were also performed. A comparison of experimental and theoretically calculated wavelengths shows that both functionals were able to reproduce the trend in wavelengths observed experimentally.


Revisiting the connection between intramyocellular lipids and insulin resistance: a long and winding road.
In the mid-1990s, researchers began to re-examine type 2 diabetes from a more 'lipocentric' perspective; giving strong consideration to the idea that systemic lipid imbalances give rise to glucose dysregulation, rather than vice versa. At the forefront of this paradigm shift was a report by Krssak and colleagues (Diabetologia 1999; 42:113-116) showing that intramyocellular lipid content, measured via the (then) novel application of proton nuclear magnetic resonance spectroscopy, served as a robust indicator of muscle insulin sensitivity in healthy individuals. A subsequent wave of investigations produced compelling correlative evidence linking ectopic lipid deposition within skeletal myocytes to the development of obesity-associated insulin resistance. But this relationship has proven much more complex than originally imagined, and scientists today are still left wondering if and how the intramyocellular accumulation of lipid droplets has a direct bearing on insulin action. Originally viewed as a simple storage depot, the lipid droplet is now recognised as an essential and sophisticated organelle that actively participates in numerous cellular processes. This edition of 'Then and now' revisits the connection between intramuscular lipids and insulin resistance and looks to future research aimed at understanding the dynamic interplay between lipid droplet biology and metabolic health.


The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma.
Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers. Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.


Strapdown Airborne Gravimetry Quality Assessment Method Based on Single Survey Line Data: A Study by SGA-WZ02 Gravimeter.
Quality assessment is an important part in the strapdown airborne gravimetry. Root mean square error (RMSE) evaluation method is a classical way to evaluate the gravimetry quality, but classical evaluation methods are preconditioned by extra flight or reference data. Thus, a method, which is able to largely conquer the premises of classical quality assessment methods and can be used in single survey line, has been developed in this paper. According to theoretical analysis, the method chooses the stability of two horizontal attitude angles, horizontal specific force and vertical specific force as the determinants of quality assessment method. The actual data, collected by SGA-WZ02 from 13 flights 21 lines in certain survey, was used to build the model and elaborate the method. To substantiate the performance of the quality assessment model, the model is applied in extra repeat line flights from two surveys. Compared with internal RMSE, standard deviation of assessment residuals are 0.23 mGal and 0.16 mGal in two surveys, which shows that the quality assessment method is reliable and stricter. The extra flights are not necessary by specially arranging the route of flights. The method, summarized from SGA-WZ02, is a feasible approach to assess gravimetry quality using single line data and is also suitable for other strapdown gravimeters.


Physics-Guided Reflection Separation From a Pair of Unpolarized and Polarized Images.
Undesirable reflections contained in photos taken in front of glass windows or doors often degrade visual quality of the image. Separating two layers apart benefits both human and machine perception. The polarization status of the light changes after refraction or reflection, providing more observations of the scene, which can benefit the reflection separation. Different from previous works that take three or more polarization images as input, we propose to exploit physical constraints from a pair of unpolarized and polarized images to separate reflection and transmission layers in this paper. Due to the simplified capturing setup, the system is more under-determined compared to the existing polarization-based works. In order to solve this problem, we propose to estimate the semi-reflector orientation first to make the physical image formation well-posed, and then learn to reliably separate two layers using additional networks based on both physical and numerical analysis. In addition, a motion estimation network is introduced to handle the misalignment of paired input. Quantitative and qualitative experimental results show our approach performs favorably over existing polarization and single image based solutions.


Dualism of Sensitivity and Selectivity of Porphyrin Dimers in Electroanalysis.
This work uncovers the application of porphyrin dimers for the use in electroanalysis, such as potentiometric determination of ions. It also puts in question a current perception of an occurrence of the super-Nernstian response, as a result of the possible dimerization of single porphyrins within an ion-selective membrane. To study that, four various porphyrin dimers were used as ionophores, namely, freebase-freebase, Zn-Zn, Zn-freebase, and freebase-Zn. Since the Zn-freebase and freebase-Zn porphyrin dimers carried both anion- and cation-sensitive porphyrin units, their application in ISEs was utilized in both anion- and cation-sensitive sensors. With respect to the lipophilic salt added, both porphyrins dimers were found anion- and cation-sensitive. This allowed using a single molecule as novel type of versatile ionophore (anion- and cation-selective), simply by varying the membrane composition. All anion-sensitive sensors were perchlorate-sensitive, while the cation-selective sensors were silver-sensitive. The selectivity of the sensors depended primarily on the porphyrin dimers in the ion-selective membrane. Furthermore, the selectivity of cation-sensitive dimer based sensors was found significantly superior to the ones measured for the single porphyrin unit based sensors (precursors of the porphyrin dimers). Thus, the dimerization of single porphyrins may actually be a factor to increase or modulate porphyrin selectivity. Moreover, in the case of cation-sensitive sensors, the selectivity vastly depended on the order of porphyrin units in the dimer. This opens a new approach of regulating and adjusting sensitivity and selectivity of the sensor through the application of complex porphyrin systems with more than one porphyrin units with mix sensitive porphyrins.


Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics.
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.


Emergence of resistance to imipenem in Enterobacter isolates masquerading as Klebsiella pneumoniae during therapy with imipenem/cilastatin.
Clinical isolates identified as Klebsiella pneumoniae by the Vitek, Enterotube II, and API 20E systems were recovered from a patient undergoing therapy with imipenem/cilastatin. These isolates were resistant to multiple beta-lactam agents, and some were even resistant to imipenem. Analysis revealed a Bush group 1 beta-lactamase, and imipenem resistance corresponded to the loss of outer-membrane proteins in strains expressing high levels of this beta-lactamase. Further characterization efforts yielded abnormal but positive results of tests for ornithine decarboxylase production and motility, and chromosomal homology to an Enterobacter cloacae ampR, ampC probe was detected. These results suggested that the organisms were actually of an Enterobacter species, perhaps Enterobacter aerogenes. Cefoxitin resistance may be a useful marker for preventing this misidentification in the future; misidentification of such organisms poses a hazard, as it may lead to inappropriate beta-lactam therapy for infections caused by organisms that have the potential for resistance due to inducible group 1 cephalosporinases.


Evidence for bovine leukemia virus in mammary epithelial cells of infected cows.
Bovine leukemia virus (BLV), a retrovirus, usually causes a subclinical infection of dairy and beef cattle, but in < 1% of infected cattle a B cell lymphoma may develop after several years of infection. BLV is transmitted horizontally among cattle, and infected animals have anti-BLV titers. Expression of BLV antigen, however, is silent in peripheral blood lymphocytes in vivo. The tropism of BLV has been assumed to be limited to B lymphocytes, because no other cell type has been found to harbor the virus in vivo. Since retrovirus-like particles had been identified in milk, and infection can be transmitted by milk, we decided to investigate whether BLV was in mammary epithelial cells. Pure cultures of mammary epithelial cells were established from cells shed into the milk of 28 cows. BLV was searched in these cultures by immunocytochemistry and the polymerase chain reaction, the specificity of the latter confirmed by Southern blot hybridization and DNA sequencing. BLV was searched immunocytochemically in mammary tissue sections from 12 cows. Antigenic and/or molecular evidence of BLV was found in the cultured cells of 20 cows. Antigenic evidence of BLV was found in tissue sections from 10 cows, indicating virus expression in vivo. Simultaneous detection of BLV p24 and cytokeratins, localized antigen expression to the mammary epithelial cells. These indications of BLV in mammary epithelial cells in vivo suggest that BLV is capable of infecting and expressing antigen in glandular epithelium in vivo and has a broader tissue tropism than was previously thought. They raise the question of how persistent mammary infection by BLV may influence the course of bovine lymphoma, and what effect the virus may have on the mammary gland.


Cerebrovascular dilation via selective targeting of the cholane steroid-recognition site in the BK channel β1-subunit by a novel nonsteroidal agent.
The Ca(2+)/voltage-gated K(+) large conductance (BK) channel β1 subunit is particularly abundant in vascular smooth muscle. By determining their phenotype, BK β1 allows the BK channels to reduce myogenic tone, facilitating vasodilation. The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK β1 site that includes Thr169. Whether exogenous nonsteroidal agents can access this site to selectively activate β1-containing BK channels and evoke vasodilation remain unknown. We performed a chemical structure database similarity search using LCA as a template, along with a two-step reaction to generate sodium 3-hydroxyolean-12-en-30-oate (HENA). HENA activated the BK (cbv1 + β1) channels cloned from rat cerebral artery myocytes with a potency (EC₅₀ = 53 μM) similar to and an efficacy (×2.5 potentiation) significantly greater than that of LCA. This HENA action was replicated on native channels in rat cerebral artery myocytes. HENA failed to activate the channels made of cbv1 + β2, β3, β4, or β1T169A, indicating that this drug selectively targets β1-containing BK channels via the BK β1 steroid-sensing site. HENA (3-45 μM) dilated the rat and C57BL/6 mouse pressurized cerebral arteries. Consistent with the electrophysiologic results, this effect was larger than that of LCA. HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK β1's role in HENA action. Finally, carotid artery-infusion of HENA (45 μM) dilated the pial cerebral arterioles via selective BK-channel targeting. In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates β1-containing BK channels by targeting the steroid-sensing site in BK β1, rendering vasodilation.


Electroporation.
Electroporation is a process in which brief electrical pulses create transient pores in the plasma membrane that allow nucleic acids to enter the cellular cytoplasm. Here, we provide information on the history, mechanism, and optimization of electroporation. We also describe nucleofection, an improvement of the electroporation technology that permits the introduction of nucleic acids directly into the nucleus.


