Intestinal giardiasis in children: Five years' experience in a reference unit.
Giardiasis is highly prevalent in children and is often mildly symptomatic. First-line treatment is metronidazole, but treatment failure is not uncommon. We describe a paediatric series, to identify risk factors for treatment failure and to analyse the safety and effectiveness of other treatment strategies. Retrospective observational study, including children diagnosed with giardiasis from 2014 to 2019. Diagnosis was based on direct visualisation by microscopy after concentration using an alcohol-based fixative, antigen detection and/or DNA detection by polymerase chain reaction in stool. Treatment failure was considered when GI was detected 4 weeks after treatment. A total of 120 patients were included, 71.6% internationally adopted, median age 4.2 (2.3-7.3) years. Only 50% presented with symptoms, mainly diarrhoea (35%) and abdominal pain (14.1%); co-parasitism was frequent (45%). First-line treatment failure after a standard dose of metronidazole was 20%, lowering to 8.3% when a higher dose was administered (p < 0.001). Quinacrine was administered in 10 patients, with 100% effectiveness. Children <2 years were at higher risk of treatment failure (OR 3.49; 95% CI 1.06-11.53; p = 0.040). In children with giardiasis, treatment failure is frequent, especially before 2 years of age. Quinacrine can be considered as a second-line treatment. After treatment, eradication should be confirmed.


To Determine the Prognostic Significance of 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan-Derived Parameters (Total Lesion Glycolysis and Metabolic Tumor Volume) in Patients of Diffuse Large B-Cell Lymphoma with Only Nodal Involvement.
The aim of this study is to evaluate the prognostic significance of 18-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET-CT) scan-derived total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in diffuse large B-cell lymphoma (DLBCL) patients with only nodal involvement. Twenty-five (age range: 22-82 years) biopsy-proven patients of DLBCL with only nodal involvement who underwent staging 18FDG PET-CT scan were included in this study. Whole-body PET-CT performed at staging and PET-derived metabolic parameters, namely MTV and TLG of all FDG-avid lesions, were calculated for each patient. Total MTV was computed by summing the volumes of all FDG-avid lesions, the volume of each being calculated at threshold of 42% of the maximum standardized uptake value (SUV) using a semi-automatic software. TLG was calculated by summing the product of volume and SUVmean of each lesion. Patients were followed up to a period of 5 years and data obtained were divided into two groups, with recurrence and without recurrence. Six patients developed recurrence on follow-up and 19 patients remained disease free on follow-up. The area under a curve (AUC) for MTV was 0.825 and for TLG was 0.623 suggesting MTV to be a good prognostic indicator and TLG poor indicator for predicting recurrence in these patients. In pairwise comparison of both the receiver operator characteristics, it was found that the difference between the AUCs of MTV and TLG was statistically significant (P = 0.0349). Thus, indicating MTV is a statistically better indicator than TLG. MTV is a better prognostic indicator than TLG in DLBCL patients.


Community care in child psychiatry. An empirical approach using the concept of travel time.
Community care is a crucial element in the organization and development of psychiatric services. The basic idea of community care is that it guarantees equal access to services for all people in need. In this study an empirical approach to community care is undertaken using the concept of travel time. The importance of distance to the use or nonuse of mental health services has been documented for a long time. But if distance is measured by travel time, additional elements, as for example the available transport system are considered relevant for the accessibility of services. It can be shown that most patients of two child psychiatric outpatient services do not accept a travel time exceeding half an hour. Outreach activities of services located in rural areas can partly compensate for the geographic disadvantage of those patients living at long distance to the service.


Late Awakening in Survivors of Postanoxic Coma: Early Neurophysiologic Predictors and Association With ICU and Long-Term Neurologic Recovery.
To examine neurophysiologic predictors and outcomes of patients with late awakening following cardiac arrest. Observational cohort study. Academic ICU. Adult comatose cardiac arrest patients treated with targeted temperature management and sedation. None. Time to awakening was calculated starting from initial sedation stop following targeted temperature management and rewarming (median 34 hr from ICU admission). Two-hundred twenty-eight of 402 patients (57%) awoke: late awakening (> 48 hr from sedation stop; median time to awakening 5 days [range, 3-23 d]) was observed in 78 subjects (34%). When considering single neurophysiologic tests, late awakening was associated with a higher proportion of discontinuous electroencephalography (21% vs 6% of early awakeners), absent motor and brainstem responses (38% vs 11%; 23 vs 4%, respectively), and serum neuron specific enolase greater than 33 ng/mL (23% vs 8%; all p < 0.01): no patient had greater than 2 unfavorable tests. By multivariable analysis-adjusting for cardiac arrest duration, Sequential Organ Failure Assessment score, and type of sedation-discontinuous electroencephalography and absent neurologic responses were independently associated with late awakening. Late awakening was more frequent with midazolam (58% vs 45%) and was associated with higher rates of delirium (62% vs 39%) and unfavorable 3-months outcome (27% vs 12%; all p = 0.005). Late awakening is frequent after cardiac arrest, despite early unfavorable neurophysiologic signs and is associated with greater neurologic complications. Limiting benzodiazepines during targeted temperature management may accelerate awakening. Postcardiac arrest patients with late awakening had a high rate of favorable outcome, thereby supporting prognostication strategies relying on multiple rather than single tests and that allow sufficient time for outcome prediction.


Multimorbidity Patterns and the Disablement Process among Public Long-Term Care Insurance Claimants in the City of Yiwu (Zhejiang Province, China).
This study aimed to identify multimorbidity patterns and explore the disablement process by utilizing the model raised by Verbrugge and Jette as a theoretical framework. This cross-sectional study used public Long-term Care Insurance (LTCI) claimants' assessment data of Yiwu city in Zhejiang Province, China, for 2604 individuals aged 60 years and older, from September through December 2018. Latent Class Analysis (LCA) was conducted using 10 common chronic conditions. Structural Equation Modeling was used to examine the disablement process. The latent classes of multimorbidity patterns were the "coronary atherosclerotic heart disease" class (19.0%), the "lower limb fractures" class (26.4%), and the "other diseases" class (54.6%). The structural model results show that coronary atherosclerotic heart disease had a significant influence on incontinence, but it was not statistically significant in predicting vision impairment and mobility impairment. Lower limb fractures had significant effects on vision impairment, incontinence, and mobility impairment. Vision impairment, incontinence, and mobility impairment had significant effects on physical activities of daily living (ADLs). Our findings suggest that different impairments exist from specific patterns of multimorbidity to physical ADL disability, which may provide insights for researchers and policy makers to develop tailored care and provide support for physically disabled older people.


Measuring phosphorylated Akt and other phosphoinositide 3-kinase-regulated phosphoproteins in primary lymphocytes.
Phosphoinositide 3-kinase (PI3K) is a lipid kinase whose activation is crucial for many biological functions in multiple cell types. One research area of particular interest for basic biologists and drug developers is PI3K signaling in lymphocytes. Inhibitor studies and PI3K mutants have demonstrated that PI3K is required for development, activation, proliferation, differentiation, and survival of B lymphocytes, as well as optimal activation and proliferation of T lymphocytes. As the actual products of PI3K can be difficult to measure, the field has often adopted the practice of examining the activation of downstream effectors of PI3K, with the most common readout being phosphorylation of Akt. This chapter discusses key pathways influenced by PI3K signaling and the advantages and caveats of using activation of these pathways as indicators of PI3K activity. In addition, we provide traditional immunoblotting methods of assaying PI3K-dependent pathway activation, as well as more recent flow cytometry-based approaches (termed "phosflow"). Although we describe assays optimized for B lymphocytes, these methods are easily adapted to T lymphocytes and other leukocyte cell types.


Supplementary and precentral motor cortex: contrast in responsiveness to peripheral input in the hindlimb area of the unanesthetized monkey.
Single-unit recording and intracortical microstimulation techniques have been employed in unanesthetized monkeys in order to ascertain the relative responsiveness of the supplementary motor cortex (MII) and the precentral motor cortex (MI) to a controlled peripheral stimulus. The hindlimb representation was explored to facilitate comparison of MI and MII sensitivity in the same animal. Two main findings have emerged: (i) Many fewer neurons in MII respond to the peripheral stimulus and those that do have much weaker responses than neurons in MI. (ii) The hindlimb representation of MII and the tail representation of MI appear to be considerably further rostral than depicted in the classical maps. The latter finding serves to resolve a discrepancy between the classical physiological and cytoarchitectonic maps for this region of cortex.


Zinc and cerium synergistically enhance the mechanical properties, corrosion resistance, and osteogenic activity of magnesium as resorbable biomaterials.
Magnesium and its alloys have the potential to serve as a revolutionary class of biodegradable materials, specifically in the field of degradable implants for orthopedics. However, the corrosion rate of commercially pure magnesium is high and does not match the rate of regeneration of bone tissues. In this work, magnesium alloys containing zinc and cerium, either alone or in combination, were investigated and compared with commercially-pure magnesium as biomaterials. The microstructure, mechanical properties, corrosion resistance, and response of osteoblastsin vitrowere systematically assessed. Results reveal that alloying with Ce results in grain refinement and weakening of texture. The tensile test revealed that the ternary alloy offered the best combination of elastic modulus (41.1 ± 0.5 GPa), tensile strength (234.5 ± 4.5 MPa), and elongation to break (17.1 ± 0.4%). The ternary alloy was also the most resistant to corrosion (current of 0.85 ± 0.05 × 10-4A cm-2) in simulated body fluid than the other alloys. The response of MC3T3-E1 cellsin vitrorevealed that the ternary alloy imparts minimal cytotoxicity. Interestingly, the ternary alloy was highly efficient in supporting osteogenic differentiation, as revealed by the expression of alkaline phosphatase and calcium deposition. In summary, the extruded Mg alloy containing both Zn and Ce exhibits a combination of mechanical properties, corrosion resistance, and cell response that is highly attractive for engineering biodegradable orthopedic implants.


The Methyltransferase DOT1L Controls Activation and Lineage Integrity in CD4+ T Cells during Infection and Inflammation.
CD4+ T helper (Th) cell differentiation is controlled by lineage-specific expression of transcription factors and effector proteins, as well as silencing of lineage-promiscuous genes. Lysine methyltransferases (KMTs) comprise a major class of epigenetic enzymes that are emerging as important regulators of Th cell biology. Here, we show that the KMT DOT1L regulates Th cell function and lineage integrity. DOT1L-dependent dimethylation of lysine 79 of histone H3 (H3K79me2) is associated with lineage-specific gene expression. However, DOT1L-deficient Th cells overproduce IFN-γ under lineage-specific and lineage-promiscuous conditions. Consistent with the increased IFN-γ response, mice with a T-cell-specific deletion of DOT1L are susceptible to infection with the helminth parasite Trichuris muris and are resistant to the development of allergic lung inflammation. These results identify a central role for DOT1L in Th2 cell lineage commitment and stability and suggest that inhibition of DOT1L may provide a therapeutic strategy to limit type 2 immune responses.


