Development of a multicomponent method for Fusarium toxins using LC-MS/MS and its application during a survey for the content of T-2 toxin and deoxynivalenol in various feed and food samples.
A reliable, sensitive and selective method was developed to determine different Fusarium mycotoxins (trichothecenes Type A and B, zearalenone) simultaneously in cereals and cereal-based samples using liquid chromatography with tandem mass spectrometry (LC-ESI-MS/MS). Sample preparation is based on a standard solvent extraction step followed by two different kinds of solid-phase clean-up procedures: using a multifunctional MycoSep material for trichothecenes and zearalenone. The average recoveries for trichothecenes ranged from 65% for nivalenol (NIV) up to 96% for deoxynivalenol (DON) and 89% for zearalenone (ZON). The limit of quantification varied between 0.02 and 10 ppb for each substance. In addition, a screening survey with 685 samples was carried out to compare contents of T-2 toxin and deoxynivalenol and to investigate potential coherence in contamination pattern.


Evidence that blood-CSF barrier transport, but not inflammatory biomarkers, change in migraine, while CSF sVCAM1 associates with migraine frequency and CSF fibrinogen.
Our objective is to explore whether blood-cerebrospinal fluid (CSF) barrier biomarkers differ in episodic migraine (EM) or chronic migraine (CM) from controls. Reports of blood-brain barrier and blood-cerebrospinal fluid barrier (BCSFB) disruption in migraine vary. Our hypothesis is that investigation of biomarkers associated with blood, CSF, brain, cell adhesion, and inflammation will help elucidate migraine pathophysiology. We recruited 14 control volunteers without headache disorders and 42 individuals with EM or CM as classified using the International Classification of Headache Disorders, 3rd edition, criteria in a cross-sectional study located at our Pasadena and Stanford headache research centers in California. Blood and lumbar CSF samples were collected once from those diagnosed with CM or those with EM during two states: during a typical migraine, before rescue therapy, with at least 6/10 level of pain (ictal); and when migraine free for at least 48 h (interictal). The average number of headaches per month over the previous year was estimated by those with EM; this enabled comparison of biomarker changes between controls and three headache frequency groups: <2 per month, 2-14 per month, and CM. Blood and CSF biomarkers were determined using antibody-based methods. Antimigraine medication was only taken by the EM and CM groups. Compared to controls, the migraine group had significantly higher mean CSF-blood quotients of albumin (Qalb : mean ± standard deviation (SD): 5.6 ± 2.3 vs. 4.1 ± 1.9) and fibrinogen (Qfib mean ± SD: 1615 ± 99.0 vs. 86.1 ± 55.0). Mean CSF but not plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were significantly higher in those with more frequent migraine: (4.5 ng/mL ± 1.1 in those with <2 headache days a month; 5.5 ± 1.9 with 2-14 days a month; and 7.1 ± 2.9 in CM), while the Qfib ratio was inversely related to headache frequency. We did not find any difference in individuals with EM or CM from controls for CSF cell count, total protein, matrix metalloproteinase-9, soluble platelet-derived growth factor receptor β, tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6, IL-8, IL-10, or C-reactive protein. The higher Qalb and Qfib ratios may indicate that the transport of these blood-derived proteins is disturbed at the BCSFB in persons with migraine. These changes most likely occur at the choroid plexus epithelium, as there are no signs of typical endothelial barrier disruption. The most striking finding in this hypothesis-generating study of migraine pathophysiology is that sVCAM-1 levels in CSF may be a biomarker of higher frequency of migraine and CM. An effect from migraine medications cannot be excluded, but there is no known mechanism to suggest they have a role in altering the CSF biomarkers.


His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia.
To identify genes that contribute to myeloid leukemogenesis we have cloned viral integration sites from a CasBrM-MuLV-induced interleukin 3-independent myeloid leukemia cell line. Genomic probes derived from cellular sequences flanking two integrated proviruses were used to screen restriction digests of DNAs from a panel of 52 hematopoietic cell lines, 30 of which were established from CasBrM-MuLV- or MoMuLV-induced mouse leukemias. Probes from one integration site (His-1) defined a region that was rearranged in 3/52 cell lines, and probes from a second integration site (His-2) identified a rearrangement in 2/52 cell lines. Both cases of His-2 rearrangements occurred in concert with viral insertions in the His-1 locus. Genetic mapping of these loci using interspecific backcross analysis assigned the His-1 locus to mouse chromosome 2 and the His-2 locus to mouse chromosome 19. In situ hybridization with a probe from the human homologous region mapped the His-1 locus to human chromosome 2q14-q21. No recombinants were observed between His-2 and Gin-1, a common site of provirus integration in Gross passage A MuLV-induced T-cell leukemias, in 131 backcross animals, suggesting that these loci are tightly linked. The His-1 locus maps to mouse chromosome 2 distinct from any known oncogene or common site of integration but near the proximal breakpoint for a deletion that is observed in over 90% of radiation-induced leukemias.


Searching for promoter activity in RIME/Ingi retrotransposons from Trypanosoma brucei: binding of a nuclear protein to their 5' extremity.
In Trypanosoma brucei only two promoters for protein-encoding genes have been characterized so far. The RIME and Ingi elements of T. brucei are similar in structure to the non-long terminal repeat retrotransposons. Internal promoters usually located at their 5' end drive transcription of several of the latter elements. During a search for promoter activity within RIME and Ingi we focused on a region at the 5' end of both elements, which we termed rime5. A 50 kDa nuclear protein was found to specifically bind to the double strand and single strand sense of rime5 DNA. However, constructs containing several rime5 fragments inserted upstream of a chloramphenicol acetyltransferase (CAT) reporter gene failed to promote both transcription and expression of this gene in transient transfection assays. Finally, we have analyzed the expression of the Ingi elements and despite the high level of transcripts detectable in the cytoplasm, antibodies raised against two different domains of the single open reading frame did not detect any component in total extracts from T. brucei, suggesting that few Ingi copies, if any, are actually active.


Demography, management and outcomes of canine physeal fractures (103 cases).
This study is a retrospective review of the demography, management, complications and outcomes of canine physeal fractures. Clinical records were reviewed for dogs with appendicular physeal fractures, and descriptive statistical analysis was applied to the data set. One hundred and three fractures were included, of which 68 had follow-up. Fractures of the distal humerus were the most common (n = 57), followed by proximal tibial fractures (n = 16). Outcome was fair for most fractures at all locations, aside from the distal humerus, where most outcomes were good. At radiographic follow-up, most physes were closed at all locations aside from the distal tibia. Implant removal to allow ongoing physeal growth was performed in only 3/18 (17%) fractures, in 15/18 (83%) implant removal related to complications. Only short-term follow-up data were present, and hence it is not possible to give a longer term indication of return to function. The management and demography of canine physeal fractures have evolved considerably from previous publications. Routine implant removal to allow ongoing growth was not regularly performed at all locations in this cohort.


Altered Parietal Activation during Non-symbolic Number Comparison in Children with Prenatal Alcohol Exposure.
Number processing is a cognitive domain particularly sensitive to prenatal alcohol exposure, which relies on intact parietal functioning. Alcohol-related alterations in brain activation have been found in the parietal lobe during symbolic number processing. However, the effects of prenatal alcohol exposure on the neural correlates of non-symbolic number comparison and the numerical distance effect have not been investigated. Using functional magnetic resonance imaging (fMRI), we examined differences in brain activation associated with prenatal alcohol exposure in five parietal regions involved in number processing during a non-symbolic number comparison task with varying degrees of difficulty. fMRI results are presented for 27 Cape Colored children (6 fetal alcohol syndome (FAS)/partial FAS, 5 heavily exposed (HE) non-sydromal, 16 controls; mean age ± SD = 11.7 ± 1.1 years). Fetal alcohol exposure was assessed by interviewing mothers using a timeline follow-back approach. Separate subject analyses were performed in each of five regions of interest, bilateral horizontal intraparietal sulci (IPS), bilateral posterior superior parietal lobules (PSPL), and left angular gyrus (left AG), using the general linear model with predictors for number comparison and difficulty level. Mean percent signal change for each predictor was extracted for each subject for each region to examine group differences and associations with continuous measures of alcohol exposure. Although groups did not differ in performance, controls activated the right PSPL more during non-symbolic number comparison than exposed children, but this was not significant after controlling for maternal smoking, and the right IPS more than children with fetal alcohol syndrome (FAS) or partial FAS. More heavily exposed children recruited the left AG to a greater extent as task difficulty increased, possibly to compensate, in part, for impairments in function in the PSPL and IPS. Notably, in non-syndromal heavily exposed children activation was impaired in the right PSPL, but spared in the right IPS. These results extend previous findings of poor right IPS recruitment during symbolic number processing in FAS/PFAS, indicating that mental representation of relative quantity is affected by prenatal alcohol exposure for both symbolic and non-symbolic representations of quantity.


Time constants of cardiac function and their calculations.
Left ventricular diastolic time constant, Tau, is the most established index to describe left ventricular diastolic function. However, the lack of a practical method for the measurement of Tau has been an uncomfortable reality which formerly kept all but a few researchers from making use of it. Recently, the non invasive calculation of Tau in an echo lab was accomplished through formulas developed by universal mathematical method. Tau was first suggested by the fact that left ventricular diastole is an active process, and we can therefore predict that there must be some other time constants which can be used to describe other active movement of ventricular muscles during isovolumic period. Similar mathematical manipulation was employed to develop formulas for "the other Tau(s)". Such Tau(s) represent new sets of indexes useful for the description of cardiac function. They are expected to be the most established indices given the fact Tau is revealing the power of ventricular muscles without interference from either preload or afterload.


Methylcellulose-immobilized reversed-phase precolumn for direct analysis of drugs in plasma by HPLC.
We evaluated a new restricted access media (RAM) precolumn for direct analysis of drugs in plasma using a column switching HPLC system. The new RAM material was prepared by the modification of the external surface of porous silica with hydrophilic methylcellulose (MC), followed by modification of the internal surface with octadecylsilane (ODS). The external surface of the MC-immobilized ODS silica material (MC-ODS) suppressed the adsorption of proteins, while the internal surface of MC-ODS retained various types of drugs, such as ketoprofen, propranolol, caffeine and atenolol in plasma samples. In addition, MC-ODS allowed direct analysis of drugs in a 1000-microL plasma sample to monitor trace amounts of analytes contained. Reduced efficiency and clogging of the MC-ODS precolumn and/or the analytical column were not observed even after the repetitive injection of plasma sample up to 40 mL. Our results indicated that the MC-ODS precolumn could be used in pharmacodynamic and clinical studies.