Pairs in copulation of the highly dimorphic genus Pristocera Klug (Hymenoptera, Bethylidae) from Madagascar solve taxonomic problems of male-female associations.
The main goal of this paper is to update the taxonomic information of the pairs of Pristocera Klug collected in Madagascar by A. Seyrig. Within this material twelve species are recognized, ten are new to science, all based on pairs collected in copulation, which are described and illustrated: P. melmani sp. nov., P. alexi sp. nov., P. martyi sp. nov., P. gloriae sp. nov., P. julieni sp. nov., P. morti sp. nov., P. mauricei sp. nov., P. makungai sp. nov., P. teetsii sp. nov. and P. zubai sp. nov.. Pristocera levicollis (Kieffer) had its female discovered, and P. cambouei Saussure stat. rev. had its lectotype designated. Sclerodermus hova Saussure is transferred back to Pristocera and considered as a junior synonym of P. cambouei. Keys for males and females to the species of Pristocera from Madagascar are provided. The Malagasy fauna of Pristocera is now represented by twelve species, all endemic to this island.


Inhibin-B and pro-alphaC-containing inhibins in amniotic fluid from chromosomally normal and Down syndrome pregnancies.
In second-trimester Down syndrome pregnancies, levels of inhibin-A (the alpha-betaA dimer) in maternal serum and amniotic fluid (AF) are significantly higher and lower than in normal pregnancy, respectively. Since AF also contains inhibin-B (the alpha-betaB dimer) and precursor inhibins, we have examined whether the secretion of these inhibin isoforms may also be altered in association with Down syndrome. AF from 45 Down syndrome and 150 chromosomally normal pregnancies between 16 and 19 weeks' gestation were analysed, blinded to whether the sample was from a Down syndrome or a normal pregnancy. The median (10th-90th percentiles) inhibin-B level in the control pregnancies increased from 310.0 (80.8-1112.5) pg/ml at 16 weeks to 459.5 (193.7-1386.8) pg/ml at 19 weeks' gestation. The corresponding figures for precursor inhibins (pro-alphaC inhibins) were 541.8 (206.9-1322.8) pg/ml at 16 weeks and 1391.8 (433.3-2652.6) pg/ml at 19 weeks. Expressed as multiples of the median (MOM), the levels of inhibin-B and pro-alphaC inhibins in the Down syndrome samples were 0.85 and 0.79, respectively. Neither was significantly different from the controls. These data suggest that, of the three inhibin subunits, abnormal production or secretion of the inhibin betaA-subunit may underlie the decreased inhibin-A levels previously observed in Down syndrome. Confirmation of this by quantitative assessment of the inhibin subunit messenger ribonucleic acids would now be useful.


Composition and Biomass of Aquatic Vegetation in the Poyang Lake, China.
The distribution of aquatic vegetation and associated community diversity and biomass in the Poyang Lake were investigated. The results showed that (1) 43 species of aquatic vascular plants were found in the Poyang Lake watershed which belonged to 22 families; (2) the vegetation of the Poyang Lake scattered in different areas which could be divided into 31 major plant communities and 5 plant zones including amphibian, emergent, floating-leaved, submerged, and floating input; (3) there were 67 aquatic plants in the lake area, and the standing stock (fresh weight) was 1519.41 t. The number of amphibians was the dominant plant species in the Poyang Lake, and the quantity and percentage of amphibians were predominant, which was far more than the other three life forms.


Spectrum of MECP2 mutations in Rett syndrome.
Mutations in the MECP2 (Methyl-CpG-binding protein) gene recently have been reported to cause Rett syndrome (RTT), an X-linked progressive encephalopathy. We have collected the results of MECP2 analysis conducted in four laboratories in France. A total of 301 RTT alleles have been analyzed, demonstrating a total of 69 different mutations so far observed and accounting for 64% of MECP2 genes in RTT patients living in France. R168X (11.5%) is the most common of MECP2 mutations, followed by R255X (10.9%), R270X (10.5%), T158M (7.8%), and R306C (6.8%). Only 10 mutations had a relative frequency > 2%. A total of 59 mutations were found in a small number of RTT alleles (from 1 to 2). These data demonstrate the high allelic heterogeneity of RTT in France and provide information relevant to the development of strategies for molecular diagnosis and genetic counseling in RTT families.


Vicious walks with a wall, noncolliding meanders, and chiral and Bogoliubov-de Gennes random matrices.
Spatially and temporally inhomogeneous evolution of one-dimensional vicious walkers with wall restriction is studied. We show that its continuum version is equivalent with a noncolliding system of stochastic processes called Brownian meanders. Here the Brownian meander is a temporally inhomogeneous process introduced by Yor as a transform of the Bessel process that is the motion of radial coordinate of the three-dimensional Brownian motion represented in spherical coordinates. It is proved that the spatial distribution of vicious walkers with a wall at the origin can be described by the eigenvalue statistics of Gaussian ensembles of Bogoliubov-de Gennes Hamiltonians of the mean-field theory of superconductivity, which have a particle-hole symmetry. We report that a time evolution of the present stochastic process is fully characterized by the change of symmetry classes from type C to type CI in the nonstandard classes of random matrix theory of Altland and Zirnbauer. The relation between the noncolliding systems of the generalized meanders of Yor, which are associated with the even-dimensional Bessel processes, and the chiral random matrix theory is also clarified.