Arsenic induces autophagy-dependent apoptosis via Akt inactivation and AMPK activation signaling pathways leading to neuronal cell death.
Inorganic arsenic (As3+), a well-known worldwide industrial and environmental pollutant, has been linked to neurodegenerative disorders (NDs). Autophagy plays an important role in controlling neuronal cell survival/death. However, limited information is available regarding the toxicological mechanism at the interplay between autophagy and As3+-induced neurotoxicity. The present study found that As3+ exposure induced a concomitant activation of apoptosis and autophagy in Neuro-2a cells, which was accompanied with the increase of phosphatidylserine exposure on outer membrane leaflets and apoptotic cell population, and the activation of caspase-3, -7, and PARP as well as the elevation of protein expressions of LC3-II, Atg-5, and Beclin-1, and the accumulation of autophagosome. Pretreatment of cells with autophagy inhibitor 3-MA, but not that of Z-VAD-FMK (a pan-caspase inhibitor), effectively prevented the As3+-induced autophagic and apoptotic responses, indicating that As3+-triggered autophagy was contributing to neuronal cell apoptosis. Furthermore, As3+ exposure evoked the dephosphorylation of Akt. Pretreatment with SC79, an Akt activator, could significantly attenuated As3+-induced Akt inactivation as well as autophagic and apoptotic events. Expectedly, inhibition of Akt signaling with LY294002 obviously enhanced As3+-triggered autophagy and apoptosis. Exposure to As3+ also dramatically increased the phosphorylation level of AMPKα. Pretreatment of AMPK inhibitor (Compound C) could markedly abrogate the As3+-induced phosphorylated AMPKα expression, and autophagy and apoptosis activation. Taken together, these results indicated that As3+ exerted its cytotoxicity in neuronal cells via the Akt inactivation/AMPK activation downstream-regulated autophagy-dependent apoptosis pathways, which ultimately lead to cell death. Our findings suggest that the regulation of Akt/AMPK signals may be a promising intervention to against As3+-induced neurotoxicity and NDs.


Biomass-based Hierarchical Porous Carbon for Supercapacitors: Effect of Aqueous and Organic Electrolytes on the Electrochemical Performance.
Biomass-based hierarchical porous carbon (SCPC) exhibits excellent electrochemical performance in electric double layer capacitors, prepared by carbonization and activation of straw cellulose. To investigate the potential applications of SCPC in supercapacitors, the effect of aqueous and organic electrolytes on the electrochemical performance of SCPC was studied in detail. In H2 SO4 , the SCPC electrode exhibits higher specific capacitance (358 F g-1 ) and outstanding cycling stability with 95.6 % capacitance retention over 10 000 cycles. The SCPC electrode shows superior rate capability with 90.7 % capacitance retention in KOH, and higher energy density of 17.9 Wh kg-1 in Na2 SO4 . The SCPC electrode exhibits ideal capacitance characteristics, superior rate capability with capacitance retention of 95.8 %, and high energy density of 36.0 Wh kg-1 in tetraethylammonium tetrafluoroborate/propylene carbonate (Et4 NBF4 /PC). The significant difference of capacitive performance of SCPC electrode in various electrolytes is mainly attributed to the difference in the electrolyte ion size, ionic conductivity, matching between the electrolyte ions and pore structure, and matching between anions and cations adsorbed on the positive and negative electrodes. This work not only establishes the relationship between the structure of SCPC and its electrochemical performance in different electrolytes, but also provides a reference for the high value-added utilization of SCPC.


Prevalence and clinical features of atypical depression among patients with major depressive disorder in China.
Little is known about the demographic and clinical features of the atypical subtype of major depressive disorder (MDD) patients in China. This study set out to investigate the prevalence of atypical depression in MDD patients in China, and identify its demographic and clinical features. The study was conducted in 13 major psychiatric hospitals or in the psychiatric units of general hospitals in China, and recruited a sample of 1172 patients diagnosed with MDD. The patients' demographic and clinical features and prescriptions of psychotropic drugs were collected using a standardized questionnaire designed for the study. The prevalence of atypical depression was 15.3%. In multiple logistic regression analyses, compared to the non-atypical depression patients, the atypical depression patients were more likely to have depressive episodes with suicide ideation and attempts (OR = 1.49, 95% CI = 1.06, 2.10, P = 0.023), depressive episodes with psychotic features (OR = 2.15, 95% CI = 1.43, 3.22, P < 0.001), seasonal depressive episodes (OR = 1.77, 95% CI = 1.12, 2.78, P = 0.014), an earlier age of onset (OR = 0.98, 95% CI = 0.96, 0.99, P = 0.001), and lifetime depressive episodes (OR = 1.07, 95% CI = 1.01, 1.13, P = 0.020). The assessment of atypical features was not based on a validated rating scale. Our results indicate that atypical depression is common in Chinese patients with MDD. MDD with atypical features may be more severe and debilitating than patients with non-atypical features.


New therapeutic approaches for advanced gastrointestinal stromal tumors.
The management of advanced gastrointestinal stromal tumor is increasingly complex because of imatinib refractory disease. Primary resistance to imatinib is uncommon, and most patients progress after development of additional genetic changes. This article reviews management strategies including surgical approaches, local modalities for progressive liver metastases, as well as novel therapeutic agents.


Transphyseal distal humeral separation in neonates: A case series.
Birth trauma is a rare condition. Typically, injury in neonates occurs as a result of obstetrical manipulation to allow delivery or from trauma sustained during a difficult passage through the birth canal. Transphyseal separation of the humerus is particularly rare. Diagnosis is not always straightforward and is prone to mistakes. There is a general consensus that the outcome is usually favorable. It is generally agreed that the fracture needs to be realigned, while the suggested methods in contention vary from a simple plaster cast to closed and even open reduction and percutaneous Kirschner wire fixation. The purpose of this study was to review our experience in treating transphyseal distal humeral separation in neonates to better define the diagnostic and therapeutic pathway. Ten consecutive cases of transphyseal distal humeral separation in neonates were treated at our institution between September 2008 and June 2021. All cases were reviewed and clinical data collected on birth injury risk factors, diagnostic workup, age at diagnosis and treatment, and type of treatment. Results of treatment and outcome were analyzed for time to fracture union, complications and clinical alignment, range of motion and residual pain at the latest follow-up. Mean age at diagnosis was 4.2 days (range 0 to 9 days) and time between diagnosis and treatment varied from three to 26 h (average 15 h). Risk factors for birth injury were present in six patients. Four patients were initially treated with closed reduction and cast immobilization, all the other cases were treated with closed reduction and percutaneous pinning. Arthrography was performed at the time of treatment in six cases. Average follow-up was 37 months (range 12 to 120 months). At the latest follow-up, all fractures had healed with full range of motion. No clinical or radiographic deformity requiring repeated surgery or physeal damage was observed. This rare lesion may occur both in the presence and in the absence of risk factors. Due to the rarity of the injury, misdiagnosis and delayed diagnosis are not uncommon. Treatment with closed reduction and percutaneous pin fixation is advisable and safe.


Complete plastome sequence of Acorus tatarinowii (Acoraceae), a traditional Chinese medicinal plant from Xishuangbanna, Yunnan, China.
The complete plastome of Acorus tatarinowii is 153,296 bp in length, with two long inverted repeats (25,752 bp for each) separating by a large single-copy (83,533 bp) and a small single-copy (18,240 bp). The plastome contained 112 unique genes, including 78 protein-coding genes, 30 transfer RNAs, and 4 ribosomal RNAs. Phylogenetic analyses showed that A. tatarinowii was closely related to A. gramineus.


Aggregated human immunoglobulin G stabilized by albumin: a standard for immune complex detection.
Stabilized preparations of heat-aggregated human immunoglobulin G (A-IgG) of restricted size were made by separating A-IgG by sucrose density gradient ultracentrifugation in the presence of bovine serum albumin (BSA). Periodic recentrifugation of stored fractions of the radiolabelled A-IgG indicated that the initial sedimentation characteristics were preserved. Pooled fractions of A-IgG stored for up to 16 months had the same functional activity as freshly prepared A-IgG of corresponding size when assessed by activation of the first component of complement and consumption of C4 and CH50 in normal human serum. It was also found that the reactivity of A-IgG in the C1q binding assay (C1Q-BA) and the conglutinin binding assay (Con-BA) was not altered by long-term storage of these A-IgG. Testing different batches of [125I]C1q and conglutinin with the same batch of stabilized A-IgG showed variations due to the instability of both [125I]C1q and conglutinin. The influence of these variations on the quantification of the levels of immune complexes in sera was reduced by using stable A-IgG as a reference. The assays were compared to determine the effect of the size of the aggregate. The C1Q-BA detected preferentially A-IgG of large size, while size had no influence in the Con-BA. These results suggest that the stability of A-IgG in BSA is such that this preparation may be used as a reliable standard for immune complex assays.


A differential scanning calorimetric study of brain clathrin.
The thermal denaturation of clathrin-coated vesicles isolated from bovine brain tissue has been studied by differential scanning calorimetry and has been compared to basket structures reformed from isolated triskelion trimers of clathrin and to isolated triskelions. The coated vesicles and reformed baskets displayed similar, yet distinct, thermal behavior. Calorimetric data of the coated vesicles exhibited a single denaturation transition peak at 55.9 +/- 0.1 degrees C, skewed to low temperatures whereas the thermograms for the reformed baskets exhibited a broad transition peak at 53.1 +/- 0.1 degrees C and a peak at 56.3 +/- 0.1 degrees C. Neither transition was reversible. The specific transition enthalpy was 11.5 +/- 1.0 J g-1 for the coated vesicles and the total transition enthalpy was 9.1 +/- 0.3 J g-1 for the reformed baskets. In contrast, isolated triskelions showed no thermal transition between 15 and 90 degrees C. Although the coated vesicles and the reformed baskets have similar stability reflecting their similar structures, the coated vesicles appear to be marginally more stable than the reformed baskets. The complexity of the transition profiles and their lack of symmetry suggest the existence of several, somewhat independent, domains unique to the cage-like structure of the coated vesicles and reformed baskets.