Chlamydial infections in women.
The impractical isolation procedures available to the general provider of women's health services make diagnosis difficult and often one of exclusion. Looking at the presence of antichlamydial antibodies in cervical secretions may be a more practical detector of infection. More research needs to be carried on in the area of isolation techniques. More importantly, nurse clinicians/practitioners need to be aware of the necessity of treating NGU contacts. As with many conditions, the asymptomatic carrier is the most important link in the control of the disease. Awareness of the potential of these infections will help in their control.


Cardiovascular Complications of COVID-19 Vaccines.
Coronavirus disease 2019 (COVID-19) has become a global public health catastrophe. Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is proven to be the most effective measure to suppress the pandemic. With the widespread application of the four vaccines, namely, ChAdOx1, Ad26.COV2.S, BNT162b2, and mRNA-1273.2, several adverse effects have been reported. The most serious type of complication is cardiovascularly related, including myocarditis, immune thrombocytopenia (ITP), cerebral sinus venous thrombosis, among others. All these adverse events undermine the health of the vaccinees and affect the administration of the vaccines. As the distribution of COVID-19 vaccines is surrounded by suspicion and rumors, it is essential to provide the public with accurate reports from trusted experts and journals. Monitoring the safety of COVID-19 vaccines is an important and ongoing process that is also urgent. Thus, we summarized the cardiovascular complications of the major types of COVID-19 vaccines, including mRNA vaccines, which are now generally considered to be innovative vaccines, and the future for vaccination against COVID-19, in addition to the underlying pathogenesis and potential therapeutics.


Biosynthetic human proinsulin, a new therapeutic compound for diabetics? A comparative study of biosynthetic human proinsulin with biosynthetic human insulin.
The biological activities of proinsulin, the endogenous precursor of insulin are different in comparison to insulin. Proinsulin has a longer biological half-life in serum and a much lower hypoglycemic potency. Biosynthetic human proinsulin has been suggested as an intermediate acting "insulin" in the treatment of diabetes mellitus, having the advantage of not including a retardation substance. For this reason it is important to establish a dose relationship in comparison to human insulin. Human proinsulin and human insulin were tested in 2 groups of healthy volunteers after i.v. application on a unit equivalent basis. 0.025, 0.05 and 0.1 units/kg of either compound were applied intravenously in a randomised order. Following human proinsulin application, the nadir of blood glucose showed a delay of 5-10 min. in comparison to insulin, however, the increase of blood glucose following the nadir was much more retarded after human proinsulin application. The antilipolytic effect of proinsulin was significantly stronger in comparison to insulin. No significant differences could be observed in the kinetics of beta-hydroxybutyrate levels and the counterregulatory response. Human proinsulin, based on a unit equivalent dosage, exerts a more pronounced hypoglycemic and antilipolytic effect, which is probably due to the longer biological half-life in comparison to insulin.


Freezing, melting and structure of ice in a hydrophilic nanopore.
The nucleation, growth, structure and melting of ice in 3 nm diameter hydrophilic nanopores are studied through molecular dynamics simulations with the mW water model. The melting temperature of water in the pore was T(m)(pore) = 223 K, 51 K lower than the melting point of bulk water in the model and in excellent agreement with experimental determinations for 3 nm silica pores. Liquid and ice coexist in equilibrium at the melting point and down to temperatures as low as 180 K. Liquid water is located at the interface of the pore wall, increasing from one monolayer at the freezing temperature, T(f)(pore) = 195 K, to two monolayers a few degrees below T(m)(pore). Crystallization of ice in the pore occurs through homogeneous nucleation. At the freezing temperature, the critical nucleus contains approximately 75 to 100 molecules, with a radius of gyration similar to the radius of the pore. The critical nuclei contain features of both cubic and hexagonal ice, although stacking of hexagonal and cubic layers is not defined until the nuclei reach approximately 150 molecules. The structure of the confined ice is rich in stacking faults, in agreement with the interpretation of X-ray and neutron diffraction experiments. Though the presence of cubic layers is twice as prevalent as hexagonal ones, the crystals should not be considered defective Ic as sequences with more than three adjacent cubic (or hexagonal) layers are extremely rare in the confined ice.


Well-being and needs of Malay carers of people with mental illness in Singapore.
Despite the importance of carers supporting the lives of people with mental illness, there are limited studies investigating the well-being and needs of Malay carers in multicultural Singapore. The Malays consist of 13.4% of Singapore's population. A mixed methods qualitative dominant research approach was used to explore the well-being and needs of Malay carers in a voluntary welfare organisation. The Kessler-10, Friendship Scale and Carers' and Users' Expectations of Services-Carer version were used to assess the needs and well-being of 17 Malay carers. Findings show that Malay carers experienced poor well-being and had numerous unmet needs. Four main themes were found: (a) Concerns related to relatives with mental illness, (b) Mental health practices related to carers, (c) Holistic support for carers and (d) Preference for greater spiritual support in mental health. Recovery-oriented mental health practice implications are discussed. Spirituality of Malay carers needs to be given greater consideration in recovery-oriented mental health services.


c-erbA encodes multiple proteins in chicken erythroid cells.
To identify and characterize the proteins encoded by the erbA proto-oncogene, we expressed the C-terminal region of v-erbA in a bacterial trpE expression vector system and used the fusion protein to prepare antiserum. The anti-trp-erbA serum recognized the P75gag-erbA protein encoded by avian erythroblastosis virus and specifically precipitated six highly related proteins ranging in size from 27 to 46 kilodaltons from chicken embryonic erythroid cells. In vitro translation of a chicken erbA cDNA produced essentially the same pattern of proteins. Partial proteolytic maps and antigenicity and kinetic analyses of the in vivo and in vitro proteins indicated that they are related and that the multiple bands are likely to arise from internal initiations within c-erbA to generate a nested set of proteins. All of the c-erbA proteins are predominantly associated with chicken erythroblast nuclei. However, Nonidet P-40 treatment resulted in extraction of the three smaller proteins, whereas the larger proteins were retained. During differentiation of erythroid cells in chicken embryos, we found maximal levels of c-erbA protein synthesis at days 7 to 8 of embryogenesis. By contrast, c-erbA mRNA levels remained essentially constant from days 5 to 12. Together, our results indicate that posttranscriptional or translational mechanisms are involved in regulation of c-erbA expression and in the complexity of its protein products.


Can we select which patients with small breast cancers should receive adjuvant chemotherapy?
To identify the risk of systemic metastases from T1a and T1b N0 breast cancers in patients treated in an academic center, and to seek factors to identify the patients at greatest risk of such failure. With the demonstration that adjuvant chemotherapy reduces the death rate from breast cancer by roughly one quarter across all risk groups, controversy has reigned regarding possible exclusions from therapy. T1a and T1b N0 tumors (1-cm diameter and smaller with negative axillary nodes) have been considered at low risk for metastasis since the report from Memorial Sloan-Kettering Cancer Center of a 90% survival rate at 10 years. Subsequent reports have suggested an even more favorable prognosis for this group. However, consensus statements advise selecting some of these women for treatment, and many do receive adjuvant chemotherapy. Sequential patients with breast cancer at the Emory Clinic were prospectively staged and followed up for outcome. The records of patients with T1a and T1b N0 tumors were reviewed for exact tumor diameter, grade, receptor status, adjuvant therapy, and outcome. A corrected data set was stripped of patient identifiers and analyzed by Kaplan-Meier methods. Subgroups were formed based on tumor grade (1 vs. 3), adjuvant chemotherapy (use vs. no use), and adjuvant tamoxifen (use vs. no use) and were compared via log-rank tests. Two hundred eighty-two women were identified. Two developed metastatic disease and one experienced a local failure after breast-conserving treatment. The estimated disease-free survival rate at 10 years was 98.7%. With only two distant failures and one local failure, there was no significant difference by grade, receptor status, or use of adjuvant chemotherapy or tamoxifen. The risk of systemic failure from such tumors barely exceeded 1% at 10 years. Unless future studies can identify a subgroup at higher risk, the cognitive changes associated with cytotoxic chemotherapy or the loss of estrogen involved do not appear to have sufficient offsetting benefit to warrant chemotherapy for this group of women.


Activation/Inhibition of Cholinesterases by Excess Substrate: Interpretation of the Phenomenological b Factor in Steady-State Rate Equation.
Cholinesterases (ChEs) display a non-michaelian behavior with positively charged substrates. In the steady-state rate equation, the b factor describes this behavior: if b > 1 there is substrate activation, if b < 1 there is substrate inhibition. The mechanistic significance of the b factor was investigated to determine whether this behavior depends on acylation, deacylation or on both steps. Kinetics of human acetyl- (AChE) and butyryl-cholinesterase (BChE) were performed under steady-state conditions and using a time-course of complete substrate hydrolysis. For the hydrolysis of short acyl(thio)esters, where acylation and deacylation are partly rate-limiting, steady-state kinetic analysis could not decide which step determines b. However, the study of the hydrolysis of an arylacylamide, 3-(acetamido)-N,N,N-trimethylanilinium (ATMA), where acetylation is rate-limiting, showed that b depends on the acylation step. The magnitude of b and opposite b values between AChE and BChE for the hydrolysis of acetyl(thio)- versus benzoyl-(thio) esters, then indicated that the productive adjustment of substrates in the active center at high concentration depends on motions of both the Ω and the acyl-binding loops. Benzoylcholine was shown to be a poor substrate of AChE, and steady-state kinetics showed a sudden inhibition at high concentration, likely due to the non-dissociation of hydrolysis products. The poor catalytic hydrolysis of this bulky ester by AChE illustrates the importance of the fine adjustment of substrate acyl moiety in the acyl-binding pocket. Molecular modeling and QM/MM simulations should definitively provide evidence for this statement.


