Dynamic magnetic resonance imaging of the female pelvis: the relationship with the Pelvic Organ Prolapse quantification staging system.
Magnetic resonance imaging (MRI) was performed to determine anatomical correlations with respect to physical examination using the Pelvic Organ Prolapse (POP) staging system. In addition, the standard POP staging system was analyzed to obtain normative data and determine any risk factors for prolapse. A total of 52 continent women 19 to 67 years old participated in our study. Pelvic MRI was performed at 1.5 Tesla. The vagina, bladder and rectum were opacified. Subjects performed pelvic floor contraction, relaxation and straining maneuvers for T1-weighted imaging. One-way analysis of variance, Fisher's exact test and multinomial logistic regression were used to analyze the data. POP stage is quantified from 0 to IV. Stage was 0 to II in 56%, 27% and 17% of cases. POP stage was not significantly influenced by the number of cesarean sections (p = 0.64) or smoking (p = 0.91) but the number of vaginal deliveries significantly correlated with stage. Women with 1 vaginal delivery were at increased risk for a stage I condition (p = 0.018), whereas those with more than 1 were at increased risk for stage II (p = 0.013). On MRI stages 0 versus I or II differed significantly in regard to bladder descent (p = 0.01 and <0.0001, respectively), while stages 0 versus I differed in regard to levator angle (p = 0.007). No significant staging differences were observed in regard to the posterior urethrovesical angle or stages I versus II with respect to all 3 MRI measurements. MRI appears to detect anatomically measurable changes in POP stage 0 versus other stages in regard to bladder descent and the levator angle and yet it is not sensitive enough to detect differences in stages I and II. It is not unusual for continent women to have a moderate degree of pelvic prolapse and previous vaginal delivery appears to increase this risk.


Benchmark dose estimation for benzene-exposed workers in China: Based on quantitative and multi-endpoint genotoxicity assessments.
Based on previous exposure studies, benzene (BZ) has been classified as a human carcinogen and occupational exposure limit (OELs) for BZ has been set to be about 1 ppm around the world. However, health hazards have still been reported with exposure below the OEL. Thus, the OEL needs to be updated to reduce health risk. The overall aim of our study was therefore to generate new OEL for BZ via a benchmark dose (BMD) approach and based on quantitative and multi-endpoint genotoxicity assessments. Genotoxicities were determined using the novel human PIG-A gene mutation assay, the micronucleus (MN) test and the COMET assay in benzene-exposed workers. Among the 104 workers with below current OELs, they exhibited significantly higher PIG-A mutant frequencies (MFs) (15.96 ± 14.41 × 10-6) and MN frequencies (11.55 ± 6.83‰) than those among the controls (PIG-A MFs: 5.46 ± 4.56 × 10-6, MN frequencies: 4.51 ± 1.58 ‰), but no difference in the COMET assay. A significant association was also observed between BZ exposure doses and PIG-A MFs and MN frequencies (P < 0.001). Our results indicate that health hazards were induced among workers with below OEL exposures. Based on results from the PIG-A and MN assays, the lower confidence limit of the BMD (BMDL) were calculated to be 8.71 mg/m3-year and 0.44 mg/m3-year, respectively. Based on these calculations, the OEL for BZ was determined to be lower than 0.07 ppm. This value can be considered by regulatory agencies to set new exposure limits and to better protect workers.


Synthetic media for preservation of corneal tissues deemed for endothelial keratoplasty and endothelial cell culture.
To compare the difference between various endothelial graft preparation methods and endothelial cell culture from tissues that are preserved in serum-based and synthetic medium. In a randomized masked study, the tissues (n = 64) were preserved in Cornea Max (serum-based) and Cornea Syn (synthetic) series for 36 days at their respective preservation conditions. Following organ culture, corneal tissues (n = 48) were used to prepareDescemet stripping automated endothelial keratoplasty (DSAEK), preloaded ultra-thin (UT) -DSAEK, prestripped Descemet membrane endothelial keratoplasty (DMEK), free-floating DMEK, and preloaded DMEK with endothelium inward and outward grafts. These tissues were preserved for another 4days at room temperature in dextran supplemented media following which they were subjected to trypan blue, alizarin red, live/dead and Zonula Occludens-1 (ZO-1) staining. A separate set of tissues (n = 16) from both the series was used for human corneal endothelial cell (HCEnC) culture. At confluence, the proliferation and cell doubling rate was calculated and the cultured cells were subjected to live/dead, ZO-1, 2A12 and Ki-67 staining. Mann-Whitney test was performed with p < 0.05 deemed statistically significant. After preparation and preservation of the tissues for endothelial keratoplasty, alizarin red showed standard endothelial morphology from both the groups. Endothelial cell loss, hexagonality and uncovered areas did not show statistically significant differences (p > 0.05) between both groups. For HCEnC, cell doubling rate was 4.7 days (p > 0.05). All the antibodies were expressed in both the groups. Hexagonality, polymorphism, cell area, viable/dead cells and Ki-67 positivity were not statistically significant (p > 0.05). Complete synthetic organ culture series is safe and advantageous for carrying out advanced endothelial keratoplasty graft preparation procedures and for HCEnC culture as it is free from animal or animal-derived products.


A comparison of three methods to evaluate change in the spontaneous language of aphasic individuals.
Three methods for evaluating change in the spontaneous language of aphasic subjects were compared. Clinical judgments (CJ) of experienced speech-language pathologists showed excellent agreement and served as a comparison with the Shewan Spontaneous Language Analysis (SSLA) and the WAB Spontaneous Speech subtest. Although reliable and easy to use, however, the CJ method does not provide comprehensive information needed for treatment planning. The SSLA, although more time-consuming, provided comprehensive information and agreed highly with CJ for detecting change. The WAB method, although almost as economical timewise as the CJ method, did not agree as highly with CJ and did not provide adequate information for treatment planning.


Fusion can mask the relationships between fundus torsion, oblique muscle overaction/underaction, and A- and V-pattern strabismus.
To evaluate relationships between fundus torsion, A- or V-pattern strabismus, and oblique muscle over- or underaction, and to explore the influence of stereopsis on these relationships. The medical records of patients with A or V patterns and/or abnormal ocular torsion seen at a single institution over nearly 30 years were retrospectively reviewed. Data collected were age, objective fundus torsion (estimated by indirect ophthalmoscopy), horizontal deviations in up- and downgaze, oblique muscle over- or underaction, and stereopsis. A total of 396 patients were included. A patterns were observed in 121 patients (30.6%); V patterns in 90 (22.7%). Of the A-pattern patients, 73.6% had superior oblique muscle overaction, whereas 71.1% of the V-pattern patients had inferior oblique muscle overaction (P < 0.0001, r = 0.71), increasing to 78.6% and 86.3%, respectively, for patients without stereopsis (r = 0.78). Of the patients with fundus intorsion, 78.7% had superior oblique muscle overaction, whereas 74.4% of those with fundus extorsion had inferior oblique muscle overaction (P < 0.0001, r = 0.79), increasing to 83.5% and 82.8%, respectively, for patients without stereopsis (r = 0.82). Fundus intorsion occurred in 76% of the A-pattern patients, whereas fundus extorsion occurred in 71.1% of the V-pattern patients (P < 0.0001, r = 0.73), increasing to 78.6% and 86.3%, respectively, for patients without stereopsis (r = 0.79). Strong correlations were found between fundus intorsion, superior oblique muscle overaction, and A patterns, and between fundus extorsion, inferior oblique muscle overaction, and V patterns. These correlations increased in patients without stereopsis, suggesting that the presence of binocular fusion can partially interfere with the close correlation of these parameters.


The structure of the lipopolysaccharide O-chain (M antigen) and polysaccharide B produced by Brucella melitensis 16M.
The surface M antigen of Brucella species has been identified as the lipopolysaccharide O-polysaccharide component composed of a repeating pentasaccharide unit containing a sequence of one 1,3- and four 1,2-linked, 4,6-dideoxy-4-formamido-alpha-D-mannopyranosyl units. A neutral polysaccharide produced by Brucella species and referred to as polysaccharide B (poly B) has been identified as a family of circular 1,2-linked polymers of beta-D-glucopyranosyl units ranging in ring size from 17 to 24 glucosyl units.


Adab and its significance for an Islamic medical ethics.
Discussions of Islamic medical ethics tend to focus on Sharī'ah-based, or obligation-based, ethics. However, limiting Islamic medical ethics discourse to the derivation of religious duties ignores discussions about moulding an inner disposition that inclines towards adherence to the Sharī'ah. In classical Islamic intellectual thought, such writings are the concern of adab literature. In this paper, we call for a renewal of adabi discourse as part of Islamic medical ethics. We argue that adab complements Sharī'ah-based writings to generate a more holistic vision of Islamic medical ethics by supplementing an obligation-based approach with a virtue-based approach. While Sharī'ah-based medical ethics focuses primarily on the moral status of actions, adab literature adds to this genre by addressing the moral formation of the agent. By complementing Sharī'ah-based approaches with adab-focused writings, Islamic medical ethics discourse can describe the relationship between the agent and the action, within a moral universe informed by the Islamic intellectual tradition.


Clinical significance of apoptotic index in non-small cell lung cancer: correlation with p53, mdm2, pRb and p21WAF1/CIP1 protein expression.
The aim of this study was to assess the prognostic relevance of apoptotic index (AI), considered alone or together with expression of several proteins controlling G1 check point (p53, mdm2, pRb and p21WAF1/CIP1) in non-small cell lung cancer (NSCLC) patients. Study group included 50 NSCLC patients who underwent curative pulmonary resection. Apoptosis was detected with the use of TUNEL technique and AI was defined as the number of apoptotic cells per 1,000 tumor cells. The expression of p53, mdm2, pRb and p21WAF1/CIP1 was assessed immunohistochemically. The mean and median AI calculated for all 50 patients was 14 and 9, respectively. Patients with lower (<14) and higher (> or =14) AI constituted 35 (70%) and 15 (30%) of cases, respectively. AI was not correlated with patient clinical characteristics, and expression of p53, pRb and p21WAF1/CIP1 . However, lower AI was correlated with over-expression of mdm2 protein (P=0.04). Median survival for patients with lower and higher AI was 43 months and 22 months, respectively, and 5-year survival probability-60 and 25%, respectively (P=0.03). In multivariate analysis, the only variable associated with shortened survival was AI (P=0.03, HR=2.9, 95% CI 1.95-3.86). These results suggest that AI correlates with mdm2 protein expression and influences survival in NSCLC.