Emerging periodate-based oxidation technologies for water decontamination: A state-of-the-art mechanistic review and future perspectives.
With the ever-increasing severity of the ongoing water crisis, it is of great significance to develop efficient, eco-friendly water treatment technologies. As an emerging oxidant in the advanced oxidation processes (AOPs), periodate (PI) has received worldwide attention owing to the advantages of superior stability, susceptible activation capability, and high efficiency for decontamination. This is the first review that conducts a comprehensive analysis of the mechanism, pollutant transformation pathway, toxicity evolution, barriers, and future directions of PI-based AOPs based on the scientific information and experimental data reported in recent years. The pollutant elimination in PI-based AOPs was mainly attributed to the in situ generate reactive oxygen species (e.g., •OH, O(3P), 1O2, and O2•-), reactive iodine species (e.g., IO3• and IO4•), and high-valent metal-oxo species with exceptionally high reactivity. These reactive species were derived from the PI activated by the external energy, metal activators, alkaline, freezing, hydroxylamine, H2O2, etc. It is noteworthy that direct electron transport could also dominate the decontamination in carbon-based catalyst/PI systems. Furthermore, PI was transformed to iodate (IO3-) stoichiometrically via an oxygen-atom transfer process in most PI-based AOPs systems. However, the production of I2, I-, and HOI was sometimes inevitable. Furthermore, the transformation pathway of typical micropollutants was clarified, and the in silico QSAR-based prediction results indicated that most transformation products retained biodegradation recalcitrance and multi-endpoint toxicity. The barriers faced by the PI-based AOPs were also clarified with potential solutions. Finally, future perspectives and research directions are highlighted based on the current state of PI-based AOPs. This review enhances our in-depth understanding of PI-based AOPs for pollutant elimination and identifies future research needs to focus on the reduction of toxic byproducts.


Cyclophosphamide-induced acute respiratory distress syndrome.
Cyclophosphamide is widely used in neoplastic and inflammatory diseases. Although several adverse events have been described with its use, acute and subacute interstitial pneumonitis leading to pulmonary fibrosis is rare and potentially fatal. This case report describes a 64-year-old man who, after the fifth chemotherapy cycle, developed a severe ARDS leading to pulmonary fibrosis in just 30 days.


Placental docosahexaenoic and arachidonic acids correlate weakly with placental polychlorinated dibenzofurans (PCDF) and are uncorrelated with polychlorinated dibenzo-p-dioxins (PCDD) or polychlorinated biphenyls (PCB) at delivery: a pilot study.
Long chain polyunsaturated fatty acids (LC-PUFA), ARA (arachidonic acid, 20:4n-6) and DHA (docosahexaenoic acid, 22:6n-3) have positive effects and environment pollutants, polychlorinated dibenzo-p-dioxins/dibenzofurans(PCDD/F) and polychlorinated biphenyls (PCB) have negative effects on neural development during early life. Placental dioxin/PCB serves as markers for cumulative exposure to fetus. Fatty acid composition of placenta depends on nutrient supply during pregnancy, serving as indicators for fetal ARA and DHA accretion. This study investigated correlation between placental PCDD/F and PCB toxic equivalent (TEQ) and LC-PUFA in 34 pregnant women from Taiwan. Placental PCDF TEQ were inversely correlated with placental ARA (p=0.020), C20:3n-6 (p=0.01), C22:4n-6 (p=0.04), C22:5n-6 (p<0.01) and with DHA (p=0.03), but ARA and DHA did not vary with PCDD, dioxin-like and indicator PCB. After adjustment for age and body mass index, a one-unit PCDF TEQ increase was associated with 1.021%w/w and 0.312%w/w decreases in ARA (β=-1.021, p=0.03) and DHA (β=-0.312, p=0.03). Since ARA and DHA were unrelated to three classes of toxins, and a weak negative association was found with PCDF, these data provide no basis for discouraging marine fish consumption during pregnancy for Taiwan women on the basis of these organics. Pregnant women should consume fish for its unique package of nutrients while avoiding few species with high organic pollutant or mercury contamination.


A comprehensive evaluation of aerosol extinction apportionment in Beijing using a high-resolution time-of-flight aerosol mass spectrometer.
An aerosol mass spectrometer (AMS) was used to measure the chemical composition of non-refractory submicron particles (NR-PM1) in Beijing from 2012 to 2013. The average concentration of NR-PM1 was 56 μg·m-3, with higher value of 106 μg·m-3 when Beijing was influenced by air masses from south in winter. Organics was the primary chemical component with a concentration of 26 μg·m-3, accounting for 46% of the total NR-PM1. The ratio of NO3-/SO42- was utilized to identify the relative contribution of stationary and traffic related resource to PM pollution. When NR-PM1 concentration was between 50 and 200 μg·m-3, NO3-/SO42-was larger than 1, indicating traffic resource contributed more than stationary resource during the aerosol growth. A new method was developed to calculate aerosol extinction coefficient (σ) as a function of aerosol optical depth (AOD) and the mixing layer height (MLH). σ derived from the new method showed a statistically significant correlation with that obtained from traditional method, which was calculated using visibility (y = 0.99x + 85 R2 = 0.69). Multiple linear regressions in dependence of chemical component were performed to evaluate light extinction apportionment. Under the overall condition, NR-PM1 contributed about 88% to the whole aerosol light extinction; organics, ammonium chloride, ammonium nitrate, ammonium sulfate, black carbon contributed 30%, 6%, 24%, 26% and 6% of the NR-PM1 light extinction, respectively. By further comparing the light extinction apportionment under the different dominated air masses, we concluded that the organics and ammonium sulfate contributed more in polluted days (36% and 23%) than that in clean days (21% and 21%). Mass ratio (MR) between NR-PM1 and black carbon (MR = massNR-PM1/massBC) was used to identify black carbon aging degree, and the result showed that aerosol mass extinction efficiency increased rapidly after MR reached about 7 in the process of black carbon aging.


Self-stunning in thyroid ablation: evidence from comparative studies of diagnostic 131I and 123I.
Twenty-six patients who had undergone recent surgery for differentiated thyroid cancer were investigated using iodine-131 iodide (120 MBq). Uptake in the thyroid bed was measured at 3 days using a dual-head gamma camera. An ablation activity of 131I iodide (4,000 MBq) was administered 3-38 (median 14) days later and uptake in the thyroid bed measured once or twice, 1-3 days post therapy. For measurements post therapy, the gamma camera was operated in the high-count rate mode with appropriate correction factors to compensate for any count loss. A further 16 patients were given iodine-123 iodide (200 MBq) as the diagnostic agent and uptake was measured at 24 h. The ablation activity was administered 5-47 (median 19) days later and uptake again measured at 24 h. In some cases, a further measurement of uptake was made within the period 1-3 days post therapy. Reduced uptake of the therapeutic administration ( P<0.001) was observed in all 26 patients given diagnostic 131I, with a median value of 32.8% (range 6%-93%) of the uptake in the diagnostic study. In the patients given diagnostic 123I, reduced uptake of the ablative radioiodine was observed in 15 of the 16 patients ( P<0.001), and overall the median value was 58.8% (range 17%-130%) of the diagnostic uptake. In one case the uptake post therapy was increased. The stunning observed in the group given 123I was significantly less ( P<0.001) than in the group given 131I. In the patients given diagnostic 131I, stunning appeared to increase in severity the longer the time interval between the diagnostic and therapeutic radionuclides, for intervals up to 25 days. Thereafter, there seemed to be some recovery of uptake capability. Overall there was no evidence of a large rapid loss of radionuclide from the thyroid bed 1-3 days post therapy. The stunning observed using 123I could not be explained by errors in the estimation of relative uptake due to different tissue absorption of the 131I and 123I photons, nor by the radiation dose delivered by the 123I. However, the ablative 131I itself may cause stunning because the cumulated activity, over the first few hours of uptake, is not insignificant when compared with all the cumulated activity from a diagnostic administration of 131I. The resultant radiation dose to the thyroid remnant, as the therapeutic radioiodine is being taken up, may be sufficient to inhibit the uptake process, thus leading to a reduction in maximum uptake when compared with that of a diagnostic activity of radioiodine.


Validation of a Monte Carlo simulation for dose assessment in dental cone beam CT examinations.
A Monte Carlo (MC) simulation for calculating absorbed dose has been developed and applied for dental applications with an i-CAT cone beam CT (CBCT) system. To validate the method a comparison was made between calculated and measured dose values for two different clinical protocols. Measurements with a pencil CT chamber were performed free-in-air and in a CT dose head phantom; measurements were also performed with a transmission ionization chamber. In addition for each protocol a total number of 58 thermoluminescence dosemeters (TLD) were packed in groups and placed at 16 representative anatomical locations of an anthropomorphic phantom (Remab system) to assess absorbed doses. To simulate X-ray exposure, a software application based on the EGS4 package was applied. Dose quantities were calculated for different voxelized models representing the CT ionization and transmission chambers, the TLDs, and the phantoms as well. The dose quantities evaluated in the comparison were the accumulated dose averaged along the rotation axis (D(i)), the volume average dose,D(vol) for the dosimetric phantom, the dose area product (DAP) and the absorbed dose for the TLDs. Absolute differences between measured and simulated outcomes were ≤ 2.1% for free-in-air doses; ≤ 6.2% in the 5 cavities of the CT dose head phantom; ≤ 13% for TLDs inside the primary beam. Such differences were considered acceptable in all cases and confirmed the validity of the MC program for different geometries. In conclusion, the devised MC simulation program can be a robust tool to optimize protocols and estimate patient doses for CBCT units in dental, oral and maxillofacial radiology.