[Clinical experience with three cases of haemorrhagic tendency--bladder carcinoma with hemophilia A, a bladder carcinoma with von Willebrand disease and a benign prostatic hypertrophy with idiopathic thrombocytopenic purpura (ITP)].
Recent understanding of the pathogenicity of haemorrhagic tendency as well as advance of management of patients with this disease makes its surgical treatment possible. Since 1979 we have experienced three male patients with haemorrhagic tendency. The first case was a bladder carcinoma with hemophilia A. He had been given 2500 unit of Conco-eight (coagulation factor VIII) before transurethral resection of bladder tumor (TUR-Bt) and was given 1000 unit of Conco-eight every eight to twelve hours for seven days postoperatively. The second case was a bladder carcinoma with von Willebrand disease. This case was also pretreated by Conco-eight before operation and we had difficulty in controlling his coagulopathy for one month postoperatively. The third case was a benign prostatic hypertrophy with idiopathic thrombocytopenic purpura (ITP). He had been given a huge dose of gamma globulin for six days before operation and on the operation day his platelet count was normalized. Since his prostate was estimated to weight over 70 g, suprapubic prostatectomy was selected. All these three cases were operated uneventfully. From this experience we believe that with proper preoperative and postoperative management, patients with haemorrhagic tendency can be operated safely.


The role of acceptance and values in quality of life in patients with an acquired brain injury: a questionnaire study.
An acquired brain injury (ABI) is a challenge for an individual's quality of life (QOL). In several chronic illnesses acceptance has been found to be associated with a better health-related quality of life. This study investigated whether this relationship is also found in patients with ABI. We also explored the impact of the perceived ability to live according to one's own values (life-values-match). A total of 68 individuals (18-65 years of age) with an acquired brain injury completed a battery of questionnaires. The relations between health-related QOL (SF-36) and disease specific QOL (EBIQ; European Brain Injury Questionnaire), and personal values (Schwartz Values Inventory) and acceptance (ICQ; Illness Cognitions Questionnaire) were investigated. An additional question measured the life-values-match. Rehabilitation professionals reported the extent of impairment involved. Acceptance was positively associated with mental aspects of health-related QOL and the EBIQ Core Scale, after demographic variables and the extent of impairment were introduced in the regression. In a post hoc analysis we found that the life-values-match mediated the relationship between acceptance and mental aspects of QOL. In patients with an ABI, promoting acceptance may be useful to protect QOL. Strengthening the life-values-match may be a way to accomplish this.


The cardiorespiratory effects of a fentanyl infusion following acepromazine and glycopyrrolate in dogs.
We investigated whether the analgesic mu-opioid fentanyl can be used safely in dogs in everyday clinical veterinary practice, with limited and non-invasive monitoring. To this end, the cardiorespiratory effects of fentanyl, administered in doses reported to be adequate for inducing opiate analgesia in spontaneously breathing canine patients, were evaluated by measuring the respiration rate, oxygen saturation (SpO2), heart rate, respiratory sinus arrhythmia (RSA), and rectal body temperature. Ten Beagle dogs, all spontaneously breathing room air, underwent three separate sessions in which they received in random order either saline, fentanyl 5 microg/kg/h or fentanyl 10 microg/kg/h. Each session started with a non-medication period, followed by acepromazine with glycopyrrolate, followed by a loading dose and infusion of saline or fentanyl, and ended with the administration of the antagonist naloxone. At the doses studied, fentanyl did not significantly change the respiration rate or have a clinically relevant effect on SpO2 or RSA, whereas it significantly decreased the heart rate and core body temperature. In the dose range tested and under the conditions described in this protocol, we conclude that fentanyl can be safely administered to healthy dogs spontaneously breathing room air.


Diastolic heart failure: recognition, diagnosis and management.
A variety of community-based epidemiological studies have suggested that 30-50% of patients with heart failure symptoms appear to have preserved left ventricular (LV) systolic function when assessed by echocardiography or similar techniques suggesting 'diastolic heart failure' (DHF) as its cause. The prognosis of these patients is characterised by morbidity and mortality similar to, but less overt than, patients with systolic dysfunction. However, rates of readmission for symptom control are broadly similar in patients with DHF or in those with systolic impairment. Thus, there are many similarities in the portrayal of both systolic and DHF but equally; there are also many key differences. Certainly, while there are several successful therapies for patients with systolic heart failure, the management of patients with DHF is poorly defined. In this review, the gaps in current knowledge and practice, which is creating this therapeutic void will be addressed.


Serum total cholesterol, triglycerides and high density lipoproteins (HDL) levels in rabbit during the course of experimental diabetes.
The study was conducted on 56 rabbits, of White New Zealand breed, male gender. The average weight of the rabbits was 3 kg. The diabetes was evoked by intravenous injection of 10% alloxan, using the single dose of 100 mg/kg. On the 7th day after administration of alloxan, serum glucose levels were determined. The serum glucose level higher than 11.1 mmol/l was considered an indicator of the presence of diabetes. All the animals included in the study were divided into five groups: the control, 21-day diabetes, 42-day diabetes, 90-day diabetes and 180-day diabetes. Serum total cholesterol, triglycerides and high density lipoproteins levels were determined with enzymatic methods. Our studies revealed a significant increase in cholesterol and triglycerides levels. That mechanism might be responsible for faster development of atheromatosis during the course of diabetes mellitus.


Fluctuations of the solid discharge of gravity-driven particle flows in a turbulent stream.
Substantial variations in the particle flux are commonly observed in field measurements on gravel-bed rivers and in laboratory experiments mimicking river behavior on a smaller scale. These fluctuations can be explained by the natural variability of sediment supply and hydraulic conditions. We conducted laboratory experiments of particle transport down a two-dimensional inclined channel, for which the boundary conditions were properly controlled. Most flow variables and the features of particle trajectories were measured using a high-speed camera. The particles were 6-mm glass beads entrained by a rapid, turbulent, supercritical water flow. Even under these well-controlled experimental conditions and despite steady supply, solid discharge exhibited significant variations with time. The objective of this paper was to pinpoint the origins of these fluctuations by investigating different flow conditions. Two experiments were done with a fixed (smooth or corrugated) channel bottom and two others were run with a mobile bed (involving layers of closely packed particles lying along the channel base, which could be entrained by the stream); in the latter case, two particle arrangements were tested. It was found that, to a large extent, fluctuations reflected the finite size of the observation window. For fixed beds, the characteristic time scale of fluctuations and their probability distribution can be predetermined by evaluating the mean and fluctuating velocities of a single particle. Solid-discharge fluctuations were exacerbated when the bed was mobile because (i) the moving solid phase and the stationary bed exchanged particles and (ii) collective entrainment of particles occurred.


A Continuous Extraction and Pumpless Supercritical CO₂ Drying System for Laboratory-Scale Aerogel Production.
Production of aerogels starts with solution chemistry and may end with supercritical carbon dioxide drying, which both require a specialized system. Here we present a complete aerogel production system that was developed and used in our laboratory over the last nine years. Our aim was to develop a supercritical dryer and a protocol, whereby the CO₂ pump can be left out, and the entire flow system is operated by the pressure of the CO₂ cylinder. Drying pressure and temperature are controlled by the combination of the filling and heating temperatures. A continuous-mode solvent exchange system has also been developed, in which the solvent consumption during the process can be reduced to one-third of the batch method. In the new medium temperature 1.5 L volume supercritical dryer, the temperature is set to a constant 80⁻82 °C, and the pressure can be in the 90⁻200 bar range, depending on the conditions. We have performed approximately 200 dryings thus far, and prepared a wide range of monolithic aerogels, from pristine silica aerogels to polysaccharides and collagen. In this paper, we have summarized not only the technical details, but also the work experiences, as well as advantages and disadvantages of the systems.


Nano-FROG: Frequency resolved optical gating by a nanometric object.
We present a technique to characterize ultrashort pulses at the focal plane of a high numerical aperture objective with unprecedented spatial resolution, by performing a FROG measurement with a single nanocrystal as nonlinear medium. This approach can be extended to develop novel phase-sensitive techniques in laser scanning microscopy, probing the microscopic environment by monitoring phase and amplitude distortions of femtosecond laser pulses.


Photodynamic therapy in Bowen's disease: influence of histological features and clinical characteristics on its success.
In Bowen's disease (BD) there is no consensus on optimal treatment. Photodynamic therapy (PDT) is an effective non-invasive treatment modality for BD with excellent cosmetic results. This retrospective study examines whether clinical and histological features of BD impact PDT response. Patients with previously untreated BD from 2002 until 2007 were identified at the Maastricht University Medical Centre. Patients treated with PDT were included. All histological slides were re-examined. During the study period 98 tumours were treated with PDT. In univariate analysis severe atypia and higher age were associated with decreased probability of clinical clearance. Higher age was also associated with an increased risk of recurrence. In multivariate analysis severe atypia remained the only independent risk factor for therapy failure. In patients with BD, severe atypia and higher age are associated with an increased risk of treatment failure after PDT.


Grafting from Starch Nanoparticles with Synthetic Polymers via Nitroxide-Mediated Polymerization.
Nitroxide-mediated polymerization (NMP) is employed to graft synthetic polymers from polysaccharides. This work demonstrates the first successful polymer grafting from starch nanoparticles (SNPs) via NMP. To graft synthetic polymers from the SNPs' surface, the SNPs are first functionalized with 4-vinylbenzyl chloride prior to reaction with BlocBuilder MA yielding a macroinitiator. Methyl methacrylate with styrene, acrylic acid, or methyl acrylate are then grafted from the SNPs. The polymerizations exhibited linear reaction kinetics, indicating that they are well controlled. Thermal gravimetric analysis and spectroscopic techniques confirmed the synthesis of the precursors materials and the success of the grafting from polymerizations. The incorporation of hydrophobic synthetic polymers on hydrophilic SNPs yields new hybrid materials that could find use in several industrial applications including paper coatings, adhesives, and paints.