Evaluation of Potassium Dichromate (K2Cr2O7)-Induced Liver Oxidative Stress and Ameliorative Effect of Picrorhiza kurroa Extract in Wistar Albino Rats.
The aim of the study was to assess the protective effect of Picrorhiza kurroa hydroalcoholic extract (PCK), a glycoside-rich extract, against potassium dichromate (PDC)-induced liver oxidative stress in Wistar albino rats. Thirty-six male Wistar rats were divided into six groups: the control group (which received distilled water), the SIL group (which received 60 mg/kg silymarin), the PDC group (which received 30 mg/kg K2Cr2O7), and the treatment groups (which received 25, 50, 100 mg/kg PCK). Administration of PDC resulted in increased levels of liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP); up-regulated peroxidation biomarkers, i.e., thiobarbutric acid-reactive species (TBARS) and protein carbonyls in serum; and decreased activities of antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT) significantly in the liver tissue. Gene expression studies of tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), growth arrest, and DNA damage-inducible protein (GADD45) revealed that there was a liver damage at the molecular level, and histopathological studies further confirmed the morphological changes by PDC administration. However, PCKs at 50 and 100 mg/kg promoted significant restoration of liver enzyme levels and the activities of antioxidant enzymes were kept close to the values of the control and SIL groups. Our current study confirms that the active compounds present in the PCK might have conferred a strong protection against potassium dichromate-induced oxidative stress.


Reporting Sysmex XN Absolute Neutrophil Count in Samples with Leukocyte Analyzer Flagging.
To provide faster laboratory data reporting, we evaluated the accuracy of Sysmex XN (Sysmex Inc, Kobe, Japan) absolute neutrophil count (ANC) in the presence of analyzer flagging. Sysmex XN and manual microscopy ANC were compared with 80 autovalidated control specimens and with 280 study specimens with analyzer flagging regarding immature granulocytes (IG) >3% or other leukocyte abnormalities. Specimens with ambiguous neutrophil clusters were excluded. A slight positive overall method bias was seen for Sysmex XN compared to manual microscopy (n = 280), 0.025 (95% confidence interval [CI], -0.023 to 0.069) × 109/L. With IG > 10% (n = 123) the bias was larger, but not clinically significant, 0.17 (95% CI, 0.060-0.25) × 109/L. No clinically significant difference was seen in neutropenic (ANC < 1.5 × 109/L) specimens (n = 91), 0.070 (95% CI, -0.013 to 0.14) × 109/L. These data indicate that Sysmex XN ANC can be reported in the presence of certain analyzer flagging to improve patient care.


Cerebrospinal fluid proteins and cells in normal-pressure hydrocephalus.
A total of 21 patients with normal-pressure hydrocephalus were examined. Cerebrospinal fluid (CSF) was collected before and after operation with a ventriculoperitoneal shunt. A slight plasma-like protein pattern indicating a blood-brain barrier (BBB) dysfunction was seen in 38% of the patients before operation. No characteristic changes could be found in the "CSF-specific" protein fraction. After the shunt operation 65% of the patients had a BBB dysfunction to macromolecules and 70% had two additional acidic protein bands in the CSF-specific fraction. Ventricular CSF protein content was 73% of lumbar CSF content when shunts were patent. Isotope encephalography showed a radionuclide accumulation at the intracranial part of the shunt system, indicating that the BBB damage might be located round the shunt catheter.


Renal transplant perfusion during aortoiliac aneurysmectomy.
Aortic surgery in recipients of renal transplants requires a method of maintaining intraoperative graft perfusion. A case is presented in which a temporary shunt from the suprarenal aorta to the ipsilateral common femoral artery was used to perfuse a renal transplant during aortoiliac aneurysmectomy. Other methods of renal graft perfusion are discussed.


Tuberculosis as the cause of diffuse parotitis.
Parotid swelling as the presenting symptom of acute tuberculosis is uncommon and often missed. Inappropriate treatment or referral can lead to serious sequelae. Because the incidence of extrapulmonary tuberculosis at all sites has been increasing steadily since 1985, this diagnosis now must enter into the differential of any individual at risk. Awareness on the part of the emergency physician will allow prompt recognition and appropriate treatment of this disease.


Optical coherence tomography angiography-guided vs indocyanine green angiography-guided half-dose photodynamic therapy for acute central serous chorioretinopathy: 6-month randomized trial results.
This study aimed to compare the anatomic and functional results of optical coherence tomography angiography (OCTA)-guided half-dose photodynamic therapy (PDT) versus indocyanine green angiography (ICGA)-guided PDT in eyes with acute central serous chorioretinopathy (CSC). One hundred and thirty-one eyes of 131 patients with acute central serous chorioretinopathy (CSC) were recruited, and randomly assigned to the OCTA-guided group and ICGA-guided group. The primary outcome measures were the rates of complete subretinal fluid (SRF) resolution at 1 month, 3 months, and 6 months. The secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal capillary flow deficit density at each scheduled visit, and recurrence rate of SRF at 3 months and 6 months. There were 110 eyes that finished the follow-up, with 56 eyes in the OCTA-guided group and 54 eyes in the ICGA guided group. OCTA-guided PDT was demonstrated to be noninferior to ICGA-guided PDT for SRF resolution rate at 1 months and 6 months (P = 0.021 and P = 0.037), but not at 3 months for acute CSC (P = 0.247). The average CRT of the ICGA-guided group was significantly lower than that of the OCTA-guided group at 3-month visit (P = 0.046), but no significant difference was found between them at the 1-month and 6-month visits (P = 0.891 and 0.527). There was no significant difference between the two groups for BCVA (P = 0.359, 0.700, and 0.143, respectively) and the deficit area on CC (P = 0.537, 0.744,and 0.604, respectively) at 1, 3, and 6 months. OCTA may replace ICGA to guide PDT for the treatment of acute CSC and their follow-up.


Limnological effects of a large Amazonian run-of-river dam on the main river and drowned tributary valleys.
Run-of-river dams are often considered to have lower environmental impacts than storage dams due to their smaller reservoirs and low potential for flow alteration. However, this has been questioned for projects recently built on large rivers around the world. Two of the world's largest run-of-river dams-Santo Antônio and Jirau-were recently constructed on the Madeira River, a major tributary to the Amazon River in Brazil. Here we evaluate the effects of the creation of the Santo Antônio dam on the water chemistry and thermal structure of the Madeira River mainstem and back-flooded valleys of tributaries within the reservoir inundated area. In contrast to the mainstem river, some back-flooded tributaries periodically developed thermal stratification, which is associated with higher water residence times. Additionally, biochemical oxygen demand, partial pressure of CO2, and organic carbon all increased in the tributary valleys inundated by the reservoir, possibly due to increased input of allochthonous organic matter and its subsequent mineralization upon back-flooding-a common feature of newly flooded impoundments. The mainstem did not show detectable dam-related changes in water chemistry and thermal structure. Although the majority of the reservoir area maintained riverine conditions, the lateral valleys formed upon back-flooding-corresponding to ~30% of the Santo Antônio reservoir area-developed lake-like conditions akin to a typical reservoir of a storage dam.


Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions.
T cells with a CD4(+) CD8(+) double-positive (DP) phenotype are present in small numbers in the peripheral blood of healthy humans and may have anti-viral capacities. Here we investigate numbers and function of DP T cells in patients with relapsing-remitting multiple sclerosis (MS), either treatment-naive or under therapy with natalizumab. Flow cytometry analysis revealed that frequencies of circulating DP T cells in treatment-naive and natalizumab-treated MS patients are comparable to healthy controls. These cells have a memory phenotype with cytotoxic potential, express high levels of CD49d and are similarly functional in treatment-naive as well as natalizumab-treated MS patients. DP T cells were enriched in the cerebrospinal fluid, but do not invade acutely inflamed MS lesions. In conclusion, DP T cells are functional in MS and may play a role in the immune surveillance of the central nervous system, but do not display functional impairment under natalizumab therapy.


Biosynthesis of placental alkaline phosphatase and its post-translational modification by glycophospholipid for membrane-anchoring.
The biosynthesis and post-translational modification of placental alkaline phosphatase were studied in human choriocarcinoma cells, JEG-3. Pulse-chase experiments with [35S]methionine demonstrated that placental alkaline phosphatase was synthesized as a major precursor form with Mr 63,000, which was then converted to a mature form with Mr 66,000, by processing of its N-linked oligosaccharides from the high-mannose type to the complex type. In addition, the two forms of the protein were found to be modified by a glycophospholipid, components of which were characterized by metabolic incorporation into placental alkaline phosphatase of 3H-labeled compounds such as myo-inositol, palmitic acid, stearic acid, mannose, glucosamine, and ethanolamine. When placental alkaline phosphatase labeled with these compounds was treated with phosphatidylinositol-specific phospholipase C or papain, the phospholipase C removed only the 3H-labeled fatty acids, whereas papain, that is known to cleave the C-terminal region, released all the radioactive glycolipid components including [3H]ethanolamine. More detailed analysis with shorter pulse-chase experiments demonstrated that placental alkaline phosphatase was primarily synthesized as a form with Mr 64,500 which was not yet labeled with [3H]palmitic acid. This form was converted by papain digestion to the above-mentioned major precursor with Mr 63,000. Taken together, these results suggest that placental alkaline phosphatase is initially synthesized as the precursor with Mr 64,500, which is immediately converted to the intermediate form with Mr 63,000 by simultaneously occurring proteolysis of the C terminus and replacement by the glycophospholipid, and finally to the mature form with Mr 66,000 by terminal glycosylation of its N-linked oligosaccharides. The glycophospholipid thus attached is considered to function as the membrane-anchoring domain of placental alkaline phosphatase.


Species-specific therapy of acute lymphoid leukemia.
In the past 10 years immunophenotyping of ALL has been demonstrated to be useful for selecting and scheduling chemotherapy. Different drug regimens are now used for T-cell and B-cell ALL than for non-T non-B ALL with the result that survival and cure of T-cell and B-cell ALL have been considerably improved. The use of different drug regimens for different immunophenotypic varieties of non-T non-B ALL is being tested. "Prognostic factors" of ALL are artifacts of data analysis and treatment and should no longer be used for guiding treatment. The administration of all-inclusive multiple-drug therapy to all patients with ALL regardless of species should also be abandoned. Minimally effective drugs can interfere with dosage and continuity of more effective drugs, and can result in side effects and sequelae that increase the mortality and morbidity of treatment. Since acute leukemias are genetic disorders of hematopoiesis the future direction of leukemic therapy is toward genetic targeting.