Homocellular conduction along endothelium and smooth muscle of arterioles in hamster cheek pouch: unmasking an NO wave.
We investigated roles for homocellular (endothelium or smooth muscle) and heterocellular (myoendothelial) conduction pathways along hamster cheek pouch arterioles in vivo (n=64; diameter, 33+/-1 microm). Endothelium-dependent and -independent vasoactive agents were delivered from micropipettes (0.5 or 1 second pulse) onto an arteriole while observing diameter changes at defined distances along the vessel. Acetylcholine (ACh) produced maximal diameter (63+/-1 microm) locally and vasodilation conducted rapidly ( approximately 10 microm response at 2 mm, <1 second). Responses to bradykinin (BK) were similar, whereas sodium nitroprusside produced maximal dilation locally without conduction. KCl evoked biphasic conduction of vasoconstriction and vasodilation, whereas phenylephrine (PE) produced conducted vasoconstriction. Disrupting the integrity of endothelium as a conduction pathway using focal light-dye treatment (LDT) abolished conducted vasodilation to BK and to KCl but not to ACh. Disruption of smooth muscle integrity with LDT abolished conducted vasoconstriction with no effect on conducted vasodilation. After LDT of respective cell layers at sites 1 mm apart, vasodilation to ACh conducted past disrupted smooth muscle or disrupted endothelium, but not beyond both sites in series. The loss of conduction after selective LDT indicates a lack of effective myoendothelial coupling along the arteriolar wall. During NO synthase inhibition (L-NA, 100 micromol/L), conducted vasodilation was abolished to BK and to KCl yet remained intact to ACh. However, after LDT of smooth muscle, L-NA inhibited conduction to ACh by 60%. Thus, conduction of vasodilation entails a wave of NO release along arteriolar endothelium that is masked when smooth muscle provides a parallel conduction pathway.


The challenges of predicting transposable element activity in hybrids.
Transposable elements (TEs) are ubiquitous mobile genetic elements that hold both disruptive and adaptive potential for species. It has long been postulated that their activity may be triggered by hybridization, a hypothesis that received mixed support from studies in various species. While host defense mechanisms against TEs are being elucidated, the increasing volume of genomic data and bioinformatic tools specialized in TE detection enable in-depth characterization of TEs at the levels of species and populations. Here, I borrow elements from the genome ecology theory to illustrate how knowledge of the diversity of TEs and host defense mechanisms may help predict the activity of TEs in the face of hybridization, and how current limitations make this task especially challenging.


Pregnancy outcomes using assisted reproductive technology after fertility-preserving therapy in patients with endometrial adenocarcinoma or atypical complex hyperplasia.
To evaluate the outcomes of pregnancy in young women (<40 years old) with early endometrial cancer or atypical complex hyperplasia who were treated by conservative management followed by assisted reproductive technology (ART). Medical charts of 11 patients treated from January 1997 to October 2007 at Asan Medical Center were retrospectively reviewed. These patients had all been treated with progestin and serial dilatation and curettage as primary fertility-preserving therapies. After pathological remission of disease, 10 patients tried to become pregnant by ART, 4 by in vitro fertilization and embryo transfer, and 6 by controlled ovarian hyperstimulation, with or without intrauterine insemination. Eight women had intrauterine pregnancies, and 6 patients had live births. Patients have been followed up for 9 to 51 months (mean, 21 months) after delivery, with no evidence of tumor recurrence. Fertility-preserving therapy followed by ART can be a good option in well-selected patients with early endometrial cancer who want to become pregnant.


Potential tumor- or organ-imaging agents. 27. Polyiodinated 1,3-disubstituted and 1,2,3-trisubstituted triacylglycerols.
A series of glyceryl 1,3-bis- and 1,2,3-tris[omega-(3-amino-2,4,6-triiodophenyl)alkanoates] were synthesized, radioiodinated with iodine-125, and evaluated for their ability to selectively localize in the liver for potential use as hepatographic imaging agents. Of the nine target compounds synthesized and evaluated in rats, glyceryl 1,2,3-tris[3-(3-amino-2,4,6-triiodophenyl)propionate] (5b) displayed rapid and sustained liver specificity. This agent was found to accumulate in the liver in concentrations of 60, 75, and 86% of the administered dose at 5 min, 30 min, and 24 h, respectively. Moreover, the 24-h liver-to-blood ratio of 235 justifies further studies in higher animal species.


[The effect of the intra- and extracellular metabolites of microorganisms isolated from various ecotopes on the catalase activity of Staphylococcus aureus 6538P].
The cell extracts (i.e., intracellular metabolites) and culture liquids (i.e., extracellular metabolites) of microorganisms isolated from various ecotopes were found to inhibit the catalase activity of Staphylococcus aureus ATCC 6538P, which resulted in a considerable inhibition of the growth of metabolite-treated S. aureus cells by hydrogen peroxide. The inhibitory effect of microbial metabolites on S. aureus catalase can be considered as a mechanism of intercellular interactions responsible for the formation of microbiocenoses.


Fractal noises and motions in time series of presympathetic and sympathetic neural activities.
We used Allan factor analysis to classify time series of the discharges of single presympathetic neurons in the cat medullary lateral tegmental field (LTF) and rostral ventrolateral medulla (RVLM) and of the postganglionic vertebral sympathetic nerve. These time series fell into two classes of fractal-based point processes characterized by statistically self-similar behavior reflecting long-range correlations among data points. Classification of a time series as either a fractional Gaussian noise (fGn)-or fractional Brownian motion (fBm)-based point process depended on the scaling exponent, alpha, of the power law in the Allan factor curve. fGn is defined as 0 < alpha < 1 and fBm as 1 < alpha < 3. The process responsible for the fractal spike trains of 11 of 12 classifiable LTF neurons with sympathetic nerve-related activity was fGn. In contrast, the process responsible for the fractal spike trains of eight of nine classifiable RVLM presympathetic neurons was fBm. The time series of simultaneously recorded vertebral sympathetic nerve discharge and the arterial pulse also were fBm-based signals. Because a fBm signal is the cumulative sum of the elements comprising the corresponding fGn signal, these results show smoothing of fractal time series in a feedforward direction from medullary presympathetic neurons to postganglionic sympathetic neurons. This may involve integration by RVLM neurons of their LTF inputs or independent fractal processes acting at different levels of the network controlling sympathetic nerve discharge. Whether feedforward smoothing of fractal signals is a feature in other neural systems is open to investigation.


[A Case of Hyaline Vascular-Type Castleman's Disease].
The patient was a 29-year-old female with a chief complaint of transient right-sided abdominal pain. A CT scan revealed homogenously contrasted tumor of 4 cm in diameter with smooth margins and clear borders in the lower part of the pancreatic head. The tumor was contrast-enhanced on MRI and stained on abdominal angiography using the proximal branch of the right colonic artery as a feeding vessel. PET scan showed moderate accumulation. Malignancy could not be ruled out, and tumor resection including the ascending colon was performed. The pathological diagnosis was hyaline vascular-type Castleman's disease in the mesentery of the colon.


Evaluation of methods of transport and cultivation of bacterial specimens from infected dental root canals.
Five different methods of transport and cultivation of bacteria from dental root canal specimens were evaluated. Bacteria were recovered from 29 percent of the specimens when they were transported in VMG IV and subcultured in PRAS medium or on the surface of blood agar in an anaerobic box. When a PRAS-peptone-yeast extract broth was used for transport and the specimens were initially subcultured in the broth, bacteria were recovered from 49 percent of the specimens. When fluid thioglycollate medium USP (BBL) and Clausen medium (Oxoid) were used for transport as well as for initial subculture, bacteria were recovered from 58 percent and 47 percent of the specimens, respectively. The high recovery of bacteria by these media could to a significant degree be ascribed to the use of the media for initial subculture of the specimens. Recovery of bacteria by fluid thioglycollate medium USP was as good or even better as with the more elaborate PRAS medium. Fluid thioglycollate medium USP in screw-capped vials requires no special equipment in the dental clinic and is recommended for use in routine dental practice.


[Virtual reduction and personalized additional fixation by Mimics software in treatment of unstable external wall type intertrochanteric fracture with proximal femoral nail antirotation].
To explore the effect of Mimics assisted virtual reduction and personalized additional fixation with proximal femoral nail anti rotation in the treatment of unstable intertrochanteric fracture of lateral wall. From January 2015 to June 2018, 11 cases of intertrochanteric fracture with unstable lateral wall injury were analyzed retrospectively, including 3 males and 8 females, aged 64 to 81 years old. There were 3 cases of A3.1, 6 cases of A3.2 and 2 cases of A3.3 according to AO classification. All patients underwent CT scanning, according to the CT scanning data, three-dimensional reconstruction of fracture was performed by Mimics soft. Virtual reduction was performed first, and PFNA was implanted after satisfactory reduction. According to the relationship between the fracture characteristics of the lateral wall and the position of the lag screw tail in the lateral wall, 4 cases were treated with PFNA and titanium cable or steel wire, and 7 cases were treated with PFNA and reconstruction locking plate.The quality of reduction and healing were evaluated by follow up, and Harris score of hip joint was performed in the last reexamination. All patients were followed up for 12 to 18 months. No postoperative infection of incision and loosening of internal fixation occurred. The time of fracture healing was 12 to 20 weeks. At the final follow up, Harris score of hip joint was excellent in 6 cases, good in 3 cases and fair in 2 cases. The treatment of intertrochanteric fracture of femur with Mimics assisted virtual reduction and PFNA is helpful to preoperative planning and improve the surgical effect.


Conservative approach for management of fractured maxillary central incisors in young adults.
Ceramic restorations could be an acceptable treatment choice for fractured central incisors. A successful esthetic and conservative result to restore damaged anterior teeth can be obtained through proper evaluation, diagnostic wax-up, guided minimal preparations, ceramic selection, and bonding protocols. Handcrafted glass-based restorations can mimic contours and shape of natural teeth.


Second transmembrane domain of human uncoupling protein 2 is essential for its anion channel formation.
Uncoupling proteins (UCP) are known to transport anions, such as Cl-, in addition to H+ transport. Although H+ transport by UCP is clearly involved in thermogenesis, the mechanism of its anion transport is not clearly understood. In this study, we examined the anion channel characteristics of the six individual helical transmembrane (TM) domains of the human UCP2. The second TM domain peptide (TM2) forms multi-state channels by assemblies of conductive oligomers. Furthermore, the TM2 exhibited voltage-dependent anion channels with properties comparable to those of UCP1 chloride channel. However, the other five TM peptides did not form UCP1-like channels. Moreover, an analog of TM2 in which two Arg residues were substituted by Ala residues did not form stable channels, implying the significance of Arg residues for anion transport. These results suggest that the anion channel structure of UCP2 protein is oligomeric and the second TM domain is essential for the voltage-dependence of this anion channel.


Lowering of ochratoxin A level in milk by yoghurt bacteria and bifidobacteria.
A decrease in the content of ochratoxin A (OA) was observed in milk samples fermented by yoghurt bacteria and bifidobacteria. OA was added to the milk before fermentation at a rate of 0.05-1.5 mg/L. No residues of OA were found in samples containing 0.05 and 0.1 mg/L of OA, fermented by S. Salivarius subsp. thermophilus, L. delbrueckii subsp. bulgaricus and B. bifidum. Yoghurt bacteria (S. salivarius subsp. thermophilus and L. delbrueckii subsp. bulgaricus) were the most effective since no residues were detected even in fermented samples containing originally 0.5 mg/L OA.