Electron microscopy of the cell: cell structure and function.
The use of the electron microscope has added much to our knowledge of the cell. The fine structure of the component parts of the nucleus and the cytoplasm is described, and their functions are indicated. The nature and structural modifications of the plasma membrane are illustrated with particular reference to function. To illustrate the interrelationships of the nucleus and cytoplasm, the theory of protein secretion is discussed, the secretion of a particular protein or polypeptide being determined by a particular nucleotide sequence in the desoxyribonucleic acid of a chromosome, that is, by a gene. This information is transferred from nucleus to cytoplasm. It is in the cytoplasm that the majority of the work is performed while the nucleus directs the work of the cell.


Molecular analysis of the psa permease complex of Streptococcus pneumoniae.
The psaBCA locus of Streptococcus pneumoniae encodes a putative ABC Mn2+-permease complex. Downstream of the operon is psaD, which may be co-transcribed and encodes a thiol peroxidase. Previously, there has been discordance concerning the phenotypic impact of mutations in the psa locus, resolution of which has been complicated by differences in mutant construction and the possibility of polar effects. Here, we constructed unmarked, in frame deletion mutants DeltapsaB, DeltapsaC, DeltapsaA, DeltapsaD, DeltapsaBC, DeltapsaBCA and DeltapsaBCAD in S. pneumoniae D39 to examine the role of each gene within the locus in Mn2+ uptake, susceptibility to oxidative stress, virulence, nasopharyngeal colonization and chain morphology. The requirement for Mn2+ for growth and transformation was also investigated for all mutants. Inductively coupled plasma mass spectrometry (ICP-MS) analysis provided the first direct evidence that PsaBCA is indeed a Mn2+ transporter. However, this study did not substantiate previous reports that the locus plays a role in choline-binding protein pro-duction or chain morphology. We also confirmed the importance of the Psa permease in systemic virulence and resistance to superoxide and hydrogen peroxide, as well as demonstrating a role in nasopharyngeal colonization for the first time. Further evi-dence is provided to support the requirement for Mn2+ supplementation for growth and transformation of DeltapsaB, DeltapsaC, DeltapsaA, DeltapsaBC, DeltapsaBCA and DeltapsaBCAD mutants. However, transformation, as well as growth, of the DeltapsaD mutant was not dependent upon Mn2+ supplementation. We also show that, apart from sensitivity to hydrogen peroxide, the DeltapsaD mutant exhibited essentially similar phenotypes to those of the wild type. Western blot analysis with a PsaD antiserum showed that deleting any of the genes upstream of psaD did not affect its expression. However, we found that deleting psaB resulted in decreased expression of PsaA relative to that in D39, whereas deleting both psaB and psaC resulted in at least wild-type levels of PsaA.


Traditional Chinese Medication Qiliqiangxin Protects Against Cardiac Remodeling and Dysfunction in Spontaneously Hypertensive Rats.
Qiliqiangxin (QLQX), a traditional Chinese herbs medication, exerted protective effect in chronic heart failure patients in a multicenter randomized double-blind study. QLQX has also been found to improve cardiac function and reduce cardiac fibrosis in spontaneously hypertension animal model. However, the effect of longterm treatment with QLQX in such a condition and the related molecular mechanisms remain largely unknown. In the present study, thirteen-week-old spontaneously hypertensive rats (SHRs) were treated by daily intragastric administration of QLQX or saline for one year. Echocardiography, electron microscopy, and Masson's trichrome staining were used to determine cardiac function, mitochondria ultrastructure, and cardiac fibrosis, respectively. Quantitative reverse transcription polymerase chain reactions (qRT-PCRs) and Western blotting were used to determine gene expressions. We found that QLQX significantly improved cardiac function and reduced gene markers of pathological hypertrophy including ANP, BNP, and Myh7. QLQX also attenuated cardiac fibrosis and apoptosis in SHRs as evidenced by downregulation of α-SMA, collagen I, collagen III, and TGF-β expressions and reduction of Bax to Bcl-2 ratio. Moreover, the damage of mitochondrial ultrastructure was greatly improved and the reduction of PPAR-α, PPAR-γ, and PGC-1α expression levels was significantly restored in SHRs by treatment with QLQX. In conclusion, longterm treatment with QLQX protects against cardiac remodeling and dysfunction in hypertension by increasing PPARs and PGC-1α.


Chronic renal failure: An autopsy study.
Diabetes and hypertension are at present the major causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. The stages 0-5 of CKD are defined according to the estimated glomerular filtration rate. The term chronic renal failure (CRF) typically corresponds to CKD stages 3-5. Cardiovascular disease is the main cause of morbidity and mortality in patients of CRF and ESRD. This study was undertaken to analyze the age and sex incidence, clinical features, etiology, pathology of various organs in detail, and causes of death of CRF patients. All autopsies performed on known cases of CRF and those who were diagnosed as CRF at autopsy at a tertiary care hospital in India over a 7-year period were studied. The highest number of cases of CRF fell within the 56-65 years age group with a male/female ratio of 1.38:1. Oliguria and anasarca were the most common presenting features. Chronic pyelonephritis was the most common cause of CRF in our study, followed by hypertension, diabetes, and chronic glomerulonephritis. Other causes included amyloidosis, autosomal poly- cystic kidney disease, and ischemic and multiple myeloma. Most common cause of death found was cardiovascular, followed by infections, cerebrovascular, metabolic, and other causes.


Gender, gestation and ectogenesis: self-determination for pregnant people ahead of artificial wombs.
In this short response, I agree with Cavaliere's recent invitation to consider ectogenesis, the process of gestation occurring outside the body, as a political perspective and provocation to building a world in which reproductive and care labour are more justly distributed. But I argue that much of the literature Cavaliere addresses in which scholars argue that artificial wombs may produce greater gender equality has the limitation of taking a fixed, binary and biological approach to sex and gender. I argue that in taking steps toward the possibility of more just practices of caregiving and family making, we must look first not to artificial womb technologies but to addressing the ways that contemporary legal and social practices that enforce essentialising, binary ways of thinking about reproductive bodies inhibit this goal.


Histobacteriology and pulp reactions to long-term dental restorations.
The prevention of degeneration and necrosis of the endodont is one of the main goals of dental treatment. Kerschbaum and Voss (1979, 1981) described that 15% of teeth showed negative results to sensitivity testing 10 years after crown preparation. Pulpal responses to dental treatment depend on many factors including thermal injury, transsection of the odontoblastic process, vibration, desiccation of dentin, pulp exposure, smear layer, remaining dentin thickness and used materials. The knowledge concerning endodontic reactions in short and medium term observation is mainly based on research by Klötzer and Langeland. Histological assessment of reactions is a well accepted method for biocompatibility testing (i.e. ISO/TR 7405). It is consistent to apply its principles to the evaluation of endodontic reactions of teeth with long term restorations. As pulpal injury is furthermore due to microleakage between filling material and the wall of the cavity the analysis of infected dentin tubules seems to be important. A consideration of the location of the tubules and of the severity of the invasion is necessary. Using a classification (grade 1-6) comprising the parameters of degenerative and regenerative reactions and bacterial invasion, 24 teeth restored with different types of fixed prosthodontic restorations were investigated. The restorations were between 0-6, 7-12 and 13-18 years in situ. Serial sections (5 microns) were stained with haematoxylin-eosin, azan, according to Goldner and J. Hopkins. 22 of 24 teeth showed typical degenerative reactions. Negative sensitivity testing occurred in teeth with no pain and no or partial necrosis. The histobacteriological assessment showed bacterial invasion of the dentin tubules of 21 teeth. From this investigation it was concluded that the proposed classification shows sufficient sensitivity for the evaluation of progressive endodontic changes of long-term restored teeth. Furthermore it was shown that bacterial invasion must be considered as a possible co-factor for the described degenerative character of the pulpal tissue.


Molecular genetic studies of gene identification for osteoporosis: the 2009 update.
Osteoporosis is a complex human disease that results in increased susceptibility to fragility fractures. It can be phenotypically characterized using several traits, including bone mineral density, bone size, bone strength, and bone turnover markers. The identification of gene variants that contribute to osteoporosis phenotypes, or responses to therapy, can eventually help individualize the prognosis, treatment, and prevention of fractures and their adverse outcomes. Our previously published reviews have comprehensively summarized the progress of molecular genetic studies of gene identification for osteoporosis and have covered the data available to the end of September 2007. This review represents our continuing efforts to summarize the important and representative findings published between October 2007 and November 2009. The topics covered include genetic association and linkage studies in humans, transgenic and knockout mouse models, as well as gene-expression microarray and proteomics studies. Major results are tabulated for comparison and ease of reference. Comments are made on the notable findings and representative studies for their potential influence and implications on our present understanding of the genetics of osteoporosis.


Update on statins: hope for osteoporotic fracture healing treatment.
Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.


Acute disseminated encephalomyelitis: an uncommon presentation of hyper IgE syndrome.
The hyper-immunoglobulin E (IgE) syndrome (HIES), also known as Job's syndrome is a rare primary immunodeficiency characterized by the clinical triad of recurrent staphylococcal abscesses of skin, recurrent cyst-forming pneumonia, and an elevated serum IgE level of > 2000 IU/ml. Although, most cases are sporadic, families with autosomal dominant (AD-HIES) and recessive (AR-HIES) traits have been reported. Very few articles were published previously on central nervous system abnormalities with definite neurologic manifestations which may vary from partial facial nerve paralysis to hemiplegia in children but Acute Disseminated Encephalomyelitis (ADEM) in a child with HIES hitherto has not been reported. Here we describe a 5-year-old male child with HIES who presented with neurologic manifestations of ADEM.


Non-Iterative Reconstruction with a Prior for Undersampled Radial MRI Data.
This paper develops an FBP-MAP (Filtered Backprojection, Maximum a Posteriori) algorithm to reconstruct MRI images from under-sampled data. An objective function is first set up for the MRI reconstruction problem with a data fidelity term and a Bayesian term. The Bayesian term is a constraint in the temporal dimension. This objective function is minimized using the calculus of variations. The proposed algorithm is non-iterative. Undersampled dynamic myocardial perfusion MRI data were used to test the feasibility of the proposed technique. It is shown that the non-iterative Fourier reconstruction method effectively incorporates the temporal constraint and significantly reduces the angular aliasing artifacts caused by undersampling. A significant advantage of the proposed non-iterative Fourier technique over the iterative techniques is its fast computation time.