Two-photon fluorescence probe for quantification of cyclosporine.
A novel ratiometric fluorescent sensor was fabricated for the fast and facile determination of cyclosporine A (CsA). Due to the narrow therapeutic index of CsA, its desired therapeutic effects are evident within a limited range of blood concentration, indicating the fundamental role of therapeutic drug monitoring in CsA pharmacological response. In this study, a two-photon fluorescence probe based on the zeolitic imidazolate framework (ZIF-8) and norepinephrine-capped silver nanoparticles (AgNPs@NE) was employed for the quantification of the CsA in human plasma samples. In the presence of CsA, the fluorescent emission intensity of ZIF-8-AgNPs@NE was quenched. Under the optimum conditions, the proposed probe determines CsA in plasma samples in two linear ranges of 0.01 to 0.5 μg mL-1 and 0.5 to 10 μg mL-1. The developed probe demonstrates the advantages of a facile and fast platform with limit of detection as low as 0.007 μg mL-1. At last, this method was applied to find CsA concentration in four patients receiving oral CsA regimen which indicates it as a promising method for on-site detection applications.


Trends in hospital acquired New Delhi metallo-beta-lactamase-producing Enterobacterales in Tuscany (Italy) from 2019 to 2021: impact of the COVID-19 pandemic.
In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) in hospitalized patients has increasingly been observed since 2018, leading in 2019 to the implementation of enhanced control measures successfully reducing transmission. We describe the NDM-CRE epidemiology during the COVID-19 pandemic in Tuscany. Data on NDM-CRE patients hospitalized in five Tuscan hospitals were collected from January 2019 to December 2021. Weekly rates of NDM-CRE cases on hospital days in medical and critical-care wards were calculated. In March-December 2020, NDM-CRE rates were stratified by COVID-19 diagnosis. Multi-variate regression analysis was performed to assess outcomes' differences among two periods analysed and between COVID-19 populations. Since March 2020, an increase in NDM-CRE cases was observed, associated with COVID-19 admissions. COVID-19 patients differed significantly from non-COVID-19 ones by several variables, including patient features (age, Charlson index) and clinical history and outcomes (NDM-CRE infection/colonization, intensive care unit stay, length of stay, mortality). During the pandemic, we observed a higher rate of NDM-CRE cases per hospital day in both non-COVID-19 patients (273/100,000) and COVID-19 patients (370/100,00) when compared with pre-pandemic period cases (187/100,00). Our data suggest a resurgence in NDM-CRE spread among hospitalized patients in Tuscany during the COVID-19 pandemic, as well as a change in patients' case-mix. The observed increase in hospital transmission of NDM-CRE could be related to changes in infection prevention and control procedures, aimed mainly at COVID-19 management, leading to new challenges in hospital preparedness and crisis management planning.


[A study on the difference between International Diabetes Federation worldwide definition and Adult Treatment Panel III in diagnosing metabolic syndrome].
To study the difference between the metabolic syndrome (MS) diagnosis made with International Diabetes Federation (IDF) worldwide definition and the Adult Treatment Panel III (ATPIII) of National Cholesterol Education Program (NCEP). Cross-sectional study and descriptive study were used. There were 1328 MS patients diagnosed with IDF and 1527 MS patients diagnosed with ATPIII. There were 199 MS patients diagnosed with ATPIII but not with IDF and these MS patients all had 3 - 4 risk factors. According to the abnormality of glucose, blood pressure and lipid regulation stated in ATPIII criteria, 759 more patients were diagnosed as MS than with IDF criteria. MS diagnosed with ATPIII criteria is more objective than with IDF criteria and ATPIII criteria has more space for further theoretical study.


A practical model of osteomyelitis-induced bone pain by intra-tibial injection of Staphylococcus aureus in rats.
Osteomyelitis is an acute or chronic inflammatory process of bone accompanied with mild to severe pain. Generally, mild to moderate pain induced by osteomyelitis can be relieved, yet severe pain cannot. Therefore, a further investigation into the mechanism of severe pain induced by osteomyelitis is needed. In this study, a traditional rat model of osteomyelitis was induced by intra-tibial injection of Staphylococcus aureus. Then, a series of tests including bone histology, blood analysis, mechanical allodynia, thermal hyperalgesia, and immunohistochemistry were performed. Four days after an intra-tibial bacterial injection, acute inflammation was observed in the bone marrow, which developed into chronic inflammation 12 days after the procedure. The results from the blood analysis confirmed the existence of bone inflammation. Significant mechanical allodynia and thermal hyperalgesia developed shortly after the injection. This osteomyelitis-induced pain behavior was reversed by Celecoxib, a selective COX-2 inhibitor. Furthermore, significant increase of both microglia and astrocytes was observed in the spinal cord. Our results suggest that osteomyelitis-induced rats display pain related behaviors and associated neurochemical changes. This study thus provides a novel practical rat model of bone inflammation induced pain.


Dynamics of interaction and effects of microplastics on planarian tissue regeneration and cellular homeostasis.
Increasing microplastics pollution of marine and terrestrial water is a concerning issue for ecosystems and human health. Nevertheless, the interaction of microplastics with freshwater biota is still a poorly explored field. In order to achieve information concerning the uptake, distribution and effect of microplastics in planarians, Dugesia japonica specimens have been fed with mixtures of food and differently shaped and sized plastic particles. Feeding activity and food intake were non-altered by the presence of high concentrations of different types of plastic particles. However, the persistence of microplastic within the planarian body was a function of size/shape, being small spheres (<10 μm in diameter) and short fibers (14 μm large and 5/6 μm length) more persisting than larger spheres and longer fibers which were eliminated almost entirely by ejection in a few hours. Transmission electron microscopy analysis demonstrated that at least part of microplastics was phagocytized by the enterocytes. Chronic exposure to small plastic did not alter the regenerative ability but caused a significant reduction of the gut epithelium thickness and lipid content of enterocytes, together with the induction of apoptotic cell death, modulation of Djgata 4/5/6 expression and reduced growth rate. The ability of microplastic to perturb planarian homeostasis is concerning being them extremely resilient against mechanical and chemical insults and suggests possible harmful effects upon other more susceptible species in freshwater ecosystems.


Angular and linear speed cells in the parahippocampal circuits.
An essential role of the hippocampal region is to integrate information to compute and update representations. How this transpires is highly debated. Many theories hinge on the integration of self-motion signals and the existence of continuous attractor networks (CAN). CAN models hypothesise that neurons coding for navigational correlates - such as position and direction - receive inputs from cells conjunctively coding for position, direction, and self-motion. As yet, very little data exist on such conjunctive coding in the hippocampal region. Here, we report neurons coding for angular and linear velocity, uniformly distributed across the medial entorhinal cortex (MEC), the presubiculum and the parasubiculum, except for MEC layer II. Self-motion neurons often conjunctively encoded position and/or direction, yet lacked a structured organisation. These results offer insights as to how linear/angular speed - derivative in time of position/direction - may allow the updating of spatial representations, possibly uncovering a generalised algorithm to update any representation.


Haplotype analysis of the CFTR gene on normal and mutant CFTR genes.
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for Cystic Fibrosis (CF) disease. Since the distribution of polymorphisms varies among populations, a comparison between the frequency of CFTR polymorphisms in patients and healthy population may further identify their role in CF disease. The results obtained from this research may facilitate the prediction of disease phenotype in prenatal diagnosis or newborn screening program as well as determine the possible associations between haplotypes and specific mutations. Blood samples collected from 27 unrelated West Iranian families contain at least one CF patient and 55 control families with no history of CF. Samples were analyzed for c.1210-12 T [5-9], c.1242-35-1242-12GT [8-10], c.744-33GATT [6-8] and c.869 + 11C > T polymorphisms by automated direct DNA sequencing following DNA extraction. Our results showed that the T7 allele is the most common allele in normal and non-ΔF508 CF chromosomes with the frequencies of 93.6% and 100%, respectively. Conversely, T9 was the only allele detected in ΔF508 chromosomes. Moreover, the c.1242-35-1242-12GT analysis showed that (TG)11 repeat was the most common dinucleotide repeat in both, non-ΔF508 and normal chromosomes with the frequencies of 91% and 71%, respectively. The c.744-33GATT and c.869 + 11C > T polymorphism analyses indicated that (GATT)6 and T allele are only found in ΔF508 CF chromosomes. Besides, the [T7-TG11-GATT7-C] haplotype was the most common haplotype in both, normal and non-ΔF508 CF subjects while the [T9-TG10- GATT6-T] haplotype was only detected in CF patients carrying ΔF508 mutation. Our findings identified an informative haplotype that could be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran.


Funnel usefulness in direct-to-implant breast reconstruction using periareolar incision with prepectoral implant placement and complete coverage with acellular dermal matrix.
The funnel has been used in esthetic breast surgery that requires a small incision. Recent advances in minimally invasive surgical techniques have led to more cases of nipple-sparing mastectomy (NSM) through periareolar incision. However, prepectoral implant placement and complete coverage with acellular dermal matrix (ADM) is almost impossible with the periareolar approach. Funnels can also be useful for direct-to-implant breast reconstruction. NSM with periareolar incision and direct-to-implant breast reconstruction were performed with prepectoral implant placement between January 2017 and July 2019. The ADM full-wrapped anatomic textured implant was inserted using a funnel without additional incisions during surgery. A total of 21 patients were enrolled, including 2 who received bilateral breast reconstruction. All operations were successfully performed using funnels with minimal periareolar incisions. Anatomic textured implants (mean: 251.7 cc, range: 90-450 cc) wrapped in ADM can be effectively inserted in the prepectoral plane using a funnel. Two patients experienced delayed wound healing of the areola that was treated by conservative wound management. Patients also experienced less pain overall, and the cosmetic result was very good. Patient satisfaction scores were also very high. While the periareolar incision is esthetically pleasing, additional resection is often necessary. However, the use of funnels ensured that no additional incision was needed even in large implants. This subsequently led to better results in terms of pain and scarring. Prepectoral breast reconstruction involving complete implant coverage with ADM using a funnel through the periareolar approach represents a good alternative to the traditional dual plane subpectoral method. This method provides good patient satisfaction without adverse outcomes.