Allelic reduction and genetic shift in the Canadian hard red spring wheat germplasm released from 1845 to 2004.
Analysis of genetic diversity changes in existing gene pools of cultivated crops is important for understanding the impact of plant breeding on crop genetic diversity and developing effective indicators for genetic diversity of cultivated plants. The objective of this study was to assess genetic diversity changes in 75 Canadian hard red wheat (Triticum aestivum L.) cultivars released from 1845 to 2004 using 31 simple sequence repeats (SSRs) markers. A total of 267 SSR alleles were detected, and their allelic frequencies ranged from 0.01 to 0.97, with an average of 0.14. Significant allelic reduction was observed at only four SSR loci for the cultivars released from 1970 onwards. However, 51 alleles (about 19%) present in pre-1910 cultivars were undetected in cultivars released after 1990 and were spread over 27 SSR loci. The proportion of SSR variation accounted for by six breeding periods was 12.5%, by four ancestral families, 16.5%, and by eight breeding programs, 8.4%. The average genetic diversity measured by three different band-sharing methods did not change significantly among cultivars released from different breeding periods, breeding programs, and ancestral families. However, genetic shift was obvious in the cultivars released over the six breeding periods, reflecting well the various breeding efforts over years. These results clearly show the allelic reduction and genetic shift in the Canadian hard red spring wheat germplasm released over time. Consequently, more effort needs to be made to broaden the wheat breeding base and conserve wheat germplasm.


Survival of the Charnley hip in coxarthrosis. A 10-15-year follow-up of 629 cases.
We present a 10-15-year follow-up of 629 hips in 555 patients operated on with a Charnley arthroplasty for coxarthrosis. Survivorship analysis showed a 92 percent prosthesis survival after 13 years, with results better in women and in higher age groups.


Cross- and Multi-Coupling Reactions Using Monofluoroalkanes.
Carbon-fluorine bonds are stable and have demonstrated sluggishness against various chemical manipulations. However, selective transformations of C-F bonds can be achieved by developing appropriate conditions as useful synthetic methods in organic chemistry. This review focuses on C-C bond formation at monofluorinated sp3 -hybridized carbons via C-F bond cleavage, including cross-coupling and multi-component coupling reactions. The C-F bond cleavage mechanisms on the sp3 -hybridized carbon centers can be primarily categorized into three types: Lewis acids promoted F atom elimination to generate carbocation intermediates; nucleophilic substitution with metal or carbon nucleophiles supported by the activation of C-F bonds by coordination of Lewis acids; and the cleavage of C-F bonds via a single electron transfer. The characteristic features of alkyl fluorides, in comparison with other (pseudo)halides as promising electrophilic coupling counterparts, are also discussed.


Acid stress responses of Lactobacillus amylovorus and Candida kefyr isolated from fermented sorghum gruel and their application in food fermentation.
Exposure of lactic acid bacteria (LAB) and yeasts to adverse fluctuations during fermentation causes stress; consequently, microbes develop adaptive responses. In this study, we investigated the physiological and proteomic responses of LAB and yeast to acid stress and their application in food fermentation. The physiological and proteomic responses of Lactobacillus amylovorus LS07 and Candida kefyr YS12 to acid stress were measured using turbidimetry, SDS-PAGE, and LC-MS/MS. The technique previously reported by the Association of Official Analytical Chemists (AOAC) was employed to evaluate the physicochemical and organoleptic properties of sorghum gruel fermented using LAB and yeast alone and in combination as starter cultures and spontaneous fermentation as a control. The growth of L. amylovorus LS07 was optimal at pH 1.0, and that of C. kefyr YSI2 was optimal at pH 4. An increased intensity of 30S ribosomal protein S2 (L. amylovorus LS07) and 6-phosphogluconate dehydrogenase (C. kefyr YS12) was observed at pH 1 and 4, respectively, suggesting increased microbial metabolism, thereby reducing the stress. Sorghum gruel produced with combined starters had the highest crude protein (10.94%), iron content (0.0085%), and organoleptic acceptability (7.29), which was significantly different from the products produced with the single starters and the control. The combined starter (L. amylovorus LS07 and C. kefyr YSI2) adapted to stress yielded foods with improved sensory properties, minerals, and reduced anti-nutrient contents.


Solubilization of the iron molybdenum cofactor of Azotobacter vinelandii nitrogenase in dimethylformamide and acetonitrile.
The iron molybdenum cofactor of Azotobacter vinelandii nitrogenase has been solubilized for the first time in dimethylformamide and acetonitrile. These solutions have the ability to reconstitute the inactive nitrogenase of the UW 45 mutant of A. vinelandii and exhibit an S = 3/2 EPR signal similar to that for the cofactor in N-methylformamide. Our ability to obtain solutions of FeMoco in these solvents seemingly refutes a previous hypothesis concerning the necessity of solvents with a dissociable proton for iron molybdenum cofactor solubility and should facilitate the spectroscopic characterization of this important species.


Preserving Well-being in Patients With Advanced and Late Prostate Cancer.
Androgen deprivation therapy, alone or in combination with androgen signaling inhibitors, is a treatment option for patients with advanced prostate cancer (PC). When making treatment decisions, health care providers must consider the long-term effects of treatment on the patient's overall health and well-being. Herein, we review the effects of these treatments on the musculoskeletal and cardiovascular systems, cognition, and fall risk, and provide management approaches for each. We also include an algorithm to help health care providers implement best clinical practices and interdisciplinary care for preserving the overall well-being of PC patients.


Evaluation of the dimensions, morphology, and position of the mandibular condyles in individuals with neurofibromatosis 1: a case-control study.
The aim of this study was to evaluate the mandibular condyles of neurofibromatosis 1 (NF1) individuals without facial plexiform neurofibroma using cone beam computed tomography images. Eighty cone beam computed tomography scans (160 mandibular condyles) were analyzed: 40 from NF1 individuals (study group) and 40 from individuals without NF1 (control group). The anteroposterior and mediolateral dimensions, height, and volume of the mandibular condyles were measured. The mandibular condyles were classified according to their morphology: healthy (absence of morphological changes), with flattening (loss of rounded contour of at least one of the surfaces), with erosion (loss of continuity of the cortical bone), with osteophyte (exophytic formation of the condyle surface), and with sclerosis (any increase in the cortical thickness in the load-bearing areas). Furthermore, the position of the mandibular condyles in relation to the joint fossa in an anteroposterior view was classified as anterior, concentric, or posterior. The study group had a higher anteroposterior dimension of the mandibular condyles compared with the control group (p < 0.05). There were no differences in condylar morphology and position between both groups (p > 0.05). The morphological alterations were not associated with sex or age in any group evaluated (p > 0.05). For both groups, the concentric position was the most common. For the study group, there was a significant difference in the condylar position between the sides (p < 0.05). NF1 individuals without facial plexiform neurofibroma present a high prevalence of condyles with a large anteroposterior dimension and asymmetric position in the joint fossa. However, no morphological and volumetric changes were observed in the mandibular condyles of them. The knowledge of the TMJ alterations in individuals with NF1 is important to establish an evaluation protocol, which would allow early intervention if indicated.


Nuclear HMGB1 promotes the phagocytic ability of macrophages.
Phagocytosis is a basic immune response to the invasion of pathogens. High mobility group protein B1 (HMGB1) is a DNA chaperone that is associated with phagocytosis. However, its influence on phagocytosis is debated. In the present study, HMGB1-mutant, HMGB1-overexpressing and HMGB1-silenced RAW264.7 cells were constructed. In addition, HMGB1 conditional knockout mice were constructed to determine the influence of HMGB1 on phagocytosis. Lipopolysaccharide (LPS) was used to stimulate the translocation of HMGB1 from the nucleus to the cytoplasm. Zymosan particles were used to test the phagocytic function of the macrophages. Our results showed that the accumulation of HMGB1 in the nucleus enhances the phagocytic function of the macrophages. By interacting with P53, nuclear HMGB1 may remain in the nucleus and decrease the negative influence of P53 on the phosphorylation of focal adhesion kinase (FAK). The increase in phosphorylated FAK promotes the formation of pseudopods and enhances the phagocytic ability of macrophages.


Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study.
The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009. There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02). Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.


[Rapid application of infliximab. Efficacy and complications].
To compare the clinical safety of the rapid infusion of infliximab (30-45 min) with the traditional one (2 h). Open, prospective study with the consecutive inclusion of 150 patients with rheumatoid arthritis (RA) and/or spondyloarthritis (AS), resistant to conventional treatment. Patients were randomly distributed to receive 1.5 or 3 mg/kg (according to medical criteria) into 2 groups of 75 patients. Group A: patients received a rapid infusion of infliximab (30-45 min) and group B: traditional intravenous infusion (2 h). The rhythm of infusion was regulated through drip counts and the rule of threes and time was counted on a digital chronometer. Data was obtained from all patients included on possible side effects, as well as efficacy parameters (visual analog scale for pain, tender, and swollen joint counts), and comparisons were made between the rapid infusion group and the traditional infusion group. All patients concluded the study without serious complications. In the rapid infusion group 3 patients had hypersensitivity in the infusion arm and erythema was present in 7 more. The presence of side effects was not significantly different in relation with the infusion speed. Differences were not found in relation to the dosage or the type of illness (RA and/or AS) either. The efficacy of Infliximab for symptom control showed no differences using both types of infusion. The absence of noticeable secondary effects associated with the reduction in the time of infusion of infliximab permits us to point out that a reduction in the time of infusion of infliximab can be a method to optimize hospital resources concerning the outpatient clinic for biologic therapy.