[Cerebellopontine angle and internal auditory canal lipomas: report of four cases and review of the literature].
Lipomas are exceptional tumors at the Cerebellopontine Angle (CPA) or the Internal Auditory Canal (IAC). We evaluate clinical, histological and radiological characteristics of the cases diagnosed in our Hospital and the results of conservative versus surgical treatment. We report 4 cases of CPA and/or IAC and review 99 previously reported in the literature. Unilateral tinnitus was the most frequent symptom (100%). All lesions showed hyperintensity on T1 and hypo/isointensity on T2--weighted MNR images. Two patients underwent a retro-sigmoidal approach without complete tumoral resection and with additional neurological consequences. Another two cases were followed up by annual MNRs. During the follow-up period (4.2 years average), neither clinical nor radiological changes were detected. The surgical resection of CPA y/o IAC lipomas is associated to a significant morbidity due to the high vascularization and the dense adherence of these lesions to the surrounding tissues. The MNR is the suitable technique for differential diagnosis between lesions at this location.


Decompressive craniotomy.
An unconscious patient with an extra-dural haematoma may not survive transfer to a neurosurgical centre for definitive care. This article describes a simple approach to a decompressive craniotomy which may be life-saving in these patients when a neurosurgeon is not available.


More dollars for New York.
With the shock from Sept. 11 still fresh, the Greater New York Hospital Association, led by Kenneth Raske, left, went ahead and did what had to be done, crunching numbers to attempt to quantify the staggering loss. Last week its hard work paid off when HHS announced another round of emergency funding to healthcare organizations that suffered direct losses from the terrorist attacks.


Role of Schwann cells in cutaneous wound healing.
Dermal wound healing is the process of repairing and remodeling skin following injury. Delayed or aberrant cutaneous healing poses a challenge for the health care system. The lack of detailed understanding of cellular and molecular mechanisms involved in this process hampers the development of effective targeted treatments. In a recent study, Parfejevs et al.-using state-of-the-art technologies, including in vivo sophisticated Cre/loxP techniques in combination with a mouse model of excisional cutaneous wounding-reveal that Schwann cells induce adult dermal wound healing. Strikingly, genetic ablation of Schwann cells delays wound contraction and closure, decreases myofibroblast formation, and impairs skin re-epithelization after injury. From a drug development perspective, Schwann cells are a new cellular candidate to be activated to accelerate skin healing. Here, we summarize and evaluate recent advances in the understanding of Schwann cells roles in the skin microenvironment.


Comparative analysis of different preservation techniques for the storage of Staphylococcus phages aimed for the industrial development of phage-based antimicrobial products.
Bacteriophages have been proven as effective antimicrobial agents in the treatment of infectious diseases and in other biocontrol applications including food preservation and disinfection. The extensive use of bacteriophages requires improved methodologies for medium- and long-term storage as well as for easy shipping. To this aim, we have determined the stability of four Staphylococcus phages (phiIPLA88, phiIPLA35, phiIPLA-RODI and phiIPLA-C1C) with antimicrobial potential at different temperatures (20°C/25°C, 4°C, -20°C, -80°C, -196°C) and during lyophilization (freeze drying) using several stabilizing additives (disaccharides, glycerol, sorbitol and skim milk). Differences between phages were observed at different temperatures (20°C/25°C, 4°C and -20°C), where phages were less stable. At lower temperatures (-80°C and -196°C), all phages showed good viability after 24 months regardless of the stabilizer. Differences between phages were also observed after lyophilization although the addition of skim milk yielded a dry powder with a stable titer after 24 months. As an alternative to facilitate storage and transportation, phage encapsulation has been also explored. Phage phiIPLA-RODI encapsulated in alginate capsules retained high viability when stored at 4°C for 6 months and at 20°C for 1 month. Moreover, the spray-dryer technique allowed obtaining dry powders containing viable encapsulated phages (phiIPLA-RODI and phiIPLA88) in both skim milk and trehalose for 12 months at 4°C. Storage of phages at 20°C was less effective; in fact, phiIPLA88 was stable for at least 12 months in trehalose but not in skim milk, while phiIPLA-RODI was stable only for 6 months in either stabilizer. These results suggest that encapsulated phages might be a suitable way for shipping phages.


Growth hormone deficiency in patients with 22q11.2 deletion: expanding the phenotype.
The list of findings associated with the 22q11.2 deletion is quite long and varies from patient to patient. The hallmark features include: conoruncal cardiac anomalies, palatal defects, thymic aplasia or hypoplasia, T cell abnormalities, mild facial dysmorphia, and learning disabilities. The 22q11.2 deletion has been seen in association with the DiGeorge sequence, velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome, isolated conotruncal cardiac anomalies, and some cases of autosomal dominant Optiz G/BBB syndrome. Short stature has been seen in one to two thirds of children reported in the literature with a diagnosis of VCFS, but growth hormone deficiency (GHD) has not been described in conjunction with this diagnosis. We present 4 patients with a 22q11.2 deletion and short stature who were found to have abnormalities in the growth hormone-insulin-like growth factor I axis. All had growth factors less than -2 SD for age and failed provocative growth hormone testing. Two patients were found to have abnormal pituitary anatomy. In our population, the incidence of GHD in 4 or 95 children with 22q11 deletion is significantly greater than the estimated incidence of GHD in the general population. Children with a 22q11.2 deletion appear to be at a greater risk for pituitary abnormalities. Therefore, those children with the 22q11.2 deletion and short stature or poor growth should be evaluated for GHD, as replacement growth hormone therapy may improve their growth velocity and final height prediction.


Multidrug resistance.
Resistance of malignant cells to cytotoxic agents is often a limiting factor to successful chemotherapy. The classical multidrug resistance is characterised by overexpression of a membrane protein, P-glycoprotein, which acts like a drug extruding pump reducing accumulation of cytotoxic agents inside malignant cells, thereby preventing their function. Resistance is expressed simultaneously towards several structurally unrelated drugs. P-glycoprotein is also expressed in many normal human tissues, e.g., in the gastrointestinal tract, and this may be the reason for intrinsic resistance observed clinically in cancers derived from certain tissues. More often multidrug resistance is acquired during chemotherapy. The physiological function of P-glycoprotein is still unknown but it may have a role in cellular detoxification and secreting mechanisms. Interest in the phenomenon of multidrug resistance centres on the correlation of P-glycoprotein expression to clinical drug resistance. Another goal is to find mechanisms by which the function of P-glycoprotein as a multidrug transporter is prevented and drug resistance reversed.


[The laboratory diagnostic of patients with tuberculosis with medicinal resistance of agent].
The article considers possibilities and means of transition to personalized treatment of patients with tuberculosis conditioned by fast development and spreading of medicinal resistance of tuberculosis agent. The technical possibilities are demonstrated for realization of this approach and also necessity of information possessing in the field of evaluation of treatment effectiveness. Also, attention was paid to relationship ofpharmacogenetics and pharmacokinetics of wide spectrum of anti-tuberculosis medications, medicinal resistance of agent and genetic conditioning of development of side-effect negative reactions to chemotherapy.


The catalysis mechanism of noble metals at electronic level.
Investigations based on density functional theory reveal that the energy band character of noble metal catalysts can be modified by changing the catalyst's configuration or using proper supports. The quantum size effects of the noble metal clusters and their cooperating effects with the oxide supports on the catalysis are shown by comparing the changes of N-O bond lengths on different catalysts. The noble metal catalysts can dissociate and activate the NO molecule by losing and regaining electrons. In addition, the coagulating effects of the catalysts play an important role in the reaction process of NO removing. The results of the computer simulations suggest that NO molecule can react with NO or CO on the NM clusters adsorbed on the oxide supports.


Microstructural and Mechanical Characterization of Colloidal Processed WC/(W5Vol%Ni) via Spark Plasma Sintering.
This study investigates the sintering behaviour and properties of WC-based composites in which WC was mixed with W5vol%Ni in concentrations of 10vol% and 20vol%. Colloidal processing in water and spark plasma sintering were employed to disperse the WC particles and facilitate sintering. The addition of W5vol%Ni improved the sintering process, as evident from a lower onset temperature of shrinkage determined through dilatometric studies. All samples exhibited the formation of tungsten monocarbide (W2C), with a more pronounced presence in the WC/20(W5vol%Ni) composite. Sintering reached its maximum rate at 1550 °C and was completed at 1600 °C, resulting in a final density exceeding 99.8%. X-ray diffraction analysis confirmed the detection of WC and W2C phases after sintering. The observed WC content was higher than expected, which may be attributed to carbon diffusion during the process. Macro-scale mechanical characterisations revealed that the WC/10(W5vol%Ni) composite exhibited a hardness of 18.9 GPa, while the WC/20(W5vol%Ni) composite demonstrated a hardness of 18.3 GPa. Increasing the W5vol%Ni binder content caused a decrease in mechanical properties due to the formation of W2C phases. This study provides valuable insights into the sintering behavior and properties of WC/W5vol%Ni composites, offering potential applications in extreme environments.


Tularemia of the middle ear.
We report the case of a 10-year-old boy with prolonged fever who was found to have tularemia of the middle ear. Otolaryngologic cases including oropharyngeal and glandular or ulceroglandular forms of the head and neck region are estimated to account for 12% of all tularemia cases, but to date we have not seen a report of tularemia in the middle ear. The possibility of tularemia may not occur to a physician because of the wide variation of clinical manifestations.


Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections.
Polymyxin B is used as a last therapeutic option for the treatment of multidrug-resistant Gram-negative bacterial infections. This study aimed to develop a population pharmacokinetic model and limited sampling strategy, a method to estimate the area under the concentration curve (AUC) by using a limited number of samples, to assist therapeutic drug monitoring of polymyxin B in Chinese patients. Population pharmacokinetic analysis was performed using Phoenix® NLME with data obtained from 46 adult patients at steady state. Various demographic variables were investigated as potential covariates for population pharmacokinetic modeling. The limited sampling strategies based on the Bayesian approach and multiple linear regression were validated using the intraclass correlation coefficient and Bland-Altman analysis. As a result, the data was described by a two-compartment population pharmacokinetic model. Through the modeling, creatinine clearance was found to be a statistically significant covariate influencing polymyxin B clearance. The limited sampling strategies showed the two-point model (C0h and C2h) could predict polymyxin B exposure with good linear relativity (r2 > 0.98), and the four-point model (C1h, C1.5h, C4h, and C8h) performed best in predicting polymyxin B AUC (r2 > 0.99). In conclusion, this study successfully developed a population pharmacokinetic model and limited sampling strategies that could be applied in clinical practice to assist in therapeutic drug monitoring of polymyxin B in Chinese patients.