Genomic predictions based on animal models using genotype imputation on a national scale in Norwegian Red cattle.
In dairy cattle, current genomic predictions are largely based on sire models that analyze daughter yield deviations of bulls, which are derived from pedigree-based animal model evaluations (in a two-step approach). Extension to animal model genomic predictions (AMGP) is not straightforward, because most of the animals that are involved in the genetic evaluation are not genotyped. In single-step genomic best linear unbiased prediction (SSGBLUP), the pedigree-based relationship matrix A and the genomic relationship matrix G are combined in a matrix H, which allows for AMGP. However, as the number of genotyped animals increases, imputation of the genotypes for all animals in the pedigree may be considered. Our aim was to impute genotypes for all animals in the pedigree, construct alternative relationship matrices based on the imputation results, and evaluate the accuracy of the resulting AMGP by cross-validation in the national Norwegian Red dairy cattle population. A large-scale national dataset was effectively handled by splitting it into two sets: (1) genotyped animals and their ancestors (i.e. GA set with 20,918 animals) and (2) the descendants of the genotyped animals (i.e. D set with 4,022,179 animals). This allowed restricting genomic computations to a relatively small set of animals (GA set), whereas the majority of the animals (D set) were added to the animal model equations using Henderson's rules, in order to make optimal use of the D set information. Genotypes were imputed by segregation analysis of a large pedigree with relatively few genotyped animals (3285 out of 20,918). Among the AMGP models, the linkage and linkage disequilibrium based G matrix (G LDLA0 ) yielded the highest accuracy, which on average was 0.06 higher than with SSGBLUP and 0.07 higher than with two-step sire genomic evaluations. AMGP methods based on genotype imputation on a national scale were developed, and the most accurate method, GLDLA0BLUP, combined linkage and linkage disequilibrium information. The advantage of AMGP over a sire model based on two-step genomic predictions is expected to increase as the number of genotyped cows increases and for species, with smaller sire families and more dam relationships.


Clinical and Immunologic Changes due to Subcutaneous Immunotherapy With Cat and Dog Extracts Using an Ultrarush Up-Dosing Phase: A Real-Life Study.
We aimed to evaluate the efficacy of and immunologic changes caused by subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog. The study population comprised patients with rhinitis and/or asthma and allergy to cat or dog from a previous safety study. All patients had specific IgE to cat and/or dog. The SCIT maintenance dose was administered using an infusion pump over a single 4-hour session, followed by monthly administration over 6 months. Data were gathered on clinical outcomes, pulmonary function, FeNO, rhinitis and asthma symptoms, quality of life (QOL), and scores for the Asthma Control Test and symptom visual analog scale were recorded at baseline and then at 1, 3, and 6 months. Specific IgE and IgG antibody responses to cat and dog allergens were determined. The study population comprised 61 patients with a mean age of 35.6 (9.7) years, of whom 40 underwent SCIT for at allergy. A significant improvement was observed in rhinitis and asthma symptoms and in QOL, use of medication, visual analog scale score, and Asthma Control Test score at 1 month; these improvements persisted at month 6. The clinical improvement with cat extract was significantly more marked than with dog extract. Nearly half of the patients (49.09%) had an increase of >0.9 in the ESPRINT-15 QOL in allergic rhinitis questionnaire, and 58.18% had an increase of >0.5 in the Asthma Quality of Life Questionnaire score at month 6. Both differences represent the minimal clinical important difference. A significant increase was observed in specific IgG and IgE to different allergens at 3 and/or 6 months. Ultrarush SCIT with cat and dog extracts has substantial clinical value for many patients.


[Term breech presentations in singleton pregnancies: a continuous series of 418 cases].
The obstetrical management of term breech presentations in singleton pregnancies usually opposes the advocates of elective caesarean section to vaginal birth. Twelve years after the Term Breech Trial and 6 years after the PREMODA study, the aims of this work are to analyze neonatal results according to route of delivery chosen before labour and to evaluate professional practices in an important continuous series of cases. This is a retrospective study including all breech singleton pregnancies that delivered at our level III labour ward at 37 weeks of amenorrhea, from 1st January 2005 to 31st December 2011. All data were analyzed in intention to treat. Of the 418 patients included during the study period, 52% of them delivered vaginally. In 81% of cases, a vaginal birth trial was accepted and 64% of these patients delivered vaginally. Severe morbidity and neonatal mortality judgement criteria were not significantly different between the vaginal birth trial and the elective caesarean groups. Our obstetrical department continues to provide residents with specific training in the management of breech presentations. In this study, 60% of breech deliveries were performed by residents. Although a limited statistical power, this study did not bring any proof in favour of elective caesarean for singleton term breech presentations. Training residents in the management of vaginal breech deliveries is feasible and highly recommended.


Anterior chamber depth and chamber angle and their associations with ocular and general parameters: the Beijing Eye Study.
To investigate the normative data of anterior chamber depth (ACD) and angle width and their associations in Chinese adults. Population-based study. The Beijing Eye Study 2006 included 3,251 subjects (73.3%) (aged 45+ years) out of 4,439 subjects who participated in the 2001 survey and who returned for reexamination. The subjects underwent an ophthalmologic examination including measurement of the anterior chamber dimensions by slit-lamp-based optical coherence tomography (OCT). Out of the 3,251 subjects, OCT measurements were available for 2,985 subjects (91.8%). Mean ACD measured 2.42 +/- 0.34 mm and the mean anterior chamber angle (ACA) was 38.3 +/- 16.3 degrees. In multivariate analysis, a shallow chamber depth was significantly associated with age (P < .001), hyperopic refractive error (P < .001), female gender (P < .001), short body stature (P = .003), nuclear cataract (P = .03), central corneal thickness [CCT] (P < .001), large optic disk (P < .001), and presence of chronic angle-closure glaucoma (P < .001). Correspondingly, a narrow ACA was associated with age (P < .001), female gender (P < .001), hyperopia (P < .001), nuclear cataract (P < .001), short body stature (P = .001), large optic disk (P < .001), and angle-closure glaucoma (P < .001). Chamber depth and angle width were not associated with presence of age-related maculopathy and diabetic retinopathy. A shallow anterior chamber and a narrow chamber angle in Chinese adults are associated with age, female gender, hyperopia, nuclear cataract, small optic disk, short body stature, CCT, and chronic angle-closure glaucoma. These data may be helpful to explain anatomic relationships of the anterior segment of the eye, and to elucidate risk factors of angle-closure glaucoma.


Influence of environmental stresses on the durability of slag-based alkali-activated cement crusts for wind erosion control.
Wind erosion is a significant environmental challenge in arid and semi-arid regions, and artificial crust creation on the soil surface has emerged as an effective approach to mitigate this phenomenon. Various methods of crust formation have been proposed to combat wind erosion in these regions. However, a comprehensive study assessing the durability of these crusts against environmental stresses has been lacking. Hence, the primary objective of the present study is to address this critical issue by evaluating the erodibility and surface strength of alkali-activated slag crusts in response to various environmental stressors. These stressors encompass ultraviolet radiation, heating and cooling cycles, wetting and drying cycles, and freezing and thawing cycles. Through wind tunnel tests, erosion rates were measured under different wind velocities and saltation bombardment conditions, while penetrometer tests were conducted to analyze surface strength. The results demonstrate that alkali-activated cementation produced robust crusts, exhibiting an impressive reduction of over 99.9 % in erosion rates compared to untreated samples. However, the introduction of environmental stresses led to a fivefold increase in erosion rates. Freeze and thaw cycles had the most detrimental effect on the alkali-activated cement crusts while heating and cooling cycles had a relatively minor impact. The wetting and drying cycles and UV radiation ranked second and third, respectively, in terms of their destructive effects on crust erodibility. Despite the observed effects, the crusts maintained their efficiency even when subjected to severe environmental stresses. Notably, the erosion rate of the treated crusts after enduring the most severe studied stress, that is five freeze and thaw cycles, was over 250 times lower than that of the untreated samples.


Field-programmable biological circuits and configurable (bio)logic blocks for distributed biological computing.
Synthetic biology applications often require engineered computing structures, which can be programmed to process the information in a given way. However, programming of these structures usually requires significant amount of trial-and-error genetic engineering. This process is to some degree analogous to the design of application-specific integrated circuits (ASIC) in the domain of digital electronic circuits, which often require complex and time-consuming workflows to obtain a desired response. We describe a design of programmable biological circuits that can be configured without additional genetic engineering. Their configuration can be changed in vivo, i.e. during the execution of their biological program, simply with an introduction of programming inputs. These, e.g., increase the degradation rates of selected proteins that store the current configuration of the circuit. Programming can be thus performed in the field as in the case of field-programmable gate array (FPGA) circuits, which present an attractive alternative of ASICs in digital electronics. We describe a basic programmable unit, which we denote configurable (bio)logical block (CBLB) inspired by the architecture of configurable logic blocks (CLBs), basic functional units within the FPGA circuits. The design of a CBLB is based on distributed cellular computing modules, which makes its biological implementation easier to achieve. We establish a computational model of a CBLB and analyse its response with a given set of biologically feasible parameter values. Furthermore, we show that the proposed CBLB design exhibits correct behaviour for a vast range of kinetic parameter values, different population ratios, and as well preserves this response in stochastic simulations.


[Results of a national therapeutic trial in 10,000 hypertensive patients conducted by 2000 general practitioners (author's transl)].
Multicenter study in 10294 hypertensive patients conducted by 2000 G.P.'s throughout France. This trial permitted to compare the effectiveness and tolerance of 3 types of antihypertensive therapy: a beta-blocker, a diuretic and a central antihypertensive agent. It also permitted to study a certain number of socio-epidemiological characteristics in that patient population, in particular with regard to cardio-vascular risk factors.


Alterations of spontaneous neuronal activity in the caudate-putamen, nucleus accumbens and amygdaloid complex of rats produced by D-amphetamine.
Changes in spontaneous neuronal activity in the caudate-putamen, accumbens nucleus and amygdaloid complex of immunobilized, locally anesthetized rats were recorded following intraperitoneal injection of 2.5 mg/kg d-amphetamine sulfate. In each site, d-amphetamine typically produced a prolonged depression of firing rate which, in most cases, occurred after an inital, brief potentiation of activity. However, the onset of the amphetamine-induced depression occurred signficantly later in the amygdala. Subsequent IP administration of either 5.0 mg/kg chlorpromazine or 2.0 mg/kg haloperidol reversed, to varying degrees, the amphetamine-induced depression of neuronal activity in each area. These results are discussed in terms of the known biochemical effects of amphetamine on catecholaminergic transmission and the alleged role of the nigro-neostriatal mesolimbic dopamine systems in the amphetamine behavioral response.