Attenuated live vaccine usage affects accurate measures of virus diversity and mutation rates in avian coronavirus infectious bronchitis virus.
The full-length genomes of 11 infectious bronchitis virus (IBV) field isolates from three different types of the virus; Massachusetts (Mass), Connecticut (Conn) and California (CAL) isolated over a 41, 25 and 8 year period respectively, were sequenced and analyzed to determine the mutation rates and level of polymorphisms across the genome. Positive selection was not detected and mutation rates ranged from 10(-4) to 10(-6)substitutions/site/year for Mass and Conn IBV types where attenuated live vaccines are routinely used to control the disease. In contrast, for CAL type viruses, for which no vaccine exists, positive selection was detected and mutation rates were 10 fold higher ranging from 10(-2) to 10(-3)substitutions/site/year. Lower levels of genetic diversity among the Mass and Conn viruses as well as sequence similarities with vaccine virus genomes suggest that the origin of the Mass and all but one of the Conn viruses was likely vaccine virus that had been circulating in the field for an unknown but apparently short period of time. The genetic data also identified a recombinant IBV isolate with 7 breakpoints distributed across the entire genome suggesting that viruses within the same serotype can have a high degree of genetic variability outside of the spike gene. These data are important because inaccurate measures of genetic diversity and mutation rates could lead to underestimates of the ability of IBV to change and potentially emerge to cause disease.


Real-time monitoring of PARP1-dependent PARylation by ATR-FTIR spectroscopy.
Poly-ADP-ribosylation (PARylation) is a fully reversible post-translational modification with key roles in cellular physiology. Due to the multi-domain structure of poly(ADP-ribose) polymerase-1 (PARP1) and the highly dynamic nature of the PARylation reaction, studies on the biochemical mechanism and structural dynamics remain challenging. Here, we report label-free, time-resolved monitoring of PARP1-dependent PARylation using ATR-FTIR spectroscopy. This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. Analyses of PARP1 activation at different DNA models demonstrate a strong positive correlation of PARylation and PARP1 dissociation, with the strongest effects observed for DNA nicks and 3' phosphorylated ends. Moreover, by examining dynamic structural changes of PARP1, we reveal changes in the secondary structure of PARP1 induced by NAD+ and PARP inhibitor binding. In summary, this approach enables holistic and dynamic insights into PARP1-dependent PARylation with molecular and temporal resolution.


The TRH test in the course of treatment of hyperthyroidism.
In nine patients with thyrotoxicosis (three patients with ophthalmopathy, one patient with T3 thyrotoxicosis) we followed plasma levels of triiodothyronine (T3) and thyroxine (T4) and the TRH induced TSH release before and under treatment with propythiouracil (PTU), carbimazole or methimazol. The patients were observed for 2-8 months and did not receive any thyroid hormones during this time. Before treatment the TSH responses to TRH were absent in all patients. After commencement of antithyroid drug therapy the T3 and T4 plasma values decreased to normal (T3) or subnormal levels (T4) within 1-5 weeks and the patients became euthyroid, but at that time the TRH test was still negative in all patients. Moreover, there was a lag between 2 weeks and 4 months in five of the patients before the TRH test became positive. The duration of this lag could not be correlated with any data of the history or the clinical signs. Several possible explanations for this observation are discussed. Our results suggest that the TRH-test is not suited for the control of the therapeutic effect of antithyroid drug therapy.


Adipose tissue regulates hepatic cholesterol metabolism via adiponectin.
Lipid metabolic disorder involves multiple tissues and organs. Hepatic cholesterol metabolism is an important physiological process, which is tightly related to obesity and lipid metabolic disorders. In this study, we examined the direct effects of adipocytes on hepatic cholesterol metabolic factors and investigated the role of potential adipocytokines in it. Male SD rats were induced by a high-fat diet (HFD) and hepatic cholesterol metabolic factors, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) and ATP-binding cassette transporter A1 (ABCA1) were measured by immunoblotting. Then the effects of adipocytes on the expressions of hepatic cholesterol metabolism proteins were examined in the co-culture system. Finally, the concentrations of several adipocytokines were detected by ELISA and the effect of adiponectin (APN) on hepatic cholesterol metabolism was confirmed by short interference RNA (siRNA) in vitro. Our results showed that adipocytes significantly increased ABCA1 and decreased HMGR in hepatocytes after co-culture. Lipopolysaccharide (LPS) treatment in this co-culture system reversed cholesterol metabolism compared with the untreated group. APN, which also decreased in obese rats, had a significant positive correlation with ABCA1 and inversed correlation with HMGR in vitro. Co-culturing with APN-silenced adipocytes partially restored ABCA1 and HMGR levels. The present study demonstrates that adipocytes regulate hepatic cholesterol metabolism partly via APN.


Retrograde esophageal dilatation in children: an alternative to the indwelling string.
Repeated esophageal dilatation for chronic strictures secondary to corrosive burns or anastomotic scarring is commonly performed by the retrograde technic in children. This requires the presence of an indwelling string, tied in a circle, entering the nose, and exiting the gastrostomy site. Long-term presence of this string frequently leads to nasal and gastrostomy excoriations and resultant patient discomfort. We advocate and describe a technic using a piece of Silastic tubing as an alternative to the indwelling string. This has met with increased patient acceptance and comfort as compared with the previous "heavysilk" or other "string" materials.


Characterization of a T-superfamily conotoxin TxVC from Conus textile that selectively targets neuronal nAChR subtypes.
T-superfamily conotoxins have a typical cysteine pattern of "CC-CC", and are known to mainly target calcium or sodium ion channels. Recently, we screened the targets of a series of T-superfamily conotoxins and found that a new T-superfamily conotoxin TxVC (KPCCSIHDNSCCGL-NH2) from the venom of Conus textile. It selectively targeted the neuronal nicotinic acetylcholine receptor (nAChR) subtypes α4β2 and α3β2, with IC50 values of 343.4 and 1047.2nM, respectively, but did not exhibit obvious pharmacological effects on voltage-gated potassium, sodium or calcium channel in DRG cells, the BK channels expressed in HEK293 cells, or the Kv channels in LβT2 cells. The changes in the inhibitory activities of its Ala mutants, the NMR structure, and molecular simulation results based on other conotoxins targeting nAChR α4β2, all demonstrated that the residues Ile(6) and Leu(14) were the main hydrophobic pharmacophores. To our best knowledge, this is the first T-superfamily conotoxin that inhibits neuronal nAChRs and possesses high binding affinity to α4β2. This finding will expand the knowledge of the targets of T-superfamily conotoxins and the motif information could help the design of new nAChR inhibitors.


Importance of Urinalysis.
A complete urinalysis is an essential diagnostic test to perform in veterinary patients. When interpreted in the context of a patient's clinical history, physical examination findings, and other diagnostic test results, a urine specific gravity, chemical analysis (often via semiquantitative dipstrip testing), and sediment examination are vital to detect both renal and nonrenal disorders. In this article, we describe the usefulness of each component of a urinalysis, the significance of and how to interpret results, and common causes of false-negative and false-positive results.


Phylogenetic position of Bupleurum sikangense inferred from the complete chloroplast genome sequence.
Bupleurum sikangense is an endemic species to China distributed in Xizang (Tibet), which has high saikosaponin content and potential medicinal value. Morphologically, it extremely resembles B. commelynoideum. In order to get a better understanding of the relationship between B. sikangense and B. commelynoideum, and on the phylogenetic status of the two species in the genus, the complete chloroplast (cp) genomes of them were sequenced. The genome organization, repeat sequences, codon usage, RNA-editing sites, and variation of their cp genomes revealed high similarity between the species. Some highly variable regions like trnK-UUU_rps16, rps16_trnQ-UUG, ndhC_trnV-UAC, petA_psbJ, accD_psaI, and petL_psbE were identified, providing potential molecular markers for differentiating the two species. Phylogenetic analysis indicated that B. commelynoideum has a closer relationship to B. chinese than that to B. sikangense. Overall, this study will not only improve our knowledge about cp genomes of these two species, and but also provide data for further research on species identification, safe medical application, conservation genetics, etc., of Bupleurum plants.


Effects of toluene on seizures induced by convulsants acting at distinct ligand-gated ion channels.
Toluene is one of the most widely used solvents. Electrophysiological studies indicated that this solvent directly affects various ligand gated ion channels including NMDA, GABA(A), nicotinic and glycine receptors. The effect of toluene on seizures induced by chemoconvulsants acting on these receptors was compared. Mice were pretreated with toluene (100-1000 mg/kg, i.p.) or corn oil followed by a timed intravenous infusion of NMDA, bicuculline, picrotoxin, nicotine or strychnine to induce seizures. Toluene increased seizure thresholds and lethal doses induced by nicotine, NMDA, picrotoxin and bicuculline, but not strychnine in the used doses. The relative susceptibility to anticonvulsant effect of toluene was in the order: nicotine > NMDA > bicuculline > picrotoxin > strychnine. These findings support a unique anticonvulsant profile of toluene and suggest that nicotinic and NMDA receptors may be more sensitive than GABA(A) and glycine receptors to toluene exposure in seizure-related neural circuits.


Triangular Test of Amanita Mushrooms by Using Electronic Nose and Sensory Panel.
This work aims to advance understanding of the differentiation of mushroom species through electronic devices that use sensors of various technologies and techniques for pattern recognition, comparing mainly volatile substances that emanate from them. In this first phase, the capacity of human olfaction to differentiate between the smell released by different wild mushrooms of the genus Amanita was analyzed by means of a triangular sensory test, comparing later the data to those obtained for the same samples with an electronic nose in a similar test. The results, still very preliminary, encourage imagining the wide application that these techniques will have and the feedback that this application can suppose for the training of the sense of human olfaction.


[Intracranial empyemas: Epidemiological, clinical, radiological and therapeutic aspects. Retrospective study of 100 observations].
Intracranial empyema is a frequent complication of ear-nose-throat (ENT) infections. Limited studies have been carried-out on cerebral empyema during recent years in Senegal. Despite new imaging techniques, diagnostic and therapeutic problems as well as outcome still remain in our regions. We report our experience compared to that of the literature. The study focused on epidemiological aspects, difficulties in diagnosis and treatment as well as prognosis of this condition. This was a retrospective study conducted from January 2008 to December 2011 of 100 clinical cases. Diagnosis was made based on contrast CT-scan. Twenty-one percent of patients received medical treatment alone, while 79% underwent surgery. The duration of the treatment varied from 4 to 8 weeks. The follow-up was clinical and radiological with a mean follow-up time of 12 months. Cerebral empyema represented 44.4 % of all intracranial suppuration cases and the mean age was 21 years. The etiology was ENT in 35%, meningitis 10%, unknown 25%. Localization was sub-dural in 57%, extra-dural in 22%, inter-hemispheric in 10% of the cases. Empyema was associated with an abscess in 7 cases. One case was located in the posterior fossa. The evolution was favorable in 78% of the cases and in 12.5% some neurologic sequelae were observed. Eleven patients died and 3% of the patients had recurrences. The frequency of intracranial empyema is still high in Senegal. Difficulties in diagnosis, therapeutics and low economic incomes account for the gravity of intracranial empyema. In spite of these risks, early stage and effective treatment is necessary to reduce the morbi-mortality, especially in young aged children.


Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases.
Rat liver FAD-AMP lyase or FMN cyclase is the only known enzymatic source of the unusual flavin nucleotide riboflavin 4',5'-cyclic phosphate. To determine its molecular identity, a peptide-mass fingerprint of the purified rat enzyme was obtained. It pointed to highly related, mammalian hypothetical proteins putatively classified as dihydroxyacetone (Dha) kinases due to weaker homologies to biochemically proven Dha kinases of plants, yeasts, and bacteria. The human protein LOC26007 cDNA was used to design PCR primers. The product amplified from human brain cDNA was cloned, sequenced (GenBank Accession No. ), and found to differ from protein LOC26007 cDNA by three SNPs. Its heterologous expression yielded a protein active both as FMN cyclase and ATP-dependent Dha kinase, each activity being inhibited by the substrate(s) of the other. Cyclase and kinase activities copurified from rat liver extracts. Evidence supports that a single protein sustains both activities, probably in a single active center. Putative Dha kinases from other mammals are likely to be FMN cyclases too. Future work will profit from the availability of the structure of Citrobacter freundii Dha kinase, which contains substrate-interacting residues conserved in human Dha kinase/FMN cyclase.


Y-shaped Bifurcated Graft to Pulmonary Arteries After Arterial Switch Operation.
Pulmonary artery stenosis is a frequent complication after arterial switch operation. This case study presented a complex pulmonary artery stenosis initially treated with bilateral pulmonary artery stenting. The patient was found to have aortic valve endocarditis and recurrent pulmonary artery stenosis. The aortic valve was replaced and the pulmonary valve was repaired, followed by interposition of a Y-shaped graft from the sinotubular junction to both pulmonary arteries. The patient had an uneventful recovery and was discharged home asymptomatic after endocarditis antibacterial treatment.


Helicobacter pylori infection and serum leptin, obestatin, and ghrelin levels in Mexican schoolchildren.
BackgroundThere is little information about the possible role of Helicobacter pylori infection on appetite-regulating peptides in children. This study evaluated the association between H. pylori infection and serum levels of ghrelin, leptin, and obestatin in schoolchildren.MethodsOne hundred seventy-eight schoolchildren, students at boarding schools in Mexico City, participated. H. pylori infection status was determined every 6 months for 1 year by a breath test using 13C-urea; schoolchildren with consistently positive or negative results were selected to participate. Age, sex, and body mass index (BMI) were recorded. Serum concentrations of total ghrelin, leptin, and obestatin via specific enzyme-linked immunosorbent assays were determined.ResultsSchoolchildren with H. pylori infection had lower concentration of leptin, -0.54 pg/ml (95% CI: -0.98 to -0.09), compared to the schoolchildren without infection, after adjustment by age, gender, and BMI. And the children with the infection had a median of obestatin lower in 0.99 ng/ml (95% CI: -1.93 to -0.06) compared with the uninfected children after adjustment by BMI.ConclusionAssociation was found between H. pylori infection and decreased serum concentrations of leptin and obestatin. These results suggest that in schoolchildren, H. pylori infection affects the levels of hormones implicated in regulating appetite and energy homeostasis.


Associated neonatal and maternal factors of osteopenia of prematurity in low resource setting: A cross-sectional study.
Determining neonatal and maternal factors that are associated with the incidence of OFP. This study employed a cross-sectional design, in which the participants were identified for clinical variables (sex, gestational age, birth weight, etc.), neonatal morbidity (sepsis, necrotizing enterocolitis (NEC), etc.), and maternal risk factors (premature rupture of membranes, preeclampsia, etc.). The data were analyzed using Chi-square test, independent t-test, and logistic regression test with p < 0.05. The birth weight ranged from 800 to 1495 g (1219 ± 225 g), of which 5 newborns (17%) were <1000 g. The gestational age ranged from 27 to 32 weeks, with a mean of 29 ± 1.5 weeks. The signs of OFP were observed in 13 (43%) infants, of which 2 (15%) OFP infants had a birth weight <1000 g. There was significant difference in parenteral nutrition duration (p = 0.018), onset of vitamin D supplementation (p = 0.019), and ALP level (p = 0.012) of infants between the OFP group and the non-OFP group. The variables associated with the incidence of OFP were parenteral nutrition duration >15 days (OR = 5.4; 95% CI 1.120-26.044; p = 0.036), ALP level >500 U/L (OR = 2.889; 95% CI 1.703-4.900; p = 0.014), and PROM (OR = 5.4; 95% CI 1.039-28.533; p = 0.045). The lack of phosphate intake, prolonged parenteral nutrition, ALP level >500 U/L, onset of vitamin D supplementation, and premature rupture of membranes are associated with the incidence of OFP.


Practice of wound closure techniques among emergency physicians and surgeons in Makkah City Hospitals in Saudi Arabia.
Wound suturing is a procedure performed by medical and surgical specialists. While there are many different suturing techniques and materials used to treat patients, the choice of which to employ depends on different variables that affect the outcome of the procedure. This is a cross-sectional study conducted to provide descriptive data regarding the practice of wound closure techniques, and to develop an awareness of scar formation factors. A total of 172 general surgery (GS) surgeons and emergency (EM) physicians in Makkah city hospitals in Saudi Arabia participated in the study. More than 50% of the practitioners favored the simple interrupted technique for the treatment of all types of studied wounds. The other most common techniques among participants were the subcuticular and vertical mattress methods, respectively, while the use of a stapler was limited to certain wound types. Regarding suturing material, polyglycolic acid was the most frequent material used by 50.1% of participants, whereas only 22% of the participants selected nylon material for wound suturing. However, this study showed a good level of awareness among participants, with significant p-values (p<0.05) of strongly agree and agree regarding the essential factors affecting wound healing and scar formation. The result provides insight into the most common suture techniques and materials used in wound closure. There are wide variations in selecting these techniques and materials among the participants. Also, we found that there is good awareness among participants about factors that lead to scar formation.


Interleukin-6 is essential for Staphylococcal exotoxin B-induced T regulatory cell insufficiency in nasal polyps.
The pathogenesis of nasal polyps is still unclear. There is increasing evidence indicating that Staphylococcal aureus (S. aureus) is associated with the formation of nasal polyps, but the mechanism has not been well documented to date. We stimulated cultured nasal polyps and turbinate tissues with Staphylococcal exotoxin B (SEB), detected the expression of pro-inflammatory cytokines (IL-2, IL-6, and IL-8) and T cell cytokines (IFN-gamma, IL-4, IL-5, IL-10, and IL-17) in the supernatants, and evaluated mRNA expression (T-bet, GATA-3, Foxp3, and RORgammat) and frequencies of CD4+CD25+ T regulatory cells (Tregs) in nasal tissues. We also evaluated the effects of blocking IL-6 with monoclonal antibodies to T cell profiles in cultured nasal tissues stimulated by SEB. Levels of IL-6, IFN-gamma and IL-4 increased significantly in SEB-stimulated nasal polyps. Meanwhile, mRNA expressions of T-bet and GATA-3 were significantly up-regulated, while Foxp3 was inhibited and the frequencies of CD4+CD25+ Tregs were decreased after SEB stimulation. After blocking IL-6, the levels of IL-10 and Foxp3 mRNA, as well as the frequencies of CD4+CD25+ Tregs, were significantly increased, while IFN-gamma and IL-4 production and the mRNA expression of T-bet and GATA-3 were significantly inhibited. SEB is able to modulate pro-inflammatory factors, T-helper type 1/Th2 profiles and suppress Treg activity in cultured nasal polyps, which were rescued by blocking IL-6 activity. Therefore, IL-6 is essential for SEB-induced Treg insufficiency in nasal polyps.


Improved surgical mesh integration into the rat abdominal wall with arginine administration.
Prosthetic meshes are used as the standard of care in abdominal wall hernia repair. However, hernia recurrences and side effects remain unsolved problems. The demand by health care providers for increasingly efficient and cost-effective surgery encourages the development of newer strategies to improve devices and outcomes. Here, we evaluated whether l-arginine administration was able to ameliorate long-term polypropylene prostheses incorporation into the abdominal wall of Sprague-Dawley rats. Meshes were placed on-lay and continuous l-arginine was administered. In vivo biocompatibility was studied at 7, 25 and 30 days post-implantation. Effectively, l-arginine administration in combination with mesh triggered subtle changes in ECM composition that impinged on critical biochemical and structural features. Lastly, tensile strength augmented and stiffness decreased over the control condition. This could help to restructure the mechanical load transfer from the implant to the brittle surrounding tissues, i.e., impact load and fatigue load associated with mechanical tensions could be distributed between the mesh and the restored tissue in a more balanced manner, and ultimately help to reduce the incidence of loosening, recurrences, and local wound complications. Since the newly formed tissue is more mechanically stable, this approach could eventually be introduced to human hernia repair.


Phylodynamic analysis and evaluation of the balance between anthropic and environmental factors affecting IBV spreading among Italian poultry farms.
Infectious bronchitis virus (IBV) control is mainly based on wide vaccine administration. Although effective, its efficacy is not absolute, the viral circulation is not prevented and some side effects cannot be denied. Despite this, the determinants of IBV epidemiology and the factors affecting its circulation are still largely unknown and poorly investigated. In the present study, 361 IBV QX (the most relevant field genotype in Italy) sequences were obtained between 2012 and 2016 from the two main Italian integrated poultry companies. Several biostatistical and bioinformatics approaches were used to reconstruct the history of the QX genotype in Italy and to assess the effect of different environmental, climatic and social factors on its spreading patterns. Moreover, two structured coalescent models were considered in order to investigate if an actual compartmentalization occurs between the two integrated poultry companies and the role of a third "ghost" deme, representative of minor industrial poultry companies and the rural sector. The obtained results suggest that the integration of the poultry companies is an effective barrier against IBV spreading, since the strains sampled from the two companies formed two essentially-independent clades. Remarkably, the only exceptions were represented by farms located in the high densely populated poultry area of Northern Italy. The inclusion of a third deme in the model revealed the likely role of other poultry companies and rural farms (particularly concentrated in Northern Italy) as sources of strain introduction into one of the major poultry companies, whose farms are mainly located in the high densely populated poultry area of Northern Italy. Accordingly, when the effect of different environmental and urban parameters on IBV geographic spreading was investigated, no factor seems to contribute to IBV dispersal velocity, being poultry population density the only exception. Finally, the different viral population pattern observed in the two companies over the same time period supports the pivotal role of management and control strategies on IBV epidemiology. Overall, the present study results stress the crucial relevance of human action rather than environmental factors, highlighting the direct benefits that could derive from improved management and organization of the poultry sector on a larger scale.