Some epidemiologic features of motorcycle collision injuries. I. Introduction, methods and factors associated with incidence.
Using official police reports and hospital admission and emergency room medical records, 1273 persons with confirmed medically treated motorcycle injury were identified in Sacramento County, California, during 1970. Less than 39% of all injured motorcyclists were identified in this study using only official police reports. The annual incidence rate was highest for 18-year-old male drivers. In addition to age of driver, risk of injury was associated with drivers of short stature (less than 173 cm) operating an intermediate or larger size motorcycle. Risk of injury was higher for drivers with training than for those without training or those who operated their motorcycles frequently regardless of type of use. Risk of injury was not related to make of motorcycle but was related to engine size. Two-thirds of the injury-producing collisions involved a motorcycle and a second motor vehicle. Motorcycle collisions occurred most fre quently during the afternoon and early evening hours and during the summer months, but peaks in incidence of collisions occurred during weeks which included a holiday.


Post-cocaine changes in regulator of G-protein signaling (RGS) proteins in the dorsal striatum: Relevance for cocaine-seeking and protein kinase C-mediated phosphorylation.
Persistent cocaine-induced neuroadaptations within the cortico-striatal circuitry might be related to elevated risk of relapse observed in human addicts even after months or years of drug-free abstinence. Identification of these neuroadaptations may lead development of novel, neurobiologically-based treatments of relapse. In the current study, 12 adult male Sprague-Dawley rats self-administered cocaine (or received yoked-saline) for two weeks followed by three weeks of home-cage abstinence. At this point, we analyzed expression of proteins involved in regulation of Gαi- and Gαq-protein signaling in the dorsal striatum (dSTR). Animals abstinent from chronic cocaine showed decreased expression of regulator of G-protein signaling 2 (RGS2) and RGS4, as well as upregulation of RGS9. These data, together with the increased ratio of Gαq-to-Gαi proteins indicated, "sensitized" Gαq signaling in the dSTR of abstinent cocaine animals. To evaluate activation of Gαq signaling during relapse, another group of abstinent cocaine animals (and yoked saline controls, 22 rats together) was reintroduced to the cocaine context and PKC-mediated phosphorylation in the dSTR was analyzed. Re-exposure to the cocaine context triggered cocaine seeking and increase in phosphorylation of cellular PKC substrates, including phospho-ERK and phospho-CREB. In conclusion, this study demonstrates persistent dysregulation of RGS proteins in the dSTR of abstinent cocaine animals that may produce an imbalance in local Gαq-to-Gαi signaling. This imbalance might be related to augmented PKC-mediated phosphorylation during relapse to cocaine-seeking. Future studies will address whether selective targeting of RGS proteins in the dSTR can be utilized to suppress PKC-mediated phosphorylation and relapse to cocaine-seeking.


Detection of abdominal aortic graft infection: comparison of magnetic resonance imaging and indium-labeled white blood cell scanning.
Infected abdominal aortic grafts rank as one of the most severe complications of vascular surgery, with high mortality and morbidity. The incidence of infection after prosthetic aortic reconstruction is 1-3%. Diagnosis of vascular graft infection can be occasionally difficult. Clinical manifestations and assessment of the extent of graft infection are usually nonspecific, and their detection by radiographic methods, such as computed tomography (CT), magnetic resonance imaging (MRI), and leukocyte -imaging, can be difficult. The purpose of this study was to evaluate the predictive value (PV) of indium-111-labeled white blood cell scanning (WBCS) and MRI in patients who were suspected of having intracavitary vascular graft infection (IGF). The study was done as a cross-control retrospective, single-center study. Fifty-eight In-111-labeled WBC scans and 59 MRIs were performed in suspected patients between January 1995 and January 2005. Among the 40 suspected patients, 35 cases of aorta graft infection were identified intraoperatively. The diagnosis of IGF was based on clinical signs, microbiological and histological examination, MRI and leukocyte imaging, and lack of graft incorporation with surrounding fluid observed intraoperatively. The positive PV (PPV) of MRI was 95% (95% confidence interval [CI] 84-105%) compared to In-111-labeled WBCS, which was 80% (95% CI 62-96%). The negative PV (NPV) of MRI was 80% (95% CI 68-92%) compared to 82% (95% CI 69-94%) for In-111-labeled WBCS. MRI showed a nonsignificant but better PPV for detecting IGF compared to In-111 leukocyte imaging. The NPVs for MRI and In-111-labeled WBCS were very near each other, with a very small advantage for In-111-WBCS. This comparison study suggested MRI as a primary diagnostic modality to investigate patients suspected of having aortic graft infections before In-111-labeled WBCS.