Biology and treatment of the mamba snakebite.
Mambas are venomous African snakes that are capable of inflicting fatal envenomation. The mambas (genus Dendrosaspis) are members of the family Elapidae [1]. Four species of mamba inhabit equatorial and southern Africa. Without medical treatment, mamba bites are frequently fatal. First aid treatment includes lymphatic retardation with immobilization and pressure wrap. Medical management requires the intravenous administration of mamba-specific antivenin.


Galleria mellonella is an effective model to study Actinobacillus pleuropneumoniae infection.
Actinobacillus pleuropneumoniae is responsible for swine pleuropneumonia, a respiratory disease that causes significant global economic loss. Its virulence depends on many factors, such as capsular polysaccharides, RTX toxins and iron-acquisition systems. Analysis of virulence may require easy-to-use models that approximate mammalian infection and avoid ethical issues. Here, we investigate the potential use of the wax moth Galleria mellonella as an informative model for A. pleuropneumoniae infection. Genotypically distinct A. pleuropneumoniae clinical isolates were able to kill larvae at 37 °C but had different LD50 values, ranging from 10(4) to 10(7) c.f.u. per larva. The most virulent isolate (1022) was able to persist and replicate within the insect, while the least virulent (780) was rapidly cleared. We observed a decrease in haemocyte concentration, aggregation and DNA damage post-infection with isolate 1022. Melanization points around bacterial cells were observed in the fat body and pericardial tissues of infected G. mellonella, indicating vigorous cell and humoral immune responses close to the larval dorsal vessel. As found in pigs, an A. pleuropneumoniae hfq mutant was significantly attenuated for infection in the G. mellonella model. Additionally, the model could be used to assess the effectiveness of several antimicrobial agents against A. pleuropneumoniae in vivo. G. mellonella is a suitable inexpensive alternative infection model that can be used to study the virulence of A. pleuropneumoniae, as well as assess the effectiveness of antimicrobial agents against this pathogen.


The specificity of environmental influence: socioeconomic status affects early vocabulary development via maternal speech.
The hypothesis was tested that children whose families differ in socioeconomic status (SES) differ in their rates of productive vocabulary development because they have different language-learning experiences. Naturalistic interaction between 33 high-SES and 30 mid-SES mothers and their 2-year-old children was recorded at 2 time points 10 weeks apart. Transcripts of these interactions provided the basis for estimating the growth in children's productive vocabularies between the first and second visits and properties of maternal speech at the first visit. The high-SES children grew more than the mid-SES children in the size of their productive vocabularies. Properties of maternal speech that differed as a function of SES fully accounted for this difference. Implications of these findings for mechanisms of environmental influence on child development are discussed.


Integrated metagenomic and metaproteomic analyses of marine biofilm communities.
Metagenomic and metaproteomic analyses were utilized to determine the composition and function of complex air-water interface biofilms sampled from the hulls of two US Navy destroyers. Prokaryotic community analyses using PhyloChip-based 16S rDNA profiling revealed two significantly different and taxonomically rich biofilm communities (6,942 taxa) in which the majority of unique taxa were ascribed to members of the Gammaproteobacteria, Alphaproteobacteria and Clostridia. Although metagenomic sequencing indicated that both biofilms were dominated by prokaryotic sequence reads (> 91%) with the majority of the bacterial reads belonging to the Alphaproteobacteria, the Ship-1 metagenome harbored greater organismal and functional diversity and was comparatively enriched for sequences from Cyanobacteria, Bacteroidetes and macroscopic eukaryotes, whereas the Ship-2 metagenome was enriched for sequences from Proteobacteria and microscopic photosynthetic eukaryotes. Qualitative liquid chromatography-tandem mass spectrometry metaproteome analyses identified 678 unique proteins, revealed little overlap in species and protein composition between the ships and contrasted with the metagenomic data in that ~80% of classified and annotated proteins were of eukaryotic origin and dominated by members of the Bacillariophyta, Cnidaria, Chordata and Arthropoda (data deposited to the ProteomeXchange, identifier PXD000961). Within the shared metaproteome, quantitative (18)O and iTRAQ analyses demonstrated a significantly greater abundance of structural proteins from macroscopic eukaryotes on Ship-1 and diatom photosynthesis proteins on Ship-2. Photosynthetic pigment composition and elemental analyses confirmed that both biofilms were dominated by phototrophic processes. These data begin to provide a better understanding of the complex organismal and biomolecular composition of marine biofilms while highlighting caveats in the interpretation of stand-alone environmental '-omics' datasets.


Developing a non-invasive diagnostic model for pediatric Crohn's disease using RNA-seq analysis.
Introduction: Pediatric Crohn's disease is a chronic inflammatory condition that affects the digestive system in children and adolescents. It is characterized by symptoms such as abdominal pain, diarrhea, weight loss, and malnutrition, and can also cause complications like growth delays and delayed puberty. However, diagnosing pediatric Crohn's disease can be difficult, especially when it comes to non-invasive methods. Methods: In this study, we developed a diagnostic model using RNA-seq to analyze gene expression in ileal biopsy samples from children with Crohn's disease and non-pediatric Crohn's controls. Results: Our results showed that pediatric Crohn's disease is associated with altered expression of genes involved in immune response, inflammation, and tissue repair. We validated our findings using two independent datasets from the Gene Expression Omnibus (GEO) database, as well as through one prospective independent dataset, and found that our model had a high accuracy rate. Discussion: These findings suggest the possibility of non-invasive diagnosis for pediatric Crohn's disease and may inform the development of targeted therapies for this condition.


The embryology of congenital heart defects.
The embryological development of the heart is an awesome and complex process. The heart is formed from groups of cells that coalesce into sheets of tissue. These sheets fuse to form a tube that grows into the atria and ventricles. The twists and turns of the developing heart tissue and the simultaneous septation of atria, ventricles, and truncus, along with a shifting of the atrioventricular canal and conus then position the portions of the heart in alignment to allow normal blood flow. Errors at any stage of embryological formation can result in specific congenital defects. Understanding the development of the heart in utero can provide the pediatric nurse a basis for understanding the physiological effects of embryological failures that result in congenital heart defects in the infant and child.


Limited access to drugs for resistant tuberculosis: a call to action.
Although the rate of new tuberculosis (TB) cases has been falling worldwide, progress toward the targets for diagnosis and treatment of drug-resistant TB is far off-track. In countries with no reliable TB surveillance system, setbacks and progression of TB control is barely reflected and little is known on the situation in the field. Interviews with health professionals in Gabon revealed limited access to first- and second-line TB drugs and important deficiencies in basic TB control. National and international action needs to be taken to meet the global TB control targets.


Effects of anion and cation inhibitors and carbonic anhydrase inhibitors upon the activity of the gypsy moth (Lepidoptera: Lymantriidae) nucleo-polyhedrovirus.
Twenty chemicals that were reported to act as anion transport inhibitors, cation transport inhibitors, and inhibitors of carbonic anhydrase activity were tested at a 1% concentration (wt:wt) for their effects upon the biological activity of the gypsy moth, Lymantria dispar (L.), nucleopolyhedrovirus (LdMNPV). Among the five anion transport inhibitors tested, flufenamic acid acted as a viral enhancer. None of the seven inhibitors of K+ enhanced viral activity and three (4-aminopyridine, diacetyl, and procaine) significantly reduced the activity of LdMNPV. All four Na+ transport inhibitors (abietic acid, amiloride, dicyclohexylcarbodiimide, triamterene) acted as viral enhancers. Triamterene was the most active enhancer, as the LC50 was reduced by approximately 1,750-fold. Five carbonic anhydrase inhibitors were tested and four (acetazolamide, hydrochlorothiazide, methazolamide, sulfanilamide) enhanced the activity of LdMNPV. Acetazolamide (a carbonic anhydrase inhibitor), amiloride (a Na+ transport inhibitor), and flufenamic acid (an anion transport inhibitor) were tested singly and in different combinations. Every combination tested (acetazolamide/amiloride, acetazolamide/flufenamic acid, amiloride/flufenamic acid, acetazolamide/amiloride/flufenamic acid) significantly decreased the LC50 from 7.79 PIB/mm2 to a value as low as 0.008 PIB/mm2 (amiloride/flufenamic acid).


[Changes in the aortic prosthesis surgical risk].
Between May 1963 and December 1976, 889 patients underwent single valve aortic replacement by prosthesis. Hospital (30 day) mortality fell, with an exponential decrease (r = 0.94, p less than 0.01) to 4 per cent in 1976. Early risk factors are studied, taking into account the changes affecting them respectively over the time period considered. The average age of the patients increased but did not significantly affect operative mortality. Cardio-thoracic ratio, sex and the duration of extracorporeal circulation had little or no prognostic value. Only classification in class IV of the N.Y.H.A. and the type of valvular disease (severe incompetence) were of clearly pejorative significance. Most deaths occurred early in a context of signs of poor cardiac output, severe disturbances of ventricular rhythym, visceral (digestive) syndromes and/or thrombotic complications. They were characterised at autopsy by sub-endocardial haemorrhagic lesions. The prevalence of these lesions and that of early deaths appeared to decrease with techniques for myocardial protection during the operation.