The Seven-parameter Diffusion Model: an Implementation in Stan for Bayesian Analyses.
Diffusion models have been widely used to obtain information about cognitive processes from the analysis of responses and response-time data in two-alternative forced-choice tasks. We present an implementation of the seven-parameter diffusion model, incorporating inter-trial variabilities in drift rate, non-decision time, and relative starting point, in the probabilistic programming language Stan. Stan is a free, open-source software that gives the user much flexibility in defining model properties such as the choice of priors and the model structure in a Bayesian framework. We explain the implementation of the new function and how it is used in Stan. We then evaluate its performance in a simulation study that addresses both parameter recovery and simulation-based calibration. The recovery study shows generally good recovery of the model parameters in line with previous findings. The simulation-based calibration study validates the Bayesian algorithm as implemented in Stan.


Molecular characteristics of the epitope in myelin-associated glycoprotein that is recognized by a monoclonal IgM in human neuropathy patients.
The antigen for the IgM monoclonal antibody from patients with IgM paraproteinemia and peripheral neuropathy is the myelin-associated glycoprotein (MAG), a minor protein component of both human PNS myelin and human CNS myelin. Sera from five patients were found to react with identical proteolytically derived fragments of MAG indicating that the monoclonal IgM from these patients is recognizing a common epitope. Furthermore, the lectin concanavalin A reacts with these fragments and deglycosylation of isolated MAG abolishes the recognition of MAG by the patient monoclonal IgM. Therefore, it appears that the monoclonal IgM from these five patients recognizes a common epitope which contains carbohydrate moieties. These data are consistent with the idea that the peripheral myelin sheath is involved in an autoimmune response directed against MAG.


How the brain controls repetitive finger movements.
Adequate interaction with our physical and social environment requires accurate timing abilities. Since planning and control of movements is closely related to sensorimotor synchronization, the investigation of synchronization abilities may allow insights into fundamental principles of motor behaviour. The finger-tapping task has frequently been used to study the synchronization of one's own movements in relation to external events. Data from behavioural studies gave rise to the assumption that it is not the peripheral event (i.e., finger-tap or pacing signal) that is synchronized but its central representation. The neural foundations of sensorimotor synchronization have only recently been investigated and are still poorly understood. The present article reviews data from neurophysiological studies investigating sensorimotor synchronization to shed light on the neurophysiological processes associated with sensorimotor synchronization. This review focuses on studies investigating neuroelectric and neuromagnetic activity associated with simple repetitive synchronization tasks.


Computerized three-dimensional study of a rotavirus model of biliary atresia: comparison with human biliary atresia.
Biliary atresia is a panbiliary disease causing obstructive jaundice in neonates and infants. The clinical spectrum can be broadly categorized into the fetal and perinatal types. A consistent animal model that accurately mimics the whole clinical spectrum of biliary atresia is not yet available. However, rotavirus infection of neonatal mice has been shown to produce atresia in the biliary system. This study investigates the three-dimensional computerized morphology of the murine neonatal model comparing with age-matched control mice. Newborn Balb/c mice were injected intraperitoneally with rhesus rotavirus within 24-48 h after birth. Control mice received 0.9% NaCl. Pups with symptoms of cholestasis were sacrificed from the 5th to the 15th postinjection day, as were age-matched controls. Their hepatobiliary tissues were prepared for three-dimensional computerized image reconstruction. Rotavirus infection caused obliteration of the intrahepatic bile ducts and single to multiple atresias in the extrahepatic bile duct. At 15 days postinjection, intrahepatic ductal proliferation appeared, and the three-dimensional appearances of the intrahepatic biliary structures were similar to the human disease. Cystic duct and gallbladder dilatation was frequently seen in this model, and this feature distinguishes it from the human disease in which the gallbladder is almost always atretic. This rotavirus murine model demonstrates many of the features of human perinatal biliary atresia, and can be used as an investigative tool to further study the pathogenesis of biliary atresia.


Dietary inflammatory index and ovarian cancer risk in a large Italian case-control study.
While inflammation has been shown to play an important etiologic role in ovarian carcinogenesis, little is known about the association between inflammatory properties of diet and ovarian cancer risk. We explored the association between the dietary inflammatory index (DII) and ovarian cancer risk in a multicentric Italian case-control study conducted between 1992 and 1999. Cases were 1,031 women with incident, histologically confirmed ovarian cancer from four areas in Italy. Controls were 2,411 women admitted to the same network of hospitals as the cases for acute, non-malignant and non-gynecological conditions, unrelated to hormonal or digestive-tract diseases or committed to long-term modifications of diet. DII scores were computed based on 31 nutrients and food items assessed using a reproducible and validated 78-item food frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake and other recognized confounding factors. Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of ovarian cancer compared to subjects in the lowest quartile (i.e., with an anti-inflammatory diet) (ORQuartile4vs1 1.47, 95% confidence interval, CI, 1.07, 2.01; p trend = 0.009). When analyses were carried out using continuous DII, a significant positive association with ovarian cancer was observed: the OR for one-unit increment in DII score (corresponding to approximately 8 % of its range in the current study, +6.0 to -6.20) was 1.08 (95% CI 1.02, 1.14). A pro-inflammatory diet as indicated by higher DII scores is associated with increased ovarian cancer risk.


Molecular simulation and experimental studies on CO2 and N2 adsorption to bituminous coal.
A coal fire is one of the most serious disasters in coal mining. To improve the efficiency of an inert gas for extinguishing the fire, the adsorption behavior of coal in CO2/N2 mixed gas was investigated in this study. Proximate analysis, ultimate analysis, solid-state 13C nuclear magnetic resonance spectroscopy (NMR), X-ray photoelectron spectroscopy (XPS), and molecular dynamics (MD) were applied to analyze and establish the bituminous coal molecular model. The adsorption behavior of bituminous coal in mixed gas mixtures with different proportions was studied using the bituminous coal model and Materials Studio (MS) software. A self-built coal adsorption experimental system was used for experiments. The adsorption of bituminous coal to CO2 is stronger than that to N2, and there is a competitive adsorption relationship between them. The amount of CO2 adsorbed by the coal gradually increases as the CO2 partial pressure rises, consistent with the Langmuir model. With an increase in CO2 pressure, the total adsorption capacity, which is divided into the rapid increase stage, slow growth stage, and stable stage, also increases. The coal adsorbs 0.5050 cm3/g, 0.7455 cm3/g, 0.9450 cm3/g, 1.0715 cm3/g, and 1.2000 cm3/g for pure N2, 2%, 5%, 7%, and 10% CO2, respectively, in the experiment. The results of the simulation and experiment show the same trend, which means that the injection of a small amount of CO2 into pure N2 will greatly improve the gas adsorption volume of the coal, demonstrating that it is feasible to improve the ability of the coal to absorb mixed gases by changing the gas concentration and consequently to increase the efficiency of inert gas for fire extinguishing and suppression.


Help a mother out: The impact of acute care surgeon response in postpartum hemorrhage.
A Code White (CW) activation is a hospital-wide alert for postpartum hemorrhage (PPH) and acute care surgeons (ACS) were added to the response team to assist in resuscitation. A multidisciplinary training program was also implemented. This study aimed to evaluate the impact of ACS involvement and training on maternal outcomes. A retrospective review was performed on all CW activations from 1/1/2015-8/31/2022. Three groups-pre-ACS response, ACS response, and ACS response + training (R&T)-were compared. 218 patients had CW activations. ACS response increased MTP activations (50.0%vs76.5%vs76.2%, p = 0.014) and TXA administration (50.0%vs96.5%vs93.3%, p < 0.0001). The ACS R&T had the highest ACS presence (53.6%vs72.9%vs96.2%, p < 0.0001), shortest operation (99 vs 67 vs 53min, p = 0.002), lowest crystalloid use (2000 vs 1110 vs 800 ml, p = 0.003), and lowest transfusion requirements. Mortality decreased from 17.9% in pre-ACS to 2.4% in ACS response and 0% in ACS R&T (p < 0.0001). ACS assistance in CW activations and multidisciplinary PPH education led to the prevention of maternal mortality. ACS are a valuable resource in this unique population.


Network modeling of signal transduction: establishing the global view.
Embryonic development and adult tissue homeostasis are controlled through activation of intracellular signal transduction pathways by extracellular growth factors. In the past, signal transduction has largely been regarded as a linear process. However, more recent data from large-scale and high-throughput experiments indicate that there is extensive cross-talk between individual signaling cascades leading to the notion of a signaling network. The behavior of such complex networks cannot be predicted by simple intuitive approaches but requires sophisticated models and computational simulations. The purpose of such models is to generate experimentally testable hypotheses and to find explanations for unexpected experimental results. Here, we discuss the need for, and the future impact of, mathematical models for exploring signal transduction in different biological contexts such as for example development.


Measurement of allantoin and uric acid in human body fluids. A potential index of free-radical reactions in vivo?
Free-radical attack upon uric acid generates allantoin [Ames, Cathcart, Schwiers & Hochstein (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 6858-6862]. Methods are described for the accurate measurement of uric acid and allantoin in human body fluids. The concentrations of uric acid and allantoin in human serum and synovial fluid are reported. It is suggested that measurement of changes in allantoin concentration may be a useful index of free-radical reactions taking place in vivo.


Curcumin antagonizes inflammation and autophagy induced by arsenic trioxide through immune protection in duck spleen.
Arsenic is a toxic heavy metal widely found in the natural environment and has adverse effects on the health of waterfowl and human. Curcumin (CUR), a natural pigment of the golden spice turmeric, exhibits excellent anti-tumor, anti-inflammatory and anti-oxidant activities. But the effects of CUR on duck spleen exposed to arsenic remain largely unknown. In this study, 75 ducks were divided randomly into Control, L-ATO, M-ATO, H-ATO and CUR + H-ATO groups to systematically analyze the underlying role of CUR. The results showed that arsenic trioxide (ATO) led to growth retardation of ducks, hyaline degeneration and sparse cell arrangement on their spleen. And in the ATO-exposed ducks, the levels of immunoglobulins (Ig; IgA, IgG, IgM) in the serum and the expression of autophagy-related genes (Atg5, P62, LC3I, LC3II, LC3II/I, Beclin-1) were significantly upregulated compared with the control ducks. Moreover, ATO also activated NF-κB signal pathway and upregulated the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-18). Meanwhile, application of CUR alleviated the ATO toxicity with the release of growth inhibition, and the reduced hyaline degeneration and distortion of the spleen capsule. CUR also suppressed ATO-induced NF-κB activation, pro-inflammatory cytokine addition and expression of autophagy-related genes. Overall, these results suggested that CUR might exert a protective effect against ATO-induced immunosuppression in ducks via anti-inflammation and autophagy restoring.