How high can we go with phenytoin?
Phenytoin is an effective anticonvulsant, but high serum phenytoin concentrations may be associated with serious toxicity. The upper limit for the therapeutic serum concentration of phenytoin is considered to be 80 micromol/L. However, in some situations higher serum concentrations are needed to control seizures. The authors describe a 9-year-old girl who needed concentrations twice the normal amount to control recurrent episodes of decreased levels of consciousness. Except for nystagmus, she had no other signs of phenytoin toxicity. This patient highlights the critical principle in therapeutic drug monitoring of individualizing drug therapy. Although some patients receiving phenytoin may achieve seizure control with "subtherapeutic" levels (i.e., <40 micromol/L), others may need supratherapeutic levels, as was the case with this patient. Clinicians should be careful not to treat "numbers" (i.e., serum concentrations), but rather the patient's clinical condition, with a careful balance between therapeutic advantage and adverse effects.


The induction of ovulation by pulsatile administration of GnRH: an appropriate method in hypothalamic amenorrhea.
The induction of ovulation by the means of a pump which assures the pulsatile administration of GnRH is a well-known method that applies to women suffering from amenorrhea of hypothalamic origin. Although a simple and efficient method to establish fertility, it is underused. Twelve patients suffering from this condition, 1 Kallmann syndrome, 4 normosmic isolated hypogonadotropic hypogonadism, and 7 functional hypothalamic amenorrhea desiring pregnancy were treated. They underwent one or more cycles of pulsatile GnRH, at a frequency of 90 minutes, either by the intravenous or the subcutaneous route. An initial dose of 5 μg per pulse in the intravenous route was administered and of 15 μg per pulse in the subcutaneous route. The treatment was monitored by regular dosing of gonadotropins, estradiol and progesterone, and the development of follicles and ovulation was monitored by intra-vaginal ultrasonography. All the patients had documented ovulation, after a mean of 17 days on pump stimulation. Single ovulation occurred in 30 of 33 treatment cycles, irrespective of the route of administration. Ovulation resulted in 10 pregnancies over 7 patients (2 pregnancies in 3 of them), distributed in the 3 diagnostic categories. For comparison, a patient with PCOS treated similarly, disclosed premature LH surge without ovulation.


Slow release of acetylsalicylic acid by intravitreal silicone oil.
To assess in vitro the potential of silicone oil as a delivery system for acetylsalicylic acid (ASA) and to evaluate in vivo the pharmacokinetic distribution of salicylic acid (SA) in the eye. In an experimental model ASA/silicone oil suspension mixed to a concentration of 1.67 mg/mL was investigated for release rate of ASA and SA. In vivo vitrectomy and intravitreal injection of two different ASA/silicone oil suspensions, both mixed to a concentration of 1.67 mg/mL, was performed on two groups, A and B, of New Zealand white rabbits. Salicylic acid concentrations in ocular tissues, aqueous, vitreous, and blood plasma were evaluated at 6 hours, 24 hours, and 5 days using high performance liquid chromatography. Salicylic acid was detected in all tissues. The highest levels were obtained in the vitreous: 745.4 microg/mL (A) and 640.0 microg/mL (B) at 6 hours. The retina followed with 332.9 ng/mg (A) and 281.3 ng/mg (B) at 6 hours and 31.6 ng/mg (A) and 48.1 ng/mg (B) at day 5. The maximum blood plasma levels were 5.2 microg/mL. Silicone oil is an efficacious delivery system of ASA in vitro and in vivo. Higher concentrations of SA were found in all ocular tissues and fluids when compared to intravenous administration of maximum doses.


Achilles Impingement Tendinopathy on Magnetic Resonance Imaging.
Haglund's syndrome is impingement of the retrocalcaneal bursa and Achilles tendon caused by a prominence of the posterosuperior calcaneus. Radiographic measurements are not sensitive or specific for diagnosing Haglund's deformity. Localization of a bone deformity and tendinopathy in the same sagittal section of a magnetic resonance imaging scan can assist with the diagnosis in equivocal cases. The aim of the present cross-sectional study was to determine the prevalence of Haglund's syndrome in patients presenting with Achilles tendinopathy and note any associated findings to determine the criteria for a diagnosis of Haglund's syndrome. We reviewed 40 magnetic resonance imaging scans with Achilles tendinopathy and 19 magnetic resonance imaging scans with Achilles high-grade tears and/or ruptures. Achilles tendinopathy was often in close proximity to the superior aspect of the calcaneal tuberosity, consistent with impingement (67.5%). Patients with Achilles impingement tendinopathy were more often female (p < .04) and were significantly heavier than patients presenting with noninsertional Achilles tendinopathy (p = .014) or Achilles tendon rupture (p = .010). Impingement tendinopathy occurred medially (8 of 20) and centrally (10 of 20) more often than laterally (2 of 20) and was associated with a posterior prominence or hyperconvexity with a loss of calcaneal recess more often than a superior projection (22 of 27 versus 8 of 27; p < .001). Haglund's deformity should be reserved for defining a posterior prominence or hyperconvexity with loss of calcaneal recess because this corresponds with impingement. Achilles impingement tendinopathy might be more appropriate terminology for Haglund's syndrome, because the bone deformity is often subtle. Of the 27 images with Achilles impingement tendinopathy, 10 (37.0%) extended to a location prone to Achilles tendon rupture. Given these findings, insertional and noninsertional Achilles tendinopathy are not mutually exclusive and impingement might be a subtle, unrecognized cause of Achilles tendinopathy and subsequent rupture.