Dry weight, triglycerides content and glucose-6-phosphatase activity of hepatocytes separated by sedimentation.
1) Isolated rat-hepatocytes were subfractionated by isopycnic or velocity sedimentation, and dry mass, triglycerides content and Glucose-6-Phosphatase activity of different subpopulations were determined. 2) Distribution of the cell dry masses and dry mass per average cell were substantially similar in all the fractions separated by isopycnic sedimentation. Velocity sedimentation allowed a satisfactory separation of cells of different dry mass. 3) Triglycerides content and Glucose-6-Phosphatase activity of cells of the different fractions obtained by isopycnic sedimentation showed no statistically significant difference. Subpopulations fractionated by velocity sedimentation differed in both triglycerides content and Glucose-6-Phosphatase activity, which were substantially parallel to the cell dry mass.


A Novel Mutation Leading to Wiskott-Aldrich Syndrome in an Ethiopian Boy: a Case Report and a Review of Literature.
Wiskott-Aldrich syndrome is an X-linked recessive primary immune-deficiency disorder very rarely reported from black African children. A 12-year old boy with recurrent sinopulmonary and diarrheal infections, eczema, thrombocytopenia, and low platelet volume was found by whole genome sequencing to harbor a predicted pathogenic c.1205dupC (p.Pro403Alafs*92) variant of a mutation in the WAS gene - confirming the diagnosis. This case report summarizes his presentation and management and provides a useful summary of the diagnosis and the responsible novel genetic mutation.


Effects of effective stereotactic radiosurgery for brain metastases on the adjacent brain parenchyma.
To evaluate whether functional and metabolic MRI can detect radiation-induced alterations in the adjacent areas after effective stereotactic radiosurgery (SRS) for brain metastases. If confirmed, these techniques may be suited for monitoring the timely stratification of patients for neuroprotective treatments after irradiation. Inclusion criteria were complete response, partial response, or stable disease on routine follow-up MR-scans. Multiparametric 3T-MRI was performed with diffusion-weighted imaging, dynamic susceptibility perfusion-weighted imaging, and two-dimensional proton MR-spectroscopy. Parameters were measured in the SRS-treated target and in the adjacent parenchyma up to both 0.75 cm and 1.5 cm from the target border. Nineteen lesions in sixteen consecutive patients met the inclusion criteria. The median follow-up time was 39 months (range, 10-142) with 41 multiparametric MR-examinations in total. We found low values of N-acetyl-aspartate up to 1.5 cm from the target borders of SRS (P = 0.043) associated with high values of choline (P = 0.004) at the end of the observation period. Lactate levels in the adjacent tissue declined over time, whereas continuously high apparent-diffusion-coefficient values were noted (P < 0.001). Multiparametric MRI can depict radiobiological effects and their time course at a distance from the effectively treated site after SRS for brain metastases, even if conventional MRI findings are inconspicuous.


Cutaneous habronemosis in horses: First molecular characterization of Habronema muscae in Israel.
Draschia megastoma, Habronema microstoma, and Habronema muscae are the etiological agents of cutaneous habronemosis, commonly known as summer sores, an inflammatory cutaneous and ocular parasitic disease of horses and other equids transmitted by flies. Here, we describe a cluster of cutaneous habronemosis in five horses that showed single or multiple typical cutaneous ulcerative wounds located on the face, lower forelegs or hindquarters in Israel with the presence of typical "sulphur granules." All affected animals were confirmed by histopathological and/or molecular methods to be infected by H. muscae. This constitutes the first report of cutaneous habronemosis in Israel in which the causative nematode, H. muscae, was identified by molecular means. Cutaneous habronemosis should be considered as a differential diagnosis in equids with cutaneous ulcerative lesions during the summer months, especially when affected animals are refractive to antibiotic treatment alone.


Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs With Trisomy 21.
The intellectual disability found in people with Down syndrome is associated with numerous changes in early brain development, including the proliferation and differentiation of neural progenitor cells (NPCs) and the formation and maintenance of myelin in the brain. To study how early neural precursors are affected by trisomy 21, we differentiated two isogenic lines of induced pluripotent stem cells derived from people with Down syndrome into brain-like and spinal cord-like NPCs and promoted a transition towards oligodendroglial fate by activating the Sonic hedgehog (SHH) pathway. In the spinal cord-like trisomic cells, we found no difference in expression of OLIG2 or NKX2.2, two transcription factors essential for commitment to the oligodendrocyte lineage. However, in the brain-like trisomic NPCs, OLIG2 is significantly upregulated and is associated with reduced expression of NKX2.2. We found that this gene dysregulation and block in NPC transition can be normalized by increasing the concentration of a SHH pathway agonist (SAG) during differentiation. These results underscore the importance of regional and cell type differences in gene expression in Down syndrome and demonstrate that modulation of SHH signaling in trisomic cells can rescue an early perturbed step in neural lineage specification.


Crystal structure of 4-methyl-sulfanyl-2-phenyl-quinazoline.
In the title compound, C15H12N2S, the methylthioquinazoline group is planar with the methyl C displaced by only 0.116 (3) Å from the plane of the quinazoline moiety. The dihedral angle between the phenyl ring and the quinazoline ring system is 13.95 (5)°. In the crystal, each molecule is linked by π-π stacking between to two adjacent inversion-related molecules. On one side, the inverted quinazoline groups interact with a centroid-centroid distance of 3.7105 (9) Å. On the other side, the quinazoline group interacts with the pyrimidine and phenyl rings of the second neighbour with centroid-centroid distances of 3.5287 (8) and 3.8601 (9) Å, respectively.


A multicenter randomized trial comparing the effectiveness and safety of a novel vascular closure device to manual compression in anticoagulated patients undergoing percutaneous transfemoral procedures: The CELT ACD trial.
This study compared the performance of Celt ACD® , a novel stainless steel based vascular closure device versus manual compression (MC) for femoral arteriotomy site hemostasis in patients undergoing percutaneous coronary procedures. Optimal access site management after percutaneous transfemoral procedures remains controversial. Patients enrolled in this multicenter, randomized open label trial underwent 6-F diagnostic or interventional procedures and were assigned 2:1 to Celt ACD® versus MC. All patients were on full anticoagulation. The primary efficacy end point was time to hemostasis (TTH) and the primary safety end points were 30-day incidence of major procedural and access site related complications. The trial allocated 207 patients to Celt ACD® (n = 148) versus MC (n = 59) at 5 investigational sites. Baseline characteristics of the two groups were similar. Median TTH was 0 (Interquartile range (IQR): 0, 0.33) in the Celt ACD® compared to 8 min (IQR: 0, 20; P < 0.0001) in the MC group. Procedural success was 99.3% in the Celt ACD® versus 98.1% in the MC group (P = NS). There was a single major adverse event due to device maldeployment and embolization with successful percutaneous retrieval. The 30-day major complication rate was 0.7% in the Celt ACD® and 0% in the MC group (P = NS). After 6-F percutaneous invasive procedures in fully anticoagulated patients, TTH was significantly reduced in patients assigned to Celt ACD® compared to patients managed with MC. The 30-day rates of vascular complications were similarly low in both groups. (CELT ACD Trial; NCT01600482) © 2017 Wiley Periodicals, Inc.


Prediction and analyses of HLA-II restricted Mycobacterium tuberculosis CD4+ T cell epitopes in the Chinese population.
The Bacillus Calmette-Guérin (BCG) vaccine has been used to prevent tuberculosis (TB), but it cannot prevent adults against TB. The Mycobacterium tuberculosis Beijing strain is the most popular strain in China, but no vaccine is designed for the Beijing strain. It is vital to design a multiepitopes-based vaccine against the Beijing strain for the Chinese population. The bioinformatics tools were used to predict CD4+ T-cell epitopes in five protective antigens based on the Chinese population-specific alleles. The antigenicity, allergenicity, toxicity, IFN-γ level, population coverage, and three-dimensional structure were predicted using Vaxijen, AllerTOP, ToxinPred, IFN-γ epitope server, IEDB, and I-TASSER, respectively. One-hundred one promiscuous epitopes were obtained from Rv1813c, Rv2608, Rv3131, and Rv3628 proteins. After screening with antigenicity, allergenicity, toxicity, and IFN-γ level, seven epitopes from Rv2608 and Rv3131 proteins were selected to be vaccine candidates. Further study determined their three-dimensional structure and the coverage in the Chinese population as high as 99%. Our study predicted seven CD4+ T-cell dominant epitopes from the proteins Rv2608 and Rv3131 of M. tuberculosis Beijing strain for the first time, which may provide a basis for improving the design of multiepitopes-based vaccines for TB.


Altered spontaneous brain activity patterns in patients with neovascular glaucoma using amplitude of low-frequency fluctuations: A functional magnetic resonance imaging study.
Neovascular glaucoma (NVG) can cause irreversible visual impairment and abnormal spontaneous changes in brain's visual system and other systems. There is little research on this aspect at present. However, amplitude of low-frequency fluctuations (ALFFs) can be used as an rs-fMRI analysis technique for testing changes in spontaneous brain activity patterns. The aim of this study was to probe the local characteristics of spontaneous brain activity in NVG patients and analyze their correlation with clinical behaviors. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were obtained from eighteen patients with NVG (8 males, 10 females) and eighteen healthy controls (HCs; 8 males and 10 females) who were matched in age, gender, and education level. We evaluated spontaneous brain activity with the ALFF method. A receiver operating characteristic (ROC) curve was used to compare the average ALFF values for altered brain regions of NVG patients with those of HCs. Compared with HCs, NVG patients had lower ALFF values in the right cuneus, right middle occipital gyrus, left cingulate gyrus, right precuneus, and left medial frontal gyrus (p < 0.001). Higher ALFF values were observed in the right superior frontal gyrus and left middle frontal gyrus (p < 0.001). Analysis of the ROC curves of the brain regions showed that the specificity and accuracy of ALFF values between NVG and HCs in the area under the curve were acceptable (p < 0.001). The patients with NVG exhibited anomalous spontaneous activity in different brain regions; these finding should establish the foundation for a more comprehensive understanding of the pathological mechanisms of NVG. Furthermore, these abnormal variations in specific brain regions can be considered possible clinical indices of NVG.