Evaluation of Intracranial Cerebral Blood Flow Velocities in Splenectomised and Non-Splenectomised Patients with β-Thalassemia Intermedia Using Transcranial Doppler Sonography.
A high incidence of clinically-silent cerebral ischemic events has been reported in splenectomised patients with β-thalassemia intermedia (βTI). These could be due to cerebral large-vessel disease. Based on the example of sickle cell disease, we applied transcranial Doppler sonography (TCD) to evaluate cerebral vessels velocity as a possible indicator of cerebral vasculopathy. In our study, we included 17 splenectomised and 13 non-splenectomised (control group) patients with βTI. Non-imaging TCD was performed and the time-averaged mean velocity (TAMV) values of cerebral arteries were measured. There was no statistically significant difference between the two groups concerning age, gender, hemoglobin and hematocrit levels, nor in the TAMV values for all examined vessels (p>0.05). A statistically significant difference was found in platelet count (PLT) (p<0.01) that was higher in splenectomised patients. Our results do not support the presence of large-vessel vasculopathy in splenectomised βTI patients and agree with recent studies reporting that cerebral ischemic events in these patients might be due to microangiopathy or venous thromboembolism.


Laser induced fluorescence bands in the FT-Raman spectra of bioceramics.
A new fluorescence band at about 1930cm-1 has been observed in the FT-Raman spectra of some bioceramics. While a fluorescence band at about 760cm-1 has been already reported in the FT-Raman spectra of hydroxyapatite and related calcium phosphates, this new band is observed for the first time. This strong band is totally absent in the anti-Stokes side of the FT-Raman spectra and therefore has been assigned as a laser induced fluorescence band. It has been concluded that in recording FT-Raman spectra of minerals, all precautions about fluorescence bands should be considered, otherwise the FT-Raman spectra may well be misinterpreted.


Forensic characteristic and population structure dissection of Shaanxi Han population in the light of diallelic deletion/insertion polymorphism data.
The genetic polymorphisms of diallelic deletion/insertion polymorphic (DIP) loci in the Shaanxi Han population are still not clearly characterized. Herein, allele frequencies and forensic application efficiencies for 30 diallelic DIP loci were investigated in 506 unrelated healthy Han individuals from Chinese Shaanxi province. Based on population data of the same 30 diallelic DIP loci, the genetic differentiations, hierarchical clustering relationships and population architectures among Shaanxi Han and other 50 populations were further dissected through genetic and bioinformatics analyses. Results indicated that most of the 30 diallelic DIP loci were relatively high polymorphisms in the Shaanxi Han population; and there were the genetically intimate relationships between Shaanxi Han and the East Asian populations. In summary, this study provided significant insights into genetic background of Shaanxi Han population, and the multiplex amplification of these 30 diallelic DIP loci was appropriate for forensic individual identification and population genetic research in Shaanxi Han population.


Spasticity.
Spasticity has been defined as velocity-dependent hyperactivity of stretch reflexes; it is therefore only one aspect of the complex syndrome produced by a lesion of the upper motoneuron. Although spasticity may be partially responsible for joint contractures, it does not produce most of the functional disability experienced by patients with upper motoneuron lesions. Paresis, fatigability, lack of dexterity, etc., account for most of these patients' complaints. The pathophysiology of spasticity is poorly understood but appears to be related to an increased excitatory state at the segmental spinal level; there is no evidence for increased sensitivity of muscle spindles in spastic patients. Several mechanisms for this increased excitability within the spinal cord have been proposed. There are different types as well as degrees of spasticity. Clinical neurophysiologic recordings of reflex activity in patients with spasticity provide the means to differentiate among the various types of spasticity, to select the therapy most likely to be effective in a particular patient, and to see the results of its employment objectively. The latter will prove whether a specific therapy is useful or not. Ablative treatment at the level of the peripheral nerve or dorsal root may be useful, particularly when spasticity is severe. Drugs such as baclofen or diazepam relieve flexor spasms but are not particularly effective against spasticity itself. Dantrolene acts to weaken muscles, but that is not often helpful. Rarely do any of these therapies increase function; there are no effective cures for paresis or related negative manifestations of chronic spasticity.


Steroid hormone receptors compete for factors that mediate their enhancer function.
Stimulation of transcription of reporter genes by the progesterone receptor (PR) was inhibited in transfected HeLa cells by co-expressing the estrogen receptor (ER) in an ER-dose- and estrogen-dependent manner. Both the N-terminal A/B region and the hormone binding domain of ER were involved in this inhibition, which was antagonized by antiestrogens and did not appear to involve direct interaction between ER and either reporter gene or PR. ER expression also inhibited activation by the glucocorticoid receptor (GR), and both PR and GR expression inhibited activation by ER, albeit to a lower extent. Similar transcriptional interference was observed between the endogenous PR and ER present in T47D and MCF-7 breast cancer cells transfected with an ER reporter gene. Moreover, transcription of the resident estrogen-induced pS2 gene was partially inhibited by exposing MCF-7 cells to progestins or glucocorticoids. We propose that these observations reflect competition for a functionally limiting transcription factor(s).


Isolation and characterization of cDNAs from Lycopersicon esculentum and Arabidopsis thaliana encoding the 33 kDa protein of the photosystem II-associated oxygen-evolving complex.
We have identified and isolated cDNA clones of the 33 kDa protein of the oxygen-evolving complex (OEE1) from Lycopersicon esculentum (tomato) and Arabidopsis thaliana and determined their nucleotide sequences. The cDNA clones and antibodies prepared against OEE1 were used as probes to examine the expression of the oee1 gene with respect to regulation by light, organ specificity, and ripening stage of tomato fruit. The steady-state mRNA level is regulated by light, being present in light-grown plants and absent in etiolated seedlings. The oee1 transcripts that accumulate during growth in the light were reduced to non-detectable or low levels by a 3-day dark treatment. The oee1 gene also exhibits differential expression in various organs of the tomato plant. Steady-state mRNA level was highest in immature leaves and absent in roots while the protein was most abundant in mature leaves and absent in roots. During tomato fruit ripening oee1 mRNA decreases to a low level in the pericarp while the protein level decreases below detection. The expression of oee1 appears to be under the control of a complex mechanism regulating both the amount of RNA and its translation.


[Not Available].
This paper presents a case report of indoor Stachybotrys toxins in Germany. In the summer of 2000, heavy rainfall and a leakage of the gutter system of an appartement house in Munich, Germany, caused a severe water damage in one of the appartments. The appartment was at that time occupied by two of the authors (ES, EU). A wall (covered with wallpaper) in one room in particular was most strongly affected, about 6-8 m(2) of the wallpaper became very wet. Large parts of this wet wallpaper were within days infested by multiple circumscribed round, grey-black colonies (0.5-5 cm in diameter) of presumtiveStachybotrys spp.. At the same time, the air in this room became very damp and oppressive. Several persons reported burning sensations on the mucous membranes of the eye, nose, and larynx, followed by headache symptoms, as soon as a few minutes after they had entered this room. Inadvertent skin contact with one of the fungal colonies by one person resulted in burning sensations immediately, but symptoms disappeared after thorough rinsing of the skin with water. The infested room was evacuated, and samples were taken from the wet wallpaper at areas (1) in the center of the most heavy fungal colony growth, (2) several cm away from colony growth, and (3) from locations which were wet but about 1 m away from visible colony growth. The samples were extracted with methanol, the extract diluted with buffer solution and analysed by competitive enzyme immunoassay (EIA) for roridin A. Due to cross-reactivity, this EIA detects several macrocyclic trichothecenes produced byStachybotrys spp.. Heavily infected pieces of wallpaper were strongly contaminated with toxins, with maximum concentrations of 1.1 microgram per cm(2) (Roridin A equivalents). Wet but visibly not infected samples of wallpaper were negative in the EIA. Considering a EIA cross-reactivity of satratoxin H (the major Stachybotrys-toxin) of 15%, the actual maximum toxin concentration would correspond to 6 microgram of satratoxin H per cm(2). As far as we know, this is the first documented case of indoor Stachybotrys toxins in Germany. The toxin concentration by far exceeds the minimum toxin level required for skin toxicity, and was considered as unhealthy. Health authorities in Munich were informed but were unable to provide assistance, probably because awareness of the importance and the possible health risks caused by indoor mycotoxins is not yet widespread in Germany. Reporting and monitoring programs for mycotoxins in water-damaged buildings seem to be necessary to provide insight into the occurrence of similar cases as the one described here.


Epidemiology and comorbidities of patients with chronic urticaria in Korea: A nationwide population-based study.
Few population-based studies have focused on the epidemiology and comorbidities of chronic urticaria (CU) or chronic spontaneous urticaria (CSU). The objective of this study was to obtain information on the epidemiology and comorbidities associated with CU and CSU in Korea. We conducted a cross-sectional analysis using a national health insurance database. An algorithm based on the International Classification of Diseases, 10th revision, was used for the identification of patients with CU and CSU, and an age-sex adjusted logistic regression model was used to assess the risk of comorbidities in these patients. The average annual prevalence rates of CU and CSU during the 4-year period between 2010 and 2013 were 3.08% and 1.40%, respectively. The prevalence rates of CU and CSU were higher in women than men (1:1.39 and 1:1.34, respectively) and peaked at 0-9 and 70-79 years, respectively. After adjustment for age and sex, the patients with CU and CSU were found to have a significantly higher prevalence rate of CU/CSU-related diseases, compared with those without CU (mean adjusted odds ratio, 8.46; 95% confidence interval, 8.10-8.83). Allergic rhinitis, drug allergies, asthma, thyroid diseases and cancers were the most common comorbidities. Stomach, thyroid, liver and prostate cancers were the most prevalent cancers. This study provides large epidemiological data on the prevalence rates of CU and CSU, and their comorbidities, in Korea. Patients with CU and CSU impose a higher burden, in terms of specific comorbidities, than those without CU.


First report of class 2 integron in clinical Enterococcus faecalis and class 1 integron in Enterococcus faecium in South China.
During 2003 to 2004, class 1 integron was detected in 8 out of 10 tested enterococci isolates, with 2 of them positive for class 2 integron. This is the first report of class 2 integron in Enterococcus faecalis and class 1 integron in Enterococcus faecium.