Effect of assembling errors on the diffraction efficiency for multilayer diffractive optical elements.
Based on the expression function of diffraction efficiency, and the phase delay function of diffractive optical elements (DOEs), the diffraction efficiency for multilayer diffractive optical elements (MLDOEs) is described with tilt and decenter assembling errors. A mathematical model of the relationship between diffraction efficiency and assembling errors of MLDOEs is proposed to analyze the effect of assembling errors on the diffraction efficiency of MLDOEs. The analyzed results from the mathematical model provide a range of values for the effect of assembling errors on the diffraction efficiency of MLDOEs. Assembling errors are important parameters for hybrid diffractive refractive optical systems, including MLDOEs, and so the proposed model will be useful for guiding the design and fabrication of such optical systems.


Manipulating Cellular Energetics to Slow Aging of Tissues and Organs.
Up to now numerous studies in the field of gerontology have been published. Nevertheless, a well-known food restriction remains the most reliable and efficient way of lifespan extension. Physical activity is also a well-documented anti-aging intervention being especially efficient in slowing down the age-associated decline of skeletal muscle mass. In this review we focus on the molecular mechanisms of the effect of physical exercise on muscle tissues. We also discuss the possibilities of pharmacological extension of this effect to the rest of the tissues. During the exercise, the level of ATP decreases triggering activation of AMP-dependent protein kinase (AMPK). This kinase stimulates antioxidant potential of the cells and their mitochondrial respiratory capacity. The exercise also induces mild oxidative stress, which, in turn, mediates the stimulation via hormetic response. Furthermore, during the exercise cells generate activators of mammalian target of rapamycin (mTOR). The intracellular ATP level increases during the rest periods between exercises thus promoting mTOR activation. Therefore, regular exercise intermittently activates anti-oxidant defenses and mitochondrial biogenesis (via AMPK and the hormetic response) of the muscle tissue, as well as its proliferative potential (via mTOR), which, in turn, impedes the age-dependent muscle atrophy. Thus, the intermittent treatment with activators of (i) AMPK combined with the inducers of hormetic response and of (ii) mTOR might partly mimic the effects of physical exercise. Importantly, pharmacological activation of AMPK takes place in the absence of ATP level decrease. The use of uncouplers of respiration and oxidative phosphorylation at the phase of AMPK activation could also prevent negative consequences of the cellular hyper-energization. It is believed that the decline of both antioxidant and proliferative potentials of the cells causes the age-dependent decline of multiple tissues, rather than only the muscular one. We argue that the approach above is applicable for the majority of tissues in an organism.


Liver calcium homeostasis modification by iron: a probable factor in its carcinogenesis.
Low molecular weight iron complexes, ferric lactate and ferric-ATP complex, induce an important increase of Ca(2+)-uptake by liver. The activity of ferric lactate increased by the presence of sodium ATP, and the steady high effect of ferric-ATP complex appear to indicate that ATP might play an important role in the in vivo formation of low molecular weight iron complexes that can induce the modification of the hepatocytes calcium homeostasis, the event that might be one of the factors triggering the malignant transformation.


The treatment of diabetes mellitus of patients with chronic liver disease.
About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.


[Monitor tables for electron beams in radiotherapy].
The application of electron beams in radiotherapy is still based on tables of monitor units, although 3-D treatment planning systems for electron beams are available. This have several reasons: The need for 3-D treatment planning is not recognized; there is no confidence in the calculation algorithm; Monte-Carlo algorithms are too time-consuming; and the effort necessary to measure basic beam data for 3-D planning is considered disproportionate. However, the increasing clinical need for higher dosimetric precision and for more conformal electron beams leads to the requirement for more sophisticated tables of monitor units. The present paper summarizes and discusses the main aspects concerning the preparation of tables of monitor units for electron beams. The measurement equipment and procedures for measuring basic beam data needed for tables of monitor units for electron beams are described for a standard radiation therapy linac. The design of tables of monitor units for standard electron applicators is presented; this design can be extended for individual electron inserts, to variable applicator surface distances, to oblique beam incidence, and the use of bolus material. Typical data of an Elekta linac are presented in various tables.