Neurotensinergic Excitation of Dentate Gyrus Granule Cells via Gαq-Coupled Inhibition of TASK-3 Channels.
Neurotensin (NT) is a 13-amino acid peptide and serves as a neuromodulator in the brain. Whereas NT has been implicated in learning and memory, the underlying cellular and molecular mechanisms are ill-defined. Because the dentate gyrus receives profound innervation of fibers containing NT and expresses high density of NT receptors, we examined the effects of NT on the excitability of dentate gyrus granule cells (GCs). Our results showed that NT concentration dependently increased action potential (AP) firing frequency of the GCs by the activation of NTS1 receptors resulting in the depolarization of the GCs. NT-induced enhancement of AP firing frequency was not caused indirectly by releasing glutamate, GABA, acetylcholine, or dopamine, but due to the inhibition of TASK-3 K(+) channels. NT-mediated excitation of the GCs was G protein dependent, but independent of phospholipase C, intracellular Ca(2+) release, and protein kinase C. Immunoprecipitation experiment demonstrates that the activation of NTS1 receptors induced the association of Gαq/11 and TASK-3 channels suggesting a direct coupling of Gαq/11 to TASK-3 channels. Endogenously released NT facilitated the excitability of the GCs contributing to the induction of long-term potentiation at the perforant path-GC synapses. Our results provide a cellular mechanism that helps to explain the roles of NT in learning and memory.


On-line measurement of intramolecular carbon isotope distribution of acetic acid by continuous-flow isotope ratio mass spectrometry.
Molecular and intramolecular carbon isotope measurements of acetic acid present in natural environments have been performed by off-line procedures. The off-line method is complicated and time-consuming and requires micromolar to millimolar amounts of sample. This limits geochemical isotopic studies, especially at the intramolecular level, on acetic acid present in natural samples. Here, we examine an on-line measurement of intramolecular carbon isotope distribution of acetic acid using continuous-flow isotope ratio mass spectrometry (CF-IRMS) coupled with an on-line pyrolysis system. This is achieved by measurement of the respective carbon isotope ratios of CH4 and CO2 produced by on-line pyrolysis of acetic acid. Results for authentic standards of pure acetic acid demonstrated the practicality of this on-line method, although the carbon isotope ratio of the methyl group could not be determined directly. The precision of the carbon isotope measurements was 0.4 per thousand (1sigma). The carbon isotope distribution determined by the on-line method was identical to that determined by the conventional off-line method within analytical error. The advantages of the on-line method compared with the conventional off-line method are that it is less laborious, requires less analytical time (less than one hour per sample) and, most importantly, uses smaller sample sizes (ca. 10 nanomole). An application of this on-line method to natural geochemical samples will provide an insight into the geochemical cycle of acetic acid.


The relative potencies of anti-influenza compounds.
The relative potencies of some standard anti-influenza compounds have been examined in vitro by plaque reduction in calf kidney cells, and in vivo by reduction in virus titers of the lungs of infected mice. Strains belonging to the four subtypes H0N1, H1N1, H2N2, and H3N2 were employed to compare the activity of amantadine hydrochloride and ribavirin. In vitro for all strains except A/NWS/OO(H0N1) amantadine hydrochloride was 3-4 times more active than ribavirin. In vivo with sensitive strains amantadine hydrochloride produced a plateau effect at higher dose levels, but at lower dose levels was marginally more active than ribavirin. The sensitivity of A/Hong Kong/1/68 (H3N2) to amantadine hydrochloride, rimantadine hydrochloride, cyclooctylamine, and ribavirin was also investigated. In vitro rimantadine hydrochloride was similar in activity to amantadine hydrochloride and ribavirin, but cyclooctylamine was considerably less active. In vivo cyclooctylamine was active only at 150 mg/kg/day, whereas rimantadine hydrochloride produced a plateau effect over a range of concentrations from 9,12-150 mg/kg/day.


Establishment and characterization of unique cell lines derived from pyothorax-associated lymphoma which develops in long-standing pyothorax and is strongly associated with Epstein-Barr virus infection.
Malignant lymphoma frequently develops in the pleural cavity of patients with over 20 years' history of pyothorax. The term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. We established four novel lymphoma cell lines (OPL-3, -4, -5, and -7) from four patients with PAL. Characteristics of the four cell lines are as follows: B-cell nature with defective expression of B-cell and T-cell surface antigens, monoclonal pattern of Epstein-Barr virus (EBV) infection in lymphoma cells (thus indicating an etiological role of EBV for lymphomagenesis), complicated chromosomal abnormalities with numerous structural and numerical abnormalities, and occasional but distinct genome instability. These abnormalities in cell character might be caused by the specific circumstances of PAL lymphomagenesis, i.e., chronic inflammation. Thus, PAL cell lines could be useful in analysis of molecular mechanisms leading to malignancy in chronic inflammation.


A Giant Lumbar Pseudomeningocele in a Patient with Neurofibromatosis Type 1: A Case Report.
This is a rare case of giant lumbar pseudomeningocele with intra-abdominal extension in patient with neurofibromatosis type 1 (NF1). The patient's clinical course is retrospectively reviewed. A 34-year-old female affected by NF1 was referred to our institution for persistent low back pain and MRI diagnosis of pseudomeningocele located at L3 level with paravertebral extension. From the first surgical procedure by a posterior approach until the relapse of the pseudomeningocele documented by MRI, the patient underwent two subsequent posterior surgical procedures to repair the dural sac defect with fat graft and fibrin glue. One month after the third operation, the abdominal MRI showed a giant intra-abdominal pseudomeningocele causing compression of visceral structures. The patient was asymptomatic. The pseudomeningocele was treated with an anterior abdominal approach and the use of the acellular dermal matrix (ADM) sutured directly on the dural defect on the anterolateral wall of the spinal canal. After six months of follow-up the MRI showed no relapse of the pseudomeningocele. Our case highlights the possible use of ADM as an effective and safe alternative to the traditional fat graft to repair challenging and large dural defects.


Cell surface comodulation of CD4 and T cell receptor by anti-CD4 monoclonal antibody.
In our study we have used anti-CD4 mAb to investigate the cell surface association between CD4 and the Ag-specific TCR complex on mature peripheral T cells. Anti-CD4 mAb was administered in vivo and in vitro and its effects on CD4 and CD3 cell surface expression were determined. In vivo, anti-CD4 mAb reduced cell surface expression of its ligand, CD4, and secondarily also reduced cell surface expression of CD3/TCR on CD4+ splenic T cells. In vitro, multivalent cross-linking of CD4 by anti-CD4 mAb and either FcR+ cells or anti-Ig mAb also resulted in decreased surface expression of CD4 and specific comodulation of CD3/TCR. The secondary reduction in cell surface CD3/TCR expression induced by CD4 cross-linking could be pharmacologically disrupted by high doses of PMA, indicating that the comodulation of CD3 with CD4 was dependent upon intracellular mediators, possibly including protein kinase C. These results demonstrate that, in the presence of anti-CD4 mAb, CD4 is functionally associated with the CD3/TCR complex, and that this association is dependent upon the activity of intracellular mediators. Such intracellular mediators might induce the coordinate down-modulation of physically unassociated CD4 and CD3/TCR molecules, or, alternatively, might promote a physical interaction between CD4 and CD3/TCR molecules.


Mapping lateralization of click trains in younger and older populations.
The main purpose of this study was to describe and compare lateralization of earphone-presented stimuli in younger and older individuals. Lateralization functions, relating perceived location to either interaural time differences (ITDs) or interaural level differences (ILDs) were determined for 78 subjects, aged 21-88 years, who responded by pressing one of nine keys to indicate the perceived location of the stimulus. All subjects were healthy, without any history of hearing loss or ear surgery and within the normal pure tone audiometric range for their age group. Interaural pure tone and click thresholds did not differ by more than 5 dB across ears. The ILD lateralization functions, ranging from 10 dB favoring the left ear to 10 dB favoring the right ear were linear. In contrast, the ITD lateralization functions were S-shaped with a clear linear component ranging from 750 micros favoring one ear to 750 micros favoring the other ear and with an asymptote from 750 micros to 1 ms. The same general shape of the ITD and ILD lateralization functions was found at all ages, but the linear slope of the ITD lateralization function became shallower with age. The ability to discriminate midline-located click trains (ITD and ILD=0) from ITD-lateralized click trains deteriorated with age, while the comparable ability to discriminate ILD-lateralized click trains did not change significantly with age. The data support two general conclusions. First there seems to be an overall reduction in the range of ITD-based lateralization due to aging. Second, there is a greater reduction in sensitivity due to aging in changes from the perceived midline position (ITD and ILD=0) when ITD is manipulated than when ILD is manipulated.


Neuropathic Pain as Main Manifestation of POLG-Related Disease: A Case Report.
Mutations in nuclear-encoded genes that are involved in mitochondrial DNA replication and maintenance (e.g., POLG) have been associated with chronic progressive external ophthalmoplegia (CPEO) phenotype. These nuclear genome mutations may lead to multiple mitochondrial DNA deletions or mitochondrial DNA depletion. On the other hand, primary genetic defects of mitochondrial DNA (such as single large-scale deletion or point mutations) have also been associated with the CPEO phenotype. Chronic progressive external ophthalmoplegia (CPEO) may be a manifestation of specific syndromes that, when clinically recognized, prompt clinicians to investigate specific genetic defects. Thus, CPEO, as part of Kearns Sayre syndrome, suggests the presence of a large-scale deletion of mitochondrial DNA. However, in pure CPEO or CPEO plus phenotypes, it is more difficult to know whether causative genetic defects affect the nuclear or mitochondrial DNA. Here, we present a patient with a long-standing history of CPEO plus phenotype, in whom the sequencing of mitochondrial DNA from skeletal muscle was normal, and no other genetic defect was suspected at first. At the time of our evaluation, the presence of polyneuropathy and neuropathic pain prompted us to investigate nuclear genetic defects and, specifically, mutations in the POLG gene. Thus, the sequencing of the POLG gene revealed p.Thr251Ile and p.Pro587Leu mutations in one allele, and p.Ala467Thr mutation in another allele. Although one would expect that mutations in POLG lead to multiple mitochondrial DNA deletions or depletion (loss of copies), the absence of mitochondrial DNA abnormalities in tissue may be explained by heteroplasmy, a lack or no significant involvement of biopsied tissue, or a sampling bias. So, the absence of secondary mitochondrial DNA alterations should not discourage clinicians from further investigating mutations in nuclear-encoded genes. Lastly, mitochondrial point mutations and single mitochondrial DNA deletions very rarely cause CPEO associated with polyneuropathy and neuropathic pain, and POLG-related disease should be considered in this scenario, instead.