Diagnostic and management difficulties in a case of multiple intracranial juvenile xanthogranuloma.
Juvenile xanthogranuloma (JXG) preferentially occurs in childhood, and its characteristics have been thought to be benign and with slow growth. JXG is classified as an inflammatory disease, which forms multiple lesions in the patients' head, neck, and other organs and typically skin. JXG is rare, and few case reports have been published in the past, particularly with multiple intracranial lesions, which as in our case, is an extremely rare finding. Patient is a 4-year-old boy who presented with polydypsia and polyuria for 1 year. He had been followed up only under l-deamino-8-D-arginine vasopressin until he started vomiting and his level of consciousness deteriorated. Then, magnetic resonance imaging (MRI) revealed multiple intracranial lesions. He underwent biopsy via small craniotomy, and pathology was confirmed as juvenile xanthogranuloma. The patient received chemotherapy, in complete compliance with JLSG-02 protocol. JXG is characteristic with homogenous enhancement with contrast matter and, most importantly, high intensity on diffusion-weighted image (DWI). The DWI was high when the degree of diffusion of water is restricted, as seen in inflammation and, additionally, the change of intensity after administration of steroid would reflect its anti-inflammatory nature. However, though the steroid therapy made high-intensity lesions decrease signal intensity, the size and the number of lesions did not change at all. As we expected, after we stopped steroid administration to the patient, his consciousness deteriorated and we found again the very-high-intensity lesions. We consider the intensity on DWI to reflect progression of the lesions.


Alterations of acid-base balance, electrolyte concentrations, and osmolality caused by nonionic hyperosmolar contrast medium during pediatric cardiac catheterization.
This prospective clinical observational study was conducted to investigate the effects of contrast medium on acid-base balance, electrolyte concentrations, and osmolality in children. For pediatric cardiac catheterization, high doses of nonionic hyperosmolar contrast medium are widely used. Forty pediatric patients (age 0-16 years) undergoing cardiac angiography with more than 3 ml·kg(-1) of nonionic hyperosmolar contrast medium (Iomeprol) were enrolled, and the total amount of the contrast agent given was documented. Before and after contrast medium administration, a blood sample was collected to analyze electrolytes, acid-base parameters, osmolality, hemoglobin, and hematocrit. After cardiac catheterization, pH, hemoglobin, hematocrit, bicarbonate, base excess, sodium, chloride, calcium, anion gap and strong ion difference decreased, whereas osmolality increased significantly (base excess -1.8 ± 1.8 vs -3.4 ± 2.3, sodium 138 ± 2.9 vs 132 ± 4.1 mm, osmolality 284 ± 5.7 vs 294 ± 7.6 mosmol·kg(-1), P < 0.01). Seventy-eight percent of the children developed hyponatremia (sodium <135 mm). No changes were seen in pCO(2) , lactate, and potassium levels. Regarding the differential diagnosis of metabolic disturbances after pediatric cardiac catheterization, low-anion gap metabolic acidosis and hyponatremia should be considered as a possible side effect of the administered contrast medium.


Development of primary leiomyosarcoma of the sternum postirradiation: report of a case.
We report herein the case of a 30-year-old man who developed a primary leiomyosarcoma (LMS) 11 years after undergoing a median sternotomy for mediastinal seminoma followed by 50 Gy radiotherapy. He was given two courses of chemotherapy, resulting in 90% tumor regression, after which resection of the tumor with adjacent chest wall structures was carried out. Reconstruction was performed using a methylmethacrylate prosthesis prepared preoperatively. Postoperatively, he received two additional courses of chemotherapy and has had no sign of recurrence for 45 months.


Disentangling Diet- and Medium-Associated Microbes in Shaping Daphnia Gut Microbiome.
Host genotype and environment are considered crucial factors in shaping Daphnia gut microbiome composition. Among the environmental factors, diet is an important factor that regulates Daphnia microbiome. Most of the studies only focused on the use of axenic diet and non-sterile medium to investigate their effects on Daphnia microbiome. However, in natural environment, Daphnia diets such as phytoplankton are associated with microbes and could affect Daphnia microbiome composition and fitness, but remain relatively poorly understood compared to that of axenic diet. To test this, we cultured two Daphnia magna genotypes (genotype-1 and genotype-2) in sterile medium and fed with axenic diet. To check the effects of algal diet-associated microbes versus free water-related microbes, Daphnia were respectively inoculated with three different inoculums: medium microbial inoculum, diet-associated microbial inoculum, and medium and diet-mixed microbial inoculum. Daphnia were cultured for 3 weeks and their gut microbiome and life history traits were recorded. Results showed that Daphnia inoculated with medium microbial inoculum were dominated by Comamonadaceae in both genotypes. In Daphnia inoculated with mixed inoculum, genotype-1 microbiome was highly changed, whereas genotype-2 microbiome was slightly altered. Daphnia inoculated with diet microbial inoculum has almost the same microbiome in both genotypes. The total number of neonates and body size were significantly reduced in Daphnia inoculated with diet microbial inoculum regardless of genotype compared to all other treatments. Overall, this study shows that the microbiome of Daphnia is flexible and varies with genotype and diet- and medium-associated microbes, but not every bacteria is beneficial to Daphnia, and only symbionts can increase Daphnia performance.


Combination of alkaline phosphatase/graphene oxide nanoconjugates and D-glucose-6-phosphate-functionalized gold nanoparticles for the rapid colorimetric assay of pathogenic bacteria.
Pathogenic bacteria are a major cause of foodborne diseases, which not only seriously threaten human safety but also cause significant losses for the national economy. Therefore, it is very important and urgent to develop a method for the detection of pathogenic bacteria with high accuracy, high sensitivity, and easy interpretation for use in food safety and medical hygiene. Herein, based upon the sensitive color changes induced by the dispersion and aggregation states of gold nanoparticles (AuNPs), a point-of-care (POCT) colorimetric assay was constructed for the rapid and sensitive visual detection of pathogenic bacteria. The POCT visual sensing system is composed of two individual elements: (1) an alkaline phosphatase/graphene oxide (GO@PEI-ALP) nanoconjugate that can release free ALP molecules in the presence of pathogenic bacteria; (2) D-glucose-6-phosphate (pGlu) and 3-aminobenzene boric acid (AMBA)-functionalized AuNPs (pGlu/AMBA-AuNPs) that are cross-linked upon the digestion of pGlu by free ALP molecules, resulting in a significant color change. Under optimized conditions, the detection limit of this sensing system for target bacteria was as low as 24 CFU mL-1 and was successfully applied to complex real samples. This proposed rapid colorimetric assay has high sensitivity, accuracy, and practicability with an intuitive signal and is expected to provide new inspiration for the detection of pathogenic bacteria.


Tetranuclear organometallic complexes containing Mo2O4(2+) and allylmolybdenum(II) moieties.
Refluxing toluene solutions of [Mo(η(3)-allyl)(O(2)CMe)(CO)(2)(pz*H)(2)] (pz*H = pzH, pyrazole, or dmpzH, 3,5-dimethylpyrazole) without exclusion of air, give the tetranuclear complexes [Mo(2)O(2)(O(2)CCH(3))(2){(μ(3)-O)(μ-pz*)Mo(η(3)-allyl)(CO)(2)(pz*H)}(2)], where two chelating acetato ligands and two "Mo(η(3)-allyl)(CO)(2)(pz*H)(μ-pz*)" fragments are bonded to a central Mo(2)O(4)(2+) moiety.


Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and parental history of myocardial infarction.
One hundred and eighty-one male and 48 female myocardial infarction (MI) survivors and 172 male and 194 female controls were studied with respect to a possible association between premature parental MI (before age 61 years in mothers and/or before age 56 years in fathers) and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). In the total series, the frequency of premature parental MI was 14% in the DD (homozygotes for the deletion (D) allele) genotypic group, 10.6% in the ID (heterozygotes) genotypic group and 6.1% in the II (homozygotes for the insertion (I) allele) genotypic group. In all males (male MI survivors and male controls combined), and in the total series, there was a significant excess of DD individuals as compared to II individuals among those with a parental history of premature MI (odds ratio 3.1 (p = 0.03) and 3.1 (p = 0.009), respectively). The ACE polymorphism may be an important genetic marker of MI risk and contribute to clustering of premature MI in families.


A Pseudomonas intracellular amylase with high activity on maltodextrins and cyclodextrins.
An intracellular amylase from Pseudomonas MSl was purified 95-fold in a 14% yield by fractionation with (NH4) 2SO4, followed by chromatographies on CM-cellulose, hydroxylapatite and Sephadex G-200. On polyacrylamide gel electrophoresis at pH 8.3 it gave a single band and its molecular weight was determined to be 96 000 from its mobility on sodium dodecylsulfate gel electrophoresis. Its activity was maximal at pH 5.5 and 50 degrees C. This enzyme hydrolyzed maltotriose and maltotetraose faster than amylose, but did not hydrolyze maltose. It also rapidly hydrolyzed a series of cyclomaltodextrins. Amylopectin and glycogen, which have branched structures, were attacked much slower than amylose. The enzyme cleaved the substrates in an endo-wise fashion and produced almost equimolar amounts of glucose and maltose as the final products from various substrates. The enzyme mechanism is discussed on the basis of quantitative autoradiographic data. The K-m values for maltotriose, maltotetraose, cyclomaltohexaose, corn amylose and waxycorn amylopectin were 1.0, 1.4, 3.5, 3.3 and 13 - 10-minus 3 g/ml, respectively. The products of the enzyme had an alpha-configuration. Thus, this enzyme is a specific alpha-amylase.


Calcific myonecrosis: a unique presentation in the upper extremity.
Calcific myonecrosis is a rare and latent condition characterized by a dystrophic calcified lesion that can present 10-64 years following initial trauma. Of the 25 cases documented in English world literature, all have occurred in the lower extremity exclusively. We report a case of a 60-year-old man with a painless enlarging left forearm mass that was subsequently diagnosed as calcific myonecrosis. Awareness of this lesion arising outside of the lower extremity is important to avoid unnecessary surgical intervention and patient reassurance.