The UBX-regulated network in the haltere imaginal disc of D. melanogaster.
Hox proteins have been proposed to act at multiple levels within regulatory hierarchies and to directly control the expression of a plethora of target genes. However, for any specific Hox protein or tissue, very few direct in vivo-regulated target genes have been identified. Here, we have identified target genes of the Hox protein Ultrabithorax (UBX), which modifies the genetic regulatory network of the wing to generate the haltere, a modified hindwing. We used whole-genome microarrays and custom arrays including all predicted transcription factors and signaling molecules in the Drosophila melanogaster genome to identify differentially expressed genes in wing and haltere imaginal discs. To elucidate the regulation of selected genes in more detail, we isolated cis-regulatory elements (CREs) for genes that were specifically expressed in either the wing disc or haltere disc. We demonstrate that UBX binds directly to sites in one element, and these sites are critical for activation in the haltere disc. These results indicate that haltere and metathoracic segment morphology is not achieved merely by turning off the wing and mesothoracic development programs, but rather specific genes must also be activated to form these structures. The evolution of haltere morphology involved changes in UBX-regulated target genes, both positive and negative, throughout the wing genetic regulatory network.


Living arrangements after divorce: cohabitation versus remarriage.
"The purpose of this paper is to examine the characteristics of all [U.S.] couple households in which one or both partners were previously married. In this examination, we will consider not only households maintained by married couples...; we will also consider households formed by cohabiting couples. In addition, we will examine the living arrangements of children in these households, with particular attention to whether children are from the current union or a previous union."


Hydrocarbon-Based Polymer Electrolyte Membranes: Importance of Morphology on Ion Transport and Membrane Stability.
A fundamental understanding of polymer microstructure is important in order to design novel polymer electrolyte membranes (PEMs) with excellent electrochemical performance and stabilities. Hydrocarbon-based polymers have distinct microstructure according to their chemical structure. The ionic clusters and/or channels play a critical role in PEMs, affecting ion conductivity and water transport, especially at medium temperature and low relative humidity (RH). In addition, physical properties such as water uptake and dimensional swelling behavior depend strongly on polymer morphology. Over the past few decades, much research has focused on the synthetic development and microstructural characterization of hydrocarbon-based PEM materials. Furthermore, blends, composites, pressing, shear field, electrical field, surface modification, and cross-linking have also been shown to be effective approaches to obtain/maintain well-defined PEM microstructure. This review summarizes recent work on developments in advanced PEMs with various chemical structures and architecture and the resulting polymer microstructures and morphologies that arise for potential application in fuel cell, lithium ion battery, redox flow battery, actuators, and electrodialysis.


[Vapor-phase gas chromatographic determination of acetate in the blood].
The suggested gas chromatographic vapor phase analysis of the blood for the direct determination of the blood acetate concentration is performed with Soviet equipment and is based on expulsion of acetic acid from its salts and other derivatives after addition of potassium bisulfate and heating of the blood sample at +105 degrees C for an hour in a hermetically sealed flask. To directly measure acetate, a certain vapor phase volume is let into the gas chromatographic evaporator after equal distribution of acetate in the gas and liquid phases is achieved. This method was used to measure the blood acetate levels in the patients with renal insufficiency treated by hemodialysis. The total content of the blood acetate in health is 1.6 +/- 0.3 mmol/l; this value essentially grows in acetate hemodialysis. In some patients acetate levels persist increased between the dialysis courses. The suggested method may be useful for monitoring the blood acetate levels in the patients treated with hemodialysis and for the detection of subjects with acetate intolerance.


Synchronization of an excitatory integrate-and-fire neural network.
In this paper, we study the influence of the coupling strength on the synchronization behavior of a population of leaky integrate-and-fire neurons that is self-excitatory with a population density approach. Each neuron of the population is assumed to be stochastically driven by an independent Poisson spike train and the synaptic interaction between neurons is modeled by a potential jump at the reception of an action potential. Neglecting the synaptic delay, we will establish that for a strong enough connectivity between neurons, the solution of the partial differential equation which describes the population density function must blow up in finite time. Furthermore, we will give a mathematical estimate on the average connection per neuron to ensure the occurrence of a burst. Interpreting the blow up of the solution as the presence of a Dirac mass in the firing rate of the population, we will relate the blow up of the solution to the occurrence of the synchronization of neurons. Fully stochastic simulations of a finite size network of leaky integrate-and-fire neurons are performed to illustrate our theoretical results.