First report of peste des petits ruminants virus lineage II in Hydropotes inermis, China.
In this study, we investigated an outbreak of peste des petits ruminants (PPR) at a Hydropotes inermis (water deer) farm in Anhui Province, China. These results demonstrated that PPR viruses (PPRVs) can infect H. inermis and also revealed that virulent lineage II PPRVs exist in China, where they have been responsible for the deaths of wild animals. The government should pay close attention to the threat of PPRV epidemiology in China.


Zero lag synchronization of chaotic systems with time delayed couplings.
Zero-lag synchronization (ZLS) between chaotic units, which do not have self-feedback or a relay unit connecting them, is experimentally demonstrated for two mutually coupled chaotic semiconductor lasers. The mechanism is based on two mutual coupling delay times with certain allowed integer ratios, whereas for a single mutual delay time ZLS cannot be achieved. This mechanism is also found numerically for mutually coupled chaotic maps where its stability is analyzed using the Schur-Cohn theorem for the roots of polynomials. The symmetry of the polynomials allows only specific integer ratios for ZLS. In addition, we present a general argument for ZLS when several mutual coupling delay times are present.


Electron impact ionization of sodium Rydberg atoms below 2 eV.
We have observed electron impact ionization of highly excited sodium Rydberg atoms in ns and nd states, n=35-51, below E=2 eV electron kinetic energy with energy resolution 0.25 eV. Measured absolute cross sections near 0 eV range from sigma(35d) approximately 7 x 10(-10) to sigma(50d) approximately 4 x 10(-9) cm(2). The energy dependence is consistent with that of widely used binary encounter approximation cross sections, and sigma(n) follows a power law in n. The measured cross sections are 14 to 24 times larger than theoretically predicted values. This enhancement may signal the effect of large polarizabilities of high Rydberg states not yet accounted for in ionization theories.


Gastric volvulus: a potentially fatal cause of acute abdominal pain.
A woman aged 67 years attended the emergency department with acute abdominal and back pain of 1-day duration with associated vomiting. The patient had multiorgan failure. Resuscitation was started with intravenous fluids and vasopressors. An abdominal CT scan was completed which confirmed the diagnosis of acute gastric volvulus. The patient was successfully resuscitated from a cardiorespiratory arrest during transfer to the operating theatre. The patient subsequently underwent a total gastrectomy with stapling of the oesophageal and duodenal stumps. The abdomen was packed and left open as a laparostomy with a planned relook 48 hours later was to be performed. Unfortunately, the patient continued to deteriorate postoperatively in the intensive care unit despite maximum organ support for multiorgan failure. A decision was made to withdraw treatment and the patient died 10 hours postoperative. This case illustrates the presentation of acute gastric volvulus at a late stage and the high mortality rate associated with it.


Amelioration of Inflammatory Cytokines Mix Stimulation: A Pretreatment of CD137 Signaling Study on VSMC.
Previous studies showed little CD137 expressed in normal vascular smooth muscle cells (VSMCs) and it is important to find a valid way to elevate it before studying its function. The level of CD137 was detected by RT-PCR, western blot, and flow cytometry, respectively. CD137 signaling activation was activated by agonist antibody and measured through phenotype transformation indicators and cell functions. Proteins in supernatants were detected by ELISA. The total CD137 elevates under different concentrations of CM treatment. Among these, 25 ng/ml CM treatment increases the CD137 expression mostly. However, flow cytometry demonstrates that 10 ng/ml CM elevates surface CD137 more significantly than other concentrations and reaches the peak at 36 h. At 10 ng/ml, but not 25 ng/ml CM pretreatment, the levels of phenotype related proteins such as SM-MHC, α-SMA, and calponin decrease while vimentin and NFATc1 increase, suggesting that VSMCs undergo phenotype transformation. Transwell, CCK-8 assay, and ELISA showed that the ability of VSMCs viability, migration, and IL-2 and IL-6 secretion induced by CD137 signaling was significantly enhanced by the pretreatment of 10 ng/ml CM. This research suggested that 10 ng/ml CM pretreatment is more reasonable than other concentrations when exploring CD137 function in VSMCs.


Systemic Capillary Leak Syndrome as a Rare, Potentially Fatal Complication of COVID-19: A Case Report and Literature Review.
Systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare and potentially lethal condition characterized by hypotension, hemoconcentration, and hypoalbuminemia; however, the cause of SCLS is still uncertain. We present the case of a 62-year-old male with flu-like symptoms who presented to the emergency department with shock. Initial evaluation revealed hemoconcentration, hypoalbuminemia, acute kidney failure, and positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite aggressive fluid resuscitation, the shock persisted, and the patient's condition deteriorated. After ruling out ischemia and septic shock, the patient was diagnosed with coronavirus disease 2019 (COVID-19)-associated SCLS. Treatment with remdesivir and intravenous immunoglobulin (IVIG), along with the restoration of intravascular volume, led to the gradual improvement of the patient's condition. The patient experienced pulmonary edema, which was managed by correcting the fluid balance through continuous hemodiafiltration. Eventually, the patient recovered without any residual organ complications. SCLS is often misdiagnosed because of its rarity and non-specific symptoms. Accurate diagnosis and understanding of the disease's pathophysiology are crucial for effective management. This report contributes to the existing literature by presenting a case of COVID-19-associated SCLS and emphasizes the need for further research on its occurrence and outcomes.


Physician reimbursement under Medicare.
Payment for physician services in the United States is directly tied to the payment system implemented in the Medicare system. The use of a code to categorize medical and surgical services, as well as a relative value system to assess physician services and reimburse them accordingly, is now well established. In light of this, it is important for physicians to possess knowledge of how this coding and reimbursement system was established, how it is updated, what means are available to modify it, and how it is used in practice. The author addresses these issues, offering a primer for the neurosurgeon on the Medicare system as it relates to physician payment.


Removal of organic contaminants from wastewater with GO/MOFs composites.
Graphene oxide/metal-organic frameworks (GO/MOFs) have been prepared via solvothermal synthesis with ferrous sulfate heptahydrate, zirconium acetate and terephthalic acid for the purpose of removing organic pollutants from wastewater. The composites were analyzed using scanning electron microscopy, infrared spectrometry, and XRD. Tetracycline hydrochloride and orange II were implemented as model pollutants to evaluate the efficacy of the GO/MOFs in water purification, in which 50 mg of Zr/Fe-MOFs/GO was mixed with 100 mL of 10 mg/L, 20 mg/L, 30 mg/L, or 50 mg/L tetracycline hydrochloride solution and 25 mg/L, 35 mg/L, 45 mg/L, or 60 mg/L orange II solution, respectively. The removal efficacy after 4 hours was determined to be 96.1%, 75.8%, 55.4%, and 30.1%, and 98.8%, 91.9%, 71.1%, and 66.2%, respectively. The kinetics of pollutant removal was investigated for both tetracycline hydrochloride and orange II and excellent correlation coefficients of greater than 0.99 were obtained. The high efficacy of these MOFs in pollutant removal, coupled with their inexpensive preparation indicates the feasibility of their implementation in strategies for treating waste liquid. As such, it is anticipated that Zr/Fe-MOFs/GO composites will be widely applied in wastewater purification.


Measurement of yield and spectrum of secondary electron emission and their characteristics under modification of conductive materials.
Surface modification technique of secondary electron emission (SEE) characteristics of materials, which is utilized to suppress or promote the SEE from material surface under electron bombardment, has extensive applications in a variety of fields. Measurement of the secondary electron yield (SEY) and the secondary electron spectrum (SES) before and after surface modification is essential for the evaluation of effectiveness and the investigation of mechanism of material modification. A SEY and SES measurement system is reported in this article. The comparative measurements of the total SEY, the true SEY, the backscattered electron yield, and the SES of nickel and free-standing vertical graphene, which was grown in situ on the surface of nickel substrate by plasma enhanced chemical vapor deposition, were performed using this system. The measurement results demonstrate that this system could facilitate the study of surface modification on the SEE characteristics of conductive materials.


Decomposition of rock micro-fracture signals based on a singular value empirical mode decomposition algorithm.
Rock burst early warning technology is currently applied mainly in microseismic monitoring. Rock burst signals indicate the micro-fracture phenomena of a rock and can transmit earthquake waves through the rock before they are finally received by a detector. A characteristic decomposition of rock micro-fracture signals was conducted by the singular value Empirical Mode Decomposition (EMD) algorithm to effectively decompose the characteristic signals of a rock micro-fracture from mixed microseismic signals, with a low signal to noise ratio to ensure prediction precision. When comparing the proposed method with wavelet decomposition and EMD, it was found that the local characteristics of the signals were retained effectively. The proposed algorithm was verified by applying it in a laboratory simulation and to the decomposition of microseismic signals from a hydro-power station. It was concluded that the improved algorithm had a better decomposition precision than wavelet decomposition and EMD decomposition and could effectively separate the characteristic signals of micro-earthquakes. This could provide a significant basis for the identification of the abnormal microseismic signals of rock micro-fractures as well as a pre-warning of rock fractures. It is therefore of practical significance to study rock fracture early warning technology.


THE FUNCTION OF CALL ALTERNATION IN ANURAN AMPHIBIANS: A TEST OF THREE HYPOTHESES.
Males of many species of anurans alternate calls with those of their neighbors in a chorus. This pattern of calling reduces signal interference and may: 1) facilitate intermale spacing because males can better gauge the intensity of neighbors' calls if these calls do not overlap with their own; 2) help preserve species-specific temporal information in calls required to attract females; and/or 3) make it easier for females to localize males in the chorus. I tested these hypotheses with three species that exhibit call alternation, Hyla crucifer, H. versicolor, and H. microcephala. Males of all three species gave more aggressive calls to high-intensity synthetic stimuli that alternated with their calls than to those that overlapped their calls. These results support the first hypothesis. Results of four-speaker female choice experiments using alternating and overlapping calls indicate that preservation of signal integrity also is important in H. versicolor and H. microcephala, species that have fine-scale temporal information in their calls. However, the third hypothesis was not supported; females failed to discriminate among alternating and overlapping calls if the problem of signal disruption was eliminated or irrelevant.