Corneal swelling and recovery following wear of thick hydrogel contact lenses in insulin-dependent diabetics.
Thick, 0.34 mm, 38% water hydrogel lenses were fitted, under a pressure patch, to one eye of 18 type I diabetic patients (aged 18-40 years) to assess the acute response to hypoxia and hypercapnia; the response was compared with that in 18 healthy, aged-matched non-diabetic subjects; the closed-eye lens wear was started mid-morning. Pre-lens wear assessments were made of acuity, intraocular pressure (IOP), central corneal thickness (CCT) and corneal appearance by biomicroscopy. The mean duration of the diabetes was 13 +/- 7 years and the average fasting blood glucose was 8.7 +/- 3.3 mMl-1. Baseline CCT values were marginally greater in diabetic patients (600 +/- 33 microns) compared with a group of non-diabetic control subjects (584 +/- 26 microns; P > 0.5). A 7.7 +/- 2.1% increase in CCT was measured after 3 h lens wear in the diabetic patients while an average 10.6 +/- 2.4% increase in CCT was measured in the control subjects (P < 0.05). The recovery of corneal thickness to baseline values in diabetic patients was slower (at 44.8 +/- 2.0% per hour) than the control subjects (53.9 +/- 2.1 per hour; P < 0.05) although recovery of corneal thickness occurred in both groups within 2.5-3h. IOP values (non-contact tonometry) were higher in the diabetic patients than in the controls (14.5 +/- 2.9 vs 12.4 +/- 1.7 mmHg; P < 0.01). Overall, those corneas with greater baseline CCT values tended to swell less than those with lower baseline CCT values (r = 0.582). Positive correlations were also found between corneal thickness and IOP and blood glucose. The diabetic patients thus tended to have slightly thicker corneas (but this could be related to blood glucose or IOP rather than true corneal disease) and also had corneas that tended to swell less with a contact lens stress test (but this could be constitutively due to the slight oedema already present). The different corneal response in diabetic patients may thus be the result of physical determinants such as initial oedema and IOP and not the result of a disease of the cornea itself.


[Voluminous mediastinal neurofibroma in a child].
Neurogenic tumors account for 30% of mediastinal tumors in children. The thoracic region is the most common site for neurofibromas. We report a case of a voluminous neurofibroma in a small girl. After 8 months of paraplegia, a 4-year-old girl underwent thoracic radiography and computed tomography as well as magnetic resonance imaging of the spine. These revealed a huge mediastinal mass continuing into the vertebral canal and compressing the cord. Histological examination after surgery confirmed the diagnosis of neurofibroma. At the follow-up examination a month later, the paraplegia had resolved. Neurofibromas may manifest as solitary tumors or may be one manifestation of neurofibromatosis. In mediastinal neurofibroma, thoracic radiography, and computed tomography can show the tumor, posterior vertebral scalloping, and enlarged neural foramina. MR imaging provides the exact anatomic location, as well as any compression and displacement caused by the tumor. This information is essential for deciding the exact extent of resection. MRI may also be helpful in postoperative management.


A benchmark in the isolated tricuspid valve surgery is necessary.
Advances in surgical techniques, enabling correction of regurgitation, and preserving the tricuspid valve, are also factors that encourage early surgical indication and improve long-term outcomes.


Focus on age at death in field epidemiology.
Age at death (AD) is an old metric recently re-evaluated for the study of longevity and mainly used in demography. Developed experience using AD in field epidemiology is summarized with cohorts followed-up for variable periods of time, frequently until extinction or close to extinction, a must to correctly adopt this metric. For practical purposes, a small number of examples is reported condensing previously published results to highlight various aspects of the problem. AD became the alternative of overall death rates when comparing cohorts reaching extinction or near extinction. AD was useful to characterize different causes of death in order to describe their natural history and possible etiology. With the use of multiple linear regression, a large number of possible determinants of AD were identified and some combinations of them resulted in large estimated differences in AD of 10 years or more across individuals. AD is a powerful tool to study population samples followed-up until extinction or near extinction. It allows to compare the life-long experience of different populations, to compare the role of different causes of death and to study the determinants of AD that are conditioning longevity.


Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses.
During the last decade, physical activity (PA) (or "exercise") has been identified as one of the main modifiable factors that influence the development of Alzheimer's disease (AD) pathophysiology. We performed an umbrella review to summarize the evidence on the association between PA/exercise and the risk of developing AD risk, and the effect of exercise interventions on the progression of AD. A systematic search was performed in PubMed, SportDiscus, Cochrane Library and Web of Science (March 2022) to identify meta-analyses assessing the association between PA and the incidence of AD, and assessing the effect of exercise interventions on patients with AD. Twenty-one studies were included. The results with strongest evidence revealed the positive effects of PA on AD risk. Specifically, meeting the WHO recommendations for PA was associated with a lower risk of AD. They also revealed positive effects of exercise on cognitive function, physical performance, and functional independence. There is strong evidence of a protective effect of regular PA against AD risk; however, the dose-response association remains unclear. Physical exercise seems to improve several dimensions in patients with AD, although research is warranted to elucidate the exercise characteristics that promote the greatest benefits.


Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS).
Extracorporeal life support (ECLS) is used for patients with refractory heart failure with or without respiratory failure. This temporary support is provided by blood pumps which are connected to large vessels. Bleeding episodes are a typical complication in patients with ECLS. Recently, several studies illustrated that acquired von Willebrand syndrome (AVWS) can contribute to bleeding tendencies in patients with long-term ventricular assist devices (VAD). AVWS is characterized by loss of the high molecular weight (HMW) multimers of von Willebrand factor (VWF) as a result of high shear stress and leads to impaired binding of VWF to platelets and to subendothelial matrix. Since ECLS and VAD share several features, we investigated patients with ECLS for AVWS. We analyzed 32 patients with ECLS and 19 of them without support. To diagnose AVWS, ratios of ristocetin cofactor activity (VWF:RCo) and collagen binding capacity (VWF:CB) to VWF antigen (VWF:Ag) were employed in conjunction with multimeric analysis. Reduced VWF:RCo/VWF:Ag ratios were identified in 28 ECLS patients. Furthermore, VWF:CB/VWF:Ag ratios were decreased in 31 patients. HMW multimers of VWF were missing in the same 31 patients. Thus, 31 of 32 ECLS patients presented with AVWS. Twenty-two of the 32 patients suffered from bleeding complications. Without support, AVWS was not detectable in any analyzed patient. Our data indicate that AVWS is a typical disorder in patients with ECLS. We hypothesize that AVWS could contribute to aggravation of bleeding tendencies in ECLS patients.


Vestibular Schwannomas in Young Patients: A 12-Year Experience in a Single Center.
This study evaluated the characteristics of vestibular schwannomas (VS) in young patients, including clinical features, treatment, prognosis, and histopathologic characteristics. We retrospectively reviewed medical records and follow-up data for 36 pediatric patients <21 years of age who were surgically treated for VS in the Chinese PLA General Hospital between 2008 and 2019. Mean patient age was 17.4 years. Mean tumor size was 2.8 cm. Hearing loss (n = 32, 88.9%) and tinnitus (n = 20, 55.6%) were the most common symptoms. Ten patients (27.8%) had impaired facial nerve function after surgery. Gross total resection (GTR) was achieved in 26 cases (72.2%). The median tumor Ki-67 level was 5%. Tumor size was related to incomplete tumor resection (odds ratio, 0.2; 95% confidence interval, 0.1-0.9) and postoperative facial nerve dysfunction (odds ratio, 24.9; 95% confidence interval, 1.2-539.1). Tumor size was nonlinearly associated with prognosis and 2.2 cm corresponded to the inflection point at which the probability of tumor remnant and postoperative facial nerve dysfunction significantly increased. The GTR and low Ki-67 groups achieved better 3-year tumor control rate. Histopathologic findings confirmed the presence of cellular schwannoma subtype in young patients. Tumor size is an important factor affecting the prognosis of VS in young patients. For large VS, surgical treatment should be the first choice, rather than wait-and-scan. VS in young patients shows high tumor proliferation and a tendency to relapse. The cellular schwannoma subtype requires special attention; an accurate histopathologic diagnosis is necessary for young patients with VS, and a closer follow-up strategy should be adopted for cellular VS.


Differential pulse voltammetry in the dorsal horn of the spinal cord of the anesthetized rat: are the voltammograms related to 5-HT and/or to 5-HIAA?
Treated carbon fiber microelectrodes were used with the differential pulse voltammetry method for in vitro and in vivo determination of indoleamines. Under these conditions a peak of oxidation current which is characteristic of 5-hydroxyindoles is recorded at 280-300 mV. Treated carbon fiber microelectrodes respond in vitro linearly over a large range of concentrations of 5-hydroxytryptamine (5-HT) and of 5-hydroxyindoleacetic acid (5-HIAA), but are 5-8 times more sensitive to 5-HT than to 5-HIAA. In vivo, the question remains as to the exact nature of the peak because the oxidation potentials of 5-HT and 5-HIAA are close together and cannot be monitored separately. Pharmacological investigations were hence carried out in order to characterize the electrochemical signal detected at 300 mV in the dorsal horn of the lumbar spinal cord of chloral hydrate-anesthetized rats. Using 250 micron long carbon fiber microelectrodes, the electrochemical signal stabilizes at 30-90 min and the peak remains constant for up to 210 min. Administration of the monoamine oxidase inhibitor (MAOI) clorgyline produced a progressive decrease of the signal which reached a decrease of 33% of control at 180 min after injection. At this time biochemical measures demonstrated a 117% increase in 5-HT and a 32% decrease in 5-HIAA in the dorsal half of the spinal cord. Reserpine provoked an increase of 20% in the electrochemical peak and the 5-HIAA outflow blocker probenecid gave rise to a sustained plateau of about 60% above control values.(ABSTRACT TRUNCATED AT 250 WORDS)


Homocysteine and cysteine loads in patients with homocystinuria due to cystathionine synthase deficiency: effects of vitamin B-6.
The metabolic response of patients with homocystinuria due to cystabhionine synthase deficiency to oral loads of homocysteine indicates: that even severely affected patients with homocystinuria have pools of cystine in their tissues; that control of sulfur amino acid metabolism favors increased concentrations of methionine rather than homocystine in the plasma; and that even patients who apparently are not B-6-responsive respond differently to the loads of homocysteine when challenged during B-6-treatment compared with their response before B-6 treatment. Loading tests with homocysteine indicate that B-6 treatment be of some benefit even in individuals who do not have an obvious biochemical response to such therapy.


Liver Transplantation Reverses Hepatic Myelopathy in Hepatitis B-Related Decompensated Liver Cirrhosis: Case Report and Review of the Literature.
Severe neurologic complications after chronic liver disease greatly affect the patient's quality of life. Hepatic myelopathy (HM) is a rare but devastating disease, in chronic liver disease. The limbs of patients with HM show slowly progressive symmetrical spastic paralysis without sensory loss. Management of this severe neurologic complication is challenging. These patients often require timely and effective clinical intervention. Although liver transplantation is one of the effective treatments for HM, the prognosis of these patients remains poor, many of them spend their lives in wheelchairs. Here, we report a patient with HM after hepatitis B virus related decompensated liver cirrhosis who recovered well after liver transplant. This work was carried out in compliance with the Helsinki Congress and the Declaration of Istanbul.