[Sodium-modulating hormones and the pressor response to sodium chloride in essential arterial hypertension].
Some predictive markers for NaCl sensitivity, related to the red blood cell membrane or to circulating proteins, have already been described in human essential hypertension. The present study was planned to investigate whether or not some hormones produced by the kidney or acting at the kidney level could be used as new markers for NaCl sensitivity. The study was conducted in 28 not previously treated outpatients affected by uncomplicated mild to moderate essential hypertension. After 15 days on a normal NaCl diet, plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP), and the urinary excretion of active kallikrein were evaluated. The sensitivity of blood pressure to changes in NaCl intake was then assessed in all patients, according to a randomized double blind cross-over design. Each patient was assigned to a high (240 mmol of NaCl/day for 15 days) or low (40 mmol of NaCl/day for 15 days) NaCl intake. During the assessment of NaCl sensitivity, the double blindness was achieved by the use of capsules containing either NaCl or placebo. Fifteen patients (11 males and 4 females) resulted as NaCl-sensitive, while 13 patients (8 males and 5 females) were classified as NaCl-resistant. Our results indicate that PRA levels were significantly lower in the NaCl-sensitive group than in the NaCl-resistant one (0.108 +/- 0.05 ng/L/s vs 0.247 +/- 0.16 ng/L/s, p < 0.007), in the presence of raised levels of plasma ANP in NaCl-sensitive hypertensives (18.08 +/- 4.61 fmol/mL vs 12.45 +/- 3.77 fmol/mL, p < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparative pathology of infection by novel diarrhoea viruses.
Examination of diarrhoeic faeces in the electron microscope often reveals viruses that are presumed to be enteropathogenic. Lesions caused by novel rotaviruses were similar to those of group A rotaviruses, but enterocyte syncytia were seen which are probably pathognomonic for novel rotaviruses. In adenovirus infection in piglets, mature enterocytes were infected and destroyed; intranuclear inclusion bodies were seen in infected enterocytes. Calici-like viruses infected mature enterocytes in calves and the lesions were similar to those described in humans infected with calici-like viruses; in both host species it was impossible to demonstrate virus particles in enterocytes examined in the electron microscope. The Breda virus infected villi and crypts in the lower small intestine and the surface and crypts in the large intestine; it was the only enteropathogenic virus to show this distribution of infection and lesions. Astrovirus infection in lambs was comparable to a mild rotavirus infection, but in calves the epithelium of the dome villi of Peyer's patches was infected. Parvovirus in cats and dogs infected and destroyed small intestinal crypt cells, causing dilated crypts and stunted villi; intranuclear inclusion bodies were prominent.


iGlarLixi, a titratable once-daily fixed-ratio combination of basal insulin and lixisenatide for intensifying type 2 diabetes management for patients inadequately controlled on basal insulin with or without oral agents.
Achieving and maintaining glycemic control is important for people with type 2 diabetes (T2D), to reduce disease-related complications and mortality; however, about half of US patients fail to meet glycemic targets. iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide for once-daily administration, was recently approved by the US Food and Drug Administration for use in adults with T2D inadequately controlled on basal insulin (<60 U daily) or lixisenatide. iGlar and lixisenatide have complementary mechanisms of action, primarily targeting fasting plasma glucose and postprandial plasma glucose, respectively. In the US, iGlarLixi is available in a 3:1 ratio of iGlar and lixisenatide, respectively, across the dosage range of 15-60 U of iGlar and 5-20 µg of lixisenatide. This study identified phase 3 trials which assessed the efficacy and safety of iGlarLixi. Relevant trials were LixiLan-O, which compared iGlarLixi with iGlar or lixisenatide alone in insulin-naïve patients, and LixiLan-L, which compared iGlarLixi with iGlar alone in insulin-experienced patients. Patients on iGlarLixi experienced greater A1C reduction and were more likely to achieve A1C <7.0% than its comparators. iGlarLixi mitigated the weight gain associated with iGlar without increasing hypoglycemia risk, and resulted in a lower frequency of gastrointestinal adverse events compared with lixisenatide. iGlarLixi provides a new approach to therapy intensification in patients with T2D. iGlarLixi showed greater A1C efficacy compared with either iGlar or lixisenatide, mitigating iGlar-associated weight gain, without increasing hypoglycemia risk, and reducing the gastrointestinal side-effects seen with lixisenatide.


Effects of attentional modulation of a stationary surround in adaptation to motion.
The effect of varying the spatial relationships between an adapt/test grating and a stationary surrounding reference grating, and their interaction with diversion of attention during adaptation, were investigated in two experiments on the movement aftereffect (MAE). In experiment 1, MAEs were found to increase as the separation between the surrounding grating and the adapt/test grating decreased, but not with the area of the adapt/test grating. Although diversion during adaptation (repeating changing digits at the fixation point) reduced MAE durations, its effects did not interact with any of the stimulus variables. In experiment 2, MAE durations increased as the outer dimensions of the reference grating were increased, and this effect did interact with diversion, so that the effects of diversion were smaller when the surround grating was larger. This suggests that diversion may be affecting the inputs to an opponent process in motion adaptation, with a smaller effect on the surrounds than on the centres of antagonistic motion-contrast detectors with large receptive fields. A third experiment showed that, although repeating the word 'zero' during adaptation reduced MAEs, this reduction was smaller than that from naming a changing sequence of digits (and not significantly different from that from simply observing the changing digits), suggesting that MAE reductions are not produced only, if at all, by putative movements of the head and eyes caused by speaking.


[Unstable angina due to communication between the coronary artery and the right pulmonary artery in patient with Takayasu's arteritis].
A sixty three year old woman suffering from Takayasu's arteritis with involvement of the aortic arch, subclavia arteries and occlusion of the right pulmonary artery, developed progressive precordial pain. Exercise electrocardiogram disclosed ST segment depression. Coronary arteriograms demonstrated no coronary stenosis, but collateral circulation arising from circumflex coronary artery to right pulmonary artery. The collateral blood flow was considered to be of great importance, and causing the coronary steal syndrome, leading to angina pectoris.